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Chapter 1: Introduction Discovery Is Still the Big Bang Stage Chapter 2: Cancer and Tumors Multi-Platform Gliknik Tackling Cancer, Immune Disease Markets Catherex Oncolytic Virus Drugs Targeting Brain, Liver Cancers Kinagen Targets Inactive Kinases; Puts a New Spin on Raf in Cancer Igenica Raises $24M in Series B to Expand Antibody Platforms Esperances Membrane Disrupting Peptides Seek and Destroy Cancer Amplyx Improving HIV, Cancer Drugs Through Better Targeting Korean Firm KAEL-GemVax Advancing Cancer Vaccine Del Mar Pharma Bets on Glioblastoma Salvage Therapy Certus Deploys Nanoparticles for Targeted Tumor Delivery GenSpera Testing Plant-Based Poison to Zap Solid Tumors Actis Biologics to Raise $380M, for Malaysia, India Ventures Ensysce Aims Nanotubes to Deliver Precise Therapeutics Concordia Pharmaceuticals First Off the Line in Ras Race Centrose Seeks Funds for Low-Tox EDC Phase I Trials Apogee Poised to Enter Clinic; SK Inhibitor Aimed at Cancer New Genesis for Viragens Anti-CD55 Cancer Program Jantibody Heats Up Antibody and Vaccine Fields with HSP70 Apexigen Exploits Unique Rabbit Physiology to Make Antibodies Chapter 3: Drug Screening and Delivery Senex Targets Aging Diseases with CKI Pathway Inhibitors Fabrus Forges Ahead with Therapeutic Antibody Platform CRO + Drug Discovery Helps DiscoveryBioMed Survive Acylin Pharma Explores Blooming Acetylation Field Ligon Turns Microarray Screening Upside Down Chapter 4: Cardiovascular and Related Diseases Verio Taking Regenerative Road to Develop Muscle, Cardiac Drugs More Oxygen, Please; NormOxys Targeting Disease Via Hypoxia Swedish Firm Cardoz Tackling Oft-Underdiagnosed Triple-A ElexoPharms First License Deal Worth Up to $41.6M from Merck InVasc Seeks Path for CKD Combo, New Targets Next Radical Therapeutix Works to Protect Precious Heart Tissue FerroKin to Eliminate Iron Overload with 1 Dose/Day
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Chapter 5: Neuroscience Afraxis Stabilizes Synapses in Fragile X, Autism, Alzheimers First Deal a Good One for NeurOp; Up to $74M for CNS Discoveries Start-Up AgeneBio Aims to Treat MCI by Inhibiting Neural Activity Sinapis Pharma Sees New Use for Meth in Stroke, Brain Injury Embera Compound Takes New Addiction Treatment Tack Chapter 6: Stem Cells and Regenerative Medicine Calling All Stem Cells; Juventas Boosts SDF-1 for Cardiac Repair Bioprinting Press: Organovos Technology to Build New Tissues Garnet Seeking Additional Funds to Advance Lead Cell Therapy Multiplatform Taiga Scores NIH Funding for HSC Technologies Chapter 7: Genetics and Genomics Blockmir Technology Gets Seed Funding, Comes Out of Stealth Molecular Templates Develops Drugs Via Toxin-Based Method Sirnaomics Takes Multitarget Approach to Gene Silencing Integrated Diagnostics Takes Proteomic Approach Alternative to Surgery for Refractory Epilepsy? Tivorsan Ready to Raise Funds for Biglycan DMD Candidate BMT Takes Shorter Approach to Develop RNAi-Based Drugs Gene Therapy Firm Renova Created from Collateral Vein Chapter 8: Immune System and Infectious Diseases VBL Turns Sights on Inflammatory Market with Novel Phospholipids JDP, with New CEO on Board, Goes for PC, Allergy Markets Daring TB Different; Early Stage Aarden Working on PTP Drugs Low-Profile Marcadia Moving Diabetes Candidate Forward ViroXis Gaining a Foothold as it Tries to Bark Up the Right Tree Inhibikase Taking on Bacteria, Viruses with Single Approach $39.6M Series A Inflames Catabasis Effort in Diabetes Immunome Harnessing Immune Systems Natural Curative Ability RetroVirox Building Antiviral Candidates for Others to Grow Western States Goes East to Advance Immune Modulators Excelimmune Aims Polyclonal Antibodies at Bacterial Disease Former Amgen Execs Fusing Antibodies, IFN at ImmunGene MabVax Pursues Two-Pronged Approach to Immunotherapies Maxygen Technology Breeds Vaccine Efforts at AltraVax Chapter 9: InflammatoryDiseases Look Out, Roche! Fast-Follower Femta Is Chasing Actemras Tail With Fibrosis Making Headlines, Promedior Closes $12M Series C Swedens BioChromix Pharma Tackles ADs Amyloid Cascade
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Genentech Colleagues Reunite to Bring Eye Drug to Market Resolve Therapeutics Targets Upstream Interferon-alfa Pathway Chapter 10: Dermatologics $12M Series A Moves Ablexis Toward Better Mouse Platform Vicept Aims to Get Red Out, Adds $10M for Rosacea Trials Valocor Says Beat It to Acne, Atopic Dermatitis and Vitiligo Chapter 11: Obesity Halsa ZAGs While Others ZIG: A New Mechanism in Obesity Litheras Phase II Fat Reduction Drug Aims to Follow Botox Model Chapter 12: Eye Diseases Aerie Sets Sights on Glaucoma With Phase II ROCK Inhibitor Altheos Raises $20M; Gets Into Glaucoma ROCK Inhibitor Game Chapter 13: Foundations Biotech VC Larry Bock Uses Start-up Spirit in Science Fest Clearitys Mission: To Change Ovarian Cancer Outcomes Myelin Repair Group Works to Develop Drugs, Cure MS OneWorld Health Seeks Biotech Solutions for Developing World
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chapter 1:
Introduction
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discovery is still
the
Thats not a theory; rather its a fact in the evolution of biotechnology drug development in the journey from concept to commercialization. Success in the biotechnology drug development world may advance with capital and culminate with cash, but it always begins with creativity. Brainstorming is relatively the easy part for the purveyors of innovative R&D, while becoming disarming VC whisperers is often more challenging than breaking down molecules for these wunderkind researchers. These companies and researchers covered in this publication are just some of the bright and optimistic young biotechs seeking to take their ingenuity to the next level by capitalizing on their newsworthy research endeavors or business development agendas to attract big pharma partners or entice VC investment. Innovation is frequently impressive to industry observers and very self-satisfying for the inventor, although it customarily comes with prospective opportunity, it has a most difficult time attracting money. Seed-stage companies usually have a great idea or two, but dont yet have a dependably accountable revenue stream or even a proof-of-concept. Early stage hopefuls have more of a foundation with advanced R&D programs, but also face a forbidding reception from VCs and big pharmas when they come calling for financial support. In the drug development world of sevenfigure funding and 10-figure profits, super angels, micro-VCs, business accelerators (aka incubators) and government grants are still the
best-friend funding options for discovery-level innovators, but such friendships usually come in four- and five-figure relationships that are patently designed to limit risk and compensate achievement before making a next-stage financial commitment. Indeed, this model is increasingly being adopted for many late-stage R&D projects; therefore, it is unlikely to change as the prototype for the early stage innovator/investor relationship or the start-up funding model. This indicates a likely continuation of the arduous process to acquire operating revenue for bright-but-broke embryonic drug development researchers. The principal issue for start-ups, early stagers and impoverished nascent bio-geniuses is still funding how much is available, whos providing it, and how much of your company is appropriate to give up to obtain it? The permeating trends in research discovery, funding models and partnering structures relative to front-stage drug developers, investors and collaborators is observable in the news that BioWorld has published on this critical market sector over the past year and continues to cover as an ongoing responsibility. Those trends indicate that innovation continues to be a burgeoning dynamic in the market cycle, but also one that continues to daunt those with the most money and resources. Fortunately, biotech gets paid to think and has continued to be uncompromisingly creative in that manner, as pharmas woes continue to include R&D stagnation and as the traditional venture capitalists acutely hone in on the mostlikely-to-not-lose-money undertakings.
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News on the most current and aggressive R&D programs and corporate initiatives from fresh and ambitious biotechnology entrepreneurs has been perceptibly advantageous in revealing the future of biotechnology and bringing together the cohorts that will overcome the inherent drug development challenges and facilitate the clinical and organizational progress that characterize every eventual success in the drug development market. As the global economy continues its less-thanconvincing effort to meticulously rebound from recession in dithering swings, innovation remains the most reliable and underfunded phase of the biotechnology drug development market, continuing to spin out bright-idea R&D in a dark economy. But the trends suggest venture firms are increasingly shying away from companies in the seed stage of life. During the second quarter of 2010, for instance, the U.S. venture industrys average seed investment was $6.8 million, according to the National Venture Capital Association. The following quarter, that number had fallen to $3.5 million. Conversely, investment in seed-stage biotech companies is increasing from literally every funding source, except the big pharma drug makers and fundamental venture capitalists. Non-profits, governments, special interests, philanthropists and angel investors are more committed than ever to address the rare and neglected disease markets that are predominantly the territory of new or emerging biotechs. The pharma and VC reasoning acknowledging the too-long-to-approval-time is understandable, but the long history of drug approval also confirms the patent fact that all drugs on the market began in the seed stage or evolved as secondary-indication therapeutics from drugs that still originated in that
phase. The road to market has a beginning that is impossible to circumvent and the newsmakers presented here embody the companies that toil in that research landscape. The fact remains evident that creative or emerging companies such as the ones covered here represent a significant opportunity for growth and profit for the immediate and impending biotechnology market, as well as for the uncertain and mired pharmaceutical market, and for the morecircumspect-than-usual investment community. Speculating on the innovation stage may be the least risky phase for investment or partnering, as it usually requires much less capital than late-stage venturing, in which any setback is a game changer, if not a game killer. However, collaboration or sponsorship opportunities with fertile-minded young innovator companies represent groundfloor opportunities that usually do not lock the investor or partner into untenable long-range commitments to see a project through to the end. Government Hopes to Lead Big Pharma and VCs by Example In May 2011, the FDA released a list of its strategic priorities for the next five years to address new global challenges and cited that the FDAs job is fundamentally different than it has been in previous eras, but that the agency will address these challenges and aim to fulfill our mission by embracing innovation and actively pursuing partnerships with federal, state, and local agencies, international authorities, academia, nongovernment organizations, and the private sector. FDA Commissioner Margaret A. Hamburg went on to convey the agencys objective to advance science and innovation by facilitating the progression of originality in its earliest stages of development. In 2011, the National Institutes of Health (NIH) has been funding early stage research projects at an increased rate and has
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increased the amounts of its biggest outlays, as well as the durations of its collaborations, to seedstage and early stage in recent months. NIH is making a documented pledge to significantly increase its funding for such projects and companies, despite the enduring prospect of budget cuts that the agency perpetually faces. Early stage clinical approvals may not be a dime a dozen, but they are more forthcoming from regulatory entities such as the FDA and EMA than the number of their late-stage sanctions, which carry more critical stakes and hold greater implications for a mass patient population of millions than a Phase I trial has on test subject groups that number only in the tens or hundreds. The promise to increase federal funding to early stage projects is a boost for young innovators, but also may be regarded as a wake-up reminder to traditional VCs and established drug companies to consider the lower-risk alternative of discoverystage investments that afford a greater window of opportunity to cash out or end a business agreement without the harsher consequences that are often intrinsic in Phase II and Phase III commitments. The FDA and its counterparts hope that is the case. Francis Collins, the NIH chief, has pledged to fund more of the early stage research and promising
compounds that the big drugmakers traditionally are disinclined to invest in too early. Its a stage that is referred to as the valley of death inasmuch as many of those early research projects fold. The valley of death needs to become a valley that leads to life, Collins said. The time is right even in a difficult budget environment, maybe especially in a difficult budget environment. He referred to recent research that found that 20 percent of innovative new therapeutics approved in recent years were derived from NIH-funded research, while the drug industrys own R&D productivity has declined. This is not an effort to turn NIH into a drugdevelopment company, Collins said. The idea is to move projects just far enough along for them to be attractive to commercial investment. With its coverage of some of the new and inventive faces of biotech, Innovations in Biotechnology 2011: New Science, Emerging Companies, Rising Stars is making an effort that BioWorld believes will prove advantageous in the identification of budding R&D and for the business development opportunities that it carries for participants.
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Though it intends to begin development of its own internal Stradobody in 2011 or so, the technology platform might prove particularly suitable for partnerships since it appears to be applicable to every antibody that acts through antibodydependent cell cytotoxicity. Glikniks raised $4 million in investor money to date and has secured grant funding, including federal grants that are supporting the ongoing trials of immunomodulators GL-0810 and GL-0817. Block said plans are under way to seek additional financing to support further R&D work, but the
company hopes to bring in additional money via partnering deals. Within the next couple of years, we expect to enter one or more pharmaceutical partnerships, he said. Gliknik is headquartered at the University of Maryland BioPark BioInnovation Center. In addition to Block and Strome, the companys management team is rounded out with Henrik Olsen, principal scientist.
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trial in metastatic melanoma. A Phase II study in squamous cell carcinoma of the head and neck was due to get under way in 2010. Other players in the space include San Franciscobased Jennerex Inc., which uses a vaccinia virus strain to target tumors, and Wellstat Biologics Corp., of Gaithersburg, Md., which has Phase II oncolytic virus programs in colorectal and cervical cancer. In addition, there are numerous earlier stage academic programs focused on oncolytic virusbased cancer therapies. One of the potential advantages of oncolytic HSv therapy being developed by Catherex is that the
treatment regimen developed by the companys scientists involves precise and timely delivery of radiation and virus to achieve a synergistic effect and enhanced efficacy, according to the company. In addition, non viral genes such as cytokines can be stably incorporated into the viral genome to overcome the resistance of some tumors to oncolytic virus therapy. The company expects that its oncolytic HSV therapies could be administered repeatedly without impairing the efficacy of treatment. Catherex also expects that side effects will be significantly more benign than widely used cytotoxic chemotherapy products.
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Raf as well as those with mutated Ras. In human tumor cell lines and animal models, RAF Blockade demonstrated single agent antitumor, anti-angiogenic and anti-lymphangiogenic effects, even in cells that were refractory to treatment with other Raf inhibitors. Kinagen also has a preclinical program targeting the alpha and beta subtypes of PDGFR with the goal of preventing restenosis after angioplasty or vascular grafts. The program also may be applicable in treating fibrotic diseases. Slack noted that the use of kinase inhibitors outside of cancer has been limited due to their lack of selectivity and subsequent side effects, but Kinagens platform has the potential to overcome these obstacles. Since its founding, Kinagen has survived on grant money and investments from its founders. The virtual firm relies on academic collaborations and CROs to do much of its preclinical work. Slack noted that the biotechs scientific advisory
board which includes Cheresh as well as former Lilly oncology R&D chief Homer Pearce, former Boehringer Ingelheim GmbH development head Peter Farina, former OSI Pharmaceuticals Inc. oncology discovery head Lee Arnold and Mass General kinase expert Keith Flaherty is not window dressing; were putting these guys to work. Yet Kinagen is in discussions to complete either a venture round or a corporate partnership within three to six months, Slack said. He noted that neither precludes the other, and Kinagen might end up doing both. On the partnering side, the firm is open to a broad discovery partnership or potentially a licensing deal. On the venture side, Slack is aiming for about $18 million, which he said would be enough to take the RAF Blockade program through clinical proof-of-concept, get the PDGFR program clinicready, and turn the crank again to see what Kinagens platform can churn out.
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Esperance was founded in 2005 when membranedisruption research at Pennington caught the eye of investors Louisiana Fund I LP, Themelios Ventures Partners LP and Research Corp. Technologies Inc. They contributed $9 million to a Series A round in 2006, but Alila said the company didnt really become operational until 2007, when he came on board. Alila set about building up Esperance, which now has nine employees and works out of the
Louisiana Emerging Technology Center incubator. He also raised $6 million in a Series A-1 round in 2008 from the firms existing investors as well as some individual investors. That money will allow Esperance to complete its ongoing Phase Ib trial with EP-100. Then we will decide whether to exit or raise additional funds, Alila said. For now though, the company remains focused on advancing through preclinical and clinical studies, he said.
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Were going to partners and VCs now that weve shown the platform works, said CEO Elaine Heron, who came on board in February 2009 and helped the firm bring in some angel funding in 2010. To date, work at Amplyx has been funded by about $1.55 million from Life Science Angels and Tech Coast Angels, as well as from Golden Seeds, an angel group that invests in start-up companies led by women. We hope to raise a Series B in the $10 million range, Heron said. Partnering also is an option. Amplyx already has partnered two programs: a preclinical
antibacterial compound is part of collaboration with an undisclosed midsize pharma firm, and an early stage antifungal program is in development with Duke University. In addition to the paclitaxel program, Amplyx also is working on its own in HIV. While the technology also could be applied to development-stage drugs to resolve toxicity hurdles much earlier in the process, Amplyx has decided to limit its initial work to approved drugs, mostly because we know a lot about their target and their toxicity profile, Mutz said, though he added that Amplyx might consider expanding the technologys use through additional collaborations.
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development of GV1001 . Behind pancreatic cancer, ongoing studies are testing the cancer vaccine in liver and lung cancers and in melanoma. And the company is not alone is targeting telomerase, an enzyme overexpressed in several tumor types. Menlo Park, Calif.-based Geron Corp. has been moving steadily ahead with its telomerase research. That firm has an autologous telomerase cancer vaccine in Phase II testing for acute myelogenous leukemia. KAEL-GemVax also is advancing a combination
program through a deal with Lytix Biopharma A/S, of Oslo, Norway, involving its vaccine and Lytixs LTX-315, a compound designed to interact with cell membranes to induce immunogenic cell stressing and rapid cell lysis. The Norwegian Medicines Agency recently cleared the companies to begin testing the combination regimen in patients with resected tumors. With its primary operations in Korea, where capital markets are flourishing, KAEL-GemVax has not suffered the same shortage of funding that plagued its predecessor. The firm closed an oversubscribed public offering in February, raising KRW24.9 billion (US$20.7 million).
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FDA in 2009. ChemGenex has filed a new drug application for patients who failed Gleevec and also had a mutation known as T3151. If it can match the success of Treanda or Omapro with VAL083, Del Mar estimates an annual market opportunity of more than $200 million, based on Avastin pricing and failure rates. Avastin is considered one of the most expensive of all drugs. Del Mars business plan is to commercialize VAL083 for post-biologic failure in orphan drug indications. Orphan drug status enables a much higher price point and seven years of market exclusivity. The company has identified a second indication for VAL083 and will expand its IND to include that probably toward the end of the year, Bacha said in 2010. Thus far, the founders have been able to move to the IND stage using internal resources, Bacha
said. It will soon undergo a formal institutional financing to bring in more funding and more individuals to participate in the company. Del Mar is oriented toward acquisition, but is open to going public, as well. We are certainly not afraid to test the public markets. We do have what we feel is a laterstage asset that is well de-risked that also has a streamlined development pathway in terms of the regulatory pathway that well follow and a very, very experienced team to make it happen, Bacha said. Del Mar is named after a California city that Bacha once lived in. Because it means the sea in Spanish, he also liked the resonance with the concept of reaching out or bridging the ocean, because the company will be commercializing technology developed overseas.
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who had previously failed therapy with naked doxorubicin. Patients also had no side effects. Scherrer called that a huge step over whats presently out there. Certus compared those results to recently approved Nexavar (sorafenib, Onyx Pharmaceuticals Inc. and Bayer AG) which improves survival from 7.9 month to 10.7 month in late-stage patients, only a little over two months difference. Those studies do not qualify as clinical studies under the FDA, but have encouraged Scherrer and his colleagues at Certus in working toward an IND, which it expects to file in 2011. Certus will develop EmboSphere for liver tumors, and TaxoSphere will have broader applications, including lung and ovarian cancer, Scherrer said. The goal for the company is development into the early clinical stages. What we are after is
to get the proof of concept in the clinic. Once thats achieved, we either try to raise additional money to continue clinical development or look for partners. Scherrer negotiated the transfer of the nanoparticle technology from the Max Delbruck Center to form a start-up in Berkely in 2008 after experiencing some difficulty in starting the company in Germany. The company currently consists of a four-person management team, with research outsourced to various CROs. Scherrer demurred to name his three other colleagues pending formal announcements of their association with Certus. Seed financing for Certus has been obtained privately, and the company is working on its first financing round. Right now we are at the point of trying to close a financing, Scherrer said.
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G202 targets the prostate-specific membrane antigen (PSMA), which initially was thought to be specific only to the prostate. But later discoveries showed it also was present in the vasculature of all solid tumors. PSMA is expressed at high levels in blood vessel cells found only at the tumor site. We take advantage of the enzymatic part of PSMA, Dionne said. Contrasting it with an antibody-based approach where only one antibody bearing a drug molecule binds to one PSMA, we have thousands of released drug molecules per one PSMA, he said. As a result, thapsigargin is delivered at very high concentrations in the tumor and stays there with a half-life of greater than 30 hours in animal models, Dionne said. Not only that, the drug is expected to kill the slowly proliferating cancer stem cells, as it kills independent of cell division, leading to a lower rate of tumor relapse compared to standard therapies, he explained. And patients potentially could be retreated with the drug without developing resistance to it. He pointed out that antibody-based approaches, while they can cause tumors to regress, also can lead to nondurable response. GenSperas G202 prodrug candidate is designed to be curative as a monotherapy. We have a drug that looks like its going to work on its own, Dionne said. The companys second candidate, G115, is
targeted to a different peptide, prostate-specific antigen (PSA), a marker for prostate cancer. PSA actually is a protease that is active only when being secreted from the cancer cell. At least two deals valued at nearly $1 billion have emerged in recent years centered on prostate cancer compounds. Cougar Biotechnology Inc. was acquired by Johnson & Johnson for $970 million, handing the drugmaker Cougars prostate cancer compound, abiraterone acetate. Medivation Inc. scored a potential $725 million deal with Tokyo-based Astellas Pharma Inc. GenSpera has managed to raise money for its early stage pipeline in an otherwise difficult financial climate for start-ups. Dionne said the companys model keeping spending low (its a virtual firm with two employees), meeting timelines and giving investors liquidity (the companys stock began trading in 2009 on the Over-The-Counter Bulletin Board) has helped to facilitate funding. Were pretty proud of where we are, he said. The company, incorporated in late 2003, has raised $11 million over the last 2.5 years in three to four funding rounds, all with increasing valuation in the worst market condition, Dionne said. In the last round, more than half were previous investors, he noted. As the former vice president of biological research and drug discovery at Cephalon Inc., Dionne was responsible for neurobiology and oncology, helping to build that companys cancer research program.
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ABPL has 18,000 square feet of research and development laboratories in Marol Naka, Mumbai, on prime real estate, which will be the site of product development. A larger, pilot plant and manufacturing center will be established on 11 acres in Khapoli. Behind the Angiozyme program is a Phase I-ready orphan product based on ligand-based technology acquired from Rockville, Md.-based Cellworks Therapeutics. Actis is seeking funds from the Indian government to start that Phase I trial. It also is developing an in-licensed medial diagnostic system developed in the U.S. that is designed to detect potential sites for breast cancer with 95 percent accuracy. Actis subsidiary Telesto Diagnostics, is expected to start marketing in Malaysia and South East Asia in the next nine
to 12 months, and shortly thereafter in the U.S. The company is making plans to build various facilities at a planned 270-acre biotech park in the Malaysian state of Malacca, through its Malaysian venture formed in 2007. Some 20 biomedical companies, including medical device, drug development and diagnostics, are slated to be housed there, the first of which is expected to be Actis subsidiary Telesto Diagnostics. An undisclosed Malaysian investor has committed $300 million for the Malacca facility, the details of which were expected to be announced shortly after. That money makes up the bulk of the funds that Actis plans to raise. Actis hopes to raise another $30 million through private equity and other investors, Saxena said.
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and several patent applications for the technology. After the spinoff, CNIs co-founder, Robert Gower, continued to chair the new company. He recruited Kirkpatrick, co-founder of ProlX Pharmaceuticals and a former professor of chemistry and biochemistry at the University of Regina, Canada, to join Ensysce as CEO in January 2009. The company now has four employees and sponsors collaborative research in carbon nanotube technology at Stanford and Rice Universities as well as M.D. Anderson. For example, Ensysce is supporting a research program at Rice that uses two alpha-emitting materials astatine and actinium complexed inside ultra-short carbon nanotubes to offer another potential delivery vehicle for cancer therapy. Holes in the walls of the ultra-short carbon nanotubes allow the alpha-emitters to enter, where they are captured and retained. Subsequent emission from the radioactive material penetrates only a two- to three-cell diameter, ensuring localization of the agents. Although Ensysce is focusing on developing its own product stream, the academic research
collaborations may also lead to enhancements of existing technologies. We have the opportunity both to partner with companies that require the delivery technologies and to take products into trials ourselves, to develop our own pipeline, Kirkpatrick said. Presently, the companys IP portfolio includes exclusive and nonexclusive licenses from several universities and research institutions for more than 80 issued patents, plus additional pendingpatent applications. Ensysce holds the licensing rights to technology developed as part of its funded research programs and, as part of its broad license agreement with Unidym, the rights to any IP required for the use of carbon nanotubes in therapeutic applications that is developed, licensed or acquired by Unidym within the next few years. The ETF funding is expected to take the company through 201 1 with a highly aggressive development timeline, Kirkpatrick said. In the meantime, shes discussing downstream funding opportunities with potential partners and examining other financing mechanisms.
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Ono, with additional milestone payments possible in the future based on clinical and regulatory progress. Concordia will also receive royalties on the sale of salirasib in Japan. The financial details were not released; Hardy said that Concordia has been funded privately from the start. Right now were not looking for any additional financing. . . . Were talking with companies interested in acquiring global rights outside of Japan for salirasib, he noted. In spite of the fact that pancreatic cancer is a notoriously aggressive cancer, often discovered in its advanced stages, few treatments have been found. Gemcitabine, marketed as Gemzar by Eli Lilly and Co., is the front-line therapy with annual sales of more than $500 million per year.
Median survival for patients with pancreatic cancer on gemcitabine is 6.2 months, with 19 percent survival at one year. We see this drug as being used in combination with gemcitabine or other therapies in the treatment of pancreatic cancer, Hardy said. Regarding future business and exit strategies, Concordias plans are as simple and laser-focused as its start-up strategy. The exit is pretty well defined, he added. The company will seek additional regional partners like Ono, as well as an additional global partner to shepherd salirasib through Phase III trials and registration studies. Whats next after Concordia for serial entrepreneur Hardy? Well start something else.
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(TAP), which consists of ImmunoGen Inc.s DM1 cancer-cell killing agent attached to Genentechs trastuzumab, known as Herceptin. Interim Phase II data recently presented at the European Society for Medical Oncology (ESMO) annual meeting showed that Genentechs Herceptin TAP (T-DM1) resulted in an objective response rate of 47.8 percent in first-line HER2+ metastatic breast cancer, compared to 41 .4 percent for patients treated with Herceptin plus chemotherapy. Additionally, the incidence of serious side effects with T-DM1 was approximately half of that reported with the Herceptin plus chemotherapy arm. Also in the hunt is Seattle Genetics Inc., which recently reported positive data from a pivotal trial of brentuximab vedotin (SGN-35). Bothell, Wash.-based ImmunoGens most advanced unpartnered TAP compound, lorvotuzumab mertansine (IMGN901), is still in early stage trials for Merkel cell carcinoma (MCC), small-cell lung cancer (SCLC), ovarian cancer and multiple myeloma. The company presented positive data at ESMO showing a
clinical benefit in 38 percent of MCC patients, including one complete response, one partial response that evolved to a complete response, and three patients with stable disease. Additionally, three of 26 SCLC patients had stable disease and another achieved an unconfirmed partial response. Seattle Genetics also reported positive SGN-35 data in anaplastic large cell lymphoma. ImmunoGens technology has attracted multiple partners, bringing in some $285 million for the company over the past decade. Centrose has a number of angel investors who want in for another round, Prudent said. And as for whether the company will seek partnerships down the road, he said, We are pretty much keeping our options open at this point. The company derives its name from the center of sugars as in sucrose, glucose, fructose. Centrose uses its Carboconnect technology as a way to attach drugs to proteins via modified sugars.
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Apogee has taken advantage of the sphingolipid technologys broad potential to obtain funding. Since its incorporation, the company has relied almost entirely on Small Business Innovation Research grants, including a grant from the National Eye Institute to evaluate the technology in retinopathy and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases in inflammatory bowel disease. Apogee also is working with the SENS (Strategies for Engineered Negligible Senescence) Foundation in
the area of regenerative medicine. To date, the company has raised about $8 million in SBIR funding. Its also gotten some state tax credit funding from Pennsylvania and recently received $825,000 from the Qualifying Therapeutic Discovery Project Program. Apogee is headquartered at the Hershey Center for Applied Research in Hershey, Penn.
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future, hopefully, sooner rather than later. Because of the anti-CD55s broad potential in solid tumors and synergy with [CD20-targeting antibodies], we believe it has early partnership potential, Brooke said, maybe even as early as IND or Phase I. While most of the firms resources are focused on its lead program, Genesis also has set up its ADP (Advanced Development Program) effort, where
we try to convert science into pragmatic drug development, he said. Genesis ADP is focused on working with academic partners to screen approved drugs for creating cocktail therapies that can be submitted under the cheaper 505(b)(2) regulatory pathway. Its collaborators to date include Wake Forest University, which is working on natural cancer resistance and the SENS Foundation, on a program focused on regenerative medicine.
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early stage technologies out of academic labs and provides the management, scientists, facilities and funding to advance the projects to IND filing, at which point the goal is to either out-license or seek independent funding. Gelfand serves as chief scientific officer both for Jantibody and for Boston Biocom. Former venture investor Frank Dinucci serves as president and CEO for both entities, while Alexey Eliseev provides scientific and business
development support for both. Boston Biocom is backed by grant funding and a $10 million investment from Pfizer Inc., which has an option to negotiate for the right to license any resulting technologies but cannot block the portfolio companies from negotiating with other parties if a mutually beneficial agreement cant be reached. Dinucci said Boston Biocom is interested in establishing similar funding relationships with other biotech and pharma backers.
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retain rights to the RabMAbs for diagnostics, research services and reagents. Apexigen inherited its Chinese connections from Epitomics, which owns a subsidiary company located in Hangzhou, China. We have a plan . . . to license out some of the China rights of some of the product candidates to some big Chinese companies, Yang said, citing the Chinese governments interest in biotherapeutics as added incentive to partner with companies in China. The company also inherits an agreement with Amorfix Life Sciences Ltd. to develop antibodies against a variety of cancer targets. Yang expects such partnerships to provide significant financial support to the company when its seed funding from Epitomics runs out. In order to support future partnerships in developing therapeutic humanized RabMAbs, the company will undertake proof-of-concept studies, showing that the antibodies can be effective, and that Apexigen can produce them to GMP standards. The crowded field of monoclonal antibody
companies divides roughly into those that own platforms and those that license that technology from the first group. Apexigen aspires to be a provider of best-in-class antibodies by exploiting the unique rabbit physiology. There are many contenders for best-in-class title including San Diego-based BioAtla LLC and Wynnwood, Pa.-based Immunome Inc. BioAtla and San Diego, Calif.-based Femta Pharmaceuticals Inc. have a similar relationship and occupy a parallel niche to Epitomics and Apexigen. Sharing a platform technology in antibody evolution and rapid humanization of antibodies, BioAtla exists as a service company while Femta is pursuing therapeutic targets and partnerships. Meanwhile, Immunome seeks to distinguish itself by offering superior native human monoclonal antibodies. Apexigen currently runs a very lean operation with only three employees, sharing facilities and resources with parent company Epitomics.
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augment or complement other therapies, rather than replacing them. In the case of Alzheimers disease therapy, Roninson said he believes the Senex drugs will be better tolerated than competitors similar drugs because they only affect aging-related changes in APP, BACE1 and tissue transglutaminase. A number of companies, notably Merck & Co. Inc., of Whitehouse Station, N.J., Eli Lilly and Co., of Indianapolis, Takeda Pharmaceutical Co. Ltd., of Osaka, Japan, and Medivir AB, of Stockholm, Sweden, have preclinical BACE inhibitors. Comentis has completed Phase I trials of its BACE inhibitor. The primary risk factor for Alzheimers disease is aging, which is associated with accumulation of various sorts of damage and cellular stress. Our compounds reduce stress- and senescenceassociated induction of all of the Alzheimers disease markers that weve looked at, Senex CEO Lawrence Friedhoff told BioWorld. This includes the genes involved in synthesis of beta amyloid, the genes involved in the synthesis of tau, as well as the genes controlling a number of other pathways that have also been reported to be abnormal in Alzheimers disease and which
may be part of the cause of this terrible illness. Friedhoff, is a drug development expert who has helped to bring a number of drugs to market including the current leading Alzheimers therapy: New York-based Pfizer Inc.s Aricept. Technically born in 2002, Senex began operations in earnest in 2004 when it received seed funding of $700,000 from the Charitable Leadership Foundation. Since then, it has racked up seven additional grants, including small business innovation research Phase I grants from the National Institute of Aging, the National Institute of General Medical Sciences and the National Cancer Institute in 2006 through 2009. Two more grants came from the National Cancer Institute. The first was a Phase II SBIR grant, and the second award was a supplement to the first, under the American Recovery and Reinvestment Act of 2009. Additional research grants came from the Alzheimers Drug Discovery Foundation in 2007 and the Department of Defense Breast Cancer Research Program in 2008.
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closed on a round of bridge financing that Smider said is less than $1 million. Pending additional investments and other business developments, the bridge round could close a second time and become a proper A financing round.
Pfizer retains equity in Fabrus, but has signed over control of the company to its founders. The Pfizer Incubator opened in 2007 with 26,600 square feet of laboratory space and a budget of $12.5 million per year to divide among the five to eight companies occupying the space.
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II compound, DK083171-03ENaC, in a ligand discovery program. An additional new grant comes from the National Institutes of Health (NIH) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) in the form of a $234,000 Phase 1 SBIR grant to screen bone cells against multiple functional endpoints for osteoporosis within the mission of NIAMS in cooperation with partners at the University of AlabamaBirmingham and Johns Hopkins. At the same time, DBM will be serving as a cell culture and engineering core under a program project grant to Johns Hopkins School of Medicine for the study of polycystic kidney disease. Schwiebert believes that dual-purpose CRO/ discovery research companies could fill an emerging void in early discovery research.
According to Schwiebert, pharmaceutical and larger biotech companies have shifted focus to late-stage programs, at the expense of early discovery research. At the same time, small biotech companies struggle to obtain operating funds at a time when venture capitalists are holding tight to purse strings. A biotech company with its own side revenue from contract services can provide some of its own funding for early discovery research, providing an option for the future when latestage assets have moved to market. If nobody is doing early discovery right now, and if it doesnt continue going forward while later-stage assets are being focused on, once those later-stage assets get to market, theres nothing behind it, Schwiebert added.
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But it also has pitfalls. For one thing, receptor blockers would tend to rev up the production of ghrelin via feedback mechanisms, and so might carry the seeds of their demise within themselves. Receptor blockers would also need to cross the bloodbrain barrier, which is a challenge, though not an insurmountable one and one that GOAT inhibitors might also face. Lastly, Cole noted that targeting GOAT might have what he termed a stoichiometric advantage namely, that one enzyme molecule makes many molecules of acyl ghrelin. While receptor inhibition has to be fairly comprehensive to be successful, even less than perfect inhibition could have a sufficiently large effect to be clinically meaningful. GOAT is an enzyme that activates ghrelin by adding an acyl side chain to the peptide. In their studies, Cole and his team prevented this activation by designing an analogue of ghrelin that binds to GOAT and inhibits its activity. When the researchers treated mice on a high-fat diet with daily injections of this GOAT inhibitor for a month, the animals gained less weight
than controls. Imaging studies showed that the inhibitor-treated animals specifically had less fat mass, but not less muscle mass, than controls. The animals glucose control was also improved. Administering the inhibitor to ghrelin knockouts had no effect, suggesting that its effects are due to its actions on ghrelin. Ghrelin modulates both weight and blood sugar levels. Cole said that there is some controversy about how. While earlier research led to a general consensus that ghrelin is an appetite suppressant, more recent studies suggest that most of the effect may be on metabolism rather than appetite. In his teams study, food intake did not differ between treated animals and controls, adding to the evidence that at least some of ghrelins actions are on metabolism. Cole would not speculate on whether that is good or bad in a biological sense. Its not clear what the best mechanisms for weight loss are. But for the psychological side, he gives an argument that certainly rings true: If you ask people would you like to eat as much as you want and not gain weight, Ill bet most people would say yes.
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In addition to its internal R&D campaign, Ligon now has collaborations with Lycera Corp. and Bayer Schering Pharma AG. Under its agreement with Lycera, Ligon worked to identify first-in-class drug candidates for immune disorders. Lycera has active programs focusing on ATPase activity within mitochondria and inhibition of ROR-gamma, a nuclear receptor in Th17 cells. The ATPase pathway may have relevance in lupus, rheumatoid arthritis, psoriasis and graft-vs.-host disease, and upstream regulators of ROR-gamma may block production of pro-inflammatory cytokines, according to Lycera. Ligons partnership with Bayer is focused on finding first-in-class targets for undisclosed therapeutic programs at Bayer. One thing that really attracted Bayer to working with us, and
whats unique about our platform, is that it works with existing chemical libraries, Bailey noted. Many screening technologies require compounds to be synthesized on common scaffolds for tagging purposes or other chemical requirements of the technology. Our immobilization approach was specifically developed by our founder Angela Koehler in Schreibers lab to be compatible with most screening collections, Bailey continued, adding that it will work with natural products and roughly 80 percent of compounds in a typical large pharmaceutical compound library. Ligons business strategy going forward is to look for collaborations with pharma partners that have invested in biology to validate a pathway, but have not been able to attack targets in that pathway directly using traditional screening methods. Ligon said that it is pursuing external collaborations in antimicrobials and CNS disorders.
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lab also was the first in the world to identify cardiac stem cells and discovered the potential therapeutic role for cardiotrophin-1 (CT-1) in cardiac cell regeneration. Verios lead muscle cell regeneration program is focused on the noncanonical Wnt pathway, Gleeson noted. The company has identified a potential biotherapeutic protein, called Wnt7a, which Verio has shown activates the development of satellite stem cells in the body, he explained. Wnt7a is a member of the Wnt gene family, which consists of structurally related genes that encode secreted signaling proteins that have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. The idea is that Wnt7a could be a biotherapeutic that actually activates ultimately the production of muscle cells, Gleeson said. Verio is investigating Wnt7a in treating sarcopenia, a muscle-wasting disorder that largely affects the elderly and is a major cause of morbidity and death in that population, he said. We think that this is a very significant area of the future, and one in which quite a number of pharmaceutical companies are now either developing programs, have established programs or are certainly thinking about establishing programs, Gleeson said. In the cardiac area, Verios scientists have demonstrated that treatment with CT-1, an Interleukin-6-related cytokine, dramatically reduces scar tissue, replaces cardiac muscle, improves contractile performance and restores
heart function following heart attack. Verios recombinant CT-1 compound, VT-101, has the potential to become a first-in-class biologic capable of restoring and repairing damaged heart muscle, Gleeson said. The company also has been investigating the use of the protein periostin to regenerate insulinproducing beta cells to treat Type I diabetes. We showed that we could double beta cell mass in the pancreas within three days with a single injection of periostin in mice, Gleeson said. This is a functional situation where we are producing beta cells that lead to islets that lead to insulin production that lead to a reduction of glucose levels, he added. The company is seeking a partner to move its periostin product, VT-201, into the clinic. While Verio is focused on using proteins or small molecules to activate endogenous stem cells, the company discovered through its investigations in muscle diseases that another firms well-known prescribed small molecule has promising results as a therapy for muscular dystrophy, Gleeson said. We have shown that in young mice, we have reversed muscular dystrophy with the use of the drug, which Gleeson said is marketed for another indication. He said Verio has filed the appropriate patent protection around the use of the compound for the application of the drug in muscular dystrophy. Obviously, we need to explore it, the business model of how we will develop it and the clinical path, Gleeson said. Its very exciting.
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in age-related macular degeneration. For now, though, NormOxys, having only recently emerged from stealth mode, is concentrating its efforts in the cardiovascular and cancer spaces. Over the next year, Tolar said the firm hopes to establish proof of concept. After that, well be starting business development activities, though he added that NormOxys platform already has caught some interest from big pharma.
Since inception, the company has pulled in about $15 million from Index Ventures and has been able to keep its burn rate low by operating its research in incubator space in Strasbourg, France. It has about a dozen employees, though we work with 20 to 30 people through universities, Tolar said. NormOxys recently established headquarters in Wellesley, Mass. corporate
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Beyond its work in AAA, Cardoz has earlier-stage programs, though the firm is not yet disclosing any details on those. Like many start-ups, its operating as a virtual company and has only a
small staff of five. In connection with the Series A financing, Sander van Deventer, of Forbion, joined Cardozs board.
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public funding for its own research projects. Besides its cardiovascular targeted compounds, ElexoPharm also is focused on hydroxysteroid dehydrogenases (HSDs) that modulate the action of steroid hormones. The company has developed nonsteroidal 17betaHSD1 inhibitors that could be used to treat estrogen dependent diseases like breast cancer and endometriosis, in which 17beta-HSD1 is strongly overexpressed.
Of the few inhibitors of 17beta-HSD1 described in the literature, most of them have a steroidal structure and the nonsteroidal compounds are not appropriate candidates for drug development as they are not selective towards 17beta-HSD2, according to ElexoPharm. Our non steroidal inhibitors are expected to have less side effects than steroidal compounds like existing aldosterone receptor blockers, Koch said.
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addition to scavenging LDL from the blood, those compounds also are believed to have antiinflammatory properties that could extend their use into other indications such as diabetes and hypertension. InVasc also has early programs targeting myocardial infarction and stroke, including a compound targeting myeloperoxidase in oxidative tissue damage. In MI and stroke, the toolbox is very limited, Johnston noted, adding that theres not a lot you can do for patients presenting with an infarct.
Prior to its first funding round, InVasc, which is headquartered just outside of Atlanta in Tucker, Ga., had raised about $1 .8 million from founders, friends and family. The new capital should allow the three-person team to add a couple more employees, though I dont see us growing much beyond 10 [people] in the next year or so, Johnston said. Earlier in 2010, InVasc picked up an additional $400,000 in grant funding, receiving two Small Business Innovations Research Phase I awards from the National Institutes of Health.
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second cytochrome P450 inhibitor, RX-1001 , and the current lead compound RX-1005. RX-1005 is a commercially available compound already in use clinically in the European Union, Brazil, Japan and China for a noncardiac indication. Radical is developing two formulations intravenous and intracardiac for patients undergoing cardiopulmonary bypass. The I.V. formulation is the most advanced program. Proof-of-concept studies in open-chest porcine models of myocardial infarction using RX-1005,
showed a reduction in the size of an infarct by 50 percent. Gottlieb said that Radical is close to being ready to begin clinical trials of RX-1005. The company is fundraising now for an angel round or Series A round to finance Phase I and Phase IIa trials of RX-1005. Pending successful completion of those studies, the company will attempt to seek B round funding to push through Phase II trials, at which point Gottlieb said the company will undergo a liquidity event.
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FerroKins clinical platform has attracted a handful of VCs, enabling the company to complete two financing rounds. Burrill & Co., Clarus Ventures and MP Healthcare Venture Management led a $15 million series A that closed in October 2008. A $12 million Series B closed in June 2010, led by HealthCap Ventures with participation from the existing investors. The new round will take the company through the next two years and allow it to complete the Phase II trial in adults as well as the Phase I/II pediatric studies scheduled to begin next year, according to Rienhoff. In 2012, we will begin a pivotal Phase III study, which should take about two years, leading to a
new drug application in 2014, he said. Once the company has demonstrated Phase II proof of concept, we are completely open to a variety of business strategies, including a partnering deal or an internal marketing program, Rienhoff added. There has been high interest in the programs particularly since we started the Phase II studies, he said. With FerroKins work force currently numbering 65 FTEs, fortunately, the Phase III studies are within the scope of a small company and the nature of the product is such that a small sales force could effectively market this drug, he added, noting that a decision will be made next year about which direction the company will take.
chapter 5:
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failures by Neurochem Inc. and Myriad Genetics Inc. Autism, too, has proven insurmountable for drug developers. Neuropharm Group plcs Prozac (fluoxetine) reformulation failed a Phase III trial. Currently Curemark LLC is in Phase III with CM-AT, which targets protein digestion disorders associated with autism, and Seaside Therapeutics LLC is in Phase I with STX107, a selective mGluR5 antagonist for Fragile X. Lichters venture firm, Avalon Ventures, has been the sole supporter of Afraxis thus far and is prepared to carry the company through its first
trial in Fragile X patients. Yet Lichter said other venture funds have already begun to show an interest, despite the start-ups early stage. As to partnering plans, we hired a VP of corporate development so that sort of tips our hand, Lichter said. Although mainly virtual, Afraxis recently hired Carmine Stengone as its vice president of corporate development. Stengone previously held positions at Phenomix Corp. and Anadys Pharmaceuticals Inc. Afraxis also hired David Campbell, another Phenomix alum, as its chief scientific officer.
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first deAl A good one for neuroP; uP to $74M for cns discoveries
Atlanta-based NeurOp Corp. snagged its first deal in a collaboration with Bristol-Myers Squibb Co. to develop small molecules for depression and other central nervous system disorders, using NeurOps platform targeted at the N-methyl-Daspartate (NMDA) receptor. Under the terms, NeurOp would get $1.5 million up front, research funding for two years, and up to $74 million in potential milestones. Founded in 2001, CNS-focused NeurOp got off the ground around 2005-2006 when it received SBIR funding and other grants. Currently, NeurOp has hundreds of compounds that are under assay collaborations, including the safety and assay collaboration with BMS, CEO Barney Koszalka told BioWorld Today. Although NeurOp has a lead molecule in the preclinical stage, the company is not in any position to declare any type of clinical candidate, Koszalka said. He added, We will have more information this summer. At that point, the company could decide whether to conduct more chemistry work or move forward with additional testing, said Koszalka, who was named NeurOp CEO earlier this month. NeurOps compounds are designed to improve the safety profile of NMDAR blockers without compromising therapeutic efficacy. We are very specific in targeting the NR2B subunit of the NMDA receptor, Kolszalka said. Competitors include Roche Holding AG, which is funding the development of Evotec AGs pipeline drug for treatment-resistant depression, EVT101, and a next-generation version of the product, in a deal valued at more than $300 million. Inlicensed from Roche in 2003, the compound, which is about to start Phase II development, is an anesthetic that is designed to inhibit the action of the NMDA receptor. Another drug in the same class, Pfizer Inc.s anesthetic ketamine (CP101,606), showed antidepressant effects with faster onset and higher response and remission rates. Its a space begging for more effective cures. Only about half of patients respond to initial therapy with currently marketed antidepressants, with remission rates of about 30 percent with the first agent and about 50 percent following use of the second agent, according to a landmark study known as the STAR-D (Sequenced Treatment Alternatives to Relieve Depression) trial. Vincent La Terza, head of corporate development at NeurOp, said in a statement that the collaboration with BMS will explore new treatment options for the millions of patients suffering from major depression who are unable to get relief from available treatments. NeurOps overall strategy is to expand its NMDA receptor platform to cover other CNS diseases beyond depression, such as neuropathic pain, ischemia, schizophrenia and Parkinsons disease. The company has offices and laboratory facilities in EmTech Bio, a life sciences incubator located on the campus of Emory University in Atlanta, where two of its founders are based. The basic research performed by NeurOps
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three scientific founders Raymond Dingledine and Stephen Traynelis of the Emory University pharmacology department, and James McNamara, chairman of the neurobiology department at the Duke University Medical Center provided the
underpinning for companys technology. Their discoveries inspired concepts and designs for improved, safer drugs to treat neuropathic pain, ischemia and neurodegenerative disease, according to NeurOp.
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Dimebon missed all its goals in Phase III trial reported earlier this year. Other recent AD deals include New Brunswick, N.J.-based Johnson & Johnson making a $1 billion-plus investment for Alzheimers programs such as Phase III-stage bapineuzumab from Elan Corp. plc, of Dublin, Ireland. And even early stage AD programs have netted promising partnerships, with Vitae Pharmaceuticals Inc., of Fort Washington, Pa., signing a potential $242 million deal with German pharma firm Boehringer Ingelheim GmbH shortly after concluding animal studies with its beta-secretase inhibitors. Like many of its fellow start-ups, AgeneBio operates primarily as a virtual company with four employees. Parshall, along with Robert
Postlethwait, vice president of business development, and J. David Leander, senior scientific advisor, are veterans of the Indianapolis pharma community, having all worked previously at big pharma firm Eli Lilly and Co. There are a number of folks with neuroscience backgrounds still located here, Parshall said of the Indiana capital. So we have access to expertise, while complementing that with global outsourcing. To date, AgeneBio has raised undisclosed seed funding and recently added $300,000 from BioCrossroads, the states life sciences seed fund. Well raise a Series A, hopefully, next year, Parshall said.
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sinAPis PhArMA sees neW use for Meth in stroke, brAin inJury
Sinapis Pharma Inc. believes that it has a found a way to provide neuroprotection to stroke patients and those with traumatic brain injury using an unlikely benefactor an intravenous, low dose form of the neurotoxic drug methamphetamine. Its an unlikely combo. Numerous stroke trials involving other neuroprotective agents have failed. And the scientific literature is filled with examples of the negative effects of methamphetamine stemming from abuse. Yet, a discovery in the University of Montana laboratory of David Poulsen showed that intravenous methamphetamine had activity in a rat model of stroke even when administered six to 12 hours after a stroke. Poulsens discovery turned out to be the most robust preclinical stroke data yet. Previous pipeline stroke compounds had only shown activity for three to four hours at the preclinical stage, and they failed to work for longer periods when tested in the clinic. To confirm the companys findings, Sinapis reproduced the stroke data in the laboratory of Michael Chopp at Henry Ford Hospital, one of the leading academic experts in stroke animal models. While methamphetamine abuse is known to cause arterial injury, stroke and brain hemorrhage and even death in humans, Sinapis compound has been shown to have a neuroprotective effect in an animal model for up to 12 hours. We would be the only ones to go to clinic with 12-hour data, Sinapis CEO Don Picker said of the companys neuroprotective stroke trial. Founded in 2009, Sinapis licensed Poulsens stroke and brain injury treatment technology from the University of Montana. Poulsen serves as the companys chief scientific officer. Currently, only one drug, tissue-plasminogen activator, or tPA, is FDA-approved to treat stroke patients, but that drug only works within the first three hours of when symptoms begin, such as tingling fingers and numbness in a foot. Most patients are not aware they are having a stroke when they experience such symptoms and usually do not go to the hospital until many hours later after the onset. As a result, only a very small percentage of stroke patients actually receive tPA. Traumatic brain injury has no approved therapy. A 2008 retrospective study published in the Journal of Trauma, Injury, Infection and Critical Care looked at substance abuse and mortality in patients with traumatic brain injury and unexpectedly found that there were possible neuroprotective properties of methamphetamine. The article also noted that there were few studies on the impact of methamphetamine use after traumatic brain injury and called for further study. One of the authors from that study is set to join Sinapis scientific advisory board. Sinapis believes its intravenous form of methamphetamine could potentially work in other areas such as heart transplants, anoxic birth injury and to prevent brain injury associated with cardiac bypass procedures. Methamphetamine currently is marketed in pill form for weight loss and attention deficit
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disorder with hyperactivity, sold by Ovation Pharmaceuticals Inc. (acquired by H. Lundbeck AS). Chattem Chemicals of Chattanooga, Tenn., has been contracted as the companys commercial supplier of the drug compound. Jacksonville, Fla.-based Sinapis has identified and has patents pending for a new use and route of administration for its intravenous methamphetamine. At lower doses, the compound inhibits cell death, as well as upregulates anti-inflammatory cytokines and promotes neuroprotection, primarily through the action of dopamine, according to Sinapis. To the companys knowledge, those multiple pathway effects have never been documented in the scientific literature in prior studies of the drug. Sinapis used its angel funding to file the investigational new drug application for a Phase I methamphetamine trial in healthy volunteers, and it is using a bridge financing to complete that trial. The first study patient is expected to be treated in June, Picker said. The company would need additional funding to conduct a proof of principle trial. Picker indicated that Sinapis hitting statistical significance in the Phase I trial would enable it to seek an adaptive, Phase II/III trial design, with 200-300 patients
and endpoints agreed upon with the FDA. The company is considering applying for grant funding from the Army to develop the compound for traumatic brain injury, though Sinapis also is seeking venture funds. But due to the many failures in the area of stroke, venture funds might be tougher to come by. The decision on which area to focus resources stroke or traumatic brain injury might be guided by whats more fundable said Picker, who has held numerous CEO and COO positions in the biotech industry. Sinapis is seeking to raise $10 million for the proof-of-principle trial. The company operates as a virtual firm, with top experts in the area of stroke and neurological conditions. Its co-founders are Howard Chandler, a neurosurgeon who provided the initial funding for the company, and Peter Von Doersten. Picker was part of a team at Johnson Matthey, a specialty chemical firms, whose work led to the development of carboplatin, currently one of the worlds leading cancer drugs with annual sales of more than $500 million annually.
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The NIDA grant will advance the cocaine treatment program through Phase I studies while supporting Emberas lead clinical development program for smoking cessation a market that represents a $3.5 billion global opportunity. Earlier this year, Embera completed animal studies in nicotine dependence that demonstrated EMB-001 to be more effective than Chantix Pfizer Inc.s $833 million smoking cessation product. The grant weve received with LSU will fund all of the preclinical work required to file an [investigational new drug application] for cocaine dependence and to execute a Phase I study, Linke said. That same work will also enable our clinical program in smoking cessation, so were moving both programs forward. Over the next 12 to 18 months, Linke plans to begin animal studies of EMB-001 in alcohol dependence and obesity the next two indications in the companys pipeline and progress quickly to human studies. In 2009, the Substance Abuse and Mental Health Services Administration classified an estimated 22.5 million Americans 13 and older nearly 9 percent of the U.S. population as substance abusers. More than 15 million were solely dependent on alcohol, and another 3 million abused both alcohol and illicit drugs. Obesity, which affects more than one-third of the U.S. population, is another promising application, since food cravings arise from the
same dysregulated brain systems that affect smokers and drug abusers. Our goal is to take these drugs into Phase II clinical development, then seek partners to help us with commercialization, Linke said. We think the best use of our resources is to develop as many indications of this drug as possible and look for partners that have existing infrastructure to help us do late-stage development. To that end, Embera has retained Exponential Pharma Ventures LLC to assist in establishing a clinical development partnership for its cocaine dependence program. The pharmaceutical partner would receive an option to license and commercialize the product after clinical proof of concept. In addition, Embera is actively raising a round of capital, led by its current investors, to fund the remaining clinical development, Linke noted. For the time being, Embera is operating virtually and outsourcing most of its development work. Linke is the only full-time employee in the companys five-person management team. We have experienced consultants in research and development, regulatory and business development who can take the company through our preclinical studies, he said. The structure has allowed Embera to use capital efficiently, but as we move forward, well be looking to bring on additional full-time resources, Linke added.
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cAlling All steM cells; JuventAs boosts sdf-1 for cArdiAc rePAir
Cleveland Clinic spinoff Juventas Therapeutics Inc. is adding a new twist to regenerative medicine. Traditional cell-based approaches to repair tissues and organs rely on the extraction of a patients stem cells before growing them in a lab and re-delivering them to the damaged site, a method that has demonstrated early success but is commercially complex, said Rahul Aras, president and founding CEO of Cleveland-based Juventas. Rather than trying to deliver the actual stem cells, the 2007 start-up is exploiting stromal cellderived factor-1 (SDF-1), a naturally occurring chemokine that is overexpressed in response to tissue injuries such as heart attacks. SDF-1 is responsible for recruiting circulating stem cells to repair the damage, essentially acting as a beacon to attract cells to the site of injury, Aras told BioWorld. The problem is that the signals that drive the repair are short-lived, he added. Cardiologist and Juventas founding scientist Mark Penn discovered that prolonging SDF1 expression for a longer period of time could result in significant tissue repair. The companys lead program, JVS-100, which encodes SDF-1, has shown promising data in animal models to date. In heart failure pig models, for instance, the drug demonstrated statistically significant improvements in key indications of cardiac function. And SDF-1s benefit goes beyond just recruiting cells, Aras said. It also sends out signals to prevent cells at the damaged site from dying. So theres a dual purpose. Juventas recently started enrolling patients in its first Phase I study. A total of 16 subjects with heart failure will be involved in the open-label, dose-escalation trial and will receive JVS-100, administered via endoventricular catheter delivery. Preclinical testing has shown were able to provide a very localized signal, Aras said. The company will look at safety, as well as key efficacy endpoints, including echocardiogram, the 60-minute walk test and quality of life, basically all the standard cardiovascular endpoints, he said. Data are expected early next year. Given SDF-1s ability to attract stem cells, its potential goes far beyond cardiac repair. Juventas already has earlier programs in peripheral vascular disease, in which SDF-1 would be delivered via direct needle injection, and for wound repair, in which the stem cell-recruiting factor would be administered topically. If successful, Juventas product would offer an off-the-shelf regenerative therapy, giving it a significant advantage over the stem cell approach. Aras said. It would be available in a vial, using standard manufacturing processes. And, while stem cells are limited to certain clinics, ours is distributable to any hospital. Like most small biotechs, Juventas plans to seek a partner after reaching proof of concept. The firm currently has four full-time employees though Aras said it probably will grow to accommodate expanding clinical programs.
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Juventas, whose name comes from the Roman goddess of youth, has raised about $10 million to date in venture capital and grant money, including a $6.9 million investment round in late 2008 led by Triathlon Medical Ventures with participating from Early Stage Partners, Fletcher Spaght Ventures, Reservoir Venture Partners,
Blue Chip Venture Co., JumpStart Inc. and North Coast Angel Fund. Grant money has come from Ohios Third Frontier fund, specifically from the programs Cardiovascular Innovation Center and Center for Stem Cell & Regenerative Medicine.
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move into the clinic. The company is interested in securing venturelevel funding Organovos work to date has been funded primarily by a $1.5 million angel round and is open to potential partnerships, hoping to bank on big pharmas growing interest in regenerative medicine. Both Pfizer Inc. and Johnson & Johnson have their own regenerative medicine units, while Novartis AG and GlaxoSmithKline plc have jumped on early stage stem cell programs through recent collaborations. And, earlier this month, small biotech CureDM LLC, of Wilmington, Del., scored a potential $335 million deal with SanofiAventis for its preclinical candidate, Pancreate, a neogenesis agent aimed at treating diabetes. Organovos initial indications also offer the firm a possibility of some government funding, since blood vessel and nerve damage are common combat injuries, Murphy added. But the companys other focus will be to leverage
the technology itself, leasing out bioprinters to universities and research institutions to expand the tissue engineering capabilities in other applications. That way, Organovo can turn to academia for the early work, without having to shoulder the cost. It also retains the right to partner any programs once theyve advanced to a certain point. The goal is to leverage the potential of the technology more broadly than we could do on our own, Murphy said. For now, Organovo is staffed by 15 employees about half of them full-time. The most recent addition to the executive team is Marie Csete, executive vice president of R&D. She previously served as chief scientific officer at the California Institute for Regenerative Medicine and her experience ranges from stem cells to organ transplants. So shes positioned to take us to the next level, Murphy said, to help us reach outside and partner with the right groups.
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that problem partly by virtue of its manufacturing process of mesenchymal stem cells. We wind up with cells that cant become other [unwanted] cell types, Henwood said. As the cells are replicated, they maintain their same genetic fingerprint. Henwood indicated that the predictability of Garnets cells could address one of the regulatory challenges for stem cell therapies. Another key manufacturing challenge for stem cell therapies has been the sheer expense of making them. Garnets process can produce the cells at an impressively low cost of goods, Henwood said. The companys process requires less feeding of the cells and less manpower, she said. Other regenerative therapies under development include a range of approaches aimed at wound and tissue repair. For example, Osiris Therapeutics Inc., of Columbia, Md. is developing stem cell products for pediatric graft vs. host disease and heart attack patients. Rockville, Md.-based
RegeneRx Biopharmaceuticals Inc. is developing Thymosin beta 4-based drug candidates in dermal, ophthalmic and cardiovascular tissue repair. GliaMed Inc. is developing compounds called regenerative immunophilin ligands, or RILs that have been shown to regenerate skin and other tissue in animal models. Its wound healing compound (GM1485) is being studied as a topical treatment in three patient populations: orthopedic surgery, plastic surgery, and burns. Cleveland Clinic spinoff Juventas Therapeutics Inc. has a lead program JVS-100, which boosts stromal cell-derived factor-1 (SDF-1), to promote cardiac repair. The company recently started enrolling patients in its first Phase I study of JVS100, administered via endoventricular catheter delivery. In its earlier programs in peripheral vascular disease, SDF-1 would be delivered via direct needle injection, and for wound repair, the stem cell-recruiting factor would be administered topically.
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little piece of the cancer and then the immune system will attack. The companys HSC technology also has applications in bone marrow transplants and for red blood cell transfusions, another issue of supply and demand, Turner added. Weve found a way use stem cells to make red blood cells in a dish and then found a way to scale up those cells. Taigas still working to determine a clear path forward with the cell technologies, but its moving ahead with the antibody and adjuvant programs, largely with the help of funding from the National Institutes of Health. Aside from about $800,000 in seed funding, the
rest of the firms cash has come from the NIH about $2.2 million all told. Those grants include a Phase I Small Business Innovation Research award to develop antibodies against influenza, Phase I and Phase II SBIR grants to develop a universal donor blood stem cell line to treat AIDS and a Phase I SBIR grant to support work on an HIV vaccine adjuvant. Additional funding will be needed as the company grows beyond its three full-time employees, but thats a challenge Taigas founders are ready for. After all, Turner and Refaeli said the firms name, which refers to a subarctic region, kind of represents a biotech start-up. There are harsh conditions, and youve got to be tough to survive.
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advance to the clinic in the next two or three years. Unlike many start-ups, Molecular Templates has
opted to forgo the virtual model. The company has a 5,000-square-foot R&D facility and 12 fulltime employees, with all research conducted inhouse.
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seeded by a $250,000 grant from the Defense Advance Research Projects Agency, was initially predicted to be in clinical trials by 2007. That program remains preclinical, according to Alnylams website, and the program was reported stalled in 2007 due to lack of efficacy. Marina Biotech, of Bothell, Washington, formerly MDRNA, Inc., reported positive in vivo results with an RNAi-based therapeutic in 2008, but no further news has come out of that program and it no longer appears in the companys official pipeline. If Sirnaomics is right, multitarget RNAi therapeutics may allow it to crack a nut that so far has resisted efforts by larger companies. Sirnaomics is involved in numerous collaborations with academic institutions in the U.S. and Asia, including the University of Tennessee, the University of Pittsburgh, Johns Hopkins University, Duke University and Hong Kong University. Sirnaomics also has ties with Silence Therapeutics plc, via the former Intradigm Corp., at which Sirnaomics President and CEO Patrick
Lu served as vice president from 2001 to 2006. Subsidiary operations in China have allowed Sirnaomics to take advantage of VC networks and local government incentives in the Suzhou Industrial Park Biobay area, outside of Shanghai. The company employs 10 people in Maryland and 15 in Suzhou. It also has operations in Guangzho, capital of Chinas Guangdong province, which the company hopes to expand. There are multiple pharmaceutical companies very much interested in our programs, and we believe theyre going to have another push for development in China of our siRNA therapeutics program, said George Ji, vice president of corporate development for Sirnaomics. The company is operating on just over $500,000 in small business innovation research grants from the National Institute of Allergy and Infection Diseases and the National Cancer Institute. Going forward, Sirnaomics will seek additional grant and partnership opportunities to fund its discovery and development programs.
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research of Lee Hood, president of the nonprofit research institute. Hood, one of the four founders of Integrated Diagnostics, also co-founded several other biotechs, including Thousand Oaks, Calif.based Amgen Inc. and Applied Biosystems LLC, of Foster City, Calif. (now part of Life Technologies Corp.). While at California Institute of Technology, where he began his professional career, Hood and his colleagues pioneered the DNA gene sequencer and other instruments. The DNA sequencer played a key role in the mapping of the human genome during the 1990s. In 2000, Hood co-founded the Seattle-based Institute for Systems Biology (ISB), which is focused on personalized medicine. In 2009, Integrated Diagnostics became the first commercial enterprise to arise from a partnership between the institute and the University of Luxembourg. The nation of Luxembourgh created a venture arm, BioTechCube Luxembourg, which is an investor in the diagnostics firm along with InterWest Partners and the Wellcome Trust.
The $30 million Series A round in September 2009 was led by venture capital firm InterWest. Last month, the personalized diagnostics firm triggered a $10 million second tranche of its Series A financing, funds that will be used to advance the development, validation and commercialization of its blood-based proteomic diagnostics programs. Integrated Diagnostics products would be classifed as in vitro diagnostic multivariate index assays, or IVDMIAs, a subset of lab-developed tests that are the subject of draft guidance recently released by the FDA. In the new draft guidance, IVDMIAs are defined as a device, which would make them subject to FDA clearance or approval. Luderer said the assumption is that the FDA will issue a final rule on IVDMIAs, and the company aims to meet or exceed any new requirement. He said he hopes to meet with FDA officials soon to seek their counsel and guidance early in the program. Luderer previously was president and CEO of BioTrove, a venture-backed molecular biological tools company that was acquired by Life Technologies Corp. in December 2009.
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The galanin gene will be delivered by Asklepios gene delivery platform, a recombinant adenoassociated virus (rAAV)-based system called Biological Nano Particles (BNP). The BNPs are made out of pieces of different adeno-associated viruses and parvoviruses, engineered to target transducing muscle tissue and to evade the immune system. Back in 2004, Asklepios was the first commercial biotech company to receive major grant funding from a nonprofit disease foundation, the Muscular Dystrophy Association. Since then, disease foundation funding has become more common as an alternative to angel or VC financing. Weve kept going while some of the biotech
zombies have gone under, McPhee said. We keep a nondilutive approach. With the longer time frames involved in moving these technologies forward, its less well suited to the VC, early exit strategies. To date, Asklepios has had just one equity investor, a parent of a child with Duchennes muscular dystrophy, who contributed $1 .5 million in series A financing in 2006 to boost the companys DMD therapy, biostrophin, now in clinical trials. Asklepios has supplemented its portfolio of grants with licensing deals with partners including Merck & Co., Medtronic Inc., GlaxoSmithKline plc, Bayer Healthcare AG, and a number of smaller deals for its BNP technology.
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manufactured. The muscle cells in the mouse model also showed as good as 50 percent less damage after contraction. At the microscopic level, biglycan-treated muscle cells had lower inflammation and muscle fibers showed decreased degeneration. One of the main approaches to developing a treatment for DMD is to fix the mutated dystrophin gene. For example, in gene therapy a viral vector is introduced to produce a functional (albeit truncated) copy of the gene. Antisense oligonucleotides are designed to splice out or skip over the mutated parts of the gene, an approach that may only work in a subset of patients. Similarly, small-molecule drugs have been developed to read through premature stop codons. Several companies, such as Bothell, Wash.-based AVI BioPharma Inc., are developing RNA-based therapies for DMD that attempt to repair or replace defective dystrophin. However, those approaches, which include exon-skipping therapy, may be appropriate only for a subset of patients with specific mutations in the dystrophin gene. In March, PTC Therapeutics Inc. and partner Genzyme Corp. reported disappointing preliminary efficacy data from a pivotal Phase IIb study of ataluren in DMD, using a six-minute walk test as an endpoint. Ataluren, which is designed
to overcome the dystrophin mutation and restore protein function, was aimed at a smaller subset of DMD patients, as is the case with most RNAbased therapies targeting the disease. Yet another approach uses stem cells with normal dystrophin to replace the diseased muscle. And protein-based therapeutics are being tested to increase muscle mass in DMD patients. As part of a $498 million deal, Acceleron Pharma Inc. and partner Shire plc are developing a Phase II molecule (ACE-031) that targets the activin receptor type IIB (ActRIIB) pathway, which plays a critical role in regulating the growth of skeletal muscle. Tivorsans approach, on the other hand, is to compensate for the loss of dystrophin by upregulating the gene expression. In the same way, Novato, Calif.-based BioMarin Pharmaceutical Inc.s BMN-195 was designed as a utrophin regulator for DMD. However, the BioMarin DMD candidate was discontinued in August due to inadequate plasma concentrations in a Phase I study. There are plenty of data to support the idea of utrophin up-regulation as a potential therapeutic target for DMD. However, biglycan as a molecule and its mechanism of action are considered unique in that it closely follows the expression of utrophin. The molecule is designed to express utrophin at the cell membrane where dystrophin normally would need to act.
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To date, BMT has operated on money from its founders, but the firm, which recently was selected as venture company by the Korean government and picked up some government funding, was planning a Series A financing, with plans to seek funding globally, including from U.S. venture capitalists. Thats one of the reasons we recruited Johannes Freuhauf, a biotech veteran with experience in RNAi and an office in Boston to help the company develop in the U.S., Dong-ki Lee said.
The firm also plans to seek funding in Korea, but that might be challenging. In Korea, theres a lot of money around waiting to invest in biotech, he said, but most is going toward the less risky biosimilars business. My opinion is that theyre afraid of investing in novel technologies. In the coming months, BMT plans to work on strengthening its IP portfolio and scouting out possible early collaborations and licensing deals.
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mice with CHF have a life span about half that of normal mice. Treatment with AC6 gene therapy could return that life span to normal, he noted. Similar data were seen in pigs. Ejection fracture is down-regulated severely in pigs with CHF, but with the gene therapy, that rose by about twothirds, Reich added. Pending successful Phase II data, Renova likely will move into Phase III testing. For that, the firm could look to partnerships to help fund and run those large trials. With the executive team in place, including Hammond, who serves as lead scientist in the AC6 study, and Andrews, who serves as chief operating officer, we have the knowledge, but to create the infrastructure needed for late-stage work would be a large task for a small biotech, Reich said.
Well find a partnership that can augment what we do best. Besides the NIH, Renovas funding has come from a handful of angel investors. It also recently won about $250,000 from the qualifying therapeutic discovery tax credit funding. But Reich said he has no plans to seek venture capital. His last company, Collateral, also opted against VC funding. It was supported, instead, by megainstitutions before going public. Id rather see the people who work at the company reap the benefits of a stock sale, he said. Renova is in the process of hiring additional staff, but Reich added that the core group already is in place. Because weve worked together so long and have succeeded in the past, we have an advantage, a good chance to succeed, he said.
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from the disease itself, but they have a premature and more severe cardiovascular event, and that is because this inflammatory process is actually promoting inflammation in their arteries, Harats said. The atherosclerosis subgroup portion of the Phase II psoriasis trial will be conducted at in the U.S. at Mount Sinai Medical Center in New York and Massachusetts General Hospital in Boston, he said. Patients in the subgroup trial will undergo PET-CT scans of chest and neck vessels to measure the level of inflammation within atherosclerotic plaques, which is known to trigger vessel occlusion. In addition to eyeing the $3 billion biologics psoriasis market, VBL also is planning to test VB201 in rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis and other inflammatory diseases, Harats said. The company also plans to launch a multicenter Phase II trial of VB-201 in rheumatoid arthritis, involving about 200 patients, Harats said. That
study, however, will be conducted in Europe and Israel, because it aims to study VB-201 first in patients who have not yet been exposed to other biologics to treat their rheumatoid arthritis. In the U.S., Harats noted, biologics are common therapies for the disease. VBLs pipeline also includes an antiangiogenic and vascular disruptive agent for cancer, VB-111, which was expected to enter Phase II trials in solid tumors in 2010, he said. Harats said his firm has sufficient funds to conduct its planned inflammatory disease and cancer Phase II studies, which he noted is uncommon for the current tough financial times. We have successfully raised a total of $76 million from venture financing and have an additional $8 million coming from [Israeli] government R&D grants, he said, noting the firms key investors KeffiGroup, Aurum Ventures and Pitango Venture Capital. We are absolutely well financed, Harats said.
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JdP, With neW ceo on boArd, goes for Pc, Allergy MArkets
JDP Therapeutics Inc., a start-up biotech that is focused on drugs for hospital use, has appointed a CEO as the company looks to begin formal clinical studies of a potential treatment for severe allergies from food or medications, for example. Founded in 2008, the Lansdale, Pa.-based company has used angel funds to take its programs through preclinical formulation and to do patent work, and is now entering the clinical phase. JDP hopes to start Phase I testing of its two compounds for allergies, JDP 205 and JDP AI in the in the first quarter of 2010, based on anticipated venture funds. Behind the allergy program, JDP has a preclinical drug candidate for high blood pressure that also utilizes a proven ingredient, which the company declined to disclose. The company hopes to de-risk its programs by reformulating undisclosed existing medication, newly appointed CEO Joshua M. Tarnoff told BioWorld. He said that the company is preparing for an eventual regulatory filing under FDAs 505(b) (2) approval pathway, which would allow the company to use much of the safety data from an existing parent compound. Under the 505(b) (2) route, Tarnoff estimated that the companys allergy relief product candidate could potentially get to market in roughly four years, if all goes well in the clinic. We recognize that investors want to get to market quickly, Tarnoff said. He described the allergy compound as a safer, newer generation injectable antihistamine for use in the hospital setting for acute care. JDP is prepared to take its allergy product through the approval process, but the company does not intend to do the marketing and commercialization. Instead, it hopes to attract a mid-size pharmaceutical partner with a hospital focus. He said the company has deliberately elected to stay out of the primary care market and instead focus on what it sees as the underserved hospital market. While the primary care market can often require 200-500 sales representatives in given target area, the allergy relief product that JDP is developing could be handled by less than 30 reps in a highly targeted marketplace, Tarnoff explained. So it would not be a big stretch to put in a sales force [of that size], he said. Jie Du , founder and chief scientific officer at JDP, said the unique formulation and special delivery of the antihistamine compound is designed to have a quicker onset without the common side effects associated with older antihistamines. JDPs injectable compound is targeted at the second-line treatment of severe allergies, such as swelling and itchiness. First-line treatment with epinephrine often is used to open the airways. Tarnoff has held corporate development and commercially based positions across a range of therapeutic areas in both the hospital and primary care settings. He served as CEO of Houston Pharma Inc. and its subsidiary Potomac Pharma
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Inc. and chief commercial officer at ViroPharma Inc. In addition, he led a $1.5 billion U.S. business unit at AstraZeneca plcs diversified products group. Raymond Tobey, vice president of medical affairs, completes staff of three at JDP.
Currently a medical consultant serving the pharmaceutical industry, Tobey started in the industry with Merck & Co., where he headed the Phase I-III clinical team for respiratory diseases. His most recent industry position was vice president of research and development at Dermik Labs.
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Its a challenging environment for start-ups, Noonan said. We have to come up with creative ways to finance. Hopefully, Aarden will be able to advance its technology using local support, getting us to the point where weve crossed that valley of death to get to institutional investors for a Series A round, he added.
That means the company plans to stay small. Cofounder and board member Chris LeMasters said Noonan and Burrows made up Aardens full-time staff, working Zhang at the university and with a handful of consultants. We may add employees as we advance, LeMasters said. But our goal is to stay as lean and virtual as we can.
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in various stages of development. Its anticancer work is preclinical while its lead candidate for HPV treatment has undergone a Phase IIb study under an investigator-sponsored IND application. Pending discussion with the FDA and IND approval, ViroXis hoped to move into Phase III in 2010. If it pursues an over-the-counter use for one of its candidates, the plan is to get it on the market in 12-18 months while the HPV candidate could potentially come to market in 2014, Castella said. If the HPV candidate advances to Phase III, ViroXis hopes to attract additional venture funding and possibly a partnership with a pharmaceutical company, Clements said. He said drug companies are becoming more interested in botanicals partly because they have the potential to get to market quicker than synthetic new chemical entities. Under the 2004 FDA guidelines for development of botanical drugs, complex, but well-defined plant extracts that have had prior human use can be taken into clinical trials and, if found to be safe and effective, may be marketed as mixtures, rather than going through the arduous process of identifying and purifying a single active drug ingredient. In issuing these guidelines, the FDA has recognized that the medicinal properties of such complex botanical mixtures may be due to the combined activity of more than one component in the mixture. Veregen ointment, a green tea extract concentrated for use on the skin, was the first botanical product approved under the FDAs botanical products guidelines. The drug, made by Germanys MediGene AG, is approved to treat genital warts, which are also caused by the HPV. It is available in the U.S. through MediGene partner Nycomed US Inc. LEO Pharma, of Ballerup, Denmark, is another
example of a drug company developing a botanically derived medical product for skin disorders. The company has a Phase III candidate, PEP005 gel (ingenol mebutate) for actinic (solar) keratosis or pre-cancerous lesions. LEO Pharma, which acquired Peplin Inc. in September 2009, expects to file for regulatory approval of the gel in the U.S. and Europe in 2011. Despite a number of over the counter remedies, there is no prescription treatment for skin warts approved in the US. Existing products work through destroying the wart rather than treating the viral infection that produces the wart. Other treatments for skin warts include freezing and surgical removal, but major problems include the associated pain and scarring and the high recurrence rate among treated patients. Although botanical-based products can take a streamlined regulatory path, they may have additional sourcing challenges compared to conventional, chemical-based drugs. Most sandalwood trees are harvested from native forests, rather than cultivated, which has led to issues of product traceability, quality and sustainability. To solve this problem, ViroXis has formed a strategic partnership with an Australian company, TFS Corp. Ltd., that can provide highly refined and well-characterized East Indian sandalwood oil that is in compliance with ISO specifications established for the oil in 2002. Sandalwood, which grows naturally in India, is not cultivated for use in drug products but TFS had the foresight 20 years ago to grow Indian sandalwood trees on ecologically sustainable plantations in Western Australia under optimum conditions to produce commercial grade oil suitable for use in a drug product, Castella said.
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Werner said Inhibikase has identified a drug with a precise mechanism of action to treat PML. If successful in the clinic, there are at least eight major pharma companies in the autoimmune space, he added. We think that will bring partners and cash, hopefully early on in development since funding for early studies is often hard to come by. Initial trials will test the compound in treating PML, but ideally, we see it as a prophylactic for people taking drugs for diseases such as MS or lupus, or for those who are immunocompromised due to HIV/AIDS. We dont think its feasible to do [prophylactic studies] initially, Werner said. Thats a next step. In the long term, Inhibikase could also look at other viruses, such as rotavirus and respiratory syncytial virus. The host-factor targeted approach also might prove useful particularly for people suffering multiple infections because of its potential to treat primary viral infection and secondary bacterial infection. We dont know if it works in humans yet,
Werner said. But if it does, it would have a huge impact on the developed and developing world. On top of that, there are possible applications in the biodefense area. Since inception, Inhibikase has raised $855,652 and expects to spend only have that money getting to the IND phase, in large part because the firm has no salaried employees, relying instead on people volunteering time and expertise. When capital becomes available, the company hopes to take those folks on full time. Thats a strategy thats not for everyones stomach, Werner conceded, though the firm so far has gotten an enormous amount of work done. Locating in the southeast also was a strategic move. While Hartsfield-Jackson international airport makes traveling easy, it was the proximity to the Centers for Disease Control and Prevention that convinced Werner to set up shop in Atlanta. The real gem here is the CDC, he said. Weve been able to talk to people in real time. Its an untapped resource for our industry.
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program sometime in Phase II, Milne said. We havent worked out the details of how best to do it. Jirousek told BioWorld that the platform is such that the firm could partner a lead asset that well
have in the clinic next year, or partner an earlier program [in a deal] that might look much more collaborative. The flexible conjugate approach offers chances for multiple new medications and a plethora of business development opportunities, he said.
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made in response to a certain bug. By nature of their screening process, some of Immunomes competitors are only able to see a small window of what the human immunome actually makes, Pelura added. The combination of our exceptional stability of our cell lines and our lack of bias enables us to see the full repertoire of what a healthy human being makes in response to disease. I think that is the best position to be in if you really want to have the very best therapeutic. Immunome licensed worldwide rights to its technology from MIT and Thomas Jefferson University, where the companys founder, Scott Dessain, generated the intellectual property. Dessain formed Immunome in 2006, but Pelura noted that there wasnt much happening until [2009], when the company began its fundraising. Pelura came on board in September. Since then, weve been raising money and moving the strategy forward, he said. Immunome just completed a financing round, led by Pennsylvania greenhouse investment fund BioAdvance Inc., with additional investment from a group of angel investors. Although the firm has yet to disclose the amount of its recent financing, Pelura said that the new funds, along with the almost $1 million in seed money from private investors the company had in hand, would be enough for us to generate our first development candidate. Immunome anticipates raising a Series A by next spring, he added.
Private investor Michael Widlitz, a former specialty markets vice president of medical affairs for New York-based Pfizer Inc., said he was attracted to Immunome because of its unique platform. It is unique because it harnesses the power of the natural human immunological system, as well as the evolution of that system, he told BioWorld. And because it uses the natural human immune system, the opportunities for finding antibodies to treat diseases are endless, said Widlitz, who brought together a group of former Pfizer executives to explore this company as potential investors. Immunomes strategy is to out-license its antibodies at the preclinical stage, but hold on to the platform, Pelura said. The company, however, plans to take its primary candidate, which is targeting Clostridium difficile, into the clinic itself, he added. Immunome is a company that will have in a few years a deep clinical program in C. diff., and will have several licensing deals under our belt for preclinical candidates, Pelura said. By targeting acute diseases, in which patients are dosed once or in short duration, with endpoint outcomes that are known in weeks and not months or years, and a regulatory pathway that is known equates to a very capital-efficient strategy that enables us to do quite a lot on less money, he said. It is the way companies have to think nowadays, because there just is not the amount of money out there that one needs to do some of these chronic programs.
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the remaining from early stage investors. The current SBIR Phase I funds would last for the next 18 months. A Phase II SBIR grant could cover another two to three-year period, Lama said. Under the grants awarded in the last 12 months RetroVirox received $872,000 to fund development of novel HIV entry drugs that could potentially overcome limitations of current therapies. The company received its last award in May to finance the discovery of anti-HIV drugs that block removal of the virus receptor, the CD4 protein. RetroVirox believes that the mode of action used in its antiviral programs has never been targeted before and holds some key advantages over other antivirals. The company takes aim at human
proteins that are needed by the virus to become infectious and enter other cells. While conventional viral entry inhibitors block binding between the viral envelope and receptor proteins, RetroViroxs approach targets intracellular intracellular proteins, which may not bind directly to viral factors. The company believes that those intracellular host factors could display higher barriers to the emergence of resistant virus, one of the major hurdles in antiviral therapy. Unlike other entry inhibitors such as the FDAapproved CCR5 blocker maraviroc (Pfizer Inc.s Selzentry), which act on one of the HIV receptors, RetroVirox molecules are efficient at blocking entry of all HIV strains, regardless of the coreceptor used by the virus, Lama said.
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less effective to address staph infection, Strox Bio believes new approaches are needed to prevent and treat such infections. The company intends to seek fast-track designation from the FDA for Saurestat based on the significant unmet medical need. According to Strox, the current worldwide cost of staph infections exceeds $50 billion. In 2008, U.S. sales of Cubicin, an injectable antibiotic used to treat MRSA, were $414.7 million. Zyvox (linezolid) for hospital-acquired S. aureus infection, had sales of $1.115 billion for 2008. Several companies are in the race to develop an antibody-based product or vaccine for S. aureus. And many of them are subject to either the cloaking or neutralization effect of Protein A, or both, according to Strox. Swiss drugmaker Novartis AG decided not pursue further development of Aurograb as potential add-on therapy to antibiotics for use treating staphylococcal infections, after Phase data showed a lack of efficacy. to a in II
aeruginosa. To enhance the efficacy, Nabi developed and added a new and patented surface polysaccharide component, 336. S. aureus Type 336, which accounts for the roughly 20 percent of S. aureus infections that do not form a polysaccharide capsule in the human bloodstream. The 336 conjugate was evaluated in a Phase I/II human trial and shown to be safe and generates antibodies in humans that are specific and mediate protection against 336 positive strains of S. aureus, according to Nabi. Biosynexus pagibaximab, a humanized IgG monoclonal antibody (mAb), was partnered with GlaxoSmithKline but was returned to Biosynexus. That antibody has completed IIa, showing promising results in preventing staphylococcal infections in very low birth weight infants. A large Phase IIb/III study has been initiated. A Phase II/III proof-of-concept trial of Intercell AGs investigational S. aureus vaccine (V710), licensed to Merck & Co. Inc., is currently recruiting, with the first critical interim analysis (surpassing futility) expected in 2011. Alopexx and partner Sanofi-Aventis are developing a Phase I mAb for S. aureus (F598). And preclinical studies of Elusyss ETI-211, which is partnered with Pfizer Inc., are nearing completion. So far, Strox has conducted very preliminary in vitro experiments and the next step will be to raise money or enter a partnership to accelerate development of its product, said Kim, an immunologist and a registered patent attorney. Once it has secured adequate financing, the company plans to hire additional management and scientific personnel. Although some research and development will be outsourced, Strox intends to move the bulk of its operations to its own dedicated laboratory. Ideally, Strox would like to begin clinical trials for Saurestat in 2010-1 1 and complete the studies in 2012-13.
Inhibitex Inc.s Veronate polyclonal antibody (IgG) failed in Phase III trials. However, Inhibitexs Aurexis humanized monoclonal IgG has completed a Phase IIa study in 60 patients with complicated S. aureus bacteremia. Nabi Biopharmaceuticals Staphvax vaccine failed to meet its endpoint in its last Phase III trial, although its reformulated vaccine called PentaStaph (Staphylococcal polysaccharide conjugate and toxoid vaccine) was purchased by GlaxoSmithKline Biologicals SA and is in Phase I. Nabis previous investigational polysaccharide conjugate vaccine, StaphVAX, contained the two main capsular types, 5 and 8, found in the outer coating of more than 80 percent of S. aureus bacteria. The capsular polysaccharide molecules are linked, or conjugated, to a nontoxic, carrier protein derived from the bacteria Pseudomonas
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is heading into midstage preclinical testing. Reilly estimated the firm is 18 months to two years away from the clinic. But WSBIs relationship with the University of Colorado gives it access to clinical tissues for diseases such as psoriasis and rheumatoid arthritis, which he said is important given the spotty history of animal model data in autoimmune diseases. Its a tough space also a crowded one, especially in RA so you need very definitive early studies in order to convince yourself you have something special, Reilly said.
So far, early data have been promising. WSBI has tested its compounds against other therapies, even going so far as to dump in additional bacteria to make sure the innate immune system wasnt impaired by the therapy. Its drug was able to allow the body to respond to the bacteria while still addressing the disease, he said. Testing to date has focused on psoriasis and RA in predictive models, but Reilly said the company could look at other diseases, as well. After all, he noted, theres no lack of targets in autoimmune disease.
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Biopharmaceuticals, which is working on a polyclonal IgM antibody for hospital-acquired S. aureus infections. Excelimmune has opted to go after staph, included the dreaded methicillin-resistant S. aureus, as its initial indication, though the firm also has received a Small Business Innovation Research grant from the National Institutes of Health to develop therapies against Clostridium difficile infection.
The company, staffed by 17 people, hasnt disclosed its total funding to date, though, according to an SEC filing, it recently raised about $4.5 million in new financing. Going forward, Zondervan said Excelimmune will focus on developing its own pipeline while expanding the applications of its polyclonal antibody platform through collaborations.
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To date, ImmunGenes funding has come from its founders and angel investors. If it succeeds in closing a promising partnership, the firm might be able to hold off going to venture capitalists for a couple more years, giving it time to further advance its programs. Khare said the company also plans to license its technology similar to licensing deals done by ADC firms such as Seattle Genetics Inc. which could bring in further milestones and royalties. Were hoping to close the first one [of those] by
the end of [2010], he said. ImmunGene currently has two full-time employees, including another Amgen alumnus, Raj Sachdev, who serves as chief operating officer. The rest of the firms work is rounded out by contractors and consultants, among those Mike Gresser, chief scientific consultant, and Linda Pullan, consultant chief business officer, both of whom also previously held positions at Amgen.
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This is an effort to vaccinate patients against essentially three carbohydrate antigens that are overexpressed on most sarcoma tumor cells, Hansen explained, noting that the vaccine is given in the adjuvant setting. The patient is treated with the best available therapy today and rendered NED no evidence of disease, he said. About 50 percent of patients will recur, and the more times they recur, the poorer their prognoses, Hansen said. So the objective is to vaccinate the patients in the NED setting and try to raise the bodys immune system in an attempt to eliminate residual tumor cells and micrometastases, he said. MabVax has licensed a variety of vaccines from MSKCC, of which its sarcoma vaccine is the most advanced, Hansen said. The company is hoping to follow along in 2011 with a Phase II program in SCLC in the adjuvant setting, he added. Although MabVax has licensed a vaccine for ovarian cancer from MSKCC, a Phase II trial in that disease is being funded by the NCI and managed by the Gynecologic Oncology Group, Hansen noted. If after that Phase II trial any evidence is accumulated that suggests the ovarian cancer vaccine is worth continued development, then that program will be rolled over to MabVax and it is our responsibility, he said. Under the partnership, MSKCC is responsible for the early development work, including the Phase I trials for the monovalent and polyvalent vaccines. At the end of that stage, we sit down and determine if it is worthwhile to continue developing, and if it is, then that program is shifted over to MabVax, and it is our responsibility to bring it forward to the patient, Hansen explained.
That early work at Sloan-Kettering is overseen by Philip Livingston, head of the tumor vaccinology laboratory at MSKCC and MabVaxs chief science officer, and Govind Ragupathi, an associate attending immunologist at MSKCC and MabVaxs vice president of vaccine technology. MabVaxs immunotherapy approach is very different from that used by Dendreon Corp. for its prostate cancer product Provenge (sipuleucel-T), Hansen noted. We are essentially activating the antibody side of the system, and Provenge is activating the cell side, he said. But he emphasized that no one can claim one is better than the other. We just dont know enough at this point in time, Hansen said. If enough high-quality antibodies can be generated in response to a cancer vaccine, then they can be beneficial and eradicate cancer, noted Wolfgang Scholz, vice president of antibody discovery at MabVax. The company is taking two approaches in its development programs, with the first being the antibody response to the vaccine in the trial so we get direct evidence, he explained. But we also actually are generating human monoclonal antibodies from patients that have responded in those vaccine trials and have responded with very good antibodies, and we are rescuing them, and then regenerating them in our laboratories to use down the road in a therapeutic, Scholz said. We are attempting to find the best antibody against a certain target and then essentially explore that antibody and bring it forward into the development process, Hansen said.
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chapter 9:
Inflammatory Diseases
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conditions. FM-302 is initially positioned for inflammatory bowel disease. The two remaining targets for which Femta has exclusive rights to BioAltas technology have not been disclosed. Stephen Keane, Femta president and chief operating officer, said each target is validated and was selected after a rigorous analysis of its scientific merit, market potential, competitive landscape and intellectual property. San Diego-based Femta has $4 million in Series A funding from Latterell Venture Partners and $3.5 million in committed services from BioAtla. That funding will carry the start-up through the end of 2010. Keane noted that Femta is truly virtual he and Emtage are the only employees, while Lonza Group Ltd. handles manufacturing services.
We dont cut any corners; we just contract everything out, Keane explained. Femta is currently seeking $5 million to $10 million in Series B funding. Latterell has already committed to the round, and Keane hopes to have a few new investors on board within six months. And in the interim, Femta is in active discussions with potential partners, Keane said. Just a few months ago, Alders ALD518, in Phase II, snared a $1 billion deal with Bristol-Myers Squibb Co., which indicates the appetite for fast-follower biologics. These are known, validated targets. If youre second or third or even fourth to market, theres a huge opportunity, Keane said. If youre a large pharma or biotech that doesnt have monoclonal antibody strengths, this will fill your pipeline.
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often applicable in multiple tumor types. Promedior is actively discussing its platform and lead compound with prospective partners, but for now, the Malvern, Pa.-based biotech is well-funded. Forbion Capital Partners led the $12 million
Series C round, with participation from existing investors Morgenthaler Ventures, HealthCare Ventures, Polaris Venture Partners, and Easton Capital. Promedior, founded in 2006 as a spinout from Trellis Bioscience Inc., previously raised $14 million in Series A funding and $15 million in Series B funding.
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initiating the regulatory package and filing an investigational new drug application, he said. No drugs have been approved to actually stop or delay the onset of Alzheimers disease. But numerous companies are working to develop therapies to fight the underlying disease. And many of those development programs are hinging on the theory that beta amyloid is at the center of the pathogenesis of Alzheimers. Although the theory has its skeptics, it is generally accepted that toxic beta amyloid affects the ability of neurons in the brain to function properly, leading to cognitive and other disruptions typically associated with Alzheimers disease. Bolstering that theory, the Alzheimers Disease Neuroimaging Initiative presented research in April 2009 at the American Academy of Neurology meeting showing a strong correlation between beta amyloid levels and cognitive decline. Another prime suspect believed to be responsible for the death and damage to nerve cells is the formation of neurofibrillary tangles in the brain. Companies are using various strategies to reduce the production and aggregation of beta amyloid, or to increase its clearance in order to alleviate its deleterious effects on the brain. Another widely held view in the scientific community is that a unit of proteins known as oligomers are responsible for blocking memory loss in the early stages of the disease. Currently available cognitive-enhancing drugs Eisai Co. and Pfizer Inc.s market leader Aricept and two other drugs in the same class, Novartis AGs Exelon and J&Js Razadyne work to ease the symptoms of Alzheimers disease. But those drugs, known as cholinesterase inhibitors, stop
working after several months and have some unpleasant side effects, such as nausea, vomiting and diarrhea. Another approved therapy in Alzheimers disease, memantine, sold as Namenda by Forest Pharmaceuticals Inc., is intended for more severe Alzheimers and also is aimed at improving symptoms. But a new crop of products in the pipeline including Elans amyloid-targeted bapineuzumab, a monoclonal antibody are being developed to slow the disease. Last year, Janssen Alzheimer Immunotherapy, a J&J affiliate, acquired substantially all of Elans assets related to the Alzheimers immunotherapy program, which Elan had shared with Wyeth. The Alzheimers immunotherapy program is continuing with Pfizer Inc., which acquired Wyeth in 2009. Although a great deal of industry and academic research has focused on beta amyloid as key to fighting Alzheimers, there are several other targets that are seen as holding promise in treating the disease. The Tau protein, in the form of neurofibrillary tangles, is considered to be a major hallmark of Alzheimers. Other potential drug targets for Alzheimers disease include heat shock protein-90, a tau-related target. Yet another target is ApoE, shorthand for apolipoprotein E, a major risk factor gene for Alzheimers. In addition, companies like EPIX Pharmaceuticals Inc. and Sanofi Aventis SA are focused on the alpha-secretase pathway in Alzheimers disease. That pathway is responsible for preventing the production of amyloid beta and stimulating the neuroprotective protein, sAPPalpha, that keeps neurons alive and healthy.
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meaningful endpoints in a relatively short timeline, Oswald said. Dry eye requires a 12- to 24-week study period, so this was thought to be the most efficient therapeutic area to study from a drug development perspective, he added. The problem is that dry eye also is notoriously complicated to treat, according to Oswald, who was lured to SARcode by the companys smallmolecule program, which breaks the chronic cycle of ocular surface inflammation. A major contributing factor in the development of dry eye is T-cell mediated inflammation and cytokine production in diseased ocular surface tissues that leads to disabling eye discomfort and reduced tear quality, he explained. SAR 1 1 18 inhibits the interaction of LFA-1 with its cognate ligand, intercellular adhesion molecule-1 (ICAM-1) a protein that is normally expressed in low levels on the surface of epithelial and endothelial cells, but is highly expressed in inflamed tissue. The blockade of LFA-1 binding to ICAM-1 is the key to treat not only dry eye but also diabetic macular degeneration, atopic dermatitis and many other diseases, Oswald said. We have a well-defined biologic pathway that could be effective for future unmet needs. Although the symptoms of dry eye are addressed by a whole raft of artificial tear products, Oswald said, Restasis (cyclosporin emulsion 0.05 percent) is the only therapy approved in the U.S. to treat the condition, which represents a $1 .3 billion market in the U.S.
Clinical studies of Restasis suggested the onset of action is nearly twice as long 24 weeks as SAR 1 1 18, according to Oswald. Unlike SAR 1 1 18, Restasis also accounts for up to a 17 percent rate of ocular burning at the same dosage, he added. A dermatologic formulation of SAR 1 1 18 also is in development as a treatment for atopic dermatitis and psoriasis to provide a potentially safer alternative to long-term topical steroids or calcineurin inhibitors. The opportunity for SAR 1 1 18 in diabetic macular edema the leading cause of blindness in working-age adults in the U.S. could be even larger, given the severity of the disease and the growing incidence of diabetes in the U.S. and abroad. The year 2011 could bring a new, catchier name for the company and, Oswald hopes, initiation of a Phase III study of SAR 1 1 18 in dry eye, named OPUS-1 . A successful outcome would pave the way for follow-on safety and efficacy studies and an anticipated new drug application filing for SAR 1 1 18 ophthalmic solution in 2014. Down the road, the company has eight compounds in its large library of drugs that are potential candidates for commercialization, he added. However, SARcode has no intention of changing its capital-efficient structure. With only six employees, the company outsources preclinical development and other functions at the point of need, according to Oswald. And although Alta and Clarus remain active members of SARcodes board, at the same time, were thinking about how we continue to move toward our Phase III program with a potential Series B financing, which also could occur early in 2011 , he said.
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production) that has been validated in recent clinical trials to demonstrate that RSLV-125 inhibits chronic IFN activation in patients. Posada has created a streamlined, recession-proof business plan to bring RSLV-125 through Phase IIa trials in three years, and then partner for late-stage trials with a large pharma, rather than conducting costly Phase III trials and waiting for a bigger payout. The company will have a low headcount, which includes 10 Seattle-based consultants, and will use university labs for R&D rather than spending on infrastructure. Posada, who identified the technology and is assembling the team, was formerly with Eli Lilly and Co. and, more recently, with GlycoFi Inc., a Dartmouth College spinoff, until Merck & Co. Inc., of Whitehouse Station, N.J., acquired it for $400 million in 2006. Since then he has headed a life sciences consulting firm. A 25-year protein design veteran, Resolves co-founder is the inventor of BMS Orencia (abatacept) for RA. He also was a founder of Trubion Pharmaceuticals Inc., of Seattle, which focused on protein therapeutics for autoimmune and inflammatory diseases before its acquisition by Emergent BioSolutions Inc., of Rockville,
Md., in August for $135 million. Posada is raising $7 million in seed financing which he expects to be completed by mid-January, and plans to raise $12 million altogether to take the company through Phase IIa trials. Resolve also has two related, preclinically validated back-up fusion protein molecules in addition to RSLV-125, which possess different mechanisms of action, and could be used for lupus nephritis, a complication of lupus, Posada said. All three molecules will be part of a completed preclinical partnering package, along with Phase I and IIa results. RSLV-125 will begin a pilot IFN signature study in early 2011 in 100 patients examining patientto-patient variability of the IFN signature to help Phase IIa trial design. Posada anticipates filing an investigational new drug application for the Phase I in the second quarter of 2012, and completing a safety study by the third quarter of 2012. The Phase IIa proof-of-concept, placebocontrolled, double-blind study should begin in early 2013 and take 12 to 15 months to complete.
chapter 10:
Dermatologics
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of Cell Genesys, where Green started his career in 1992, and Abgenix. This is a group of individuals who know the antibody space and are interested in developing far-reaching technologies that serve as the basis for engines for drug discovery, Green said. So when we initiated discussions with Third Rock Ventures, it was a very productive discussion, he said. Third Rock and Pfizer Ventures, Green added, have been a great team that is helping the company. He noted that Ablexis board members also include Third Rocks Cary Pfeffer and Lou Tartaglia, who he said are contributing significantly to the companys strategic plans, both from the business side and the technical side. For competitive reasons, Green said he could not disclose details about what differentiates Ablexis AlivaMab Mouse technology from Amgens
XenoMouse or BMS HuMAb, for which he said there have been large waves of candidate drugs in clinical development that have come from these platforms. But, Green said, we felt there were several opportunities to improve upon the platform to provide a more efficient and robust transgenic animal platform for the discovery of human therapeutic antibodies. He emphasized that Ablexis business model is not currently based on the discovery of therapeutic products, but on providing a very large unmet commercial need for robust and efficient human therapeutic antibody discovery platforms. Experienced antibody drug developers are seeking transgenic mouse platforms, because of their tried and true nature, their efficiencies, their ease of use, and the direct discovery of very high-potency drug candidates, and multiple candidates to provide backup for later stages of development, Green said.
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vicePt AiMs to get red out, Adds $10M for rosAceA triAls
Founded in August 2009 to develop products for skin disorders, Vicept Therapeutics Inc. recently added $10 million in Series A funding to push into Phase II with its lead program designed specifically to address erythema associated with rosacea. Were going to be jumping into Phase II studies in the second half of [2010], said President and CEO Neal Walker, a dermatologist who co-founded the Malvern, Pa.-based specialty pharma firm around an alpha-adrenergic receptor technology for use in developing topical skin treatments. Vicept has raised a total of $16 million in the Series A round, led by investors Vivo Ventures, Sofinnova Ventures and Fidelity Biosciences. Those funds should get the firm through the end of Phase II with V-101 in rosacea and allow it to advance a second product aimed at various forms of bruising and purpura. While there are existing treatments available for rosacea, most are not effective against erythema, the facial redness. V-101 works by binding with the adrenergic receptor present on blood vessels and clamping down on them, Walker said. Its the dilated vessels that cause the redness. Roughly 16 million to 17 million people in the U.S. suffer from rosacea, and about 80 percent of those experience the redness, so its a rather large market opportunity, Walker told BioWorld. The main pharmaceutical ingredient in V-101 is not new. Vicepts technology is based on a group of molecules that have been used for years since the late 1960s actually, in ocular and nasal indications, he said. Drugs such as Afrin (pseudoephedrine), for instance, act on the alphaadrenergic receptors. That means Vicept has a good shot at applying for approval of V-101 under the less risky 505(b)(2) regulatory pathway, though Walker pointed out that its still a new topical dosage, so weve got a lot of work ahead of us. Funds from the latest round are expected to get V-101 through Phase II testing. After that, the company will consider its options. When starting a company, I think you have to plan to take [a drug] all the way through on your own, Walker said, though partnering is certainly on the table. Earlier in the pipeline, Vicept has a topical program designed to reduce actinic purpura, bruising associated with accumulated sun damage that typically affects the elderly, as well as bruising from injectable procedures. A lot of people dont realize how life-altering dermatologic conditions such as rosacea can be, Walker said. And the companys mission is reflected clearly in its name, a reference to two Latin words: vita, meaning life, and receptus meaning to take back. Its about giving people their lives back, Walker said. In connection with the financing, Albert Cha, of Vivo Ventures, Thomas Beck, of Fidelity Biosciences, and Arnad Mehra, of Sofinnova Ventures, are joining Vicepts board. Also on the board are Walker and Stephen Tullman, who serves as chairman.
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Those compounds target integrin-linked kinase (ILK). Valocors early results indicated that its ILK inhibitors are as effective as calcineurin inhibitors such as Protopic (tacrolimus) by Astellas Pharma Inc. and Novartis Elidel (pimecrolimus), but without the broad immunosuppressive effect. The drugs also come with a black-box warning from the FDA regarding cancers that have developed in some children who used them. One set of ILK inhibitors had a surprise effect that Valocor is now pursuing they stimulated melanin production, resulting in darker pigmentation. The company is now pursuing that class of compounds as a possible therapy for vitiligo, an
autoimmune disorder that destroys the skins pigmentation. If we could help pigment the skin and also temper the immune response, we may have a beneficial effect in vitiligo by two mechanisms, said Wattier. For a business strategy going forward, Wattier said, Were open to a variety of strategies. Right now our plan is to move these programs to the inflection point so we have options. He added that Valocors most likely path will be to raise a few rounds of financing, using those funds to add value to the portfolio, and then go for either an IPO or big pharma partnership.
chapter 11:
Obesity
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Earlier in its pipeline, Halsa is working on a program that involves blocking proteolysis induction factor receptor (PFIR), interrupting the mechanism by which cancers cause muscle wasting. To date, Halsas ZAG and PFIR work has been funded without venture capital. The firm raised about $500,000 around its 2007 launch from angel and high net worth investors, and it also received $1 million from the Texas Emerging Technology Fund. Speros said Halsa is currently fundraising and aims to close a $5 million second round in mid-2010, which may or may not include VCs. Houston-based Halsa was founded based on research conducted by Michael Tisdale at
Aston University in the U.K. The university had nonexclusively out-licensed some of its intellectual property, and the Halsa team spent seven years reassembling the patent portfolio prior to launching. Halsa now hold exclusive rights to the use of ZAG in obesity and diabetes. For now, the firm is running lean, with just a few employees supplemented by advisors, consultants and contractors. Potential partners are already sniffing around Halsas programs, and Speros said the start-up is exploring its options. We dont view this as something we could or should take forward all the way on our own, he said, but the optimal stage to partner has yet to be determined.
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would be given to healthy people who, despite diet and exercise, have a bulge of fat theyd like to get rid of. Its an application where a lot of snake oil is being sold, if you will, and wed like to bring a little science, Dobak said. Phase IIa data released in March showed that the optimal dose of LIPO-102 was well-tolerated and reduced mean abdominal circumference by 3.47 cm (p=0.017) after eight weeks. Data from a second Phase IIa trial released last week showed mean abdominal circumference reductions of 1.2 cm versus 0.1 for placebo (p=0.048). The effects were sustained for six to 12 weeks. Dobak said Lithera plans to initiate Phase IIb studies soon and hopes to conduct its end-ofPhase-II meeting with the FDA by late 2011. Lithera plans to pursue a 505(b)(2) pathway for approval. While insurance providers would likely cover LIPO-102s orphan indications, the body contouring application would be an out-ofpocket expense for patients. In this way, the
business model would be similar to Botox, which is approved for medical conditions like cervical dystonia pain, eyelid spasms (blepharospasm) and eye muscle problems (strabismus) as well as for cosmetic wrinkle reduction. Botox garnered $1.3 billion in 2009. Dobak believes the opportunity for LIPO-102 as an alternative to lipsuction surgery in the body contouring market could be similarly lucrative. He explained that about 150,000 people undergo antiwrinkle surgery annually, while seven times that amount, or more than one million, opt for Botox. Since 350,000 people get liposuction annually, applying the seven-times multiple leads to a LIPO102 patient population of roughly 2.5 million. Lithera, a largely virtual operation with 10 employees, has raised $21 million in two rounds of venture capital from Domain Associates and Alta Partners. The biotech plans to raise a Series C round in the next six to 12 months. Dobak noted that while Lithera is prepared to advance its programs as far as necessary alone, it is also talking to potential partners.
chapter 12:
Eye Diseases
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Within its Rho-kinase inhibitor pipeline, Aerie identified a series of compounds that also hit a second drug target, resulting in exceptional efficacy, tolerability and duration of effect, van Haarlem said. He declined to name the target but said an investigational new drug application for a lead candidate in the AR-13165 series will be filed in 2011. In addition to drugs, Aerie is developing a delivery system designed to address the compliance problems common with glaucoma eye drops. Long-term animal studies are underway to determine whether an insert or implant is most appropriate, but the goal either way is to provide sustained drug delivery over one to two years.
Aerie is testing the system with Xalatan but eventually plans to apply it to AR-12286, AR13165 and various combination products possibly including Xalatan. Aerie, named for the lofty nests of keen-eyed birds of prey, raised a $10 million Series A follow-on round in 2009. Van Haarlem said discussions are ongoing regarding future financing plans. And while the company is keeping all our options open regarding partnering, van Haarlem noted that glaucoma clinical trials are not exceptionally expensive and the regulatory path is well-defined. We are maintaining the option to go it alone, he added.
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2009. Although Xalatan will go generic in 2010 and many other glaucoma drugs are already generic, the new mechanism offered by Rho-kinase inhibitors could be a value-driving differentiator particularly given that 40 percent to 50 percent of glaucoma patients require more than one drug, and many develop resistance as they cycle through the existing options. Wende Hutton, general partner with Canaan Partners, likened glaucoma treatment to the hypertension field, where there is a lot of switching between drugs and trying various combinations in search of something that works for each patient. But she noted that as multiple compounds are
combined, eye irritation can build. So if you have a drug with fewer side effects, it will be selected for first-line treatment, she explained. Altheos is not the only biotech hoping to tap into that opportunity. Japanese firm Santen Pharmaceutical Co. Ltd. has a Rho-kinase inhibitor in the clinic for glaucoma. And Aerie Pharmaceuticals Inc. is in Phase IIb glaucoma trials with of Rho-kinase inhibitor AR-12286. There is room for a couple of these drugs to open up this new class, said Hutton. While Altheos may or may not be first to market, the biotech is hoping for best-in-class performance.
chapter 13:
Foundations
Biotech Foundations is a new BioWorld Today column that recognizes biotech-related nonprofit organizations, as well as those founded by biotech industry luminaries.
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And for his part, Bock said many of the lessons he learned from biotech have transferred well to the nonprofit world. I could at least go up to an investor and promise theyll get a lot more out of it than they put in, he said. Bock runs the USA Science & Engineering Festival like a biotech start-up: He has a business plan, and he provides regular updates on that plan to his sponsors. He also maintains virtual operations his group has no offices and no infrastructure, and it outsources functions like logistics and public relations.
One major difference between running a nonprofit and running a biotech is employee motivation. In biotech, I could always incentivize people with equity, Bock said. While there are no stock options for the science festival, Bock still believes in paying competitive salaries to get the best people on board, reasoning that one really good employee is more effective than 10 people sharing a job for partial salaries. But Bock admits he is amazed how incentivized people are just by doing good. For more information, usasciencefestival.org. go to: www.
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focused on women who are diagnosed with cancer today and need help today, Shawver explained. We are not about early detection, and were not about cures for the future. Our mission is simply to help women and their physicians who are facing difficult treatment decisions. Using that mission as a platform to raise grants and other funding requires the foundation to run a lean operation. With only one full-time and three part-time employees, plus volunteers and consultants, the organization operates almost virtually. Shawver hopes to expand the staff as more physicians and patients seek out the foundations services. We want to stay up to date with the latest technologies and markers that match to drug efficacy, she explained. Today, those technologies consist of a battery of chemical markers, mutational analyses and DNA amplification tests. Tomorrow, the science might encompass circulating tumor cells or microRNA, she added. Until recently, Shawver served as CEO of San Diego-based Phenomix Corp., which ceased operations last month. As an entrepreneur-in-residence at 5AM Ventures, in Menlo Park, Calif., shes temporarily devoting additional time to Clearity. The foundations board members and officers also volunteer their time. Partners such as molecular diagnostics company Illumina Inc., of San Diego; advisory firms Blueprint Life Science Group, of San Francisco; and New York-based public relations firm Porter Novelli Life Sciences offer
in-kind services and underwrite educational and other events. To date, the foundations signature achievement has been to facilitate a system to transfer ovarian cancer samples from hospital pathology labs to specialized testing facilities, Shawver said. In April, she also presented a poster at the American Association for Cancer Researchs annual meeting in Washington, describing the dynamic range and expression of ovarian cancer markers that matched to drugs in a subset of patients in the foundations database. Long term, the Clearity Foundation hopes to improve the survival rate and quality of life for women with ovarian cancer. Shawver also wants to educate payers about the value of tumor profiling. Across all cancers, only 25 percent of patients respond to chemotherapy, so many patients get toxicity without benefit at a cost, she said. If patients and their physicians could choose from among five therapeutic options to treat recurrent cancer, why not pick one where theres some rationale to expect a response? she asked. Shawver hopes the evidence on ovarian cancer that the Clearity Foundation is gathering today will lead to an appropriate clinical trial design where the data can be tested formally. I chose to start a foundation because I couldnt find anything out there that was focused on recurrent patients, she said. I knew how frustrated I was when I was trying to get my tumor profiled. If youre Jane Doe off the street, its even more difficult to get access to the latest diagnostic tools.
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companies. None of the original scientists who started with our foundation wanted to be associated with a company, but nonprofits are a lot less threatening. And by being associated with us and exposed to our partners, they lost that distrust and apprehension of working with companies. I think you need that buffer, and I think youll need it for another 10 to 20 years. Johnsons trademarked model is called the Accelerated Research Collaboration (ARC). He pointed to at least five ways it differs from traditional research and drug discovery models: First, the ARC model requires sharing discoveries without the delays associated with publishing scientific papers. Second, experiments in the ARC model fit into an overall research plan focused on identifying therapeutic targets. Third, an aggressive IP policy protects discoveries and reduces risk for commercial development. Traditionally, Johnson said, university technology transfer offices are discouraged from investing in IP protection for biological discoveries. Fourth, the ARC model promotes relationships with biotech and pharmaceutical companies to encourage evaluation and licensing for drug development and clinical trials. Fifth, the ARC model measures success in the delivery of patient treatments, not the publication of scientific papers. While the foundation cant yet take credit for delivering patient treatments, it can point to a number of significant accomplishments for an 8-year-old organization. More than 150 potential targets (proteins, genes, pathways or transcription factors) have been identified. Two dozen new
research tools with application to neurological disease research have been developed. Two U.S. patents have been issued, and 18 more patent applications published. More than 80 articles have been published in peer-reviewed scientific journals. Moreover, Johnson has raised more than $43 million from MS patients and entrepreneurs and the first clinical trial is expected in about 2014. Yet, Johnson said, he gets a mixed message from other foundations about the ARC model. Those interested in the ARC model are mostly smaller and younger organizations, he said. Legacy organizations are entrenched in doing it the way theyve always done it. Many nonprofits behave like mini-NIHs in terms of giving out grants, Tung noted. We think the real value that a nonprofit can add is by participating in every step in the value chain. Johnson believes it is only a matter of time before the new model delivers a cure for MS and demonstrates that theres a better way to discover and develop drugs. When you look at what weve done to produce 150 targets, and understand that weve only spent $28 million, you realize that a very small amount of money can have a dramatic impact, Johnson said. We cant change the way money is given out, but we can try to incent people. Small changes can have dramatic impacts, and were trying to demonstrate that. When we do, then there will be a groundswell to try to move more money in this direction.
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are devoted to problems that primarily affect the poorest 90 percent of the worlds population, according to Chin. Even with the Bill and Melinda Gates Foundation donating some $2 billion to $3 billion annually to nonprofit health foundations for drug development, thats less than half of what the big pharmas Sanofi, Pfizer, Merck spend, Chin said. The advantage of the nonprofit structure is that were not constrained to pursuing drugs that will generate a large return, he added. That being said, we dont have access to the capital markets, and this is a very capital-intensive business. With the Seattle, Wash.-based Gates Foundation providing nearly two-thirds of its funding, the iOWH has achieved several significant milestones. The institute developed the antibiotic paromomycin intramuscular (IM) injection as a new treatment for VL, a deadly disease transmitted through the bite of an infected sand fly. Paromomycin IM injection is an off-patent aminoglycoside antibiotic that has been marketed in the U.S. as an oral formulation to treat intestinal parasites. Approximately 500,000 new cases of VL occur annually worldwide more than 90 percent of them in India, Bangladesh, Sudan, Brazil and Nepal. The largest Phase III trial ever performed for VL concluded in November 2004. The iOWH, in collaboration with the Special Programme for Research and Training in Tropical Diseases at the World Health Organization (WHO/ TDR), treated 666 VL patients in India. The following year, the institute received orphan drug designation for paromomycin IM injection to treat VL from the U.S. FDA and the European Agency for the Evaluation of Medicinal Products. Gland Pharma Ltd., of Hyderabad, India, agreed to manufacture the drug, and in 2006 the drug controller general of India approved the injection
to treat VL. In May 2007, paromomycin IM injection was included on WHOs model list of essential medicines. This fall, the iOWH expanded the paromomycin program to Nepal and Bangladesh. In 2006, the institute implemented a program to combat diarrheal disease, developing antisecretory drugs as an adjunct to oral rehydration therapy to reduce stool output and shorten the duration of diarrheal episodes. In 2008, iOWH entered a research collaboration with F. Hoffmann-La Roche AG, of Basel, Switzerland, that allowed the institute to screen more than 780,000 molecules from Roches compound library to identify a potential new drug to treat diarrheal diseases. In 2009, the iOWH successfully completed its first screening campaign and identified up to 40 new drug leads for additional study. Subsequently, the iOWH signed a collaboration agreement with Novartis AG, also of Basel, that will allow the institute to select promising drug candidates that are ready for preclinical testing. Currently, the institute is working with the Novartis Institutes for BioMedical Research to treat infectious diarrhea by inhibiting the cystic fibrosis (CF) transmembrane conductance regulator chloride channel. Because infectious diarrhea often is caused by over-activation of the CF channel, a CF channel blocker could help to reduce fluid and electrolyte loss, according to the Institute. The Gates Foundation also has given the iOWH $64 million to develop and prepare for large-scale commercialization of semisynthetic artemisinin, an ingredient in artemisinin-based combination therapies (ACTs) for malaria. The iOWH is partnering with Paris-based SanofiAventis SA with a goal of commercializing ACTs with semisynthetic artemisinin in 2012, making the institute the first commercial or nonprofit
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pharmaceutical company to develop a product from synthetic biology, according to Chin. With the inherent need for partnerships at every point along the development pipeline, nonprofits have a more diverse roster of stakeholders than for-profit enterprises, according to Chin, ranging from governments and health care delivery systems to academics and individual donors. The
iOWH has attracted great partners, both from biotech and big pharma, he said. Nevertheless, global health is something the industry cares about more and more, Chin added. Five years ago, if we had approached a big pharma company, we would have been sent to their PR department. Now, were sent to the head of R&D.
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S11438 ISBN:978-1-934863-47-3