Momentous Alzheimer’s Disease Readouts

Neurotrope (NTRP) will release its Bryostatin Phase 2b top line data this week (company’s guidance). The primary efficacy endpoint is based on Severe Impairment Battery Scale (SIB). Entry criteria was based on the MMSE score. Secondary efficacy endpoints were based on – Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI), and Mini-Mental State Exam (MMSE).

Considering 70% of all phase two drug trials fail, and even more so with Alzheimer’s Disease (AD) indications, this will be a cage fighting, raw, win or lose, zero or hero event.

We are long NTRP and we wrote about our thesis right here. We are comfortable with our position given our utility curve, our assessment of the situation, its risk and reward potential.

We have the utmost respect for investors going into the event with a short or long position based on their assessment. This is not easy; it shows conviction with a position under imperfect information.

Given the history of AD trials results, it is understandable that many label this situation as a failure from the get go. To be clear, we are handicapping the probability of success and its associated payoff much differently.

ProMIS Neurosciences (PMN.TO) is conducting a cohort study to demonstrate the prevalence of 5 strains (5 epitopes) of soluble toxic oligomers in the cerebrospinal fluid (CSF) of 100 cadavers at the University of British Columbia of patients who had been diagnosed with AD. The results of this study could confirm and present a profile of heterogeneity in AD patients. Based on these results, ProMIS monoclonal antibodies (5 mabs) could be used to create CSF diagnostics for early detection in patients at high risk of the disease.

These mabs could also be used by researchers to advance AD’s science turning PMN’s IPs and therapeutics portfolio into a platform.

The cohort study results should readout before the end of May (our expectation).

In addition, PMN is running blood based screening assays to detect these toxic oligomer strains at the molecular level (5 epitopes). If PMN can overcome the challenges posed by the hypothesis that toxic oligomers have a very short half-life in blood, the company could be in a position to provide a data readout this summer or fall.

We are long ProMIS Neurosciences and we wrote extensively about it here.

Let's Go!

Michael Bigger. Follow me on Twitter and StockTwits.

Disclaimer: We are long the securities and some of their associated derivatives. The likely outcome of an investment in early stage biotech companies is a loss of principal. Take our opinions with a grain of salt. If you find yourself relying on our views to make an investment decision it means you definitely did not do your homework about these situations. Please do not rely on our views, instead use the information as a jumping off point to begin your own independent due diligence.


Neurotrope Tidbits


An Alzheimer's Watershed Event on our Doorstep?

Nature Journal recently published this article pointing to the existence of different clinical subtypes or strains of Alzheimer's.
The article topic shines a bright light on ProMis Neurosciences (PMN.TO), a small Canadian biotech company, that has postulated the existence 5 different strains of Alzheimer's and has used its algorithms and computers to identified 5-epitopes characteristic of prion strains of A-beta. ProMis has developed 5-monoclonal antibodies (mabs) that bind to these prions epitopes-stopping their propagations and toxicity in animal models.
ProMis has a potentially transformative event over the next 2 months. It is in the midst of a +100 Cerebral Spinal Fluid (CSF) Cohort investigation from Cadavers of confirmed Alzheimer's victims. It will provide insight into the prevalence of different A-beta strains and their association with more or less progressive subtypes of the disease. The results of this study are expected in Q1 of this year.
These results could change the way we think about Alzheimer's as being one disease with a one size therapeutic fitting all to Alzheimer's being a disease with a few subtypes, each requiring a specific therapeutic for treatment, effectively turning the Alzheimer's world upside down.
Alzheimer's research could be a large beneficiary. The research community could use these ProMis mabs to pursue different avenues of research along these subtypes for the ultimate defeat of Alzheimer's disease. That is a big deal.
Stay tuned!
Michael Bigger and Eden Rahim. You can follow Michael on Twitter and StockTwits.

 We are long Promis Neurosciences.

Our Second Alzheimer's Investment: Neurotrope

On Friday, Neurotrope, Inc. (NTRP), a company focused on developing drugs to treat neurodegenerative diseases including Alzheimer's disease, announced that it entered into a definitive securities purchase agreement with accredited investors to raise approximately $20.2 million in a private placement of common stock and warrants exercisable for common stock. We acquired 1.5 million NTRP securities in this transaction. Press Release
To understand our investment rational, I will defer to an email conversation I had with an investor and a portfolio manager that knows NTRP inside out.
Thoughts on Neurotrope (NTRP)?  I know you follow the Alz space closely.
 Portfolio Manager:

I know NTRP very well. I met management in Boston a couple weeks ago.  I have accumulated 400,000 shares quietly this year, on way to a million shares.  I have poured through all Dr. Alkon’s papers, and everything else published. I will send you a bunch of stuff if you want. You know my rule that when it comes to CNS (Central Nervous System) indications I invest earlier stage than I generally do for other indications. Bryostatin, a Protein Kinase C epsilon activator was originally sourced from a marine organism, but is now synthesized in a 27 step process. It has been shown to stimulate neurotrophic growth factors such as BDNF/NGF/OGF/, and thus synaptic growth and function. Dare we even think disease modifying? Oh, it also activates amyloid degrading enzymes (ECE, Neprilysin, IDE).

 In summer 2015 in dumpster diving through everything written Alzheimer’s related, including all the trials on Alzheimers I came across Bryostatin P1. Much is already known about Bryostatin’s safety from failed Cancer trials, so safety is not an issue such as with mAbs like Aducanumab causing Edema. When the P1 of 9 severe patients (3 placebo (Aricept / NMDA), 6 treatment – 3 each on 2 different doses) was completed, some patients in the treatment arm requested that the FDA grant them compassionate use permission given the significant improvement they seen in only a month on the drug. Remember it was a safety trial.  The company provided the FDA with videos, which Dr. Alkon will send me, indicating the remarkable improvement in functionality.  NTRP has tons of non-controlled data they have never published but is with the FDA and behind their granting of the compassionate use.

They are recruiting in a 150 patient proof of concept trial, initially for 2 doses, but the FDA recently gave them permission to use a single dose since they have already seen leads to material changes, and speeds up the trial. Topline readout should occur Q1 next year (2017).

I was part of the group led by a hedge fund that voted to replace the former CEO and some board members with Dr. Suzanne Wilke and others.

This company has reputable scientists from the Rockerfeller Blanchette foundation with vast experience in Alzheimers and CNS indications.  Dr. Alkon was on Charlie Rose as an expert way back in 1993!!!

I will send you some stuff later today. But at a US $20 million enterprise value (post transaction), this stock should be worth 10X right now, and 50X current if the phase 2 data corroborates the research.  The FDA is DESPERATE to shuttle through any therapeutic that is showing disease modifying activity in AD.  If Anavex (AVXL) can have multi-hundred million mkt cap so can NTRP. NTRP has the ear and eyes of the FDA, and back by reputable science and scientist.

Neurotrope Patents Portfolio

If Bryostatin shows any benefit for patients, we believe its valuation will approach Axovant's (AXON) valuation minus the Vivek Ramaswamy factor.

At Bigger Capital we have a significant position in Promis Neurosciences (PMN.TO) which has developed 5 monoclonal antibodies (MABs) targeting 5 different strains of Alzheimer's disease associated with toxic misfolded Amyloid Beta proteins (Toxic Oligomers). Neurotrope addresses the synapses side of the equation.

Our AD investments are focused on small biotech companies that have more promising mechanism of actions (MOAs) than big pharma, and that are trading at a discount to their intellectual property cost. Intellectual properties that are novel and not anchored on 10 to 20 years old science hypothesis that have not created meaningful benefits for AD patients.

We are looking to make additional investments in the space and the first twelve minutes of this video will help you understand why we want to allocate more capital to the mechanism of actions located at or near this real estate. Let us know if you find anything. 

Michael Bigger. Follow me on Twitter and StockTwits.

Disclaimer: Bigger Capital and related entities are long more than 17million shares of PMN and 1.5 million NTRP securities. The likely outcome of an investment in early stage biotech companies is a loss of principal. Take our opinions with a grain of salt. If you find yourself relying on our views to make an investment decision it means you definitely did not do your homework about this situation. Please do not rely on our views, instead use the information as a jumping off point to begin your own independent due diligence.


Help Me Identify Alzheimer's Microcap Winners

A year ago, I made an investment in a tiny Canadian development stage biotech company: Promis Neurosciences (TSX:PMN). Promis focuses on novel, disease modifying therapies for the treatment of neurodegenerative diseases, particularly Alzheimer's and ALS.

What's fascinating about Promis is the Alzheimer's Mechanism of Action (MOA) they have identified with their computational platform. Here is a 15 minutes video explaining it in very simple terms.


I'm ready to double down and invest more money in small firms that have intellectual properties related to this MOA. If you know such firm, let me know. Cheers!

Michael Bigger. Follow me on Twitter and StockTwits.


The Village Idiot: Cosi

The village idiot in strict terms is a person locally known for ignorance or stupidity(Wikipedia). Cosi, throughout its twenty years existence, has excelled in both categories. If stupidity were an Olympic discipline, Cosi would win gold.

The village idiot usually develops a fan base composed of people who likes to root for the underdog. I have been rooting for Cosi since it appeared in Manhattan in the late 90s.

I've always paid attention to the company and its stock price. As a deep value investor, I'm attracted to the potential of highly distressed situations. I've passed on the investment many times in the past seeing no potential in the village idiot.

That changed two years ago when RJ Dourney, a successful Cosi franchisee operating Hearthstone out of Boston, became its CEO.

I was super excited by this development and I decided to invest.

RJ sounded really, really good until he announced publicly that New York location upgrades would be completed by the second week of July 2015. I decided to organize a visit of the New York locations with eight Cosi investors. It was a disaster. The locations looked like shit, the customer experience was shit. It was embarrassing and maddening as none of the narrative had materialized. Our spirit was deflated.

That's when I became obsessively focused on analyzing the delta between management's narrative and the customers experience at the store level. Holy crap, those two things were on two different planets: management stories were fictional and could not be substantiated by customer experience. Was that a wrong move to have trusted the narrative of RJ?

I decided to sell my position on the pop to $.90 a few months ago. I unloaded only half of my position as the stock started to drop hard to $.17.

About a week ago I went to Boston and decided to bring my family to COSI located at MIT. For the first time ever I felt like a proud owner of the COSI business. The customer experience and the food were awesome. My youngest son agreed. He has been negative on COSI since day 1. The Pork Belly Ban-Mhi sandwich turned him off completely. What a stupid dish! The Mac n Cheese with the Buffalo Blue topping on the other hand ... 

We've been fooled many times by the village idiot so we decided to visit another location. Our visit to Cosi Plainview was also fantastic. What a change from previous visits during which I almost popped a few cerebral veins many times.

Maybe our whining, screaming, and bitching, are starting to bear fruits. We don't know yet. But at its current valuation and based on these limited number of visits I decided to increase our Cosi position to 1.5 million shares and keep the pressure on the company to unlock its potential.

Don't go out and buy the stock. A village idiot is still a village idiot until proven otherwise. Cosi is in a tight financial spot and it will most likely fail unless it raises more money. The Cosi Board must be restructured and management must be augmented by managers who are obsessive about the customer experience and innovative marketing, not cheer-leading.

Michael Bigger. Follow me on Twitter and StockTwits. 


Promis Neurosciences Posters AAIC 2016


Multi-Billion Dollar Microcap Opportunity Hiding in a Dark Alley


Upcoming ProMIS Neurosciences Investor Call

If interested, please visit the "Investor Calls" page and submit the required form in order to register and Scott will keep you informed of the call-in details and any other logistics as we move closer to the call. 

A quick note on how Scott likes to treat investor calls. Scott treats the hour or so that we are able to speak with a CEO or management as pretty sacred time; these folks are trying to run a business and, speaking from experience, taking an hour or more out of the day can become a burdensome thing to do. He never records the calls and the recaps of the calls will always be high level and never granular, no matter how much "in the weeds" we get on the call. He does this to encourage openness on the call, and to build trust between himself and the management team. 

You can read Scott's original ProMIS investment thesis here

Of interestPromis Neurosciences Investment Thesis.

Michael Bigger. Follow me on Twitter and StockTwits. 


White Paper Highlights the Importance of an Alzheimer's Patent Filing 

The Promis Neurosciences team just published this white paper about ALS and Alzheimer's. We believe it highlights the importance of the novel target (epitope) patent filed by the company on November 9th. 

How many precision therapeutics are needed to treat a significant portion of patients with ALS and Alzheimer’s disease? 

ALS and misfolded SOD1

ProMIS has identified and patented (genus patent in USA), or has patents pending around the world, the epitope sites on misfolded SOD1 for ALS. SOD1 is 153 amino acids in length; the total number of epitopes, discovered using our proprietary methodology, on the misfolded forms of SOD1 is 8, of which two are not "active".

Therefore, we anticipate at most 6 precision therapeutic antibodies would be needed to cover ALS patients whose disease is related to misfolded SOD1.

We are actively seeking pharma collaboration to exploit this opportunity in ALS.

Alzheimer's and misfolded beta Amyloid 

Beta Amyloid, containing 43 amino acids, is a third the length of SOD1 and it too can only misfold in a limited number of ways. Using both ProMISTM and Collective Coordinates, the science team at ProMIS Neurosciences is zeroing in on identifying the maximum number of epitopes on misfolded beta Amyloid. Using these proprietary techniques our science team anticipates a total of about 8 different epitopes on misfolded strains of beta Amyloid, the first of which was submitted for patent protection on Nov.9, 2015 (and announced on Nov. 12, 2015). Having located the exact site of this first epitope, our science team is now identifying the exact location of each of the remaining seven epitopes, which upon confirmation shall also be submitted for patent protection.

Accordingly, it is anticipated that no more than 8 different therapeutic antibodies will be needed to treat the majority of Alzheimer's patients whose disease is related to misfolded beta Amyloid. In fact, we are reasonably confident the number of different precision therapeutics needed may be less than this as interestingly, the first epitope submitted for patent on Nov. 9th is common to at least two different misfolded strains of beta Amyloid.

Of interest: Promis Neurosciences Investment Thesis.

Michael Bigger. Follow me on Twitter and StockTwits.