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.

Mesoblast’s heart failure drug works best on very sick patients

Mesoblast [$MESO] is a company developing a handful of stem cell therapies. Right now, they have Phase 3 trials running for heart failure, low back pain, graft vs. host disease, and rheumatoid arthritis. This article will focus on MPC-150, which is the treatment MESO is testing for congestive heart failure (CHF).

MPC-150 is currently in a Phase 3 trial. The trial is testing whether injecting  150 million stem cells into the heart can improve cardiac function. Specifically, the researchers will be monitoring to see how many heart-failure related major adverse cardiac events (HF-MACE) each study group suffers.

Data from the Phase 2 studies suggests that MPC-150 will probably get a pass in Phase 3, but there are some issues with the program overall which I’ll discuss below.

Effective at Treating HF-MACE

In Phase 2 studies, researchers found that a dose of 150 million stem cells was more effective than smaller doses. On the chart below, you should be able to see that the highest dose (labeled as “150M” on the x-axis) had the greatest effect. This chart is showing the “Left ventricle end systolic volume” (LVESV) and “left ventricle end diastolic volume” (LVEDV), which are measures of how much blood is left in the heart after it pumps. Less blood remaining means that the heart is stronger and pumping more efficiently.

Smaller doses were not statistically effective.
A dose of 150 million stem cells showed the greatest improvement in cardiac function

Here you can see that the control group had an increased end volume, whereas in the 150 million stem cell dose, end volume went down. That’s good news, and in Phase 3 the researchers are testing a dose of 150 million stem cells.

However, this treatment seems to work best in patients who are very sick. This next chart shows the difference in patients who had an end volume of less than 100 milliliters (“baseline LVESV < 100 mL”) and patients who had an end volume of more than 100 milliliters (“baseline LVESV > 100 mL”). Remember, less is better.

MCP-150 works best in patients with baseline LVESV of more than 100 mL.
Sickness of patients affects how well MESO’s drug works

As you can tell, the treatment seems to be more effective in the sicker patients. This isn’t necessarily a bad thing, but it’s important to know. What I would have liked to see here are some comparisons between treatment groups, instead of just showing that the treatment was more effective against the placebo. Still, the Phase 3 trial for MPC-150 is also going to be tested on the sickest patients, so this is again good news — and about 60% of patients fall into the “sickest” group.

And finally, over a 3-year period following the same group of sickest patients, 71% of patients treated with placebo had a HF-MACE event, while none of those treated with MPC-150 did. This last piece is the strongest bit of evidence for the efficacy of MESO’s drug.

No difference in cardiac function a year after treatment, did not improve other things

However, there are a few issues. First, while the Phase 2 trial produced some improvement in cardiac function at 6 months, at the 12 month mark the MPC-150 group was no longer statistically different from the control group. This fact was ignored during $MESO’s press briefings, of course.

Second, there was no significant improvement in any of the other measures that I had expected to see improve. The biggest of these was in functional exercise capacity. The MPC-150 group was no different from the placebo group in how far they could walk during the 6-minute walk test. Given that the treatment theoretically works by improving cardiac function and helping the heart regrow a bit, I had expected to see the walk test improve. This also means that there won’t be an improvement in quality of life for the patients.


Ultimately, I can’t argue with the result that MPC-150 is keeping the sickest group of patients from having HF-MACE events. Those data were excellent and hard to refute. However, the other issues mentioned above keep me from thinking that this is a slam dunk. Given that the Phase 3 trial is testing HF-MACE on the sickest group of patients, I think that MESO will probably get a Phase 3 pass. That said, I don’t like that cardiac function declined back to the control group at 12 months, and I don’t like that no other measures of effectiveness improved.

When I invest in a biotech, I prefer it to be something like $AKAO, where there’s no doubt in my mind that the treatment works.

Prediction: Probably Phase 3 Approval

Since the Phase 3 trial is testing the most successful parts of the Phase 2 trial, MPC-150 will probably get a Phase 3 pass. Still, my lingering doubts about the ultimate effectiveness of the treatment will keep me from investing in $MESO.