Harnessing the power of precision medicine to treat Alzheimer s and ALS February, 2016

Transcription

1 Harnessing the power of precision medicine to treat Alzheimer s and ALS February, 2016

2 2 Forward looking statement: safe harbor This slide deck may contain certain forward-looking information. Such information involves known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements to be materially different from those implied by statements herein, and therefore these statements should not be read as guarantees of future performance or results. All forward-looking statements are based on the Company s current beliefs as well as assumptions made by and information currently available to it as well as other factors. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this slide deck. Due to risks and uncertainties, including the risks and uncertainties identified by the Company in its public securities filings, actual events may differ materially from current expectations. The Company disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise

3 3 Agenda Overview ProMIS Opportunity: Targeting prion driven diseases like Alzheimer s and ALS with precision therapeutics ProMIS top priority: build a portfolio of breakthrough precision therapies against beta Amyloid prions that sets a new standard for disease modifying therapy in Alzheimer s and Down s syndrome Financing plans: 2-3 rounds to an M&A exit in 3-5 years

4 4 Executive Summary: ProMIS Neurosciences ProMIS Neurosciences is focused on the overlap of two high opportunity areas: Neurodegenerative Disease (Alzheimer s and ALS) and Precision Medicine Publically traded on the TSX (PMN) Developing a portfolio of proprietary Precision Therapeutics, based on the science of Dr Neil Cashman, an established leader in Mis-Folded Proteins Completed a financing and announced a new leadership team in June

5 ProMIS management team brings substantial experience 5 EXECUTIVE MANAGEMENT SCIENCE LEADERSHIP Eugene Williams: Executive Chairman - SVP Genzyme - Founder Adheris - CEO, DART Elliot Goldstein, MD: CEO - COO, Maxygen - COO, DART - CEO, British Biotech Neil Cashman, MD : CSO - Professor of Medicine at the University of British Columbia, Neuroscientist at the Brain Research Center, and Academic Director of the Vancouver Coastal Hospital ALS center Steven Plotkin, PhD: Chief Physics Officer -Biophysicist & UBC Associate Professor, recognized internationally for his fundamental contributions to the energy landscape theory of protein folding

6 ProMIS cap table summary: significant management commitment 6 Shares Millions Common shares outstanding Fully diluted Management+Board (% of fully diluted) 38.0 (20.3%) includes 22.5 MM options

7 Two outstanding advisory boards 7 Scientific Advisory Board experts in neurodegenerative disease & toxic prions Business Advisory Board Renowned specialists in biotech business, diagnostics & monoclonal antibodies Director of the Center for Translational Research in Neurodegenerative Disease at the U. of Florida. SAB co-chair. Neil Cashman, MD, Professor of Medicine at U of British Columbia & Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases. SAB Co-chair. Associate Professor of Neurology and Research Professor at Emory University Yerkes National Primate Research Center. Mara Aspinall, MBA, Exec. Chairman of GenePeeks. Past CEO Ventana,the global leader in tissue based cancer diagnostics. Nigel Burns, PhD, > 20 years biotech experience, esp. in the field of monoclonal antibody design and manufacture. CEO & Founder of Sweet Spot Therapeutics. Michael Higgins, MBA, entrepreneur-in-residence at Polaris Partners & Director of Voyager Therapeutics. Previously, COO and CFO at Ironwood.

8 ProMIS plans to build a valuable precision therapeutics portfolio over a 3-5 year timeframe, leading to M&A exit 8 Program: Validate and patent up to 6 precision therapies in Alzheimer s Partner ALS programs Alzheimer s preclinical product development First IND filings: Goal Clinical Trials in Alzheimer s and Down s Syndrome* $2.5MM raise at $2MM Pre $2.0MM raise $10-20MM raise to initiate full product dev t Follow on raise to initiate clinical trials (if necessary) Possible M&A Exit Possible M&A Exit Financial * Down s syndrome patients have early onset Alzheimer s driven by beta Amyloid

9 9 Agenda Overview ProMIS Opportunity: Targeting prion driven diseases like Alzheimer s and ALS with precision therapeutics ProMIS top priority: build a portfolio of breakthrough precision therapies against beta Amyloid prions that sets a new standard for disease modifying therapy in Alzheimer s and Down s syndrome Financing plans: 2-3 rounds to an M&A exit in 3-5 years

10 ANA meeting, Sept prions drive disease 10 ProMIS CSO Neil Cashman speaker at President s Symposium at the leading Neurology Science meeting - Evolving Concepts in Prion Biology: How Many Neurodegenerative Diseases are Caused by Prions? Strong consensus now that different strains of prions drive neurodegenerative diseases, including Alzheimer s and ALS - Consensus has emerged over last ~1-2 years Dr. Cashman recognized as leader in the field Explains past Alzheimer s drug trial failures

11 Defining key terms 11 Prion Epitope Precision Medicine -A propagating, (spreading) toxic variant of a protein whose normally folded form is inert or benign. -In AD, neurotoxic misfolded strains (prions) of beta Amyloid propagate by acting as a template for neighboring normal beta Amyloid strands (monomers) causing them to take on the toxic misfolded shape. -Target site on a protein that can be recognized by the immune system. -Therapeutic antibodies (monoclonal antibodies) can be created to bind specifically to an epitope target. -Binding of a therapeutic MAB to its target epitope can neutralize, or otherwise render the corresponding protein inactive. -The science of identifying patients likely to respond to a specific therapy using a precise biologic marker, or companion diagnostic. - Matching the right drug to the right patient

12 12 ProMIS: core science foundation Prions Drive Neurodegenerative Diseases Prions: misfolded, neurotoxic propagating variants of otherwise healthy proteins Prion variants are a small percentage of the total protein population To be effective, immunotherapy must selectively target prions Failure to selectively target prions can lead to: - target distraction which reduces efficacy - breaking up inert plaque, causing AEs There are multiple strains of prions precision therapy will likely be required

13 ProMIS Neurosciences has proprietary technology to target prions and create breakthrough therapy in prion driven diseases like Alzheimer s 13 - Prions present different epitopes than healthy or normal protein - These are unique and patentable targets for monoclonal antibody therapy - ProMIS Neurosciences has two big data, modeling technologies that can predict epitopes unique to prions - ProMIS TM a U.S. process patent issued in Collective Coordinates - a patent was filed in ProMIS has identified six epitopes that may selectively target the prion form of beta Amyloid patent filings started in Nov will be completed by Q ProMIS is conducting validation studies with cadaveric brain tissue from Alzheimer s patients to demonstrate prion selectivity of our targets

14 ProMIS Product Development process is built on proprietary discovery technology that identifies Disease Specific Epitopes 14 Mab Therapy Promis, CC Big data modeling In Vitro Validation Validated Epitope target Validated Epitope target Companion Diagnostic Mab Therapy Validated Epitope target Mab Therapy Companion Diagnostic Companion Diagnostic

15 15 ProMIS Disease Area Strategies Seeking investors Alzheimer s - beta Amyloid - Tau Seeking Partners ALS - SOD1 - TDP43 - Largest remaining area of unmet need in industry - Numerous past clinical trials with disappointing results until Biogen s Aducanumab - ProMIS strategy address the causes of previous program failures - Treated too late - Included wrong patients - Targeted wrong epitopes - ProMIS has extensive patent portfolio, significant in vitro and in vivo data - Goal: avoid the types of issues which led to failures of earlier immunotherapies in other prion driven diseases - Selectively target SOD1 prions - Develop clear biomarkers to ensure inclusion of correct patients in trials

16 16 Agenda Overview ProMIS Opportunity: Targeting prion driven diseases like Alzheimer s and ALS with precision therapeutics ProMIS top priority: build a portfolio of breakthrough precision therapies against beta Amyloid prions that sets a new standard for disease modifying therapy in Alzheimer s and Down s Syndrome Financing plans: 2-3 rounds to an M&A exit in 3-5 years

17 17 Alzheimer s is the largest remaining unmet need in medicine. we are at an opportune time 6 MM US and Canada Starts developing 15 years before diagnosis - 10 s of millions developing disease today Rapidly growing disease, already ~$500BB direct and indirect cost Will bankrupt Medicare if treatments are not found Biogen trial results in Dec with Aducanumab led to $20BB market value increase Axovant IPO at $1.3BB with product that is not a fundamental disease modifying drug

18 Alzheimer s science: prions are the bad actor Critical to selectively target prions, vs. monomer or plaques. 18 Amyloid Precursor Protein 1) Secretes beta Amyloid Monomer.. Misfolds into toxic prions in the presence of other prions 3) Propagates Growing number of toxic beta Amyloid prions 4) Catalyzes Neuronal Death and cognitive decline beta Amyloid Monomer 2) Aggregates Inert Form - plaques Neurotoxic form (Prions) Toxic TAU Prions catalyzed by beta Amyloid Prions - Prions spread by infecting /recruiting monomer - Monomer can aggregate into inert plaque - Prions are outnumbered by monomer and plaque - Therapies that bind to monomer and plaque will see reduced efficacy and side effects

19 19 Alzheimer s has seen numerous expensive failures with a recent partial success Bapineuzamab: - Failed product Solanezumab: - Failed initially, looking for value in subpopulations Aducanumab - $20BB successful trial, but with limiting side effects - Pfizer/J&J - Failed to meet primary endpoint -Significant side effects (ARIA-E) Amyloid Related Imaging Abnormality with Edema - Lilly - Failed to meet primary endpoint in study of moderate and mild AD patients - Good efficacy signal in subset of mild patients - Trials ongoing in earlier patients - Biogen - Studied early disease (MCI mild cognitive impairment) - Strong efficacy signal in highest dose arm - Biogen chose to go to pivotal/approval trial - But high level of side effects (ARIA-E) in highest, efficacious dose group

20 Targeting the right epitopes is critical; the comparative binding helps explain product clinical results Antibody Name Sequence Bind Monomer Bind Oligomer {prion} Bind Fibril ARIA-E Aducanumab EFRH No? Yes High 20 Bapineuzamab DAEFRHD Yes? Yes High Solanezumab KLVFFAEDVGS Yes Yes? Low Andrew S. Fein HC Wainwright Ideal product profile: selective binding of oligomer, no binding to monomer or fibril Increasing non-clinical data supports the hypothesis that {disease} toxicity is associated with oligomeric {prion} Abeta vs. higher order structures such as fibrils and plaques - Andrew Fein, HC Wainwright Andrew S. Fein, H.C. Wainwright & C0. report, August 11, 2015

21 ProMIS goal: set a new standard for beta Amyloid immunotherapy through precision targeting 21 HI ProMIS Precision Portfolio Clinical Success/ Benefit Aducanumab Solanezumab Bapineuzamab Lo Lo Hi Epitopes chosen to preferentially target prions/oligomers

22 ProMIS s next generation, prion targeted, precision therapies designed to address the causes of failure of earlier therapies 22 Selectively target prions, avoid target distraction, ARIA-E Higher chances of strong efficacy signal, lower chances of dose limiting side effects Diagnostics to ensure right enrollment, right patient selection Enables smaller, more focused trials with time and cost savings, higher odds of success due to excluding patients whose disease is not driven by the prion our precision therapy is targeting Early treatment key to success ProMIS companion diagnostics could eventually enable treating before symptoms arise, preventing or significantly delaying symptoms

23 By mid 2016 ProMIS will complete the validation of up to 6 differentiated, precision therapeutics against beta Amyloid 23 Mab Therapy Promis, CC Big data modelling In Vitro Validation Validated Epitope target Validated Epitope target Companion Diagnostic Mab Therapy Validated Epitope target Mab Therapy Companion Diagnostic - Six novel epitope targets identified, patent filings ongoing - In vitro validation with brain tissue of AD patients target completion in Q2 - Goal: show biologic proof of concept - prion selectivity - Positive findings would substantiate our likely differentiation Companion Diagnostic - Up to six unique, selective and potential breakthrough products with companion diagnostics - Goal: first clinical trials in 2018/19

24 24 Agenda Overview ProMIS Opportunity: Targeting prion driven diseases like Alzheimer s and ALS with precision therapeutics ProMIS top priority: build a portfolio of breakthrough precision therapies against beta Amyloid prions that sets a new standard for disease modifying therapy in Alzheimer s and Down s syndrome Financing plans: 2-3 rounds to an M&A exit in 3-5 years

25 ProMIS plans to build a valuable precision therapeutics portfolio over a 3-5 year timeframe, leading to M&A exit 25 Program: Validate and patent up to 6 precision therapies in Alzheimer s Partner ALS programs Alzheimer s preclinical product development First IND filings: Goal Clinical Trials in Alzheimer s and Down s Syndrome* $2.5MM raise at $2MM Pre $2.0MM raise $10-20MM raise to initiate full prod devel Follow on raise to initiate clinical trials (if necessary) Possible M&A Exit Possible M&A Exit Financial * Down s syndrome patients have early onset Alzheimer s driven by beta Amyloid

26 26 Alzheimer s disease in Down s Syndrome patients may be an opportunity for rapid clinical proof of concept 400,000 Down s Syndrome patients in the US, life expectancy increasing with better care By age 65, 75% of Down s Syndrome patients have Alzheimer s disease - Source: WSJ, Jan 21, 2016 Down s Syndrome includes a genetic error (trisomy 21) which leads to dramatically more Amyloid Precursor Protein.which secretes more beta Amyloid monomer which means more recruits for propagating beta Amyloid prions. Beta Amyloid driven Alzheimer s may start as early as the teen years

27 Near term funding: $1MM - $2MM PIPE can extend cash life by 6-12 months, enabling completion of key value drivers 27 Projected timeframe for ~ 6 AB epitope IP filings, and cadaveric validation $200k Protential timeframe for ALS partnering range 5 months..to 9 months Monthly Cash Burn $100k Current Cash Life $1MM PIPE raise with accelerated beta Amyloid program $2MM PIPE raise with accelerated beta Amyloid program Q Q Q Q4 2016

28 28 Near term potential catalysts Additional identification & IP filings of beta Amyloid targets Scientific and Business Advisory Boards Results of in vitro validation studies in cadaveric brain tissue from AD patients Potential partnering deal in ALS Potential grant funding

29 ProMIS: investment thesis 29 Consensus that propagating, mis-folded proteins drive diseases like Alzheimer s and ALS Recent identification of multiple strains of mis-folded proteins, i.e., multiple new targets for breakthrough therapy ProMIS proprietary technologies are uniquely suited to address these new targets ProMIS is building a portfolio of precision therapeutics (a drug and a companion diagnostic to identify appropriate patients) that could be fundamentally game changing, offering disease modifying therapies for Alzheimer s and ALS The investment markets recognize value in Alzheimer s

30 30 Contact: Eugene Williams, Executive Chairman +1 (617) Elliot Goldstein, MD, CEO +1 (415) Website: Twitter: Linked In: