This biopharma has a promising Alzheimer’s drug in the pipeline. But please note that these shares are speculative, so please don’t overload your portfolio with them.
Synaptogenix, Inc. (SNPX)
From BI Research
Given my keen interest in Anavex, I have been exposed to a lot of other companies elbowing for attention in the Alzheimer’s space. Recently Synaptogenix was brought to my attention.
Let me just start with Synaptogenix’s approach to improving Alzheimer’s symptoms. The company’s drug, Bryostatin, activates something called protein kinase C (PKC) epsilon that is already in the brain from birth and helps build the synaptic wiring in the brain in one’s early years. But its ability to do so can weaken over time, especially in Alzheimer’s patients. Bryostatin reactivates PKC epsilon and that neural/synaptic network which helps rebuild connections in the brain. And with an electron microscope they can see Bryostatin does this. Furthermore, “Clinically meaningful improvement in cognition (MMSE) and ADL-severe (activities of daily living) correlates with an increase in PKC epsilon,” which therefore serves as a biomarker. At this point, Bryostatin is administered with infusion therapy on a ~biweekly basis, but the company expects to be testing an oral version in Phase 3, or perhaps both.
The company had $31 million of cash as of 6/30. It is not just a magic glob of gray matter up there. “There are trillions of synapses in the brain forming networks that enable the brain to do all that it does. Synapses are tiny connectors that permit a neuron (or nerve cell) to pass an electrical signal to another neuron. When abundant and working correctly, synapses allow neurons to communicate with each other effectively. However, fewer, or defective synapses means less connectivity in the brain, a weaker nervous system and ultimately impaired cognition. In fact, synaptic loss is the major correlate of Alzheimer’s disease and other dementias, and has been shown to occur in very early stages of such diseases” … not the presence of amyloid plaques or tau.
The correlation between amyloid and Alzheimer’s is actually rather weak. And I’ve heard this before: Autopsies of the brains of people in their 90’s, that were sharp as a tack till the end with no sign of Alzheimer’s, were nonetheless riddled with amyloid plaques and tau. The brain is the most incredible ... thing ... in the universe. It enables you to think, understand, talk, move, feel, reason, and see in incredible detail (think about that last one). You basically have a computer in there that is all wired to transmit electrical impulses.
So, does this drug really work? The company has done two pilot Phase 2 studies that were placebo controlled. And let me first say the company is not just testing on mild to moderate Alzheimer’s. The company kicks it up a notch testing on moderate to moderately severe Alzheimer’s patients … and they are seeing improvement (that increases with time) especially in moderates, not just a slowing of decline. Looking at both trials the p-value (degree of significance that the results are unlikely to be by chance) was 0.001, where the FDA just needs to see less than 0.05 (5%). And the improvement in Severe Impairment Battery score (SIB) was 4 points over baseline. A peer reviewed article on this is expected soon, which should help get the word around.
Now let me note that in the first pilot Phase 2 trial the company discovered that patients on memantine (the generic for Namenda), which many Alzheimer’s patients take to reduce confusion, saw little benefit from Bryostatin. Turns out memantine was blocking Bryostatin from working. When the patients are tested that are not taking memantine then the drug worked great and the scores on the Severe Impaired Battery test improved 6 points over the course of the study vs. a 2 point drop for those on placebo. Therefore memantine/Namenda has become an exclusion criterion for future clinical trials. And here is one of the things that really speaks to me—the positive effect of Bryostatin was persistent at least one month after ending dosing (at 11 weeks), indicating to me that indeed new “wiring” was in place that naturally continued to work even after dosing stopped.
One patient’s MMSE (cognition) score improved from 3 (severe!) to 12, but when the dosage was reduced along the way the score dropped down sharply to 6-7, then when increased back to the higher level the patient’s MMSE score went back to 12. Dose dependence is something very important to see in such tests. And the level of biomarker PKC epsilon mirrored the MMSE cognitive score. In addition, the patient’s activities of daily living score also improved.
A 100 patient 6+ month third trial, a full-fledged Phase 2, is now 80% enrolled and hopefully will be fully enrolled by year end, with readout in ~Q3 2022. And it seems likely that, given the earlier trials involved just 11 weeks of dosing, 28 weeks’ worth would provide even stronger benefits as more rewiring takes place. Even during the 1l week trial which was also examined at 15 weeks, the benefit increased over time with the number of doses. The trial is supported by a $2.7 million grant from the prestigious NIH (National Institutes of Health), which will cover about 25% of the cost. That’s an impressive ally. Bryostatin has a favorable safety profile which of course is very important. The drug has been safely administered in over 1,600 patients (1,500 of these were in failed testing on cancer patients) and the current trial has also reported no safety issues to date.
This is something many Alzheimer’s drugs cannot say. Many of them cause gastrointestinal and other problems that cause patients to stop taking them. Like Anavex 2-73, Bryostatin is potentially helpful on other central nervous system diseases such as Fragile X and Multiple Sclerosis, both of which are moving into clinical trials. In addition, Bryostatin’s PKC epsilon- Synaptic Growth Factors activation mechanism may be effective on autism, Parkinson’s disease, traumatic brain injury and even stroke, which are in the pre-clinical phase. On 8/5, Synaptogenix signed a memorandum of understanding with Nemours A.I. DuPont Hospital to initiate a trial to treat Fragile X Syndrome using Bryostatin, which has been granted orphan drug status by the FDA. The trial will be supported by the Fragile X Research Foundation. In a recent Nature publication, co-authored by the Fragile X Research Foundation and Synaptogenix scientists, “Bryostatin was shown to successfully treat both Fragile X cognitive and Autism Spectrum Disorder deficits in animal models.”
And let me just say something about the President and founding Chief Scientific Officer. He’s an internationally known pioneer in research on brain-based neural networks with 30 years in this field at the National Institutes of Health and another 15 years as Founding Director of the Blanchette Rockefeller Neuroscience Institute where he and his team developed neuro-restorative therapeutics for degenerative disorders of the central nervous systems. He has authored hundreds of scientific articles and several books. So, let’s just say, he has the goods and I think we are in very good hands.
Despite trading 300,000 shares on an average day, SNPX has only 6 million shares outstanding. This means its market cap is barely $60 million dollars, as compared to Anavex’s $1.3 billion and Cassava’s $2.5 billion. Yet, Synaptogenix is the only one that has bonafide placebo controlled studies showing improvement in Alzheimer’s disease, especially in more advanced cases. (Anavex’s 32-patient Phase 2 trial was not technically placebo controlled, but I argue that because the lower dose really didn’t work it was essentially acting like a placebo.) The case here is the same as for Anavex.
The potential market cap for a company that has a treatment that really helps Alzheimer’s patients is about $20 billion (at least 2 times revenue for a $10 billion/yr. drug). And this is supported by Biogen’s market cap appreciation when its aducanumab seemed likely to be approved (and eventually was… to great controversy since it barely works). Imagine what would happen to a company’s market cap if the drug actually significantly improved Alzheimer’s symptoms!
Even if the company has to issue another 30 million shares (which would raise almost $300 million … way more than needed) to get there, that would imply a market price of over $500 a share, in theory … ($20 billion/36 million shares). Ok, it would be acquired along the way. Use $100 a share, whatever, there is tremendous upside here for this overlooked company. And I believe it has a good shot. Now, imagine combining this drug with A2-73’s SIGMAR-1 activation approach and put that in a clinical trial.
I like having a second horse in this exciting race. Don’t bet the farm, these biotech’s can be risky and volatile as we well know, but- Buy.
Tom Bishop, BI Research, biresearch.com, October 4, 2021