Transcript

- Is Texas Stem Cell Policy Good for Texans?

A Texas Tribune Festival stem cell debate between Rep. Rick Hardcastle (R-Vernon, Texas), CellTex executive vice-president Andrea Ferrenz, founder of Texans for Stem Cell Research David L. Bales, and University of Minnesota bioethicist Leigh Turner, held September 21, 2012. Moderated by Scott Braddock.
Note: Audio begins in the middle of Hardcastle speaking.

HARDCASTLE: will tell you Im a whole different man than I was while I was progressing with M.S. Uh, some of the ones in the audience saw me jump up on the stage like this, about nearly a year ago, and two years ago, I couldnt have sat down and crawled up on this stage, much less jumped. So, you know, and its about patient access and making sure they get what they pay for. MODERATOR: Uh huh. And what we say they get what they pay for, were talking about and, of course, youre representing the company where this treatment was done, in Sugarland, talk about the cost is $25,000 to $30,000 what do they get for that? FERRENZ: Well, first let me say that, uh, we are actually a laboratory, so Representative Hardcastle and other patients, they have to work with their doctor and their doctor decides their form of treatment. So if a doctor believes that stem cell therapy, particularly the type of stem cell therapy we work with in our laboratory, called mesenchymal stem cells, if they believe that that is going to be effective for their patient, then they essentially notify our lab, they identify the number of cells, so to speak, for the patient. You asked what does a patient get? The cell count, that we call it, is directly tied to efficacy, so that determination of working with the doctor and deciding how much they need is an extremely important part of this. And uh, then what happens is the patient would go to a surgeon, of their choice, and have a small amount of fat removed. Thats then sent to our lab, and using the technology that weve developed with our partner, we can separate from that small amount of fat the patients own mesenchymal stem cells. And then create duplicate copies of it and it takes time. The cells grow at a natural rate, so to speak, you can think of it, and then coordinating with the physician is then, get the patient scheduled so that then the cells, when theyre ready, can be returned to the physicians office and then the physician gives them to the patient. So thats what they get. MODERATOR: So, and I think you, its a misconception that you would as you said, youre dealing with your doctor. Its not like youre driving down to Sugarland and then you go right in to CellTex and get your cells switched out and then youre good to go, right? Its not like that? FERRENZ: It doesnt work like that. MODERATOR: Its not like a movie, right?

FERRENZ: Nope, it doesnt work like that. MODERATOR: I hope were setting the stage about right here right now. Professor Turner, you have some questions about what they do at CellTex? Youve raised some concerns? TURNER: Ive raised some concerns, yeah. Do you mind if I take a step back from CellTex for a minute? I mean, I understand your question, but uh- MODERATOR: Im going to mind it, but go ahead. TURNER: I think that when were talking about stem cell policy in Texas and if its good for Texans, theres multiple policies in play, and its important to keep in mind that theres different frameworks that we can talk about today. Ive been very focused on CellTex, but in a sense, when it comes to public conversation, I think theres much more going on in Texas than just CellTex. In terms of policies, Representative Hardcastle has pushed forward policies concerning adult autologous stem cell banks, so we could talk about just that. Theres the Texas Medical Board and their investigational agent policy. David, I think, is encouraging us to think much more broadly in terms of not just sort of mundane level of policy but sort of a vision of stem cells, of stem cell research in Texas, and I think we can think about that as a policy. And then I would also say that Texas has a problem. What I mean by that is that its like Florida, California, Arizona, in that there seem to be a number of clinics in Texas that are already administering stem cells to customers, patients. In some instances they may be in compliance with state and federal law; in other instances, I would say the available evidence indicates that they are not in compliance. I ended up, before coming here, I just checked to see how many clinics are there in Texas where you can obtain stem cell procedures, and I ended up finding 20, and then three what I would call stem cell banks, that have relationships with clinics. And thats the part, to me its that last category that I think is, in many ways, most worrisome. So some of you, if you may have noticed, the Houston office here in Texas, the FBI, just issues an announcement that two individuals in Texas pleaded guilty because they were involved in unlawful administration of stem cells. And that to me is especially the category that its not the only policy, but its where Texans and other individuals are most vulnerable. MODERATOR: So you would say then, that what weve heard in various news reports and such that stem cell tourism is that going on in Texas? TURNER: Well, theres kind of a dual-phenomenon taking place. There are examples of Texans crossing the border in to Mexico, for example, or going to other countries and getting access to stem cell procedures. Theres also some people have gone

online, on YouTube, and theres a Texan who passed away after having a stem cell procedure in Mexico, and some friends of his made a video. Theres other examples of people who have not just gone for procedures but been harmed as a result. Theres also what I think is the more recent dimension to all of this, is that Texas itself, its not just a matter of Texans going abroad but there are clinics here in Texas, so that local individuals can go there, and then presumably from elsewhere, other states in the US. MODERATOR: And Representative Hardcastle, thats exactly what youre trying to keep from happening, is that sort of stem cell tourism, right? And you mentioned before that you didnt want to have to go out of the country to do this, that youd like to be able to do it here. HARDCASTLE: Ive investigated all of the clinics out of the country, some on the continent, some off the continent. You know theres absolutely no reason why we cant do this here. The FBI, the two men hes talking about with the FBI, were involved with a clinic in Mexico, and selling stuff across the state lines, which brings a whole nother picture to the realm of things. Policy-wise, our whole goal was to make sure that didnt happen in Texas. I dont care if youre a back institute, stem cell lab, or if youre CellTex or if youre MD Anderson doing cancer research, which does a lot of stem cell research, or Scott and White, which has a whole building for nothing but stem cell research. We want to make sure that the efficacy has some line there in somewhere, and we go from there so we dont get in to a Mexico problem. MODERATOR: And whats your confidence that that isnt happening to a large extend right now? Do we know that? HARDCASTLE: No, Im very confident that its not happening. Every lab that I know of, and every doctor thats used them that I know of in Texas, and I dont nearly know all of them, but theyre concerned with the same efficacy that I am. I know doctors that are using this extensively in spine and neck surgeries and going to foreign countries to get their stem cells because they have efficacy laws on how they produce the stem cells or what kinds they use. By the same token, I know a lot of people that went out of the country to have a treatment, and didnt know whether they were getting umbilical cord stem cells or their own stem cells they didnt know what they were getting. But they were that desperate for some kind of treatment. MODERATOR: And because this is, you know, as you have mentioned before, pioneering, were in a different sort of, a new place, with a lot of this technology and a lot of whats being done. What does CellTex do? What does the industry do as a whole to try to police itself a little bit on some of this stuff, to make sure that if people have those concerns, that its not happening?

FERRENZ: Its important to understand that the phrase stem cells has become kind of a buzzword. For instance, youll see nanotechnology is another one. So people throw phrases into their websites, into their advertising, what have you, and theres a wide variety of technology that is actually related to stem cells. And whats key for regulators, FDA, Texas, whomever, is to really look at the product, to really look at whats going on in each individual circumstance. So, as an industry, we have regulations that are directly applicable to us, like any other type of industry. We follow those. Its the nature of being in the medical products industry that youre highly regulated. MODERATOR: And David, you know your group works with a lot of people, you hear from a lot of people who are looking for sort of an avenue towards hope, right, when theyve got people who have suffered in various ways. What are those familys concerns about the safety and legitimacy about how the business is run? BALES: Well, you know we get emails and phone calls on a regular basis from people saying my son was paralyzed in a car wreck six months ago, should he go pay $25,000 to come to Houston to get stem cell therapy? and I just I just say, you know, you need to ask questions. Have they been part of a clinical trial? Is there any data showing what has happened to the people before that may have had a clinical trial for whatever disease it is, and what were the results? And so, I just you know, I talk to a lot of smart people on a regular basis and they say, be very careful and make sure that you know what youre getting in to and it works. And so, were all for helping people. We want these people who are in wheelchairs to walk again, we want the blind to see again, we just want to protect the safety of the citizens first. MODERATOR: Professor Turner, you mentioned this idea that Texas and stop me if youve heard this one Texas versus Washington, that Texas sort of, is in a way, flying in the face of the FDA when it goes ahead with a policy like this that maybe lets some of these companies get away with things that may be FDA violations, at least thats the way you see it, is that right? TURNER: Yeah, thats the point that I tried to make. When I wrote a letter to the FDA about CellTex, that was basically my concern. And I would say, again, just to step back one second before going directly to your question, I mean, there are many companies in Texas, there are many researchers in Texas, who wouldnt frame it in polar terms. So theyre not thinking Im going to do it the Texas way, Im not doing it the federal way. Theyre submitting investigational new drug applications to the FDA, theyre developing clinical trials, phase I and phase II, theres a lot of important, meaningful research in the area of stem cells here in Texas. When it comes to CellTex, I just mean, to be specific about that, the reason I wrote to the FDA is that this looks to me like a clear example of a company that isnt in compliance with federal law and Im sure Andrea will want to rebut that but the reason Im saying that is that there are kind of two pathways when it comes to

regulating stem cells in the United States, when it comes to federal law, federal regulations. Theres one category where you dont need to submit an investigational new drug application to the FDA, you dont need to bring a drug to market. The other category is one where you do, and so you need to submit an IND application to the FDA, and youre basically on the pathway of bringing a biological drug to market. Everything Ive seen in the public realm, all the evidence I can find, indicates that what CellTex is doing is theyre involved in more than minimal manipulation of stem cells, theyre also expanding mesenchymal stem cells, theyre processing them, its taking place over the course of weeks in their laboratory setting. Theyre also involved in whats called non-homologous the clinics involved with them are involved in non-homologous administration. So youve got stem cells coming from fat tissue from the abdomen, theyre being processed in a lab setting, then theyre being administered to people for a variety of purposes. So given to people with M.S. for example, or Parkinsons Disease, and Im sure you can add to that list. But thats the category where once you make a decision to go down that road, while its more costly, while its more labor-intensive, thats the investigational new drug, biological license application, new drug application pathway you can try setting it up FERRENZ: Let me respond to that. MODERATOR: Youll get your chance Im good at this. Go ahead and finish your thought. TURNER: Sure, well, the last thing is, of course this is going to be a strong point/counter-point, but I would also say that when it came to the FDA sending inspectors to the CellTex manufacturing facility, I mean, they characterized it as a biological drug manufacturing facility. They went through the process that takes place. So to me, thats a part of a more complicated story because there is certainly more than just an inspection of the site and I imagine CellTex is having back-and- forth right now with the FDA. But I would say, seeing that on that form is an indication that at least at present, thats how the FDA sees what CellTex is doing. Now, to me, there is no way CellTex should be releasing stem cells to clinics when they are not doing proper phase I, phase II, phase III clinical trials, demonstrating safety, demonstrating efficacy, going the IND FDA route. Its dangerous. MODERATOR: Alright, well Im going to have you respond to that, go ahead. FERRENZ: Thats a lot. Okay. Im going to start with the letter. So the letter was frankly shocking. Theres a lot of allegations in there based on frankly, misinterpretation of the law. So, uh, what I like to call Internet facts in the letter.

Its just simply not the case. So, lets go then forward in time to the 483 and understanding how FDA regulates stem cells. Theres actually multiple categories FDA can identify as applicable to stem cells. So Leigh identified two there are actually more than that. And two key factors that he pointed out, the minimally manipulated and homologous use, lets look at those for a minute. So, what we do is no more than minimally manipulated. Thats a tongue twister for you. Because the FDA defines it as have the significant biologic characteristics of the cells, have they changed through your processes. Thats actually the legal definition of that term. So, what we have very carefully shown, in fact this has been published in peer reviewed literature, Stem Cells and Development, is that the exact process that we use, here are the biologic characteristics of mesenchymal stem cells, heres the process, we establish what are the characteristics at the beginning of the process, what are the characteristics at the end. We meet that definition of mesenchymal stem cells retaining their biological characteristics. So, that was one point that he made. The next point that he made is this idea of homologous use and he talked about patients with different diseases and how a physician determines if mesenchymal stem cell therapy might be applicable to them, thats the physicians job. Now, homologous use I feel like Im doing a Food and Drug Law 101 class so homologous use is also defined by the law. Homologous use says when the cells go back in to the person, do they perform the same basic function? Thats the beauty of regenerative medicine. So we send back to the physician that persons exact stem cells, they get put back in to the patient, and its their body deciding what to do with that. Its a tool that all of us have we all have mesenchymal stem cells, all of us have this ability to essentially kind of heal yourself at the most basic level. And they are through out your body. We take it from fat because thats easily accessible for most people. Uh, but, you literally have mesenchymal stem cells everywhere. So, it does meet the homologous use definition, we are appropriately regulated by the FDA. And so lets talk about that 483, because people get very excited about the 483. Uh, back in April we had two FDA inspectors come and visit us. And this is normal. The FDA regulators come to any regulated entity and we are an FDA registered establishment and thats part of their job. So they stayed with us for two weeks, looked at literally everything we do, and weve talked about this in a press release our laboratory, we have a contract manufacturer, which is a company from Korea that we license the technology from. And, um, they literally saw everything. And we continue operations. And one of the things we saw is that cells go to physicians. And in the end, the last day, the inspectors give you a 483 that lists they put in the box of what type of establishment it is this biological drug manufacturer. Well, that is not an official position of the agency, that is a kind of exit interview that the inspectors do.

So of course, yes, talked to the agency, we have regular conversations with them, we are a regulated entity. Um, they will inspect us again, thats the nature of doing business as a medical product company. Uh, and weve shown them, through dialogs, through materials, that we are, fall in to the category thats called an HCT/P, but it is this category that says because you are giving this person back their exact cells, that you dont have to go through a pre-approval process. Youre still lawful, your product is legal, but you dont go through a pre-approval process. So uh, that's a lot of information to throw at people, but Leigh brought up a lot. MODERATOR: [unclear] Well, its all on Twitter now. FERRENZ: Its all on Twitter? TURNER: [unclear] something thats strictly on point? MODERATOR: Sure. TURNER: You mention the article in Stem Cells and Development, and I brought that with me today. And what I find so interesting I was sitting out in the lobby beforehand, and the interesting thing about this article is that your partners, RNL Bio, doing research in South Korea, they have the same basic regularity framework as exists here in the United States. They did submit an investigational new drug application to the Korean food and drug administration. So they actually did go through that pathway. So do you have an investigational new drug application submitted to the FDA? FERRENZ: Okay, so you said that they have the same basic regulatory framework. They actually dont. They do have a Korean FDA, but by law in Korea stem cells are drugs. Their legislature passed that as a matter of law. We have a much more diversified system in our regulatory categories, uh, they do not have the equivalent of an HCT/P, and you can go in to the HCT/P regulations and it specifically says in the regulations talks about stem cells. TURNER: It is very similar and one of the things they point out is that they did submit an investigational new drug application to do their research thats exactly what RNL Bio and CellTex needs to do here in the United States they also pointed out that their manufacturing facility they use conforms to current good manufacturing practices, which is what your lab is supposed to do, and that 483 you received from the FDA? Thats not a normal response when the FDA comes in. I mean, thats the Keystone Cops version of running a stem cell facility. FERRENZ: Okay, thats actually weve talked about TURNER: Its a long list of problems. HARDCASTLE: Lets go back to Texas, is what I want FERRENZ: Alright, lets go back to that.

[unclear] Well, sure FERRENZ: He just called us the Keystone Cops! I get to talk about that! TURNER: The list includes things like MODERATOR: Hang on a second, Leigh. TURNER: those products arent supposed to go in to humans. MODERATOR: I got you. FERRENZ: So. We actually put this in a press release, too. Um. Ive already mentioned that RNL is our contract manufacturer. So, their people who run our facility all read, write, and speak Korean. So, we literally do follow the GTP. We do insure that our products are viable, intact, they maintain their integrity as stem cells. The issue when you have an auditor? Any kind of audit? Is that its kind of the if its not documented, I havent seen it kind of a thing. So they saw everything; we have stacks of SOPs, but they were all in Korean. All the records that the technicians write, theyre in Korean. Because its a Korean staff. Now, we worked with them during the two weeks they were there, and translated as much as much as we could! And we also provided all of this material to professional, independent translation services; they translated everything. We literally provide everything to FDA. I mean, we continue operating. Its actually just simply not the case. MODERATOR: And you know, all of the language that is used, I mean, some of it, I only English, but it sounds Korean to me, so I get a little bit lost. So you mentioned that here in Texas, we have our policy, and when people hear all of this back and forth, uh, they make think, well, then what are the folks closest to home doing to make sure these questions are addressed? HARDCASTLE: Our goal from the start, and the regulating agencies in Texas, you know we have a track record here. The first stem cells ever used were bone marrow transplants for leukemia patients; very few people realize thats a stem cell. We now do that transplant in Texas and Medicaid pays for it; if its umbilical cord stem cells instead of bone marrow, its a whole lot easier to match than bone marrow. You know, you can go on the bone marrow list and be on there forever and never get the call. But you can match an umbilical cord and we actually have a cord blood lab in Texas. Following these same regulations were watching companies like CellTex and other companies and going forward with the same type of regulation, to make sure the patients are getting what theyre paying for and the doctor and the patient have the right to make that decision. MODERATOR: And this is also difficult because and David, you and I have talked about this, too the idea that somebody might have an experience with this where,

as the representative said, they feel like a miracle happened and then others would say, well, I felt like nothing happened. And you would say thats just the case? HARDCASTLE: Our legal system in Texas covers that. And all of the people that are doing any kind of stem cell treatment you see that in writing, in a release, before you ever sign up for treatment, it doesnt matter if its cancer treatment, investigational treatment on Parkinsons or an M.S. treatment in Houston. Because all of it is some degree of your chance of it working on you compared to it not working on someone else. MODERATOR: When we are looking at something that is so new, a lot of the question and then theres the back and forth, and stuff comes off the blogs, and theres the things that you look at and say okay, its legitimate stuff that Im looking at, and it can get very emotional, very heated. I was warned that would happen. But the pushback on this is that people in Texas want this; theyre paying money for it. They do get to sign that, that says look, theres no guarantee here, is that not fair, with any procedure, especially for one thats so new? TURNER: Well, in a sense, I mean in a broad sense, everyone wants what is on offer here, which is effective treatments for MS and Parkinsons Disease. I mean, we probably all have a family member or a friend who falls in that category. Its a question of how you get there. Its a question of whats taking place. Um, I worry about exploitation of hope and desperation. In terms of should we just let people make their own choices, no, I think thats a dangerous thing. What I mean by that is there needs to be some protective mechanisms in place so that people arent exposed to the most exploitive forms of medicine. So I would say that I think there are a lot of questions that can be fairly asked of CellTex. Again, the good thing about the FDA 483 letter is that you kind of have the CellTex PR machine making various claims of what they are doing, and then there is a critic like me coming in from outside Texas, offering a strong-form kind of criticism the good thing about the 483 is theres at least something out there thats not from either of us, and you can take a look at it, and try to come to some of your own conclusions. And I would say, one of the things in that document, I mean, it points out really elementary problems with that manufacturing process. So, for example, this is coming to your point, the question is, what is it people are consenting to? What is it that theyre being told? So I would say, if they are not being told, for example, and again to go back to the inspection report, one simple thing is that part of the manufacturing process involves a reagent supply and this is how its characterized: for research use only, caution, not intended for human or animal diagnostic or therapeutic uses. Now is that something has every person who obtained stem cells manufactured at a CellTex facility did they all consent to having this as part of that process? A reagent supply

that is in fact not for use in humans or animals? Were they told that? Was that on the list that was disclosed? MODERATOR: Do people know what theyre getting in to? When they sign that form? And I guess, you know, I think its a fair point to say that when somebody is going through something that is terrible, they there is in a lot of ways a sense of desperation so they may just say, yes, this is it, and they dont really look through all of that and they sign it. But then thats on them, right? FERRENZ: Patients have rights, yes. So certainly, yes, if they have decided that they want this therapy, they have the right to do that so long as it does not contravene any law. Uh, to go back to the point about the 483, it is very important to understand that when various reagent suppliers send their material, they may include a statement like that its a kind of disclaimer that they put in. This is well understood and what you do is you establish, by working either with that manufacturer or you work with independent contractors that can establish that that reagent is in fact appropriate for the use that you have. So yes, we have made sure that all of those things listed in the 483 are appropriate for use um, it can be done either working with the supplier or with someone else. Reading a document without context, without understanding the law, without understanding the facts, its subject to misinterpretation. And if youre so focused on one particular document, youre missing the complexity of food and drug law. HARDCASTLE: Well, I want to go back to his first statement, about reaching out for hope, and Im going to calm down and say this very calmly, cuz I promised I wasnt going to get in a fight with Leigh while we were sitting up here, but we do that with cancer drugs, too. The same year I was diagnosed with cancer, that little pin right there you only get from MD Anderson if a child dies taking cancer treatment. And I never signed any release, I never saw any release, that said they were going to give her poison; I wanted whatever they could give her to try to keep her alive. And so, youre talking about several different arguments here, you know, because we all go for the best we can get of what we think will work and what our doctor thinks will work and on the regulation side, we do a good job of regulating doctors in Texas. We now do a good job regulating labs in Texas, to where they cant sell me something thats not there. I actually get to see it, I actually get to see the tracking code where it came from me to start with. You know, I actually get to warm it up myself after it comes out of the cryogenic freezer, and put it in my body, and boy whats different from that treatment and me going in and having my blood cleansed by dialysis and putting it back in my body? MODERATOR (or BALES, unclear): Im just going to say, I chose to sit in the middle. You uh HARDCASTLE: I promise Im not going to fight with him:

MODERATOR: Sure, you hear these emotional arguments. People say I have a sick kid or you know, you are suffering from an illness, give me whatever its going to take, because they want to get passed it, they want to get better. What do you tell them? TURNER: I agree. But what I would argue is give them in an appropriately designed clinical trial context, dont charge them for something that hasnt been established, so dont charge them $25,000, dont charge them $30,000. Develop a carefully designed clinical trial, start at phase I, try and deal with dose and toxicity, and go from there to phase II. And also start doing things like create appropriate scientific mechanisms; create blinding for example, so that people who have financial benefit, if something is made available, dont actually know who is getting what. Thats sort of a classic component of designing a clinical trial. Randomize different branches. So I mean, this whole notion of trying to promote access, sure I support that. I think thats an important thing. I think thats what David here is trying to promote. Its just a question of how that is done. Right now there are no effective stem cell interventions on the market in the United States or in any other country, for MS or Parkinsons Disease. So when someone is charged $25,000, $30,000, for a therapy or an intervention, its not something thats been established in any kind of meaningful, credible sort of way. The company that CellTex partners with, RNL Bio, its a very controversial, very worrisome company. There have been they have had clients, patients, who reportedly have died after receiving stem cell infusions. Now, the mere fact that when someone who is seriously ill dies after receiving stem cells I mean, in fact, again, thats when you need to have an appropriate environment in which its being assessed a kind of clinical trial environment again, I would say for any of you who are following this conversation, do your own homework, take a close look at RNL Bio. I think the idea of having companies in Texas, looking elsewhere around the world for partners, trying to develop innovative therapies, is a good thing. Im actually very surprised that an American company would partner with RNL Bio, because of its past practices and its past controversies, where many of the stem cell infusions and injections theyre giving people havent been in the context of any sort of meaningful clinical trial. So part of this conversation is a question about type of access, and I would say were not at a point where anyone should feel entitled to charge $25,000, $30,000 for access to an intervention where safety and efficacy hasnt yet been established. If CellTex or any other company wants to begin running phase I clinical trials, first trying to establish safety, moving on from there to efficacy, not charging people along the way especially not charging them if they are going to get placebos as a part of the process, and being very frank in terms of being forthright about the

informed consent process, having it appropriately reviewed, by IRB and the FDA, that strikes me as the framework that companies, universities, and research institutes in Texas ought to be following. [garbled several people talking over one another] HARDCASTLE: In talking about doing your research, though, I want to talk about one of his statements because you talk about doing your research the guy died at RNL Bio before I had my treatment and that was put out to water way before I had my treatment a year ago, that it wasnt the effect of the stem cells that caused that him to die. TURNER: But one of the individuals involved in that review process I mean, it was by an organization that doesnt have any official credibility HARDCASTLE: No, by the Korean government! TURNER: There have been multiple investigations. One of the individuals involved was Glenn McGee, a former CellTex vice-president. Again, it doesnt mean that hes wrong, but it does raise these kinds of conflict-of-interest questions about you know, is that the most independent analysis of what occurred? And again, I say, if you want to do an effective job at figuring out what happened with that RNL Bio this is CellTexs parent organization. They claim to have treated over 15,000 individuals now, and yet when you look at their clinical studies, its less than 100 individuals. Now if theyd actually had all 15,000 people in clinical trials with the published, peer-reviewed data, well, we could look and see: so, in phase I, what happened? In phase II, what happened? In phase III RNL Bio, as I recall, doesnt have any phase II clinical trials. But if all of that was there, where you could see safety well- established, evidence of benefit, efficacy established, and some harm, that would be useful information. But youre not doing it in a clinical trial context. When its not being published, its very difficult to know what kind of conclusions to make because most of it is not meaningful research. Going back to your point about drawing on stuff in the public domain, I would encourage you and your colleagues at CellTex to put as much as possible about your practices put it on the internet! MODERATOR: Okay, I want you to stop there. I want to see a show of hands, how many people have questions? Alright, start making your way to the microphones, well get to you in just a moment there is a lot there about your company. FERRENZ: Yeah, there sure is. Uh, where to start? So, you talk really fast, Leigh, and you throw out a lot of false information, frankly! I understand your concerns, I do, but I

MODERATOR: To frame it up, what, I mean, to the point, because all the blizzard of words I do that too, sometimes but all of the words, it sounds like it adds up to youre moving way too fast on this and people are making money on something that we dont know is proven. FERRENZ: Okay, lets get to that. There are literally decades of research on mesenchymal stem cells, and what they do in your body. Literally decades. And you said that RNL has not done research, RNL has not done clinical trials. Thats not the case. TURNER: They have done some, no question. FERRENZ: Theyve done a lot of research, in fact. Now, regardless of the purpose of the clinical trials, whether its RNL or some academic institution, it is well- established what mesenchymal stem cells do in your body. So, there is no question that what we are providing to physicians who choose to provide it in therapy with their patients that we know what the body is going to do with it. Audience Question and Answer Period MALE: I dont follow this particular controversy, but listening to yall I have a simple suggestion: it seems to me that if youre not going through full FDA testing for safety and efficacy, maybe you should CellTex and the physician involved should only get paid if they work. MODERATOR: What would you say about that? FERRENZ: Well um, thats an interesting concept for any type of medical therapy, frankly. I mean, the logic would apply to anyone. As far as whether there is safety and efficacy, there certainly is literally decades of that data out there. MALE 2: Would your company go for that deal? [unclear] FERRENZ: It is very expensive to run a clean room, so in a sense that you are selling a product and a physician has decided that he wants to coordinate that with you, youre providing that to the physician. LARRY KING, HOUSTON: MD Anderson just announced the moon shot five billion dollars cancer research any guesses or ideas how much may go in to stem cell research? HARDCASTLE: You know, theyre doing as much or more as anyone in the state. Part of the laymans argument and I wont get scientific against being stuck in research is we had the best-ever breast cancer trials two years ago and its still stuck in research. And anything you have an 80 percent success rate with, there ought to be a way to speed it up, getting out it out to the real people. So I dont know

how many total dollars of that will go in stem cell research, but I know the whole 14th floor of MD Anderson hospital is a stem cell lab, and a cord blood bank, because they are BALES: Well, Ive been talking to some of our medical advisory committee members, which constitute some of the leaders in the state: Dr. James Willerson, of the Texas Heart Institute, Darwin Prockop, head of A&Ms regenerative medicine program, and what theyve discussed and were going to put out a white paper at our symposium, this is a shameless plug, October 19th at the state capital, we're going to have some of the leading doctors and physicians in the state talking about the latest research that theyre doing but maybe change the dynamic, the paradigm of how clinical trials are done. So instead of Dr. Willerson and CellTex going and doing a clinical trial for heart, Dr Prockop and InCell doing one for cornea and 18 months later coming out and saying this is what we found, what if you had 10 clinical trials that were all interrelated, and the word were using is collaborative transparency. So in real time, if somethings working in Dr. Prockops lab that isnt working in Dr. Willersons lab, maybe they can change in midstream and that might be a way to expedite the clinical trials. And in that situation, instead of having the placebo-type trials that youre used to in drugs, why dont we just change the amount of dosage. So in Willersons trial they may get 20 million and in Prockops they get 50 million, so there may be a way for the smart guys to spend more time talking to each other and maybe the people who are sick and there are over 1.2 million Texans living with a chronic disease or illness maybe we can get those people help quicker. BOB KAFKA, DISABILITY RIGHTS and NOT DEAD YET: Just one thing I want to caution in terms of unintended consequences in terms of some of even the terminology, like suffering, are you going to cure, etc. Many people dont wake up every morning saying, oh my god are you going to cure me? Theres a big debate in the disability community over cure versus care and again, no one is against stem cell research; thats a given. Many people want it to go forward, but again. You really almost set a negative, almost inferior thing about a person with a disability someone with M.S. Ive had a spinal cord injury for 39 years. If there was a stem cell treatment that would make a person without a disability I would probably say yes, but again, I do not appreciate being called suffering. You set a tone of inferiority that is a self-fulfilling prophecy, and let me just give you an example. I used to be the president of the Texas Paralyzed Veterans, and a gentleman went to Russia for some steroid-type cure, and all of a sudden I started to get all of these phone calls from all of these people I had never heard from, and literally they were sitting at home waiting for the cure, not doing anything with their lives. And were not talking about folks who couldnt be productive in the community, but that hope that you talk about and so again, its just to realize that this is a growing number of people, the vast majority yes, would say please cure me, make me better. But again, there is a large number of who go on with disabilities, traumatic disabilities like myself, that really you know, want stem cells to go forward but dont want to be talked about totally in medical terms, because thats what happens the

doctors talk about us in medical - like we dont do anything but live with our disabilities, not participating. Its a plea to include individuals, that perspective, as legislation goes forward. A lot of times its usually seen not so much as disability rights but in a religious context, of people that dont like stem cells. And you know, it happens in so many areas, that its not just religious zealots in terms of that, but also the disability rights community. So its just sort of a question about how you can include that, but also just a caution. Thank you. MODERATOR: Thank you for that, and we appreciate your perspective on that. Representative, when you do go forward, when the legislature goes forward with anything on this, is that something thats considered? In your situation, you say miraculous. Hes somebody who says you know, maybe thats not quite the right tone to use when we talk about people who have disabilities. HARDCASTLE: Well, I I had, I grinned while he was talking, I was not laughing at you, I was grinning at you, because before the US Congress Health and Human Services Community, they asked me before my testimony if I represented a disabled community. And you know, I walked in there on my own I did have to lean on the podium a little bit, because I used to shake, and so I understand what youre talking about. Legislation as I see it, the issue changes every time the legislature meets in Texas because ten years ago, when I was diagnosed, our big debate was over embryonic versus adult versus umbilical cord. The big debate right now is over okay, were going forward with all this, and similar to what David said, Ive heard so many things going good, you know, cancer-wise or whatever, with stem cells from different Texas hospitals or Johns Hopkins or whomever. And the question then becomes are we protecting the citizens, and we think that we got the policy in place in Texas to protect the citizens. Will that change? Every two years. I would guarantee it, it will change every two years. Because we will find something new that needs to be looked after. But coming from a state that doesnt want to be an over-regulator and doesn't want to be a burden, and you know, our attorney general is in a wheelchair from a back injury. He wants to see this go forward just as much as anybody else does. Today, it doesnt have anything to do with his condition. I couldnt describe it medically but its a permanent break. MODERATOR: Professor Turner, where is that balance? David says lets have a moon shot, the representative says were working our way through this. You have more concerns and more questions? Wheres the balance? TURNER: To me, the best balance is one that emphasizes innovation and bringing product to the market, bringing effective and safe interventions to patients, but does it in a way thats not rash, not hasty, and has appropriate safety mechanisms in place. To me, the current existing framework of having both local IRB review and FDA oversight is a good and effective way of doing that. If people have criticisms and

want to talk about the speed at which the FDA moves, I mean, I think thats a sort of worthwhile kind of critique to offer, a worthwhile point to make, but that kind of critique is very different from trying to go around the FDA. I would respond to your comment about evidence in the public domain I mean, Ive done the best I could to do a lot of research, to look with care, to not just try to go off on my own fantasy about the 483 but try to read it and work within the constraints. But I would say that if you feel youre misunderstood, that CellTex is misunderstand, or there is inadequate information in the public domain, I would encourage you and your colleagues to try to correct that by putting as much information in the public realm, as shared and accessible as possible. Ill give you an example: I gather that CellTex feels local IRB review is adequate, and you mentioned in one of your letters to me when you were threatening me with a lawsuit, that TABS MODERATOR (or BALES, unclear): Again, Im sitting here in the middle, right here. TURNER: I know. But you mentioned the particular IRB, Texas Applied Biomedical Services, and I look at that and I see a website where theres no information, for example, about what members are there, and so I would say I think it would be helpful for everyone to know who is serving for reviewers for your studies, if thats the IRB thats reviewing you. Are there clinician investigators reviewing? Are there suitably trained scientists? Are there health law specialists? And so on. Maybe you could tell us the name of a few right now, but if not, why not just put something like that up on your website, or put it on the TABS website? I asked the woman who runs TABS, Joyce Heinrich, and she said, her response was that should would review my request, but when it comes to something as simple as IRB members, why not just put it up there? Why hide it? Why not be frank and forthright? MODERATOR: He uses terms like hide it. As far as the question about whether or not people really know whats going on, and trying to figure out whether information that is deemed worthy of being made public is being made public, what would you say about that? FERRENZ: Well, CellTex is a pioneer. We are really on the forefront of regenerative medicine in the lab services we provide. So certainly critics want to know everything about us. Critics want to evaluate every aspect of what were doing. And to a certain extend, were willing to have fair dialog, but I think that its when you ask me if TABS can put something on their website continue your dialog with TABS. Well have a dialog within reasonable parameters, but part of the nature of being on the forefront, we understand, of being on the forefront, is to face the critics. But there is real potential in supplementing mesenchymal stem cells for a variety of uses that go to the very nature of stem cells, and for physicians in private practice, in clinics outside of academia, outside of institutions, to have access to that for their patients where they think its potentially beneficial thats a great leap for medical treatment.

MODERATOR: Alright, we have to time for one more question. It goes to the editor of the Texas Tribune, Emily Ramshaw. EMILY RAMSHAW: I just have a question for Representative Hardcastle, and that was, Rick Perry obviously also had a stem cell treatment, right before he went out on the campaign trail. You appear to have had an incredible reaction; he complained the entire way he was running for president how bad his back still hurt, about how he wasnt sleeping, which would largely lead me to believe that he didnt have the same result that you have had. Have the two of you talked at all about your shared experiences? HARDCASTLE: Not more than every other week. You got to understand the difference, Emily. He had a major back surgery, and he had stem cells to treat it. And again, Im not going to give a scientific example, Im going to give the cowboy answer. We had a Navy SEAL who all of us knew who had similar back surgery in January. Rick took off his back brace in July or the 1st of August and went on the campaign trail. That Navy SEAL was still in his back brace when I saw him again in September. You know, youre not talking apples and oranges. Yes, I talk to him fairly regularly. His overall heart test has gotten better, hes jogging again, his back has gotten better. Did he push it too quick behind his major back surgery, to go on the campaign trail? Thats a question a lot of us who know him will ask him now, but I dont think that has anything to do with the stem cells, because I think the stem cells did what they were supposed to do to his back and did it efficiently and timely and several of us that are around him a lot saw that and know it. Would we have chosen a different time for him to have had his back fixed? Probably. Because timing is everything MODERATOR: Okay, were out of time. Thank you all for coming, and a round of applause for this panel.