Neurotrope is attempting to treat Alzheimer’s Disease with Bryostatin

Neurotrope, Inc. (OTC:$NTRP) is the latest in a long line of companies attempting to take on Alzheimer’s disease. Right now, it’s too early to invest in the company. However, there are some promising signs, so I’m going to lay out what I know so far about NTRP. Once Phase 2 data is released and NTRP stock is listed on the NASDAQ index, I’ll do another review to see if Neurotrope is worth buying.

  • The company is betting big on the future; they plan to list on the NASDAQ at the same time that they release Phase 2 data
  • The drug, Bryostatin-1, has a lot of pre-clinical safety data and animal trials behind it, but we need to see if human trials will show the same results
  • More than 120 drugs have unsuccessfully attempted to treat Alzheimer’s Disease. The odds are against NTRP and Bryostatin
  • If the company can pull this off, we will likely see ten- or twenty-fold growth

Background / Finances

At the moment, Neurotrope is listed in the “QB” section of the OTC (“over-the-counter”) markets. The QB section is for companies who are filing regular reports with the Securities and Exchange Commission. As such, the QB section is a bit more “legit” than the more commonly-known “pink sheets” – OTC stocks which follow essentially no rules whatsoever.

Regardless, the OTC markets are not a good place to be. NTRP, to their credit, recognize this – in mid-January, they engineered a 32:1 reverse stock split, scooting the share price from pennies up to the 7-dollar range. Since then, the value of the stock has doubled, and one share is sitting at around 15 bucks right now. All of this was Neurotrope setting the stage for a listing on NASDAQ. There are certain financial requirements a company must meet in order to be listed on the NASDAQ, and by increasing the price of their shares, NTRP checked one of the boxes.

It was the reverse split that originally caught my eye. NTRP is betting on the future, and betting big: they are planning to file with NASDAQ as they release the Phase 2 data for their first drug. The full set of data is supposed to be released in April.

So what are they studying, anyway?

The Drug

I mentioned in the first sentence that Neurotrope is the latest in a long line of companies trying to defeat Alzheimer’s Disease (AD). To be precise, NTRP is the latest in over 100 different attempts to create a drug that will treat Alzheimer’s disease. So far, every one of these attempts has failed. There are a handful of drugs which can help treat the symptoms of AD, but none which can stop the disease’s progression. Neurotrope hopes to change that.

Neurotrope’s drug, called Bryostatin-1, is actually a biological compound that comes from sea sponges, of all things. Bryostatin’s main mechanism of action is the activation of Protein Kinase C Epsilon (PCKe). To explain why this is important, I need to back up a bit.

Alzheimer’s Disease is characterized by two things:
1) a buildup of amyloid plaques in the brain
2) a decrease in synaptic density (i.e. the branching connections between neurons)

This is something of a “which came first, the chicken or the egg?” problem. Most drugs have attempted to treat the amyloid plaques, but research has repeatedly shown that it’s synaptic density which matters for brain function. This is a guess, but I think most researchers assumed that if they could stop the plaques, they could stop the synapse breakdown. So far, that obviously hasn’t been the case.

Back to PCKe. PCKe is an enzyme which does a whole bunch of things to promote synapse formation. This post is getting long already, so I won’t detail them, but rest assured that PCKe is helpful. Since Bryostatin-1 strongly activates PCKe, and therefore strongly promotes synaptic growth, the thought is that Bryostatin might help reverse Alzheimer’s.

There is some precedent. Animal studies were very promising; Bryostatin-1 managed to completely reverse mental retardation in adult mice. Obviously, this is a staggering result, and if it can be duplicated in humans, Bryostatin has serious potential. However, different “variants” of Bryostatin (e.g. Bryostatin-6, or whatever) have shown really promising results in animal studies, only to fall flat in human trials later.

Ultimately, this is why I am counseling you to wait until the Phase 2 data is released before buying shares in Neurotrope. Alzheimer’s Disease is staggeringly difficult to treat, and it’s entirely possible that NTRP will join the 100-odd other failures.

Last Thoughts

At the end of January 2017, Neurotrope announced that they signed an agreement with Stanford University to synthetically create Bryostatin-1. Not only was this a key step towards commercial viability (as literally tons of sea sponges were required to produced grams of Bryostatin), but the deal is another datapoint suggesting that Neurotrope has something special going on.

I intend to do another review after the Phase 2 data is released. For now, I simply suggest that you keep an eye on this one. The odds are certainly against Neurotrope, but if they’re right about having a paradigm-shifting treatment, then this could be a huge growth opportunity.

Heat Biologics’ Phase 2 drug HS-410 is safe


On November 30th, Heat Biologics ($HTBX) plans to present the top-line Phase 2 data of their new drug HS-410. I read the data, and so far it looks good! HS-410 appears to be safe and the treatment makes sense. However, HTBX still hasn’t shown that HS-410 is actually an effective treatment — a Phase 3 pass might be difficult. For now, though, HTBX is a company worth watching.

The Drug

HS-410 is a drug designed to help the immune system fight cancer naturally. Normally I am very pessimistic about immune-oriented cancer therapies, but in this case it makes sense. HS-410 treats non-muscle invasive bladder cancer (NMIBC), and the current standard of care for NMIBC relies on the immune system as well.

Basically, the treatment for non-muscle invasive bladder cancer is to scrape the cancer cells out of the bladder, then put a bacteria that’s a lot like tuberculosis into the bladder so that the immune system comes in and fights any cancer that might be left over. This bacteria — called BCG — is supposed to activate a specific type of T-Cell (immune system cell) called CD8+. HS-410 is targeted to activate the same type of T-Cell, and the researchers seem to be hoping that the two treatments will stack.

The Research

Since HS-410 is activating the same type of T-cell as BCG, the researchers designed a multi-arm study, which is smart. Basically, it works like this: If a patient is going to get BCG, they get slotted into one of three groups. Group 1 tests a low dose of HS-410. Group 2 tests a high-dose of HS-410. Group 3 tests BCG by itself as a control group. Group 4 is for patients who won’t get BCG, to test HS-410 by itself.


Study Design
Study Design


There are a few ways that HS-410 could work. If 410 amplifies the response of BCG, that would be great! If 410 works by itself, that would almost be better, as patients would prefer to get an injection (HS-410) than get a drug pushed up through the urethra into the bladder (BCG). I don’t know about you, but that doesn’t sound like much fun at all.

The Results

Everything looks good, so far. The drug is looks like it’s quite safe. The researchers are reporting that recurrence-free survival (no cancer) was about 85% after a year, but didn’t mention which arm (or arms) that was. I took a look at some of the historical research behind BCG to see how that stacks up, and it appears to be about the same. We’ll have to wait for the complete data to see the differences between arms, but right now it looks like this is going to be a Phase 2 pass. The Phase 3 trial is where they will really need to demonstrate that the drug has an effect.

Potential Market

Bladder cancer is the 5th most common cancer in the United States. There are two paths to success for this drug: boosting the efficacy of BCG or being able to replace BCG. The FDA has granted HS-410 fast track status, which is also a good thing.

We will need to see the full set of Phase 2 data in order to make a prediction about Phase 3, but for now, a Phase 2 pass seems almost guaranteed.

Prediction: Phase 2 Pass