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. Please continue reading on Page 2!

Slowly Removing the Mask of the Phantom of the Stem Cell Opera: BioGatekeeper

BioGatekeeperThe technology to change just about any human cell into a super powerful kind of stem cell called induced pluripotent stem cells (iPS cells or iPSC) has great potential not only to help millions of patients, but also to make companies millions or even billions of dollars.

Many scientists have been on the trail of cellular reprogramming, as this process of making powerful stem cells is called, but it was Dr. Shinya Yamanaka who finally got it to work first and the predominant intellectual property in this area so far has been the so-called “Yamanaka Patent”.

A mysterious organization called BioGatekeeper, Inc. has filed a legal challenge to the Yamanaka Patent seeking to cancel it (for more on this see here and here).

Who is BioGatekeeper?

So far the stem cell field does not know, but I’m convinced the truth will come out.

Another question is why BioGatekeeper would want to hide. The seemingly obvious answer is they want to avoid potential negative PR. However, another perhaps complimentary notion is that BioGatekeeper wants to avoid being identified because it is really a team effort, there are several parties behind it, and frankly some of this group do not want to publicly be associated with the others.

One of the most fascinating things for me as I’ve been following this story is the large number of different possible people and companies that have been suggested to me by people in the know as being behind BioGatekeeper.

Even if none of these are behind BioGatekeeper (whether alone or collectively) it is intriguing that there are so many companies who might want a slice of the iPS cell pie and so might be very happy to see the Yamanaka Patent nullified.

I suppose it is also possible that BioGatekeeper chose that name not only to put on the appearance of a do-gooder, but also using some kind of reverse psychology they wanted to attract attention and get publicity via this mystery. If the latter is the case, then I guess I’ve fallen for their trick.

Whatever their motivations, it’s also interesting how quite a few of these potential BioGatekeepers can one way or another be linked to the same law firm(s) that seem to be involved.

The cell reprogramming intellectual property arena has many players, is interconnected, and brings into play some of the say attorneys over and over.

The best current prediction is that behind the mask of BioGatekeeper, behind that temporary curtain of anonymity, are several different parties who each have a financial interest in nullifying the Yamanaka Patent. As the clues continue to pour in, the stem cell field will determine who they are and what they are up to soon enough.

Interview with Jane Lebkowski on Asterias FDA-approved Stem Cell Trial

Jane LebkowskiThe BioTime subsidiary, Asterias, has received FDA approval for a combined Phase I/IIa clinical trial of OPC1 for treating spinal cord injury.

BioTime (BTX) and Asterias (ASTY) have picked up the portfolio of the former Geron clinical trial using oligodendrocyte precursor cells (OPC). Asterias also acquired a second element from Geron in the form of a lung cancer treatment based on stem cells that sounds quite intriguing.

To learn more about this exciting news I interviewed Jane Lebkowski, President of Research and Development at Asterias.

1. What are the most important things for the stem cell community to know about Asterias getting the FDA approval to move forward with this Phase 1/2a trial?

Asterias BioTimeLebkowski: There are a couple of very interesting points.

In the first clinical trial by Geron, safety was established in patients with thoracic spinal cord injury. Now, with this current FDA clearance and the new clinical protocol, we will test AST-OPC1 in a different patient population, those patients with complete cervical spinal cord injuries. We think this population will be the first target for registration trials for AST-OPC1. Patients with cervical injuries have more extensive paralysis involving both the lower and upper limbs. Because of both the anatomy of spinal cord in the cervical spinal cord region and superior ways to assess restoration of upper body movement, we believe testing of AST-OPC1 in this patient population will provide a better opportunity to assess potential clinical benefit of the cells.

Another important point of the new trial is that will test escalating doses of AST-OPC1. The first clinical trial performed by Geron tested a single low dose of the cells. In the new Phase 1/2a trial, we will escalate doses into the range where we feel we can see potential clinical activity.

2. What are the doses in the new trial versus the original one?

Lebkowski:  The dose used in the Geron trial was 2 million cells. The new trial will start with a dose of 2 million cells in the first cohort and then escalate to doses of 10 and 20 million cells in cohorts 2 and 3.

3. The patients that originally received OPC1 when Geron was starting things have now been followed for a relatively long time. How are they doing?

Lebkowski:   There have been no safety problems observed in these patients that were associated with the cells, injection of the cells, or immunosuppression used in the first clinical trial. We haven’t seen measurable neurological improvements in the patients, however these patients were administered only a low dose of cells. Importantly, there were no immune responses observed which targeted the cells. By MRI, there were indications of tissue sparing effects (reduced cavitation) in four out of the five patients in the original trial.

The device and procedure used to administer the cells in cervical spinal cord injury patients are essentially the same as those used in the first trial in thoracic injury patients.

When the product was owned by Geron, it was referred to as “GRNOPC1”.  It is now called “AST-OPC1” to reflect its new owner, Asterias Biotherapeutics.

4. What does the involvement of CIRM mean for the whole process?

Lebkowski:  CIRM will be helping to co-fund this new clinical trial. This funding can now be activated with the FDA clearance.

5. What will the time course be like for this trial? 

Lebkowski:  We plan to start the trial in early 2015 with data becoming available as the trial progresses through the cohorts. 

6. In a broad sense, what does this clearance and the trial mean?

Lebkowski:  Although the first trial was small, a good safety profile was established enabling more advanced testing of AST-OPC1 in clinical trials where both safety and efficacy can be potentially measured. The clearance also shows more broadly that human embryonic stem cell based therapies are progressing in their development. The field is advancing beyond the feasibility stage now.

8. Can you tell us briefly about Asterias’ lung cancer program?

Lebkowski:  A second Asterias product is AST-VAC2, which are human embryonic stem cell derived dendritic cells. These cells are modified to express telomerase, a protein typically expressed in cancer cells. The aim is to use these telomerase expressing dendritic cells to stimulate immune responses against cancer cells. We are now preparing for clinical trials with this product. 

A List of Top Biologists to Follow on Twitter

Who should you follow on Twitter?

Actually, it very much depends on your interests and what you want to get out of it.

neuroskeptic

Below is my list of top biologists/biology writers that I, with all my many biases (see below) recommend to you to follow on Twitter, in no particular order (actually alphabetized).

Check out their Tweets. Engage them with a question or reply to them with a valuable link. See what happens.

The nice thing about Twitter is you can essentially experiment with it on who to follow. If you follow someone say for a week and it seems like it’s not of much interest to you then you just unfollow them.

There are some amazing scientists on Twitter including some pseudonymous bloggers such as Neuroskeptic (see avatar above), DrugMonkey, and Dr. Isis. Stay tuned for a hopefully soon upcoming blog post on anonymity and identity in science social media that I’ve been working on now and then.

Call me crazy, but I like to include an ample helping of people/organizations with whom I do not always see eye-to-eye amongst those that I follow on Twitter as it makes me think in a different way. I also like to follow people who are literally throwing themselves into life as an experiment. Maybe even causing trouble in a sense with strong opinions. You might note a preference for cell, developmental and molecular biology as well as the biomedical sciences. I confess to it. I also greatly value diversity so that is reflected in my list.

I also have a bias towards people/organizations that tweet regularly. Therefore, I’ve left off some fabulous biologists who might only tweet a few times a year.

Admittedly I’ve probably left off some more greats from all of those who I follow and please leave your favorites in the comments and I am betting I’ll be needing to expand the list below from your awesome feedback. And, yeah, please consider following me too at @pknoepfler

Well, here’s the list with a big hat tip to Kelly Hills for her valuable input and suggestions.

 

Perspectives: RIKEN itself fails to reproduce STAP & big CDB shake up expected soon

Nikkei is reporting that the RIKEN internal attempt to replicate so-called STAP (acid bath) cells has failed. Update: apparently, although RIKEN calls the efforts preliminary, the team tried to make STAP an amazing 22 times and 22 times it failed.

The rumors for weeks in the stem cell gapevine that RIKEN itself could not get STAP to work, even with the help of Dr. Haruko Obokata, have been confirmed by Nikkei. Obokata was first author on both Nature STAP papers, which were retracted. One of Obokata’s mentors and a STAP paper co-author, Dr. Yoshiki Sasai, recently committed suicide at least in part likely due to issue related to STAP. See a tribute to Dr. Sasai here.

STAP cell embryo

The best that the RIKEN team could get in the replication attempt, according to Nikkei sources, was a “faint” hint of pluripotent markers “nowhere near” to that observed in iPS cells or embryonic stem cells. STAP cells were supposed to be not just pluripotent, but also totipotent, allowing for contribution to an entire embryo (see image at left from the STAP work). Now that claim seems light years from reality. For more background on STAP and a timeline of the events see here.

This may be the final straw that pushes RIKEN to formally declare that STAP cells do not exist, a conclusion that I think the world of science has mostly already come to some time ago.

This latest twist is no surprise and just adds to the continuing STAP sadness, but hopefully is another step toward an end for the STAP disaster.

Unfortunately, however, this could get even worse.

Nikkei also reports that tomorrow RIKEN will announce a major shakeup at the RIKEN Center for Developmental Biology (CDB), where much of the original STAP work took place, that could mean as much as half of the scientists at the CDB moving to other RIKEN units and in a few cases losing their jobs (update: new reports and sources indicate that most RIKEN employees leaving the CDB will be transferred to other RIKEN units and not lose their jobs). That seems grossly unfair as most of the affected people would probably have had nothing to do with STAP. This anticipated personnel cut would be just another level of tragedy to the STAP story.