New Interview With Masayo Takahashi (高橋 政代) on IPSC Trial: Guest Piece by Michael Cea

By Michael Cea
Stem Cell Analyst & Advocate
(editor’s note: piece was originally posted on Michael’s blog here; follow Michael on Twitter @msemporda)

 

Having followed closely the developments in programs using pluripotent based therapeutics I was fortunate during ISSCR2015 to have the opportunity to sit down with Dr Masayo Takahashi to discuss her pioneering efforts to translate Shinya Yamanaka’s groundbreaking iPS technology for debilitating retinal conditions.Masayo Takahashi

As most everyone is aware, the first iteration of the program, for advanced Wet AMD, has entered the clinic and been safely administered to the first patient – a milestone achievement for the field, which has been widely covered by the media, especially in Japan. However, as I learned first hand, this first step is but a part of a comprehensive strategy to address most retinal diseases by way of various cultured cell transplantation methods, depending on the patient condition – including suspension therapies and multi-layered organoid developed tissue. This was best described by Masayo “what I have said to the Japanese regulators is that ideally we need all cell types – sheets, suspensions, auto, allo – and the surgeons will choose which to use for each patient.”

Monkey stem cell RPEsBefore relaying the key segments of the interview, I wanted to express some thoughts of how practical and committed to the patient Masayo is. Her clinical practice is at the very heart of her professional vision – to bring relief to those that come to her for help. Disappointment again and again in not being able to help drives her passion for new therapies. She is both confident and open to the process that has already taken more than a decade and a half of her research. The goal being, in time, to have all the tools necessary to deliver on the promise to her patients and fulfill on that hope, that is very real and apparent today – something she couldn’t point to just a few short years ago. Her new message is very clear now “visual impairment is not as bad as they think and you can change that world – so there is hope – yes.”

Cheers

Interview:

Q: There is a lot of hype in the field how have you addressed that?

MT: When I started to do the regenerative medicine work the media broadcast our efforts and many patients came and they expected I could help them. But 10 years ago I was very nervous because after hearing the news they were disappointed in front of me so I started to talk to the media and educate. Every month we worked with media so gradually within this period they learned and suppressed their expectations so in Japan the hype isn’t so high anymore.

Q: Does the Internet makes things easier for patients to understand?

MT: People who can connect with the Internet can understand but the older people still don’t have access to the Internet and rely on the newspaper and TV but sometimes they’re informed wrongly as a result so I still struggle.

Q: Is that due to the technical language and complexity of the science?

MT: Common sense is different from the medical reality but the regenerative medicine area is very focused so we can use the media to inform the public correctly. Regenerative medicine won’t cure everything but if you think in a different way you can do many things. The “hope” should be the correct one. People need to learn the way of thinking of the scientists – in Japan people are very clever and gradually they have understood. So if you teach correctly they can understand gradually. It’s important to relay the correct information. Media sometimes tries to simplify as a need or belief in the communication method yet they lose the true message. Stem cells are a specific area with many unknowns – yes – it’s like a “black box.”

Q: You started using ES neuronal cells then moved to iPS and retinal cells

MT: Yes, a little background. I started in 2000 with ES cells and proved in mid-2000 using primate ES cells that we could treat some retinal diseases but we hesitated to move to the clinical stage because the risk of immune rejection. By that time iPS cells came out and I was very happy as I knew the last hurdle would be solved w/ iPS cells so we immediately started research using those cells and after 5 to 6 years of translational research in preclinical studies we started the 1st patient clinical application last September and we will judge the safety and effect 1 year later this September. We announced mid-term results in March and so far we don’t observe any immune rejection without any immunosuppression, which we expected as a result of using autologous iPS cells.

There was a famous paper in the journal Nature that the autologous iPS cells invoked immune rejection in a mouse model but I think the research design wasn’t very good. They transplanted kind of a tumor which would be rejected – not the iPS cells but the tumor.

Q: Was the surgery difficult for the lady (1st patient)?

MT: Yes the surgery was the most risky part. We were worried a little but the procedure was successful with no adverse events so far.

Q: And the next patient?

MT: We tried, we prepared but decided to go quickly to the allogeneic because the cells are already there from Shinya Yamanaka’s cell line stock. He made the 1st iPS cell line and they have come to our lab.

Q: Have they been approved as clinical grade by the Japanese regulators?

MT: Yes but about the protocol, we will apply within this year for approval. We should reapply as it’s allogeneic, different from autologous.

Q: Will this line be available to others?

MT: Shinya Yamanaka will distribute to various centers with one of the institutions being mine. So there will be a Spinal Cord Injury protocol, maybe the Parkinson’s disease trial will go to an allogeneic protocol, the hematopoietic (platelets) will also. So the various protocols will use that cell stock.

Q: Japan is moving very quickly, is that of concern in the community or is that in your mind appropriate?

MT: Most patients are supportive but some people worry we move too fast but really we prepared, labored and accumulated the data and the people who don’t know the whole data usually say you have the risk – that’s very stressful. So actually we don’t care what they say because they don’t know. Maybe it’s a social balance.

Q: Are you taking the trials also outside of your home market?

MT: In the near future. We made a start-up company, Healios, they made an IPO last week, they plan to do a clinical trial in 2 or 3 years time in the US as they need the time to apply the protocol.

Q: I’d like to get your opinion on the use of a monolayer versus the selection of a suspension protocol.

MT: The people who don’t know the disease think the big sheet is the best but there are many, various situations with the disease, various stages, various lesion sizes, so some patients need a large sheet. Ours is 1 x 3mm, people in the US are preparing a 3 x 5mm sheet, so some people don’t need such a big sheet and earlier stage patients don’t require a big incision, so cell suspension is more feasible.

Q: What is your current disease state target?

MT: Advanced Wet AMD and we pull out the neovascular tissue, so a big defect of RPE, and cell sheets are appropriate but if the neovascular damage isn’t large we don’t want to cut and therefore cell suspension is better.

Q: The market is fragmented – is there a synergy with other programs?

MT: The regenerative medicine area is different than the small molecules, it’s more adaptable, so the judgment should return to the clinical scene and not the big pharma. The clinical reality will determine application and the Japanese government knows very well about this issue and we cooperated to make the new law. The Ministry of Health accepted that regenerative medicine is different than small molecules and that all is needed is a small number of patients to get approval, which is a great advance, a revolution.

Q: Is safety sufficient in a small population study?

MT: Of course the accumulation of the animal data needs to be reconfirmed by 10 or so patients for safety but the statistical significance of the efficacy needs more patients to prove the probable efficacy. Companies can sell the products based on smaller numbers so we don’t need big big pharma for promoting regenerative medicine. Companies can sell but they must register and prove efficacy within 7 years with regular exams. Success will be a collaboration between regulatory and academia with insurance reimbursement playing a commercial role which is incredible and kind of a risky law. The background of that is that academia promoted the regenerative medicine mainly so we cooperate very tightly with government and will decide where to provide treatment after approval with rules later.

Q: Do you plan enhanced cell products?

MT: Manipulated cells can work better, yes. So far natural cells are the most feasible, as regulators don’t like manipulated cells or “supercells.” In future but for now natural cells are good.

Q: Can you speak to the adult cell types?

MT: MSCs are safe. iPS/ES are hard to control so are limited to institutes that can maintain them/control them properly but the industrialization for a standard treatment iPS/ES is very good because we can have one lot otherwise many donors and always a lot of changes so that’s not very good industrially. In the future the ES & iPS cells people can control will be the way to industrialize and standardize treatment.

Q: What are your future plans / next steps?

MT: Our next steps are to have combined stem cell sheets – not only RPE but RPE with Photoreceptors and perhaps the vessel layer. Like a dream in our institute, that has a very high developmental biology focus, we talk about the whole retina with blood vessels and will try to deliver the entire retina for retinal disease conditions that destroy all the layers. For now we are working on monolayers, suspension, photoreceptors, combined layers and ganglion etc with 2016 for the allo, 2017 for the Healios suspension and 2018 for the photoreceptors.

Q: Are you collaborating with other institutions – is that part of your plan, UCL for example?

MT: We are not actually collaborating. We have a communication and information exchange, like a think tank. We know how they promote and we are doing very well. We don’t have to hide. They use similar technology adapted from our work. The aim is to make a standard treatment.

Q: Is ownership not an issue?

For the company it’s an issue – I don’t care. Patients don’t care. Healios is very good and they are in contact with the NIH group and the Ali group (UCL) – maybe they collect good procedures from the world.

Q: Are companies in Japan are looking at this sector as a team approach – does this help?

MT: Yes, society of regenerative medicine companies in Japan are maybe 100 companies now under the F.I.R.M association. Fuji, industry, pharma – all diverse companies. Not as a Keiretsu but more an association. Companies are now interested unlike 5 or 6 years ago. I told many companies to help us but they didn’t in the beginning but now they do. The government has helped a lot having supported the industry 10 years ago but they see the reality now as we have the clinical application.

Q: How do you see yourself, as a leader, role model – is there pressure?

MT: Shinya Yamanaka is like an Emperor now – everyone adores him. About the pressure, we have accumulated the data so I don’t fear anything. I have a scheme for 10 years plus and a plan. I know all – from the cells, the pluripotency, genes, animals, disease, patients and social and no worries only a process to move along. There are some against us but if I listen to their talks I’m not convinced by them, I mean persuaded, something wrong in their logic. As a role model – maybe I should behave myself! Patients happiness is what I believe – not papers or money, not interested. Patients first, outpatient clinic is very important to me.

Q: How do you view Lucentis/Eylea?

MT: Wonderful – we saw AMD 25 years ago and there was nothing at all. So we just explained the disease as incurable for 10 years but finally it came out, it was wonderful. We knew AMD very well and knew Lucentis wouldn’t cure everything. The treated patient had 10 injections before surgery and her condition deteriorated from 0.3 to less than 0.1 even though she had the available treatment, so we stabilized her visual acuity with radical treatment without any injection.

By way of disclosure: I have no conflict of interest, financial relationship with anyone or company mentioned in this article.

Yamanaka Interview on Clinical Use of Pluripotent Stem Cells

Dr. Shinya Yamanaka

Dr. Shinya Yamanaka.                                           Photo from CiRA, Kyoto University

I invited Nobel Laureate Shinya Yamanaka to do an interview on the future of clinical translation of induced pluripotent stem cells (iPSC).

He provides some intriguing new insights into the iPSC field and the broader stem cell arena.

PK: The Takahashi Team’s active Clinical Study using iPSCs to make RPEs to treat Macular Degeneration has generated a great deal of excitement. Can you please share your perspectives on the importance of this work and the team involved? 

SY: This is the first study to apply iPSC technology to human care. This is a very important study, because if it succeeds it will show that iPSCs can be safely used in humans and also their potential for cell transplantation treatment. We collaborated with Dr. Masayo Takahashi of RIKEN CDB by evaluating the safety of the iPSCs and iPSC-derived cells that were used for the cell transplantation. She is an excellent researcher, and I am not surprised that her team is the first to have succeeded in this transplant.

PK: Any cutting edge investigational clinical work such as this has some risks. Could you please comment on the potential risks in this iPSC trial? Are there some elements here such as preclinical data, the number of cells used, or the target tissue of the eye that lower risks?

SY: One of the major concerns is whether transplanted cells such as the RPE sheets will cause tumors. In our collaboration with Dr. Masayo Takahashi’s team, we evaluated the safety of iPSCs and iPSC-derived cells by genome and epigenome analysis. While we minimized the risk to a level acceptable for clinical trials, we really cannot confirm how the cells will respond until we actually do experiments with humans, which is why this project is so important. One advantage of treating age-related macular degeneration is that it is easy to detect any abnormalities in the eyes, which is why the disease is a good starting model for iPSC-based treatment.

PK: As the inventor of iPSCs did you imagine 7-8 years ago that a patient in a clinical study in 2014 would already have received an iPSC-based treatment? How was this rapid translation from bench to bedside possible?

SY: I was surprised that after the announcement of human iPSCs in 2007, Dr. Takahashi told me that she would bring iPSC to the bedside within five years. I thought it possible technically speaking, but doubted it could be done so soon, since we needed to improve the technology and get government approval. It took 7 years, which is remarkable considering the work required. Both the accomplishment and the speed at which it was achieved are testaments to Dr. Takahashi’s leadership and her strong team.

The rapid transition is because many bright and passionate people are in the iPSC field. The funding and infrastructure provided by the Japanese government is also a major factor, as these have encouraged excellent scientists to enter the field.

PK: We are also starting to hear more about Dr. Jun Takahashi’s Team’s important work towards using iPSCs to treat Parkinson’s Disease. Can you please tell us more about that?

SY: Prof. Jun Takahashi’s team at CiRA is working on cell therapy for Parkinson’s disease, aiming to transplant iPSC-derived dopaminergic neural progenitor cells into PD patients’ brains. Early results suggest this treatment can be effective, and his team has established the protocol for transplantation. They are now focusing on validating its safety using monkey models. We hope his work will soon reach the operating room within the next few years.

PK: What other clinical applications of iPSC technology are in the works and that might begin clinical studies in the next few years?

SY: There are two major clinical applications of iPSCs, namely regenerative medicine and drug discovery. CiRA has a number of researchers working on either or both. For regenerative medicine, Prof. Koji Eto at CiRA is working on generating platelets via iPSCs, and we expect this will also proceed to clinical research in a few years. Besides work at CiRA, a team at Keio University has a plan to conduct clinical research on patients with acute spinal cord injury in four to five years, while Osaka University and Keio University hope to transplant iPSC-derived cardiac myocytes into patients with heart diseases within a few years. CiRA is collaborating with these teams as well.

Regarding drug discovery, you may have heard recently of CiRA’s Prof. Noriyuki Tsumaki’s paper about statins effects on bone growth, which was published online in Nature last month.

PK: Some in the media are taking about a certain tension between clinical iPSC work in Japan and clinical iPSC work in the US. Do you believe such a tension exists and if so, why? What does it mean for the iPSC field overall?

SY: I am not sure what “tension” means. I understand that both competition and collaboration exist between the US and Japan.

PK: How do you view hESCs today? Are there hESC clinical trials or potential applications that are of particular interest? What is your view of the argument by some that hESC are no longer needed?

SY: Human ESC was a great discovery for regenerative medicine and also instrumental to the discovery of iPSC and the type of medical treatments we are aiming to apply iPSC. At the same time, the ethical issues that hESC possess mean that as iPSC technology improves, hESC will be less needed. Still, iPSC is a new technology, and its safety and efficacy still needs to be confirmed. In addition, there may be some therapies for which hESC are better than iPSC. Thus, I think basic and clinical research of hESC is also important and should be done in parallel with iPSC research.

PK: What excites you most about the stem cell/regenerative medicine field right now today?

SY: I am excited about the possible number of people treated with iPSCs. This field has great potential to provide treatments for currently incurable diseases. Hopefully, within 5 years, we will refer to Dr. Masayo Takahashi’s AMD work as just one of many patient studies using iPSCs.

PK: Where do you see the iPSC field and the broader stem cell field in say 5-10 years?

SY: It is pretty amazing how much it has changed in the past years, so predicting the next 5-10 years is very difficult. I certainly hope we will see more diseases being treated with iPSC and related technologies such as direct reprogramming. I also hope that iPSC will be used more widely and routinely in drug development.

PK: What advice would you give to young scientists today who are excited about a career in stem cells/regenerative medicine?

SY: Through biomedical research, you could help thousands of patients in the future. Stem cells provide unprecedented opportunities in stem cell therapy and drug development. Biology of stem cells itself is extremely interesting. I hope many young scientists will enter to this field.

StemCells Inc. leadership interview: Pipeline, Financials, IP Conflict with Neuralstem, CIRM, & more

GregSchiffmanStemCells, Inc. is a top biotech company developing stem cell-based therapies. They have a deep pipeline that includes already ongoing trials for a variety of diseases. I invited company leadership to do an interview and they graciously accepted.

Below is the interview with CFO Greg Schiffman (picture at left from LinkedIn) including what I thought were some tough questions from me and very detailed answers from Shiffman. Thank you, Greg.

1. Where does the company stand today in terms of product development, capitalization, and such? What are its strengths? What are potential areas for improvement or development?

We currently have three active programs underway two clinical and one pre-clinical.  The two clinical programs are in the spine, spinal cord injury (SCI), and in the eye, dry age related macular degeneration (AMD), and the pre-clinical program is in the brain focused on Alzheimer’s disease.  Both clinical programs have completed enrollment of the Phase I/II clinical trials and we have plans to initiate controlled proof of concept Phase II studies in both indications in the second half of this year.  Both indications have large unmet medical needs.  We have released interim results for both of the Phase I/II programs.  We have not seen any safety issues associated with the cells.  In addition, we have seen preliminary signs of efficacy in both programs.  Our pre-clinical efforts are focused on filing an IND for Alzheimer’s disease in 2016 following which we could move this program into the clinic.stemcellsinc-logo

We just completed a $20 million gross equity financing.  If you include the proceeds from the equity financing and warrant exercises that occurred in the month of July, the company had approximately $37.8 million dollars of cash and marketable securities at the end of June.  This provides us with a strong balance sheet to move our programs forward.

We believe that we have a unique platform utilizing our proprietary HuCNS-SC® human neural stem cells that have the potential to address numerous indications affecting the CNS.  This would include white matter brain disorders such as leukodystrophies, multiple sclerosis, cerebral palsy and transverse myelitis.  Other potential indications could include Alzheimer’s, spinal cord injury, dry age-related macular degeneration and centrally mediated lysosomal storage disorders.  We have performed pre-clinical work in many of these indications and we have selected one indication, where there is a large unmet medical need, in each major organ of the CNS the brain, eye and spine to pursue clinically.  The cells have shown a very favorable safety profile and all of the pre-clinical and clinical findings have shown signs of efficacy.  This is a very exciting time for the Company as we are now rapidly generating a significant amount of clinical data which will help to provide much greater insight into the potential clinical benefit we can bring to patients.

2. What unique challenges does the stem cell/cell therapy/regenerative medicine biotech sector face overall say compared to a pharma company producing a chemical-based drug and how is StemCells, Inc. approaching those hurdles?

Anytime you are pursuing a new therapeutic paradigm you encounter additional regulatory hurdles and scientific scrutiny.  StemCells, Inc. has very methodically pursued the science.  We have published all of our work so that others can critique the findings.  It has taken a significant amount of time and resources pursuing the science to understand the potential of the platform we are building.  However, it enabled us to move forward with our clinical programs on a very strong scientific foundation.  In addition, given the nature of our cells which engraft into the host, replicate, migrate within the host and differentiate into the cell types associated with the CNS, our early clinical trials faced significant safety hurdles as this was the first time that these cells would be transplanted in humans.  The first indications had to be fatal diseases and the subjects were in the most advanced stage of the disease.  In addition, we were limited to one surgeon and a single site for patient recruitment.  We would treat a patient following which safety data was generated and submitted to the FDA for review.  After review we were able to begin looking for the next patient to be transplanted with the cells.  The clinical trials moved forward very slowly given these hurdles.  However, given the favorable safety profile we have shown in both the spine and eye, as well as the favorable safety profile demonstrated in our previous clinical work in the brain for both Batten disease and Pelizaeus-Merzbacher disease (PMD), we are now able to proceed forward at a much more rapid pace, consistent with other biologic clinical trials, with our Phase II studies.  In 2015 we plan to have between 10-15 sites enrolling patients for each of our clinical programs and expect to be able to complete the enrollment in about one year.  As we continue to move forward with the clinical efforts, and hopefully to an approved therapeutic, we expect that there will be additional hurdles to overcome including physician and patient education on this new platform of stem cells.  This is an exciting opportunity; and we are comfortable in our role as pioneers breaking new ground.

3. How important has CIRM funding been for StemCells, Inc.?

StemCells, Inc. has spent over a quarter of a billion dollars pursuing our science.  This includes pre-clinical and clinical work as well as building out our manufacturing capabilities.  We have completed two Phase I/II clinical trials in fatal childhood brain disorders, PMD and Batten’s disease, have two active Phase I/II clinical trials ongoing in SCI and AMD, and are about to initiate two Phase II controlled studies in each of those indications.  All of this has been funded by the Company.  We are also working to file an IND in Alzheimer’s disease.  This would enable the company to begin clinical trials in this indication.  CIRM is funding half of the expected costs for filing the IND in Alzheimer’s in the form of a forgivable loan.  The total funding from CIRM for this effort is up to $19.3 million dollars.  This investment was important for the Company to be able to pursue this activity in parallel with the other clinical programs we have underway.  As a small biotech we need to prioritize investments and without this funding this program would be on hold while we pursued our other clinical programs in spinal cord injury and dry age related macular degeneration.  CIRM’s decision to fund half of the costs of the IND is allowing us to pursue this activity today.  This accelerates the timeline for a potential therapy for this disease that affects so many people.  Should the program be successful, CIRM will see a significant financial return on the investment.  However, if you look at the investment that has been made in our platform technology and the ongoing clinical investments we are making, the $19.3 million from CIRM, which is to be disbursed over the next four years, to help fund half of the costs of filing the IND in Alzheimer’s disease is very important to the timing of our Alzheimer’s disease clinical program but not to the overall clinical agenda StemCells is pursuing.

4. Which of your products/programs are closest in the pipeline to getting to patients? What excites you the most?

Our two most advanced programs are the SCI and AMD programs.  We are very excited about both of these programs and the potential they may bring to dramatically affect patients afflicted by each indication.  We believe that the AMD program is probably the program that will move forward the fastest given the number of people affected by the disease and the nature of the treatment.  The interim results we presented at the International Society for Stem Cell Research (ISSCR) showed very promising early signs of clinical benefit.  We showed a 70% reduction in the rate of geographic atrophy.  Geographic atrophy is the progressive loss of two important retinal tissue layers, the photoreceptors and the retinal pigmented epithelium.  Degeneration of the macula is the cause of vision loss in dry AMD.  We also saw an improvement in visual acuity in 4 of the 7 patients as evidenced by their ability to detect differences in light and dark referred to as ‘contrast sensitivity.’ These results exceeded our expectations.  We will have final results from this study next year and, based upon the strength of both the safety and efficacy findings, we are initiating a Phase II controlled study in AMD later this year.

We are also encouraged by or SCI program.  We have seen clinical benefit in our Phase I/II trail where patients are seeing multi-segmental gains and a return of function in the cord in half of the patients. This indicates that something that was not working in the spinal cord, now appears to be working following transplantation. This is even more significant because of the time that has elapsed from the date of injury, which ranges from 4 months to 24 months across the subjects with sensory gains.  Our next study in SCI will occur in the cervical or neck region.  This is the section of the cord that controls motor function of the upper extremities.  The cervical cord directly controls motor function of the upper extremities.  Thus, these patients may represent a population in which regaining, or enhancing, upper extremity motor function may be more readily anticipated.  Even a gain of one to two motor segments in the cervical spinal cord could allow for additional function in the upper extremities. No one has been able to run a study using stem cells in this patient population previously.  Given the safety profile of our cells in the previous SCI study where we recruited patients with thoracic injuries, the FDA is now permitting StemCells to enroll patients with cervical spinal cord injuries.  This has the potential to significantly improve the quality of life for victims of SCI and at the same time reduce the overall cost to the healthcare system.

5. Besides HuCNS-SC, do you have other cell products in the works? Does the company have interest in reprogramming and iPS cells? ES cells? Adult stem cells such as MSCs?

All of our current clinical efforts are leveraging our HuCNS-SC human neural stem cells platform.  We have performed pre-clinical work using a proprietary platform of human liver stem cells, however, in order to focus our efforts we are not actively pursuing this technology at this point in time.  We think our HuCNS-SC cellular platform has tremendous potential and we want to move or AMD and SCI clinical programs forward as rapidly as possible.  Nevertheless, we are constantly evaluating new technologies that we think have potential as this remains a constantly evolving field.

6. There has been quite a bit of discussion in the media and on social media about former CIRM President Alan Trounson joining the board of StemCells, Inc. shortly after departing from CIRM. Can you comment on this situation and perhaps clarify the realities of this situation as there has been a fair amount of speculation about this?

We are not prepared to provide any additional information beyond the public comments the Company has already made, except to say Dr. Trounson is a very accomplished leader in the stem cell field and we are delighted to have him join us as a director.

7. A former employee of StemCells, Inc. has filed suit against the company and made certain allegations. I am not going to ask you about that suit specifically (unless it is something you want to discuss), but I wanted to give you an opportunity to talk about the  steps the company takes for handling its cells and products, quality assurance, GMP practices, and such. Can you please tell us some of the ways by which the company maintains standards for its products? How confident are you in your products?

We are very focused on the processes we use to manufacture our products.  You should know, the elements of manufacturing practices that concerned Mr. Williams were immediately and carefully reviewed by the Company.  The Company’s primary concern has always been, and will continue to be, the safety and tolerability of stem cell transplantation in its clinical trials. Over the years, we have consulted with multiple experts in the field and we believe our processes, procedures and controls, as fully described in our regulatory filings, are appropriate for a company at our early stage of clinical development and comport with applicable guidelines and regulations.

8. Can you tell us some about the IP portfolio of the company? Are there elements that you are particularly excited about? What is the situation with Neuralstem in a nutshell on the IP front?

We have established a strong base of intellectual property surrounding human neural stem cells.  In addition, in 2013 we further strengthened our patent portfolio with the outright acquisition of previously licensed patents from Neurospheres Holdings in addition to the acquisition of a number of patents from NsGene which complement our portfolio.  The patent portfolio from Neurospheres, which was based upon the groundbreaking research by Samuel Weiss and Brent Reynolds at the University of Calgary, has repeatedly been recognized as the seminal intellectual property pertaining to purified populations of human neural stem cells.  Today, we believe we have the broadest and deepest IP portfolio of any company in the neural stem cell space.

StemCells has been engaged in a long-standing patent infringement suit against Neuralstem, Richard Garr and Karl Johe.  Our suit alleges infringement of six patents, owned by StemCells, claiming populations of human neural stem cells, their proliferation and their use, inventions arising from the groundbreaking work of Drs. Samuel Weiss and Brent Reynolds while at the University of Calgary.

We are pleased that recently the judge in the case denied Neuralstem’s motion for summary judgment and moved us one step closer to a final resolution in the case by scheduling the first part of the trial to begin this December.  It is certainly welcome news that our case will finally have its “day in court.”  In light of the judge’s rulings, we can anticipate trial on the merits next year and, I sincerely hope, a speedy and final resolution of our various patent and business tort claims against Neuralstem.

It is important to understand why we filed this lawsuit in the first place.  Over the years, StemCells has made a considerable investment in its patent portfolio, which now consists of dozens of issued patents worldwide.  Both the Company’s Reynolds and Weiss patents and its other patents, whether owned or exclusively licensed by StemCells, have been licensed out, on a non-exclusive basis, to several companies for sizeable licensing revenues in return for freedom to operate.  Our SEC filings describe these patents and our licensing activities in detail.  The Company’s proprietary cells, the HuCNS-SC cells, are protected by multiple patent families held by the Company. This lawsuit is not about StemCells’ freedom to operate, there are no claims of infringement against STEM; but it is challenging Neuralstem’s freedom to operate and we seek injunctive relief and substantial damages from them.  We contend that Neuralstem has willfully infringed our intellectual property and we owe it to our shareholders to do everything in our power to protect the investments we have made, on their behalf, in this groundbreaking neural stem cell technology.  We look forward to the prospect of presenting our evidence and our arguments to the judge and jury.

9. The stock has had a bit of tough month in terms of PPS. What would you say to the average shareholder out there?

There is always a lot of noise when you are pioneering breakthrough new technologies.  We think that there are areas investors should look at carefully to help guide their investment decisions. First, StemCells has attracted a world-class team of professionals, with the experience and expertise needed to drive success.  Second, our clinical trials have attracted partnerships with world-leading researchers, hospitals and institutions.  Third, StemCells holds a wealth of valid patents that protect our technology.  Fourth, we are rapidly accruing clinical data that validates the findings of our preclinical models. Two of our clinical programs addressing major medical conditions (SCI and AMD) are rapidly advancing towards controlled Phase II trials. Risk decreases with each regulatory milestone reached.  Fifth, StemCells has a sound balance sheet and a strong cash position.  Sixth, our diversified clinical program addresses multiple major medical conditions affecting large populations, two of which (AMD and Alzheimer’s), target aging populations that are rapidly increasing around the world.  There is short term volatility in micro-cap stocks, often associated with noise unrelated to clinical progress and clinical outcomes.  We believe that we are well positioned and have a very exciting platform technology that has the potential to address many conditions of the CNS that have not been able to be addressed by traditional approaches.  Should we be successful in moving one or more of these programs forward, we believe that there is significant value creation potential for our shareholders.

10. What’s your outlook on the future for the company? Are you optimistic? Where do you see StemCells, Inc. in say 5 and 10 years?

I am very optimistic about the potential for StemCells, Inc.  We have spent over 15 years pursuing the science and early stage clinical trials.  This has been done very methodically, which was important to establish a strong foundation for our late stage clinical work.  We are now at a stage where we will quickly generate significant amounts of clinical data providing much greater insight into the potential of our platform technology.  Over the next five years we would expect to have final results from our ongoing Phase I/II studies in SCI and AMD as well as final results from the Phase II studies we plan to initiate later this year.  In addition, if we continue to see results consistent with our interim clinical findings,  we should be well underway with our pivotal Phase III registration studies.  This is truly an exciting and transformative period for the Company.  If the technology is successful in the Phase III studies, in 10 years we could have multiple approved clinical products on the market.  The Company would actively be pursuing additional clinical programs, using our HuCNS-SC platform, to address other unmet medical needs in the CNS.  It would also be pursuing some of the other exciting technologies that we are investigating today.