• The die is cast
  

Posted: November 15th, 2011

"The die is cast"

- Julius Caesar by William Shakespeare

In what appeared to be an “out of the blue” release after the markets closed yesterday, Geron announced that it was ceasing all stem cell operations. If you are reading this, you already know that Geron was the largest player in the stem cell world; owners basically of all Embryonic Stem Cell technology. They had one ongoing trial in the U.S., for acute spinal cord injury. I believe they may have transplanted 4 patients since the trial began (close to 2 years ago). That trial has been stopped. Additionally, I read that they have already given back the CIRM money (to California) and it is assumed that all those research programs are also closed down. Geron is going to become an oncology company according to their release.

Since we are pursuing many of the same indications as Geron, with a similar method (injection of our CNS stem cells as opposed to their injection of their ES derived cells) I have received many inquiries already asking about the effects of this sea change in the stem cell landscape. It will take a while to sort out of course, but here are my initial thoughts.

On a very macro level, it leaves Neuralstem as the only company with an ongoing U.S. trial of stem cells in the spinal cord, for any indication. We are scheduled soon to begin the cervical injection phase of our ALS trial in Atlanta. This upcoming trial was highlighted recently in a FoxNews Atlanta story and you can see the piece on our web site (or theirs). I suspect the profile of our trial may now be raised somewhat. But the stakes have already been raised quite a bit for this trial as a result of the encouraging signs we have seen from the first 12 patients as reported by Dr. Eva Feldman (our overall Principle Investigator) at the last ANA annual meeting.

These patients only received injections in the lower back area. Those segments of the spinal cord related mostly to the lower extremities. As Dr. Glass (our site PI in Atlanta) says in the FoxNews piece, if we can see the same signs of improved function in the muscles controlling breathing that we have seen in lower limbs in the earlier patients, we will have truly changed the course of this terrible disease.

Which brings me to my second observation, one that is perhaps not fair, but nevertheless true. I think that if Geron had seen the same signs of potential efficacy in their Spinal Cord Injury trial that we have seen in our ALS trial, this announcement never would have happened. First in human feasibility trials like this are never designed (design approval by the FDA) to demonstrate efficacy. They are all about safety. That is why the criticism is not, strictly speaking, fair. The FDA often will not let you design the trial to optimize the chance to see these early signs. But we (and everyone else) are also always looking for “green shoots”, early signs that there is biological activity, survival of transplanted cells, or best of all, some return of function. With encouraging evidence of any combination of these things, one can leverage the safety data created in a safety trial to move forward. For whatever reason(s) Geron’s trial did not produce this result.

As more facts about their decision to leave the field come out, I’m guessing the plot will thicken, not thin. There will be more questions than answers for investors.

For the patients and caregivers who have passionately supported Stem Cell research in general, this must seem a terrible blow. For a nascent industry, it is certainly a shock to the system whose repercussions are still largely unknown. But at Neuralstem, frankly, we have always believed that our technology was far more likely to prove safe and effective; and far more user friendly to the regulatory and manufacturing issues which have held the field back. We may have to prove this now under a hotter spot light, but nothing else changes for us. As the ALS trial proceeds we continue to aggregate the human safety data on our cells which combined with pre clinical animal proof of principle data will enable trials in stroke, and spinal cord injury and MS and a host of other diseases. We Have seen the green shoots, we are Not retreating. We have always felt that our technology provided the answers that held the field back. It would appear (for the time being at least) that the field has been left to us alone to prove it. We relish the opportunity. The die is indeed cast.