ProMIS Neurosciences: therapies for neurodegenerative disease based on a proprietary discovery platform

Transcription

1 ProMIS Neurosciences: therapies for neurodegenerative disease based on a proprietary discovery platform Toronto Stock Exchange (TSX) ticker: PMN.TO OTCQB ticker: ARFXF October

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 available online at 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. 2

3 ProMIS Neurosciences Overview Growing portfolio of antibody therapies targeting toxic oligomers, the root cause of neurodegenerative diseases like Alzheimer s, Parkinson s, ALS Unique discovery platform enabling creation of highly selective antibodies for human toxic oligomers - traditional antibody creation strategies ineffective Highly experienced management team TSX listed PMN.TO OTCQB listed - ARFXF 3

4 ProMIS is developing a portfolio of antibodies targeting toxic oligomers that drive neurodegenerative diseases H H H H H H ProMIS Technology Platform: Rational Design of highly selective mabs against human toxic oligomers Neurodegen (AD, other dementias, Parkinson s, ALS) Other Amyloid beta Alzheimer s Tau Alzheimer s TDP43: ALS & Frontotemporal Dementia SOD1: ALS Alpha -synuclein Parkinson s & Lewy Body Dementia PMN310 IND enabling development Tau Lead Selection TDP43 Lead Selection Alpha synuclein Lead Selection PMN310 Phase 1, ascending dose study in AD patients; biomarker data Tau Humanization and Preclinical Development to IND TDP43 Humanization and Preclinical Development to IND SOD1 Humanization and Preclinical Development to IND The 1-2 punch in AD disease modifying Tau Phase 1, ascending dose study in AD patients; biomarker data TDP43 Phase 1, ascending dose study in ALS patients; biomarker data SOD1 Phase 1, ascending dose study in ALS patients; biomarker data The 1-2 punch in ALS disease modifying 4

5 Alzheimer s Disease, ALS, other dementias: the epidemic of neurodegenerative disease In spite of medical advances, AD still represents a pressing and growing unmet medical need Will Bankrupt Medicare if Therapy is not developed Direct and Indirect Costs Today in the US $500BB.. and the number is tripling by

6 Neurodegenerative diseases: in need of disease modifying therapy attacking the root cause FTD Alzheimer s LBD CTE Parkinson s ALS No Therapy Marginal Symptomatic Therapy Effective Symptomatic Therapy Disease Modifying Therapy FTD = Frontotemporal dementia LBD = Lewy Body dementia CTE = Chronic traumatic encephalopathy 6

7 Toxic oligomers are the root cause of neurodegenerative disorders and are the target for therapy Native protein Prion-like propagation Neurotoxic oligomers Toxic aggregates Toxic Oligomers Drive Disease Ab, Tau Alzheimer s SOD1, TDP43 ALS TDP43 Frontotemporal dementia a-synuclein Parkinson s, Lewy body dementia Causative role of toxic oligomers recently highlighted by Dr. Eliezer Masliah, Head of National Institute on Aging, at AAN 2017 and Dr. Jeffrey Cummings, Director of Cleveland Clinic, Center for Brain Health, at CTAD

8 Therapies that may address the root cause are generating high values: ProMIS discovery platform is generating a broad portfolio of oligomer selective assets Target Preclinical examples of value (partnering deals) Phase 2 examples of value (market cap increases) ProMIS Status Amyloid beta (Alzheimer s) Aducanumab 2014, ~$15BB BAN , ~$17BB PMN310 on track for H clinical trial initiation Tau (Alzheimer s, other dementias) Prothena/Celgene -$50MM upfront, potential $700MM downstream Final epitope (target) identification ongoing TDP43 (ALS, Frontotemporal dementia) Prothena/Celgene -$50MM upfront, potential $700MM downstream Initial data with selective antibodies, several epitope targets Alpha-synuclein (Parkinson s, Lewy body dementia) BioArctic/ABBVIE - $60MM upfront, potential $675MM downstream Initial data with selective antibodies, several epitope targets 8

9 ProMIS is focused in an area with great value creation potential neurodegenerative diseases Scientific understanding of disease has reached an inflection point, leading to significant large pharma interest and deal making - the next immuno-oncology, rare disease. space Past failures = $BBs of scientific and clinical information Innovative small companies have been the source of most assets in development ProMIS brings a unique and highly effective discovery platform to the area, now with a track record of creating highly selective antibodies targeting the root cause toxic oligomers Lead program PMN310 positioned to be best in class anti-amyloid therapy in Alzheimer s 9

10 PMN310: potential Best in Class therapeutic asset in AD Potentially best in class therapy for Alzheimer s, targeting toxic oligomers of amyloid beta Aducanumab and BAN2401 Phase 2 successes, support value of targeting amyloid beta Both products developed over 10 years ago tremendous advances in scientific understanding of disease since then. ProMIS applied state of the art, proprietary approaches to antibody design and picked the best of over 300 candidates to create PMN310 PMN310 - blocks cognitive deficits in a mouse model using toxic oligomers; blocks in vitro prion-like propagation and neurotoxicity PMN310 shows scientific evidence of superior therapeutic potency vs. aducanumab - better binding to human toxic oligomers, probable ability to avoid ARIA-E and dose higher, less target distraction due to not wasting therapeutic ammunition on the wrong targets 10

11 There are four types of amyloid-beta in the brain.only one is highly toxic Non Toxic Toxic Ab monomer Low molecular weight oligomers dimer (2), tetramer (4), dodecamer (12) Non Toxic Non Toxic High molecular weight aggregates* (protofibrils) Amyloid plaque Soluble - Numerous scientific studies have shown that plaque is not toxic..monomer is not toxic - Toxic oligomers are the neuron killers that drive disease * Yang et al, 2017, J Neurosc: HMW soluble aggregates in brain homogenate with MW of 70kDa 600kDa ( monomer equivalents) 11

12 ProMIS unique discovery engine overcomes the challenge of creating antibodies that selectively target human toxic oligomers Usual approaches to antibody creation inadequate, don t lead to high selectivity Synthetic oligomers are not identical to human toxic oligomers ProMIS approach: Predict and Validate - Unique capability to predict target epitopes only exposed on human toxic oligomers - Antibodies generated against these epitope targets - Screen many candidates for selectivity, including patient bio-samples - Confirm functional performance blocking propagation, neurotoxicity - Pick lead candidates Growing track record of success 12

13 Administration of PMN310 to mice: prevents loss of short-term memory formation caused by toxic oligomers THE EXPERIMENT Mice are tested for discriminating objects after brain injection of: Buffer (vehicle) - normal response Toxic Aβ oligomer PMN310 and buffer (vehicle) PMN310 and Aβ Oligomer Discrimination Index Vehicle THE RESULTS * * # AβO PMN310 + vehicle PMN310 + AβO N=12 per arm, *different from AβO (p < 0.05), # different from vehicle (p <0.05) AbO +/- Mab 7 days Novel Object Recognition Assay Control mice remember a familiar object when re-exposed to it and spend more time exploring a new object Oligomer-injected mice lose the ability to discriminate between known and novel objects and spend equivalent amounts of time exploring both Discrimination index = (Time exploring new object time exploring familiar object) / total exploration time Results press released January 9, 2017, 13

14 In vivo improvement of hippocampal synaptic and inflammation markers suggests cognitive benefit came from preventing neuronal damage Preservation of hippocampal synaptic proteins Decrease in hippocampal marker of inflammation PSD-95 (pg/ug total protein) # Vehicle PSD-95 * * # AβO PMN Mab + AβO PMN Mab + Vehicle # SNAP25 (pg/ug total protein) # Vehicle SNAP25 #* * # AβO PMN Mab + AβO PMN Mab + Vehicle TNF-α (pg/ug total protein) # Vehicle TNF-a * #* #* AβO PMN Mab + AβO PMN Mab + Vehicle *Different from Vehicle (p<0.05); # Different from AbO (p<0.05) 14

15 Binding the right form of amyloid beta is critical: the toxic oligomer is the target and PMN310 is the first oligomer selective antibody therapeutic Bapineuzumab Phase 2 failure Phase 3 failure ARIA-E side effect Solanezumab Phase 2 failure Phase 3 failure Aducanumab Phase 2 success ARIA-E side effect PMN310 Selective binding to oligomers -> Expected improvement in efficacy & safety MONOMERS - binding wastes therapeutic ammunition FIBRILS (Plaque) - binding wastes therapeutic ammunition - contributes to ARIA-E side effect OLIGOMERS* - the right target * Synthetic oligomers 15

16 Superior selectivity for the toxic oligomer is the key to best in class Non Toxic Toxic Ab Monomer Low molecular weight oligomers dimer (2), tetramer (4), dodecamer (12) Non Toxic High molecular weight aggregates* (protofibrils) Non Toxic Amyloid plaque Toxic oligomers are the least abundant form of amyloid-beta in the brain Both aducanumab and BAN2401 had a strong dose response curve higher dose enables greater efficacy Both had ARIA-E which limited dosing due to plaque binding Binding other forms of amyloid reduces drug available for the toxic oligomer..and likely reduces efficacy 16

17 PMN310 shows superior binding to toxic oligomer-enriched fraction from human AD brains vs other antibodies directed against amyloid beta 50 Binding Response (RU) Binding of antibodies to the toxic oligomerenriched LMW fraction of soluble human AD brain extract was evaluated by surface plasmon resonance (SPR) Results representative of over 10 SPR runs with extracts from 11 different AD brains huigg1 = Background control 0 Humanized PMN310 Aducanumab Bapineuzumab huigg1 Source for comparative antibodies: Creative Biolabs 17

18 PMN310 has the selectivity to be best in class Selective for Amyloid toxic oligomer PMN310 Selectivity Selective for Aggregated Amyloid Binds Monomer All BACE inhibitors Bapineuzumab Solanezumab Crenezumab Aducanumab BAN2401 Failed Studies Phase 2 positive Signal Best in Class 18

19 Phase 1 trial design: with patients in higher dose arms, biomarkers can give a signal suggesting therapeutic benefit early in clinical development 40 mg/kg AD Patients 3 Monthly doses in AD patients - ~4.5 months exposure Dose Escalation Design 0.3mg/kg - HNV 1 mg/kg - HNV 20 mg/kg AD Patients 10 mg/kg AD Patients 3 mg/kg AD Patients Growing list of validated biomarkers (blood, CSF) Possible to see biomarker trends suggesting dose dependent treatment effect (preserving neurons, synapses) 9 Months Time HNV = healthy normal volunteers 19

20 ProMIS is developing a portfolio of antibodies targeting toxic oligomers that drive neurodegenerative diseases H H H H H H ProMIS Technology Platform: Rational Design of highly selective mabs against human toxic oligomers Neurodegen (AD, other dementias, Parkinson s, ALS) Other Amyloid beta Alzheimer s Tau Alzheimer s TDP43: ALS & Frontotemporal Dementia SOD1: ALS Alpha -synuclein Parkinson s & Lewy Body Dementia PMN310 IND enabling development Tau Lead Selection TDP43 Lead Selection Alpha synuclein Lead Selection PMN310 Phase 1, ascending dose study in AD patients; biomarker data Tau Humanization and Preclinical Development to IND TDP43 Humanization and Preclinical Development to IND SOD1 Humanization and Preclinical Development to IND The 1-2 punch in AD disease modifying Tau Phase 1, ascending dose study in AD patients; biomarker data TDP43 Phase 1, ascending dose study in ALS patients; biomarker data SOD1 Phase 1, ascending dose study in ALS patients; biomarker data The 1-2 punch in ALS disease modifying 20

21 PMN310 is a best in class opportunity in AD: the three largest products in industry history were not first in class, but best in class the inventors identified improvements to existing drugs ProMIS following the best in class playbook in AD Peak Sales $BB s $12BB $16BB $25BB Taking advantage of proof of biology developed by earlier products: the scientific rationale for aducanumab and BAN2401 positive Phase 2 data, when all other A-beta programs failed Used ProMIS proprietary science platform to design an improved product, which may yield superior clinical results Lipitor Humira Sovaldi/Harvoni (Pharmasset) Cholesterol RA, Crohn s Hepatitis C Past programs with clinical results allow us to compare PMN310 scientifically to programs with known results PMN310 showing scientific advantages in therapeutic potency 21

22 Pharmasset created substantial value developing Sovaldi with a best in class strategy Pharmasset Market Value M&A exit IPO $150MM $5.8BB Before Gilead Acquis. $11BB Gilead Acquis. April 2007 November, 2011 Sovaldi at preclinical stage PMN Sovaldi with Phase 2 data PMN

23 ProMIS Neurosciences: summary Developing best in class therapies targeting the root cause of Alzheimer s and other neurodegenerative disease the toxic oligomers Neurodegenerative disease an area of increasing deal making, attractive values at preclinical and early clinical stage ProMIS proprietary discovery platform generating numerous differentiated products in dementia, ALS, and Parkinson s disease; potential partnering opportunities Numerous near term catalysts preclinical data from multiple products, potential partnering Pursuing NASDAQ listing Lead product PMN310 in Alzheimer s disease on track to Initiate clinical trials in 2019, generate Ph 1 biomarker data in early 2020 (when aducanumab pivotal trial reads out ) Potentially superior clinical data vs aducanumab and BAN2401 due to greater selectivity for root cause and ability to dose higher 23

24 ProMIS has successfully raised $20MM in 6 rounds, at increasing values $100MM $50MM Financial Status $20MM $2MM $2.5MM at $2MM Pre $1MM at $9MM Pre $1.5MM at $24MM Pre $2.7MM at $26MM Pre $4.8MM At $50 MM Pre $7.3MM At $84 MM Pre Common stock MM Warrants 27.4 MM Restart July 2015 May 2016 Sep 2016 Feb 2017 Sep 2017 April

25 Experienced leadership team Name Gene Williams Elliot Goldstein Title Executive Chairman CEO Years of Experience Prior Experience Former SVP at Genzyme, with senior roles integrating commercialization, drug development, and deal making Recently the CEO of Dart Therapeutics, an Orphan Disease drug development company Founder and director of Adheris, which became the largest company in the patient adherence/compliance area Held positions as SVP of Strategic Product Development at SmithKline Beecham (now GSK) Chief Operating Officer and Chief Medical Officer of Maxygen Chief Operating Officer at DART Therapeutics Neil Cashman Chief Science Officer 25+ Holds the Canada Research Chair in Neurodegeneration and Protein Misfolding Diseases, Serves as the Director of the University of British Columbia ALS Centre, Awarded the Jonas Salk Prize for biomedical research in 2000 Steven Plotkin Chief Physics Officer 20 Professor at UBC in the Department of Physics and Astronomy since 2001 Appointed as the Canada Research Chair in Theoretical Molecular Biophysics Associate member of the Genome Sciences and Technology Program, the Bioinformatics Program, and the Institute for Applied Mathematics at the University of British Columbia Dan Geffken CFO 25+ Founding Managing Director of Danforth Advisors Served as the Chief financial officer of Homology, Inc, GenePeeks, Inc., Transkaryotic Therapies, Inc., Cidara, Inc., Apellis, Inc. and Stealth BioTherapeutics, Inc. Johanne Kaplan Chief Development Officer 25+ Former VP of Research at Genzyme Associate Immunopathologist at SmithKline Beecham where she established an Immunotoxicology program Her work has resulted in over 60 scientific publications and multiple patents James Kupiec Chief Medical Officer 25+ Former VP, Global Clinical Leader for Parkinson s disease, and Clinical Head of the Neuroscience Research Unit for Pfizer, Inc Clinical focus on development of therapies for neurodegenerative disorders Held positions at Sanofi-Synthelabo and Ciba-Geigy Pharmaceuticals 4

26 Independent board of directors Name Anthony Giovinazzo Richard Gregory Bill Wyman Johannes Roth Years of Experience Prior Experience President and CEO of Sunovion CNS Development Canada ULC President, CEO and a Director of Cynapsus Therapeutics from 2009 to 2016 and one of the three original inventors and patent holders of the company s Parkinson s focused technology Chief Scientific Officer & Executive VP for Research at ImmunoGen Held a variety of roles at Genzyme and Sanofi-Genzyme, including Vice President for Gene Therapy, Head of Corporate Research and Head of R&D Co-founded the management consulting firm, Oliver Wyman & Co Former President of the Management Consulting Group called Booz Allen and Hamilton Founding director and partner at FiveT Capital Holding AG A board member of Insilico Biotechnology AG Pat Kirwin 30+ Senior partner at Kirwin LLP Advises and represents businesses in a range of industries and sizes from local to multinational 26 5

27 Scientific/business advisory board Scientific Advisory Board (SAB) Name Todd Golde, MD, PhD. Years of Experience 20+ Prior Experience Director of the Center for Translational Research in Neurodegenerative Disease at the University of Florida Lary Walker, PhD. Bill Mobley, MD, PhD Associate Professor of Neurology and Research Professor at Emory University Yerkes National Primate Research Center Dean for Neurosciences Initiatives, Distinguished Professor of Neurosciences, and Florence Riford Chair for Alzheimer Disease at the University of California, San Diego Sharon Cohen, MD 20+ Mara Aspinall, MBA 25+ Business Advisory Board Medical Director and Principal Investigator of Toronto Memory Program FRCPC in neurology from the Royal College of Physicians of Canada and a fellowship in Behavioural Neurology from the University of Toronto Executive Chairman of GenePeeks Former President and CEO of Ventana Medical Systems, a division of Roche Group, a worldwide leader in the development and commercialization of tissue-based cancer diagnostics Nigel Burns, PhD. Michael Higgins, MBA CEO and Founder of SweetSpot Therapeutics Ltd Served as Senior Vice President of Cambridge Antibody Technology Currently an Entrepreneur-in-residence at Polaris Partners Previously at Genzyme, served as Vice President of Corporate Finance and Vice President of Business Development, and was involved with multiple business units, including Cell Therapy, Gene Therapy and Orphan Diseases 27 6

28 Thank You Please feel free to contact us with any additional questions. Eugene Williams, Executive Chairman +1 (617) Elliot Goldstein, MD, CEO +1 (415) Website: Twitter: LinkedIn: 28