Following Pluristem’s initial public offering, I interviewed its current Co-CEO and President Yaky Yanay. In that interview, we spoke about Pluristem’s upcoming milestones, a list that was topped by a study being conducted and funded by the US National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID), testing whether the company’s PLX-R18 cell therapy solution could successfully treat Acute Radiation Syndrome (NYSE:ARS) –sustained following high exposure to nuclear radiation. Following the recent results, I interviewed Mr. Zami Aberman about the company’s latest success.
In my opinion, the ARS trial results were one of the company’s most important milestones. The results indicated an 85% survival rate compared to 50% in the placebo group, which is about a 70% improvement—a significant success.
To understand the significance of these results, let’s begin with an earlier trial conducted on mice. It was performed several times and showed survival rate of almost 100% compared to ~30% in the control group (or 3x better). A fact that went largely unnoticed is that each mouse (weighing 25g) was administered with 2 million cells - 80 million per kg. Why is this important? Because in the most recent trial, the non-human primates (NHPs) were administered 4, 10 and 20 million cells each, depending on the dosage group. This means NHPs were given a smaller dosage per weight than the mice. If the NHPs weigh about 160 times more on average than the mice, an equivalent injection would have contained 320 million cells. However, Pluristem’s scientists decided that administering 320 million cells to each NHP would be too much.
If we go deeper into the trial, we see that it had two parameters: survival rate and blood cells recovery. Significant recovery in blood platelets was observed in mice, Red, White blood cells and weight recovered as time passed. In the current trial blood was tested as well but results weren’t released except a phrase saying that the trial demonstrated a trend towards enhanced neutrophil and lymphocyte recovery. We’ll probably get the results soon. So why only a “trend”? Probably because the groups were too small to show statistical significances. The current trial is a calibration one. If a trend is seen even in the small trial then in my view it’s a success.
One of the most interesting pieces of news that came with the trial’s results was that the NHPs that received the cells but hadn’t been exposed to radiation were not negatively affected by the treatment. This is critical for effective implementation in case of disaster, when rescue teams won’t have time to check if victims were exposed to radiation or not before administering treatment. Since the cells are safe for those who weren’t exposed to nuclear radiation, the recommendation will be to inject the cells as soon as possible in any case, without having to risk potential damage. For those who were exposed, receiving treatment as quickly as possible may mean the difference between life and death. Aiding in the rapid administration of Pluristem’s cell therapies is the company’s unique mobile thawing device, which can prepare doses quickly, on-site.
Regarding females survival – in each group there were 3 female NHPs except for the group that received 10 million cells which had 4 female NHPs. The results in the control group showed, only single female NHPs survived while in the treatment with 4/10/20 million cells; only one female NHPs didn’t survive. So, the success was 67% and 75% recovery in 4 million cells and 10 million cells respectively vs. 33% in the control group which means double chances of survival with Pluristem’s cells. With 20 million cells there was also a 67% survival rate but this dosage was too high even in Pluristem’s opinion.
Now let’s look at the male NHPs. In the control group only a single male NHPs didn’t survive compared to 100% survival with 4 and 10 million cells. I will repeat – all male NHPs that were exposed to radiation survived! In 20 million cells dosage, a single male monkey didn’t survive. Feminists, don’t be mad, these are the trial results. Treatment with Pluristem’s cells resulted in 100% survival of male and 75% survival of female.
Pluristem summarized trial results with 4 and 10 million cells to the SEC, results of both male and female NHPs showed 85% survival, compared to 50% in the control group (13 treated with cells vs. 6 in the control group), which is a 70% improvement. In other words, in a case where 1000 are exposed to radiation, 850 will survive with Pluristem’s treatment.
How does Pluristem’s treatment compare to other treatments currently available?
In an analysis recently published by H.C. Wainwright & Co, it was shown that AMGN’s treatment (NUEPOGEN) achieved 79% survival rate Vs. 40.8% in the control group, but in that trial, the animals were supported by additional medical treatments such as antibiotics, anti-inflammatories and blood transfusion. That is because this treatment is incapable of treating blood platelets or red blood cells.
Pluristem’s cells, conversely, require no additional treatment or pre-screening, indicating its advantages as an antidote to ARS. The fact that PLX-R18 seems to lead to improvement in the whole blood system and in chances for survival, and has no side effects, could have implications for another field that Pluristem could potentially take on—cancer treatment.
Pluristem co-CEO and Chairman Mr. Zami Aberman had some very interesting things to say on these subjects:
Nir: Hello, Mr. Aberman and congratulations on the success in the ARS trial.
Zami Aberman: Thank you. I’m thrilled for our investors and supporters who are following our progress.
Nir: First I’d like to talk about the trial itself. The trial was done on only a small amount of NHPs, Why?
Zami Aberman: The trial’s purpose was to investigate feasibility. Conducting trials on NHPs is expensive and thus it was performed on a small number of animals to prove feasibility. One should keep in mind that this is a preliminary trial for a larger trial that will include between 100 to 150 NHPs, depending on FDA requirements. We found that in order to prove statistical significance we’ll need 20-25 NHPs in each group – males, females, with and without exposure to radiation. The trial protocol isn’t closed yet and will be determined according to FDA requirements.
Nir: So far you’ve published the survival results and not the blood details. Blood details will be published soon, but can you explain the distinction?
Zami Aberman: Investors need to understand that we are dependent on the US National Institutes of Health (NYSE:HIH), as they conducted and funded the trial. They agreed to release data that was already analyzed, because they understood we have an obligation to our investors. As announced we plan to release additional data from this study during the RITN conference on July 26.
Nir: You’ve succeeded in the trial, and I’m interested to know how you plan to proceed from here? What to expect?
Zami Aberman: Our next step is to apply to government agencies like BARDA in order to secure financing for the pivotal trial, and to work on extending our cells’ shelf-life from two years to five years.
Nir: To my understanding, the process involves submitting a summary and then, within 30 days, if it’s approved, you submit a full request. The answer is received within 60 days. If it is approved, you can begin negotiating a contract. Are you ready to submit and will the submission be published?
Zami Aberman: Generally speaking, the process is similar to what you described. We’ll submit a request for the costs of the pivotal trial in the amount of $30-40M. In addition, there’s a cost for the treatment itself. They may want to be equipped already with several thousands of cells ready for administration.
Nir: As I understand it, in the past there was the cost of manufacturing the cells and here you’re talking about an additional cost for the treatment. Is there a difference?
Zami Aberman: There’s no difference. The cost of a life-saving treatment using PLX-R18 cells is about $50K – $80K/year. Pluristem can’t charge the HHS for such an amount, so we are finding creative ways to offset the costs in a way that benefits everyone.
Nir: Can you approach other countries? What about Japan and Korea?
Zami Aberman: According to the agreement, the US will be the first to be equipped with our PLX-R18 cells for the treatment of ARS. Of course, we can offer the treatment to other countries, and there is definitely an interest. Once the treatment has been approved, the cells will be made available to those countries as well.
Nir: The trial results showed success. What do you think about them?
Zami Aberman: I was happy that PLX-R18 cells showed success in NHPs, as many companies fail to successfully replicate trial success from smaller animals to NHPs. The results we received are important in order to carry out our next steps and support the pivotal trial. Soon we’ll publish more data that will shed more light on the advantages of our treatment.
Nir: From personal experience with a member of my family, cancer treatment with radiation is a very difficult process that may affects the patient’s hematology and immune system. Can Pluristem’s PLX-R18 cells be used for supporting cancer treatment?
Zami Aberman: At the moment, the FDA and the Israeli Ministry of Health approved an initial trial to verify the safety profile for the treatment of bone marrow failure. If successful, we can start fulfilling those requests for supportive treatment.
Nir: Are there any trials about supporting cancer treatment in Fukushima?
Zami Aberman: In Fukushima, there are ongoing studies for the treatment of other component of ARS such as GI, Lung and Skin. We are currently focused on receiving approval for treating H-ARS. Our trials indicate that our cells may be able to help the blood system recover in cases such as patients who have undergone chemotherapy treatment or suffer from genetic dieses such as aplastic anemia.
Nir: Does Pluristem intend to pursue the indication of cancer support treatment?
Zami Aberman: We’re actually waiting for the completion of the ARS trials and approval of that treatment. FDA approval will mean the cells are safe and efficient for treating radiation damages, and might be eligible for “off label” use
Nir: Can you say that any patient with a problem in the blood system that requires faster recovery will be able to reach out to Pluristem?
Zami Aberman: If and when the cells are approved, the potential exists.
Nir: When do you think the approval will be received (if and when the trials succeed)?
Zami Aberman: We are hoping for approval during 2018. The upcoming year will definitely be an interesting and important one for the company.
Nir: Any message to the investors? Are you planning to add institutional investors or other big investors?
Zami Aberman: First and foremost, I’d like to thank our investors for their support. I want them to know that we’re headed in the right direction and that in the next year we hope to achieve many more milestones. We’re in the middle of several trials and hope to reap their fruits in the near future. We’re in touch with potential investors all the time, and believe that in the near future, additional institutional investors will invest in Pluristem.
Nir: We didn’t have time to talk about Pluristem’s other trials. We’ll leave it to the next interview. I’d like to thank you for your time and wish you and Pluristem success.
Zami Aberman: Thank you and good luck to all of us.
Several interesting points that were raised in the interview:
- The process with United States government is well underway. According to my calculation, the contract will be signed in the coming months.
- Radiation trials will begin according to my understanding in November-December 2017.
- Results for the radiation trials should arrive by end of Q2 2018.
- Cells approval is dependent on the FDA and will probably occur from mid Q3 to Q4 2018.
- Pluristem might be aiming at developing Cancer supportive treatment in the future, which is a multibillion dollar market
- In my opinion, Pluristem’s stock price is very low and doesn’t reflect even 10% of its potential. If Pluristem indeed does enter the field of Cancer supporting treatments, which is a huge market, it will be hard to even estimate its potential. If the radiation treatment is approved it will mean that the US will equip itself, according to Manhattan program, with 1 million treatments. If we take into consideration the Mezoblast treatment cost in Japan ($60K-$175K per treatment), you can estimate that Pluristem’s treatment cost will be ~$50K-$75K per treatment. This is my assumption only. We’re looking at possibly huge potential, and this is before taking into account the CLI, IC, Orthopedic indications, DMD, preeclampsia and other potential indications of Pluristem cell therapies.
Disclosure: I am/we are long PSTI.