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. 


COSI Earnings Calls Notes

Q2 2015 Earnings Call August 13, 2015:

  • turnaround strategy at Cosi is on course and part of the key to this process has been the refresh initiative.

  • we are meeting or beating our expectations.

  • we are cash flow positive at the unit level.

  • We expected to see a 10% lift in comp store sales as a result of the refreshes, and we have. Now, we expect and we need to see a 40% flowthrough on those incremental sales, and we are seeing that flow-through.

  • we needed to be able to refresh a unit for between $20,000 and $150,000 and we are right on target.

  • So, we've now refreshed six units. We have seven that are currently in process and we have another 10 to 20 that will be done by year's end. All 55 that we are scheduled to complete will be done by first quarter of 2016.

  • we have enough cash on the balance sheet to do what we have planned

  • in 2016 our franchise growth will accelerate. We will get into double digits. The second is, come September we are going to start talking about how big this could become.

Q1 2015 Earnings Call May 14, 2015:

  • No current plans to raise additional funds

  • COGS & Labor Costs: Q1 was painful, it’s behind us.  I am very happy with the corrective trend line that we are seeing in Q2

  • Where we have deployed our refreshes, where we are operating at a high level, we are seeing double-digit comp store sales.

  • We have markets that are running behind.  These markets will turn.

  • “world-class” coffee.

  • Where we have deployed two of the three components to a refresh, we are seeing double-digit comp store sales.

  • We will open 1 corporate & seven franchise restaurants this year.

  • In September, we will lay out our franchise growth strategy.

  • When asked about first unveiling a flagship refreshed store, answer was June 1.

  • Entire system (55 stores) will be done by 1Q ‘16.

  • On course for cash flow breakeven by December 2015.

  • Come June: a series of coffee initiatives.

  • I’m excited with what I see.  I’m probably more excited today than I was a year ago.

Q4 2014: March 26, 2015:

  • Focus on cleaning up the brand, bringing clarity & establishing who we are.

  • Decrease menu by 25% while retaining 99% of our transactions.

  • Price increase in test restaurants with zero pushback.

  • New menu launch to deploy in 2Q.

  • Refreshes are underway

    • Image (facelift)

    • Speed (ease guest use) through technology

    • Reintroduce brand

  • by Q4: self-service kiosks begin to deploy.

  • Deploy cost control for COGS and labor

  • Cash flow positive by year end 2015.

Q3 2014: November 13, 2014:

  • Period 10 [October]: first time Cosi has achieved positive comparable sales in over two years

  • So the 10 critical points have been deployed and we've seen tremendous traffic increases as a result of that

  • engaged David Montrose to develop 10 Cosis in Miami

  • Our catering business is lighting it up. I am very excited by the results we're seeing in our catering business in fourth quarter and we have something up our sleeve for 2015 that's going to be a game changer for what we all refer to as catering.

  • We see fourth quarter of 2015 coming in at about 10% to 12% store level cash flow.

  • As a total for the year, we have projected $2 million for the refreshes.

Q2 2014: August 14, 2014:

  • The senior team is in place.

  • While we are seeing multiple markets where we are seeing significant increases in comps, we haven't seen it everywhere.

  • we are seeing significant comp gains with the markets where we have what I will call early-adapters.

  • There are four key strategic initiatives that are in play right now.

    • The first is the continued deployment of that operating system.

    • The second is that we are right-sizing our menu.

    • The third area is physical plant root.

    • The fourth is a marketing strategy that we have had in test now for 60 days, that we are seeing significant gains where we have tested. That will continue to deploy, specifically in our suburban restaurants as the year continues.

Q1 2014: May 15, 2014:

  • We have also experienced sharp sales declines in three locations in the Philadelphia market where we tested various operational and menu initiatives.

  • you are going to watch a very talented team come together and take an aggressive position to move this forward. We are not going to sit back, take it slow, and see if we can slowly move this forward. This team is very focused on taking an aggressive position to correct the past trends.

  • merchandising focus where we have increased the number of items that we sell per location, we've increased the number of SKUs that we sell at the unit level, and we are seeing a sizable uptick in comp store sales where that initiative has been fully embraced.

  • making technology a competitive advantage. You are going to see that happen over the next 12 months.

  • We have a refresh project that will launch within 30 days. We'll have our first location up and running with this refresh in Manhattan

we'll be fine as we move through the balance of the year to be able to execute our plan, given the capital we have.



ProMIS Neurosciences Announces Third Quarter Results

Here are the few things I am focused on. I really like the fact the company has a very small burn rate and it is also in a good position to unlock the potential of its IP.

Press Release.

As at September 30, 2015, the Company had working capital of $1,019,456. These funds are expected to fund the operations of the Company into the second quarter of 2016. 


The Companys priorities for the next year are to focus on identifying and developing precision medicine solutions for AD and ALS.

Regarding AD, the Company will continue to expand its Intellectual Property (IP) estate by identifying novel epitope targets on misfolded strains of proteins beta Amyloid and Tau. The Companys proprietary technique, ProMISTM, and potentially other complementary and proprietary computational methods under development, will be employed to identify and confirm such novel targets. Subsequent to identification of these targets and submission of initial IP claims, the Company will be in a position to enter the product development phase by elaborating and developing specific therapeutics and companion diagnostics aimed at these targets for Alzheimers disease.

Regarding ALS, and given the Companyrobust IP estate, in particular its ownership of the exclusive rights to thegenus patent relating to misfolded SOD1 in ALS, ProMIS Neurosciences is actively looking to achieve a collaborative development partnership in this field.

On Thursday, November 12, Bigger Capital will be hosting an investor dinner for an exclusive group of investors.  At the dinner, investors will have the opportunity to network and to meet management of ProMis Neurosciences.  ProMis is a development stage biotech company harnessing the power of precision medicine to conquer Alzheimer’s disease and ALS.

We believe ProMis could be an acquisition target for many big pharma companies in the likely event that it’s precision technology uncovers targets critical to treating Alzheimers’ and / or ALS.  At the current Enterprise Value of $8mm, we believe the risk / reward profile of acquiring this powerful technology is quite compelling.  

 If you are interested in learning more about this opportunity, please read our detailed investment thesis and join us on Thursday.  Space is limited. For logistics, please contact Michael Bigger, using the contact button located at the top of the blog page. 

of Interest: Promis Neurosciences Investment Thesis

Michael Bigger. Follow me on Twitter and StockTwits.

Disclaimer: Bigger Capital and related entities are long 14.3MM shares of PMN. ProMIS is in a re-launch mode and it is not suitable for the majority of investors. The likely outcome of an investment 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. 


Alzheimer's, Light at the End of the Tunnel

This is a fifteen minutes webcast discussing exciting new research regarding the mechanisms driving Alzheimer's disease, pointing toward a future of early diagnosis and effective treatment. ProMIS Neurosciences Inc. is a development stage biotech company harnessing the power of precision medicine to conquer Alzheimer’s disease and ALS.

Michael Bigger. Follow me on Twitter and StockTwits.

Alzheimer's: Light at the End of the Tunnel (w/ Q&A) - ProMIS Neurosciences from ProMIS™ Neurosciences, Inc. on Vimeo.





ProMIS Neurosciences Updated Investment Thesis

 "Harnessing the power of precision medicine to treat Alzheimer's and ALS"


This post was written by Michael Bigger in collaboration with Dr. Greg Kenausis. Kenausis' contribution is highlighted by using italics. With the permision of the company, we are including non-confidential slides for your review.





Ticker: PMN.TO

Stock Price: $.08 CDN

Market Cap: $9.3MM

Enterprise Value: $8MM

Debt: None.

NOLs: $28.5MM

Share Count: 153MM

$ symbol is used for USD unless CDN is stated.



ProMISTM Neurosciences, Inc. (PMN, Toronto Stock Exchange), is a development stage biotech company that discovers and develops precision medicine solutions for early detection and effective treatment of neurodegenerative diseases, in particular Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). A precision medicine solution includes both a drug and a diagnostic to select patients most likely to respond. The market size for drugs to treat Alzheimer’s alone has been estimated at up to $20 billion per year.

The enterprise value of ProMISTM  of $8MM is very low and could in returns of up to 5 times or even greater given the company's strategic technology and intellectual property. Never in my life have I seen a situation with such enormous potential and catalysts already at work to realize the potential trade at such low valuation. 

The Science and Intellectual Property (Source: Company and Dr. Kenausis)

The Company’s scientific foundation is centered on the growing knowledge base relating to diseases characterized by the presence of abnormal, misfolded proteins. Numerous diseases exhibit protein misfolding, among them certain cancers, and several neurodegenerative diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD).

Recent published evidence indicates that for a given misfolded protein there exist multiple prion-like strains, each strain representing a specific target against which therapeutics can be developed. Accordingly, as its primary objective, the Company will focus on the discovery and development of precision therapeutics supported by companion diagnostics directed against the several strains of beta-amyloid (Aβ) in Alzheimer’s.

Historically, Alzheimer’s disease (AD) has been a frustratingly stubborn pathology for modern medicine to tackle. It is already a huge market and demographic trends indicate strong growth ahead for that market. To date, no genuinely effective therapies have been developed. The difficulties start with merely diagnosing that a patient has the disease. Until not too long ago, it was necessary to conduct a post mortem histological examination of brain tissue to confirm for certain whether a patient had AD. Of late, some progress has been made on this front, but physicians still need to conduct an array of evaluations, many of which are inevitably prone to reporting, analysis and interpretation error (e.g. family history, cognitive testing, etc.). Some advances have also been made recently involving the use of MRI and PET for AD diagnosis, but these techniques remain developmental and early-stage. The point is that diagnosing the presence and type of AD remains indirect and tricky.

In AD patients, certain proteins found in brain cells (i.e. beta amyloid and tau proteins) form unusual aggregates, and they have long been known as symptoms and potentially agents of AD. The presence of these malfunctioning proteins is an indicator of AD and would therefore be a useful target for a diagnostic application as well as for therapeutic applications. 

Why is a diagnostic of AD so important for developing successful therapies? 

For one thing, without effective diagnostics of AD, it obviously becomes very difficult to prove any novel treatment approach because ill-defined clinical study patient populations will invariably obfuscate any effect that a therapy may or may not have. Furthermore, AD may turn out to consist of an array of different types of the disease, like cancer, with each type responding optimally to different therapies. In any case, the development of a successful diagnostic would likely greatly facilitate the development an optimal target for potential therapies. 

The pharma industry has been attempting to target these errant proteins in hopes of stopping the disease progression or even reversing it. Big pharmaceutical companies like Roche, Pfizer, Eli Lilly and Johnson and Johnson did their best to come up with treatments based on an immunotherapy approach. That is, they developed antibodies or antibody-like molecules that, once administered, would help to destroy and clear these errant proteins. Until late last year, all clinical trials failed. However, at the end of last year, Biogen finally showed that such a therapeutic approach can produce a sizable benefit to AD patients. 

A gold rush is now underway to develop the most effective antibodies that would target these errant proteins, particularly beta amyloid. This is where ProMISTM Neurosciences with its proprietary ProMISTM technology has a big opportunity. ProMISTM is a statistical thermodynamic algorithm that predicts how proteins degenerate into their diseased (misfolded) forms and thereby provides a model of all the potential target regions of the protein (i.e. epitopes) against which an antibody can be designed and produced. This approach would allow to develop a specific therapeutic antibody and its related companion diagnostic, i.e. a precision medicine solution. 

The ProMISTM technology works and has been validated previously on many cancer types and neurodegenerative diseases such as Creutzfeldt-Jakob disease. Of course, ProMISTM is not the only method of identifying epitopes, and the race to find such AD epitopes is very competitive and includes many pharma companies with formidable resources at their disposal. ProMISTM does however appear to have the advantage of being a theoretical and rational approach to epitope identification while almost all other approaches are more trial-and-error/hit-or-miss. 

Based primarily on the research discoveries in Dr. Cashman’s lab, the Company has exclusive access to critical IP and proprietary know-how in the field. The Company’s patent estate consists of eight patent families issued or pending. ProMISTM utilizes its computational discovery platform, ProMIS, to predict novel targets known as Disease Specific Epitopes (DSEs) on the molecular surface of misfolded proteins. ProMISTM owns the exclusive rights to the Genus patent relating to misfolded SOD1 in ALS, and currently has a preclinical monoclonal antibody therapeutic directed against this target. 

In addition, Dr. Cashman’s lab just received a $1MM CDN grant for new discoveries which could augment the value of ProMISTM intellectual property portfolio without diluting shareholders.

History, Re-Launch, New Strategic Direction (Source: management) 

ProMISTM was an unfocused company under the tutelage of the last CEO. While building a very valuable portfolio of intellectual property since becoming public in 2008, the company ran out of cash in 2015. 

In July 2015, a new management team came on board, the company successfully raised US $2.0MM, and the Board was reconstituted. 

The four-member senior management team includes Dr. Neil Cashman, the Company’s current Chief Scientific Officer and Steven Plotkin, the company's current Chief Physics Officer. In addition, two pharmaceutical industry veterans and biotech entrepreneurs, with over 60 years’ cumulative experience in key aspects of drug development and commercialization have joined the team: Eugene Williams as Executive Chairman and Dr. Elliot Goldstein as Chief Executive Officer. 

I had several discussions with the management team and I am very impressed by their candor and their vision for ProMISTM. I furthermore take confidence in the commitment of the Board to represent what is best for shareholders based on the relationship formed through previous experience in similar situations with Director Johannes Minho Roth.   




 The Investment Case 

The near term investment case for ProMISTM really relies on the company successfully securing the rights to AD epitopes that it discovers. With such IP, the company or just its epitope related IP would likely be a very desirable and strategically important acquisition target of many big pharma companies. Ideally, a bidding war would erupt driving the valuation to levels orders of magnitude greater than where it stands today. The time frame for this to develop would likely be in the range of one to three years if all goes well. 





ProMISTM is an early stage biotech company. The risk that the company doesn't deliver on its opportunity is highly elevated. The stock could very well trade to zero. 

The company will require a significant amount of capital to cross the finish line. The ProMIS team must achieve significant accomplishments along the way and management must communicate its vision in a narrative that keeps investors excited about the opportunity for further investment. 




Of Interest: Promis NeuroSciences One-Pager.

Michael Bigger. Follow me on Twitter and StockTwits.

Disclaimer: Bigger Capital and related entities are long 14.3MM shares of PMN. ProMIS is in a re-launch mode and it is not suitable for the majority of investors. The likely outcome of an investment 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.