To understand the value of Ocata Therapeutics (NASDAQ:OCAT), it is important to hear, and read, what its Chief Scientific Officer has to say about his research, as well as some of their clinical trial investigators. I would strongly recommend taking the time to listen to Dr. Lanza's presentation at the Common Good Forum on June 8, 2015.
The purpose of this second article by an Ocata Therapeutics investor for 4 years is to explain how myself and others became interested in the scientific research of Dr. Lanza. Many of us have personal interest stories that lead us to learn of Dr. Robert Lanza and the diseases he claimed his cells could help, if not cure. We lost my husband's brother to multiple sclerosis in May 2015. I was invested before my husband, but once he heard Dr. Lanza talk about the power of his mesenchymal stem cells (MSCs) for multiple sclerosis at the annual shareholders meeting in Palm Springs in 2013, he also decided to invest in Advanced Cell Technology, now Ocata Therapeutics.
My mother-in-law was legally blind before her death with age-related macular degeneration, that advanced to wet macular degeneration.
When my husband found out that two of his golf buddies and one buddy's wife, were afflicted with dry age-related macular degeneration, he told them he would have me send them information about Ocata's clinical trials for same. Two of these friends have contacted Wills Eye Institute in Philadelphia for information on Ocata's RPE Phase II trial and are praying they can get into the trial. When I told one of his friends he would have to go to Miami, Philadelphia, Boston, or Los Angeles he replied "I'd go to the moon if I had to."
Dr. Carl Regillo, Trial Investigator at Wills Eye Institute is quoted as saying:
Vision as a sense is highly valued. In general, people fear death as their number-one medical fear, and number two is losing their vision. We're in a charged, anxious area when people have vision problems.
I thought it would be interesting, and relative to the value of Ocata's scientific research, to hear what has been said about Ocata's clinical trials by the medical professionals. Because of the controversy surrounding the use of embryonic stem cells, please note the comments by many quoted below emphasizing "no embryo being destroyed." It seemed very important to them to get this point across, because the use of the term "embryonic stem cells" is so widely misunderstood by the general public. In my own experience, friends hear the term "embryonic stem cells" and they shut down, call it a "slippery slope." The company has more recently begun emphasizing they are NOT using embryonic stem cells, rather "fully differentiated stem cells," such as retinal pigment epithelial cell (RPE) cells."
October 3, 2012 -- The world we know is changing, Biotech Nation:
Dr. Gunn: Today on Biotech Nation, we talk about a stem cell treatment which is nondestructive to embryos. Better yet, it is being tested on both forms of macular degeneration, as well as Stargardt disease, the most common form of juvenile macular degeneration.
Gary Rabin is the Chairman and CEO of Advanced Cell Technology, also known as ACT. We have been hearing about the promise of stem cell therapies for years. ACT is now testing their's.
Gary Rabin: We have treated seven patients and all seven of the patients have told us that they have significant changes in their vision. We create our cell lines through a nondestructive method of embryonic stem cell research, so the normal way that embryonic stem cells are created is through the removal of the inner cell mass of the embryo. When you do that, you destroy the embryo. We don't do that. We take a single cell from a very early 8-stage embryo. We remove it and it doesn't change the fate of or harm the embryo in any way.
Dr. Gunn: So best case, are we just a few years away from maybe a real product that anybody can have?
Gary Rabin: That's what our plan is.
2013 Annual Shareholder's Meeting:
Dr. Robert Lanza: Of course we have the pigment of eye disease that is our primary project. That includes retinal pigment epithelium for the clinical trials for macular degeneration, but we are also studying a range of other cell types for a number of other diseases such as glaucoma, advanced blindness, uveitis and corneal repair. We also have our single-blastomere program. We have now created an entire Master Cell Bank that hopefully can be used for future clinical trials, that would be ethically compliant and xeno free.
Early last year we published data in the Lancet on our first two patients. We have now of course treated another 28 patients and as Gary mentioned to date we have not seen any major safety concerns related to stem cell treatment. There are clear signs of long-term engraftment and survival.
What you are seeing is very robust engraftment in many if not most of these patients. During the one-year follow-up period, patients in both the Stargardt's and the dry AMD trials have shown significant improvement in visual acuity in the RPE treated eye. Vision in one of the patients for example improved from 20/400 to 20/40 in the first month.
On mesenchymal stem cells (MSCs):
So why use embryonic or induce pluripotent-derived MSCs versus these adult sources. The reason is pretty obvious. We can have off-the-shelf therapy available for immediate use. We can create a virtually unlimited supply of these cells. They are very easy to derive. They can be expanded to very large numbers in vitro. In fact we can get 30,000 times more units of the ES-derived MSCs than you can get from bone marrow MSCs. They are more youthful. They live longer and these hemangioblast-derived MSCs yield exponentially greater yields than other methods.
One of the studies involved multiple sclerosis and this is in the EAE mouse model. In the animals that are untreated, normally they have clinical score of 2-4. That means that they are partially or have complete leg paralysis. By contrast, in the animals that got an injection of our ES MSCs, we saw that the clinical score was less than one and there was no paralysis. Interestingly, in the same model, when we used bone marrow-derived MSCs, we saw that the impact was variable or minimal and those animals still showed paralysis.
I just mentioned a few of the potential applications of MSCs, but again, there are literally hundreds of potential applications. There are over a hundred autoimmune diseases including MS, osteoarthritis, lupus, aplastic anemia and of course a whole range of other systems including the liver, kidney and pulmonary diseases. But importantly, these cells are ideal for clinical translation because there is no need for immunosuppression.
And I finally want to mention that we are also studying these MSCs in the canine indications. We have a program for treating orthopedic disease including osteoarthritis and disc disease. We are also studying several inflammatory diseases including sepsis and acute pancreatitis and we are also looking at a number of immune-mediated diseases including irritable bowel syndrome disease, chronic hepatitis, glomerulonephritis and Crohn's disease. So we have filed, as Gary had mentioned, an INAD with the FDA to treat 10 of these indications listed here and again, naturally induced diseases in large animals such as dogs provide an excellent model of human conditions and they may provide a more robust assessment of safety and therapeutic end points than we would obtain from inbred rodent models. We have initiated a collaboration with Tufts University School of Veterinary Medicine. They have a very large population of suitable animals and they are world experts at regenerative medicine. We have already received IACUC (Institutional Animal Care and Use Committee) approval to begin the first of these studies, and in addition to the obvious veterinary applications, these studies will help inform and optimize our human medical trials."
We have asked repeatedly what is happening with the MSC canine trials and results, why has there been no application for veterinary medicine? The company has not been at all forthcoming with shareholders about these trials. We only have "leaks" to know what is going on.
Dr. Anthony Hoffman, Trial Investigator, Cummings School of Veterinary Medicine, Tufts University, at a presentation at the Denver Zoo on February 3, 2015:
The other area is that before stem cells have been injected into people, they've gone into animal models, mostly rodent models, and then there are a few safety studies that are done in large animals, and nobody looked at a realistic animal model that had a disease like people. And that's a really important point, and that is what I spend all my time doing, is trying to convince the NIH to work with these natural occurring disease models in our pets.
So just to conclude, are there any questions about the clinical trials we're doing?
Q: There's a number of clinical trials with Ocata that are no longer listed, so I think it was 6 dogs, 6 indications. Any word as to when those results might be published.
Dr. Hoffman: Can't comment on that. I'm very sorry about that. Industry trials, I'm signed into a nondisclosure agreement so all I can say is those trials have been discontinued, at least temporarily. It's just something I can't comment on. It's a good question though. You've been paying attention to our web site.
Q: Some of your results were reported in the some of the articles about the dogs that have fistulas.
Dr. Hoffman: That's correct. That's referred to as a leak. That's an interesting thing isn't it? And those dogs were doing very well weren't they?"
Q&A at the July 22, 2015, shareholders meeting and questions on the canine MSC trials:
Q. I'm an investor. Regarding the Tufts trials on the dogs, when might we expect to see published papers or more data on what's happening?
Dr. Lanza: So it's in process.
Paul Wotton: We've got a publication strategy around all of those so they'll be coming out.
Dr. Lanza: It's in the peer review process.
As shareholders have received so little information from the company, about trials which they have funded for so many years, we are left to surmise that the "publication strategy around all of those" can only be interpreted as after the Astellas Pharma, Inc., tender offer is completed. Yet you will recall in my first article, the Schedule 14D-9 stated "Until the tender is completed, it will be business as usual for Ocata and Astellas."
Fighting Blindness Symposium for patients, Florida, 2013. Dr. Dean Elliott, Trial Investigator, Mass Eye & Ear:
So the company that does this is Advanced Cell Technology. They are a publicly traded company on the stock exchange, and they are located in Santa Monica, California, as well as a Marborough, Massachusetts, and they are engaged in the only human embryonic stem cell study in the world.
So this is the most important slide of the whole presentation here. Embryos are not destroyed to make this line of cells. Everybody always asks this ethical question. It's very, very important. When I did the stem cell surgery in our operating room, we actually had several nurses that didn't want to participate because they heard it was stem cells and for ethical reasons they didn't want to get involved. ... it is important to know that embryos are not destroyed. This is a cell line that was created in 2005 and they take one cell out of this cell line and they reproduce this cell forever. They will never need to do anything else in the future to create the donor cell line. The cell line has been created and did not destroy anything and they take those cells and they turn them into other cells in the body.
Now we'll show you some results for some other patients, because they have a little more follow up than in my patient. Here's a patient with Stargardt's... here's week one you already see some pigmentation, so the cells that are injected aren't pigmented, but they start to pigment as they start to mature, so this is good. This means the cells are in the right place and they are actually taking. And here's the same patient at week six. There's even more pigmentation under the retina. This is pretty good, very encouraging -- it's like about three to four times the size. That's good. Those are cells that have now found their home, and they located themselves in the right place. That's just what we want.
So here's another patient with Stargardt's... here's the patient at one month after surgery. You see some new pigmented cells, and two months after surgery you see more pigmented cells. That's exactly what you want. So far so good. The cells are finding the right place and they are growing.
Here's another patient, same thing, and once again, at one month and three months, we've got pigmented cells all over the place, which is good.
So the results in terms of vision, in both the Stargardt's macular dystrophy patients and the dry AMD patients, vision has actually started to improve.
Throughout the six patients so far in the AMD study we have had no problems, and that's really what the study was designed to do, make sure there are no complications. The same thing with Stargardt's. Really there have been no complications in any of these patients so far."
In Philly Style Magazine, Dr. Carl D. Regillo, Chief of Wills Eye Institute Retina Service, Ocata's Trial Investigator, says he is taking on the number one cause of severe vision loss in patients over 60 from macular degeneration. He says it is a huge public health risk as the elderly population expands and growing rapidly. He has injected pigment epithelial cells derived from a line of human embryonic stem cells and says the patient recovered uneventfully.
What we're doing is a cell transplant. We inject the cells under the retina, where they set up shop, grow, and proliferate. The great hope-and the great promise-is that they will allow cells to repopulate and rejuvenate. They should help support, nourish, and protect dying tissue to minimize vision loss. Replacing lost or damaged cells with functional and healthy cells could slow vision loss, and perhaps even reverse the effects of disease. And we see evidence that it's working.
On March 23, 2013, I had the distinct honor of attending a Regenerative Medicine Conference sponsored by Emory University in Hilton Head, South Carolina. Dr. Lanza was the keynote speaker. He shared with the audience about Ocata's ability, using their patented hemangioblast technology, to create platelets and universal, scalable blood. This technology, he said, would be important to the country with huge military applications on the battlefield, as well as to the country for natural disasters or terrorist attack and stated that such research needs funding by the likes of US Dept. of Health and Human Services Biomedical Advanced Research and Development Authority (BARDA). Little did he know how important such a thing might be some day with the increased threat of terror on our homeland almost 3 years later.
One can't help but wonder, how is the United States allowing this technology to leave and be owned by a foreign country?
Lanza on Lancet, October 16, 2014:
LANE: Hello and welcome to the latest Lancet podcast. Richard Lane with you on Thursday, October the 16th. This week we're discussing stem cells on October the 15th, we published a study following up two early studies published by the Lancet a couple of years ago about the potential of human embryonic stem cells transplanted into the retinal epithelium of people with Stargardt's macular dystrophy and also age-related macular degeneration. To find out more, let's hear from one of the authors of the paper who I interviewed for the podcast.
LANZA: I'm Robert Lanza and I am the Chief Scientific Officer at Advanced Cell Technology. We're a biotech company that is in the area of stem cells and regenerative medicine.
LANE: The current study, this actually has follow up on 18 patients, some with Stargardt's and some with macular degeneration, the older population. How does this study relate to those two earlier studies?
LANZA: They relate very much. You know, despite the great promise and the unlimited capacity of embryonic stem cells for self-renewal, that raises serious potential for a long-term safety concern. This includes in the long term to develop tumors, potential immune rejection, and the risk of differentiating unwanted cell types. So in this particular study, we treated, as you mentioned, 18 patients and they were followed for a median of 22 months to determine if the cells were safe in the long term. So the primary end point of these studies was safety, so the patients were followed for up to over three years and there were no adverse safety issues related to the transplanted tissue, and structural evidence did confirm that the cells had survived and continued to persist in most of the patients after transplantation of the cells. We didn't see any rejection, no adverse proliferation or tumors. No unwanted or ectopic non-RPE tissue in any of the patients, and also anatomical evidence to confirm successful engraftment which included increasing pigmentation at the level of the RPE level. Also, the vision of most patients improved after transplantation of the cells. So overall, the vision of the patients improved approximately 3 lines on the standard visual acuity chart, whereas the untreated fellow eyes didn't show similar improvement in visual acuity. The patients also reported notable improvements in their general and peripheral vision, as well as near and distant activities. Of course both Stargardt's and dry AMD are progressive diseases, and the goal of the therapy is to prevent the progression of the disease. To that end, 17 of the 18 patients improved.
LANE: What are your expectations for what might be possible in the next 5 to 10 years in regenerative medicine?
LANZA: I think there are a lot of exciting things that hopefully we'll start to see being translated into the clinic. For instance, we just published a paper just a few weeks… and actually a couple of months ago as well, where we actually took some of our cells that are called mesenchymal stem cells that we created from embryonic stem cells, injected them into animals that had multiple sclerosis and the untreated animals were completely paralyzed. One injection of these cells and the animals were moving around, jumping around in their cage quite normally. We went into another model of rodents that get spontaneous lupus and these animals started to die due to kidney failure from lupus nephritis and we went in with injections of our cells and we were able to prevent not only the death of those animals, but we were able to prevent all the morbidity associated with kidney failure. So I think you're going to see a lot of exciting applications like this starting to move into the clinic in the next few years.
LANE: What about the availability of the stem cell lines themselves, embryonic stem cells? Is there enough supply?
LANZA: Absolutely. As a matter of fact, all the patients that we treated were generated from a single cell that we derived from an ace/ace embryo, and that line is immortal because embryonic stem cells grow forever. So we have enough cells, if you have an embryonic stem cell line, you would have enough cells to basically treat everyone on the planet. It turns out that both embryonic stem cells, as well as the iPS cells, which are also another form of pluripotent stem cells, they have an enzyme called tolermase up-regulated which allows them to essentially grow forever, they are essentially immortal."
Dr. Steven Schwartz, Lead Trial Investigator, Jules Stein/UCLA, at UC/Berkeley February 17, 2015:
"I'm gonna talk to you this morning about human embryonic stem cell derived retinal pigmented epithelium which is a mouthful, and I will explain it to you. We've been transplanting patients with macular degenerations, and we reported recently in The Lancet which is a medical journal about the mid and long-term safety results. We started this at UCLA in collaboration with a guy called Bob Lanza who's a stem cell scientist, and then I rolled it out to some of my friends at other good centers....at Harvard and at Wills Eye Hospital in Philadelphia and Palmer in Miami.
So, all of you probably know what stem cells are. They have the capacity to differentiate into any cell type. When we started this work a long time ago, there was a lot of controversy around stem cells because President Bush and his friends...and I can feel comfortable saying this here at Berkeley....felt like we were breaking Biblical edicts I'd say. That's the nicest way you could explain that was very non-literal....non-linear. But the truth is...these are blastomere-derived human embryonic stem cell lines that are from a cryo-preserved parent embryo prepared in 2001. It was not an abortion sourced...not an abortion source. It was a family that had in-vitro fertilization. They had 4 or 5 kids. They had a couple of extra embryos. One cell was taken and it grew up the cell line.
I'd much rather catch the disease a lot earlier. To me, this is sort of the ideal transplant candidate, 20/50 to 20/60 vision. We know it's safe. We know there are photoreceptors there.
We watched visual acuity. There was a safety parameter and then an efficacy parameter. We saw at 6 months to a year best corrected visual acuity increase in 4 of 9 patients with AMD greater than 15 letters, and a number of others were unchanged and same thing with Stargardt's. We saw a number of patients improve.
So, 35 patients treated to date....now 36....with exposure for up to 3 years. Well tolerated. Most of the adverse events are with immunosuppression. So, this study was the first to demonstrate mid to long-term safety survival and possible biological activity of pluripotent stem cell progeny into humans with any disease...not just ocular disease. The human embryonic stem cells were well tolerated for up to 37 months...it's actually more than that now. There were no serious adverse safety issues attributed to the transplanted cells in any of the patients. Ultimately, the goal would be to treat such patients earlier in the course of the disease potentially increasing the likelihood of photoreceptor central visual maintenance or rescue. The results suggest that human embryonic stem cell derived cells could provide a potentially safe resource of cells for the treatment of a variety of unmet medical conditions of tissue loss or dysfunction."
Dr. Steven Schwartz on panel discussion on blindness on the Charlie Rose Show, April 22, 2014:
The truth is, it's a very surprisingly, astonishingly, straightforward method by which stem cells can be induced into certain cell types and it just turns out that retinal pigment epithelium are relatively low-hanging fruit in terms of being easy to induce the transformation to a terminally differentiated cell type. It's also important to realize that the retinal pigment epithelium are really attractive targets for stem cell therapy. It's protected by an immune privilege. It's inside the blood retinal barrier or blood brain barrier, and it's surgically accessible.
We've today transplanted a number of patients. These early stem cell studies seem safe. They seem astonishingly to be giving us a signal that there might be some restoration of vision. I wanted to share with you the first patient that we transplanted, a young lady who was a set designer and lost her vocation because of her blindness."
At 35:10 Cathy's story:
"When I was younger I played a lot of competitive tennis, and I think when I was like in my later teens, I started playing a little more poorly. It was seeing the lines or the ball not quite as precisely, and calling the lines and stuff was a little more difficult. I woke up one morning and I looked across my room and I have a piece of furniture there, that's kind of this large armoire and it has a lot of carved detail on it, and I actually had my head to the side and I opened the operated eye and I looked at it, and for the first time I could see the detail in it, that I hadn't been able to see from the distance I was lying down. After that I just got up and I started looking at everything around the house, and looked at the grass, I mean looking at everything with one eye and then the other eye, because you know they only operated on the one eye, and I could see it a lot better than I had before, and I thought, wow, maybe there is something here that will really be working you know. It was pretty exciting."
July 22, 2015, Shareholders Meeting Paul Wotton said:
The photoreceptor progenitor program I think is very, very exciting from the data I've seen of the animal models. I know Bob is certainly excited about the data he's seen, and potentially that could be an add-on product to the RPE product, but also it's going after some different areas as well like retinitis pigmentosa, which cannot be treated by RPE replacement. ...this is actually really interesting. The work we have done at the University of Oxford by Professor MacLauren, who is probably the world's leader in this type of protocol. We were treating mice, in fact rats on the next study slide, with photoreceptor progenitors we have manufactured with human embryonic stem cells or induced pluripotents and then looked at treating mice that were bred to be blind basically, and guess what, when we treated them with photoreceptor progenitors, those blind mice, all three of them, were able to see again.
At the same meeting, Dr. Lanza had this to say about photoreceptor progenitor program:
Photoreceptors, progenitor program, very, very exciting. I think it's one of our lead pipelines that we're hoping to progress towards the clinic. We've got quite a bit of data on multiple animal models. Paul just showed you some of the data, very, very impressive. We're seeing various openings in neural protection, as well as new photoreceptors that are appearing to be connecting up that were already lost so that's very, very exciting. As you know, the RPE program the main aim is to prevent the loss of the photoreceptors. Of course right now, once you've lost your vision, it's over, but with these photoreceptor progenitors, we're hoping to actually reverse the blindness, actually go in say for instance in patients with retinitis pigmentosa, you go in and reconnect to the new photoreceptors with the cones. It's a paradigm change and as I indicated, is exciting. With the new funding, hopefully we can move that ahead more aggressively and hopefully get the IND enabling studies completed and get that into the clinic sooner than later.
When Dr. Paul Knoepfler, Associate Professor, UC/Davis, read Dr. Lanza's patent on mesenchymal stem cells he said this on his blog: "125 claims - wow. If all he (Lanza) says (about hemangioblast-derived MSCs) is true, this could be HUGE."
That concludes my quotes from presentations by Ocata's CSO and some of the clinical trial investigators. Please note in closing, Dr. Lanza calls his research "A paradigm change…."
I'm sure I speak for many long shareholders that it boggles the mind the value of this paradigm shift of Regenerative Medicine and that it is being sold for $359 million dollars, when we know the treatments for age-related macular degeneration and Stargardt's macular degeneration alone is worth billions. How many more billions of dollars are Dr. Lanza's mesenchymal stem cells and hemangioblast-derived blood platelets worth?
How Ocata's CEO and BOD thought the shareholders would be happy with this deal, with many way under water still at this price, shows just how out of touch with their shareholder base they are.
It is shocking to the long shareholders that this paradigm shift in medicine and the research of "one of the best (American) stem cell scientists in the world" and the intellectual property of an American start-up biotech company will move overseas.
The fight is not over. It seems the shareholders won the first round with the offer expiring December 2015 without more than 50% of shares tendered. The shareholders are buoyed by the recent SEC filing of GAMCO Investors, Inc., reporting purchasing and owning 5% of the company since the tender offer. Obviously someone besides the long shareholders are beginning to grasp the value of Ocata Therapeutics.
Disclosure: I am/we are long OCAT.
I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.
Additional disclosure: I am the owner of a Medical Transcriptionist service for 26 years. I have personally transcribed the meetings quoted in this article verbatim.