Throughout recorded history, one will discover key points in the timeline where revolutions and abrupt adjustments have ushered in dramatic changes to the status quo. For example, consider the American Revolution where the United States won its independence from the British Empire, or the Russian Revolution of 1917 that removed the Czars and gave rise to Communism. These revolutions would shape the political and power structure of the entire world for centuries to come. Of course, not all revolutions are social/political affairs and revolutions can also take place take place in areas like industry, religion, and science too. What all revolutions, regardless of type, have in common is that they will have that one catalyst or spark that ignites the revolution. That one special event that sets into motion the chain of events that will forever change the landscape. This spark is not the cause of the revolution but merely the tipping point.
That being the case, it is with utter excitement that many investors watch to see where this spark will ignite and usher in the coming stem cell revolution in the world of medicine. Today, current medical standards and practices often treat the symptoms of underlying problems but fail to address the root cause of some major health concerns. It is at this critical juncture where the stem cell revolution will change the landscape. With new procedures and technologies, stem cell companies will change the face of medicine and how we will live our lives. That being the case, let’s investigate a few companies that just might ignite that spark.
One cannot initiate a discussion of stem cell companies without starting with Geron (GERN). Geron is a company that develops biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, and diabetes. GERN’s pipelines run fairly deep and besides stem cell technologies it has multiple Phase 2 trials dealing with cancer therapies. That being the case, the real catalyst for the company is the Phase 1 clinical trial dealing with treatment of spinal cord injuries with stem cells. If GERN is going to be the catalyst that starts this medical revolution then it will begin in this trial.
What GERN has done is to derived Oligodendrocyte progenitor cells (GRNOPC1) from Human Embryonic Stem Cell (hESCs). Oligodendrocytes are naturally occurring cells in the nervous system that have several functions. They produce myelin (insulating layers of cell membrane) that enables the cells to conduct electrical impulses, plus they also produce neurotrophic factors that support the maintenance of nerve cells. When these Oligodendrocytes are lost in spinal cord injuries, the results are a loss of the myelin and neuronal function that in the end will cause paralysis in many patients. In animal models, Geron was able to show improved functional behavior using GRNOPC1 at the injury site seven days after injury. After much review, the FDA then granted approval for a clinical trial and Phase 1 testing of GRNOPC1 in patients with spinal cord injury began in October 2010. Two clinical sites were opened for patient enrollment in 2010, and the remaining 5 were opened in 2011.
In late July 2011, Geron stated that a second subject was enrolled and received GRNOPC1 in the ongoing Phase 1 clinical trial. The treatment was administered by investigators at Northwestern Memorial Hospital and Northwestern University Feinberg School of Medicine. The company also went on to state that the preliminary data from the first two patients showed no safety concerns or serious adverse events. That being the case, Geron received clearance from the FDA to expand the eligibility criteria for the trial to allow inclusion of a wider range of patients.
For the second quarter of 2011, the company reported a net loss of $21.1 million. Net loss for the first six months of 2011 was $45.5 million and the company ended the quarter with $192.2 million in cash and investments. The total operating expenses for the second quarter of 2011 were $21.9 million which broke down to research and development expenses of $16.5 million and general and administrative expenses of $5.3 million. The company also stated that the cash reserve plus the income Geron receives will be sufficient to fund the current level of operations through at least December 2012. Geron also states that future capital requirements will be substantial as several trials are moving forward.
So will Geron be the one who will strike first with its stem cell therapy? Phase 1 trials have been going on for awhile and so far all we have really heard is that the therapies are safe but we are still unsure as to how effective they are. It is obvious that the trial is very ambitious and if successful will be a game changer, but one must worry if the company will run out of funding before they get to that point. It will be most interesting to watch as events unfold in this company’s future.
If Geron is not moving at the pace you want, then you might want to consider fast acting Advanced Cell Technology (ACTC). Advanced Cell is a biotechnology company focused on the development and commercialization of human embryonic and adult stem cell technology in the field of regenerative medicine. In early 2010 the FDA granted orphan drug status to Advanced Cell for an embryonic stem cell derived treatment for a specific form of blindness, Stargardt’s Macular Dystrophy.
Later that same year the company was cleared by U.S. regulators to test a therapy made from embryonic stem cells in patients with macular degeneration. Advanced Cell wasted little time and by July 2011 the company announced the dosing of the first patients in each of its two Phase 1/2 clinical trials for Stargardt's macular dystrophy and dry age-related macular degeneration (dry AMD). These patients were treated at the David Geffen School of Medicine at UCLA and at UCLA's Jules Stein Eye Institute. Notice that the trial is Phase1/2 thereby speeding up the trials. Both the Stargardt's trial and the dry AMD trial will enroll 12 patients each, with cohorts of three patients each receiving an ascending dosage of the stem cells as the trials move forward. The initial dosing was relatively small (50,000 cells) and the early indications were that the patients tolerated the surgical procedures well. In late September 2011, the independent Data and Safety Monitoring Board (DSMB) overseeing the Company’s two trials authorized ACTC to move forward with enrolling and treating the next set of patients in each of the trials.
If that was not enough, then on top of the U.S. trials one must consider what is going on in Europe. At the same time the DSMB made its announcement, Advanced Cell received clearance from the U.K. Medicines and Healthcare products Regulatory Agency to begin similar Phase 1/2 clinical trial for Stargardt’s Macular Dystrophy. It should also be known that the European Medicines Agency previously granted Orphan Drug designation for the company's RPE cell product for use in treating SMD. At this point it should be noted that macular degeneration in the U.S. is a $30 billion market with relatively no competition. Add a European market to the mix and the numbers go even higher. To add fuel to the fire one has to consider a recent statement from the CEO when he stated,
For now, it will have to suffice to say that we are extremely pleased and believe that these trials will validate our earlier pre-clinical findings. In the meantime, we have begun to set our sights on expanding our clinical trials to in Europe, having been recently approved to begin our SMD trial in the United Kingdom, and various countries in Asia.
What should be taken away from this is that the pre-clinical animal findings were extremely successful and if this carries forward in humans then the sky is the limit for the company. Also this is the first time that any testing in Asia had been mentioned. And if all that is not enough, one must also consider the Advanced Cell’s Phase II-approved Myoblast autologous adult stem cell therapy for the treatment of chronic heart failure advanced cardiac disease, myocardial infarction, and ischemia; as well as the Hemangioblast (HG) program for the treatment of blood and cardiovascular diseases which is currently in preclinical development.
As wonderful as all Advanced Cell’s programs sound, there are still lots of risks with the company. The company basically has no revenue and for the second quarter of 2011; net cash used in operations was $3.2 million. Needless to say the expenses will only increase as the company pushes forward on its clinical trials. Advanced Cell ended the 2011 second quarter with cash and cash equivalents of $16.1 million and will burn through that rather quickly. Add to this a couple newly filed lawsuits and a 1.7 billion share count and we find Advanced Cell in a race for funding. Advanced Cell has stated that several top pharmaceutical companies are closely following the trials and if the company can prove it can eliminate macular degeneration, it is almost certain it will get a joint venture or even a buyout. Until such time though, investors will have to wait and see if this company will be the spark that lights the fires of stem cell revolution.
If the fast moving world of Advanced Cell seems a bit much then maybe Neuralstem (CUR) might fit the bill. CUR is a biopharmaceutical company, it focuses on the development and commercialization of treatments for central nervous system diseases based on transplanting human neural stem cells and small molecule drugs. The company uses its neural stem cell technology as a tool for use in the small-molecule drug discovery, as well as to create cell therapy biotherapeutics for the treatment of central nervous system diseases, various neurodegenerative conditions, and for the regenerative repair of acute diseases. Since our article focuses on stem cells, we should focus on CUR’s cell therapy side of the house.
Different regions of the brain and spinal cord house different, specialized cells. Neuralstem's technology enables the isolation and expansion of human neural stem cells from each of these regions of the developing central nervous system (CNS) in virtually unlimited numbers from a single donated tissue.
The goal of cell therapy is to replace and/or repair dead or diseased cells. Unlike other stem cell technologies, Neuralstem is growing regionally specific cells that are already suited to the task prescribed to them once transplanted into the CNS. In spinal cord indications, for instance, the company will be using human spinal cord stem cells only. Additionally, once inside the body, Neuralstem cells also do not become any cell other than that to which they are programmed to be.
If this cell therapy is successful the goal is to be able to treat such aliments as brain cancer, spinal cord injuries, stoke, Huntington’s Disease, Ischemic Spastic Paraplegia, and Lou Gehrig’s disease (ALS). Of all these aliments, CUR has decided to attack ALS first with their stem cells. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord, leading to complete paralysis, and eventually, death. According to the ALS Association, as many as 30,000 Americans have the disease, and about 5,600 people in the U.S. are diagnosed with ALS each year.
Currently there is no cure. Neuralstem initiated the first FDA-approved stem cell trial for ALS in January 2010, at Emory University. The Phase I safety trial was to evaluate the safety of the cells and surgical technique used to apply them. The study was designed to enroll up to 18 patients. At this point the story starts to get rather exciting for the company and patients. As the major news outlets started to pick up on the story they turned their attention to one patient in particular, Ted Harada. According to the company, Ted was told in May 2010 that he probably had ALS, and then in August 2010 the doctors confirmed the diagnosis. By the time Ted entered the trials in March 2011 he had deteriorated to a point where he walked with a cane, quit his job, and was having trouble performing even the simplest tasks. However, two weeks after getting the stem cell injections into the lower spinal cord he started to show some improvement. His breathing improved and now he no longer needs the cane to walk. If accurate, this would be a major medical breakthrough.
It should be noted though that of the 12 patients in the trial, two have died. One of the patient with ALS had progressed much further than Ted and was already in a wheelchair. The interesting aspect would have been what might have happened if the injections were place into this patient’s cervical spinal cord (neck) instead of the lower spinal cord. The other patient died of a heart attack.
Investigators since have stated that the conditions of eight of the remaining 10 patients have not changed. Based on these results the team is asking the FDA to allow the trial to continue by injecting stem cells higher on the spine into the cervical spinal cord.
As exciting as this all is, once again the finances of the company are going to come into play. The company does not generate any revenue and the financing has come primarily from the sale of securities. As of June 30, 2011, the company had cash and cash equivalents on hand of $6,141,843. In the first half of 2011 the monthly cash burn rate was approximately $900,000. Needless to say, CUR will need to raise additional capital to fund their operating expenses and future expansion. With the trials so early on in their stages it is almost certain that the additional financing requirements will result in dilution to the existing stockholders.
The question becomes if CUR will become ultimately successful and find a treatment to ALS. If so then one must wonder if the other listed ailments might be treated in a similar manner. Will they be the ones to ignite the spark?
In conclusion, there are many more stem cell companies trying to address current health issues. Most share the same problems in that they just lack the funding to continue their work. That being the case they continually have to go back to the equity markets and further dilute stock holders to a point that new potential investors have little interest. On the opposite side of the equation, if any of these companies can prove their stem cell technologies can address these unmet medical needs then the sky is the limit for them and their stock price. Big Parma will waste little time in either partnering or acquiring the companies to further their hold in the market place. Until such time we as investors are all left to wonder who will be first to usher in the coming revolution.
Disclosure: I am long ACTC.OB.
Additional disclosure: Will initiate a long position in CUR once funding issues are addressed.