HARNESSING THE POWER OF PRECISION MEDICINE TO TREAT ALZHEIMER S DISEASE AND ALS (LOU GEHRIG S DISEASE) Toronto Stock Exchange (TSX) ticker: PMN.TO June 2017 1
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 www.sedar.com. 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
Investment Highlights ProMIS is developing a portfolio of personalized, best in class disease modifying therapies Monoclonal antibodies that target the root cause of Alzheimer s Disease (AD) AD has tremendous market value potential Greatest unmet need in medicine Expected to increase Decades of research disappointments have yielded new insights about AD s root cause Pointing a new direction to effective therapy Our platform technology patented processes can identify Disease Specific Epitopes Potential targets for additional antibody drugs and diagnostics ProMIS Neurosciences is publicly traded on the Toronto Stock Exchange (TSX) ticker: PMN.TO 3
The ProMIS Story has Two Main Components The Root Cause of Alzheimer s has become clear ProMIS is creating Best in Class therapies - The neuron killer is the Toxic Oligomer Form of beta-amyloid - Not beta amyloid plaque - This explains past failures and partial successes in clinical trials - Confirmed by a growing body of scientific evidence - ProMIS proprietary discovery technology has created products that selectively target the toxic oligomer, the root cause of AD - Biogen s aducanumab works, and will likely be first in class therapy - ProMIS is building a strong base of scientific evidence that PMN310, our lead program, is anticipated to be better than aducanumab 4
ProMIS is Developing REAL Solutions to an Immense Problem Acting faster than any competitor our proprietary technology platform has enabled us to capitalize on these new scientific insights about the root cause of AD Creating a portfolio of monoclonal antibody products with validated improvements anticipated over competitive products Our portfolio has the potential to change the standard of care in AD 5
AD Impacts Millions and Costs Billions The number of AD patients and associated costs are rising rapidly $500B Cost in the US, combining direct medical and indirect costs May bankrupt Medicare if the current trends are not reversed Fastest growing cause of death 1 Reviewed in Bloom 2014, JAMA Neurol Healthy Brain Brain with Mild Cognitive Impairment >15M Patients in US Brain with AD 1 >5M Patients in US 6
Amyloid beta (Aβ) Exists in Multiple Forms in the Brain The three forms of Aβ are monomer, oligomers, and plaque Monomer is created constantly in the brain as Amyloid Precursor Protein (APP) breaks down Monomer aggregates into oligomers, which then may further aggregate into fibrils and plaque Sometimes oligomers take on a toxic form = prions. Prions multiply rapidly (propagate) by causing new monomer (which is being created all the time) to take on the same toxic form nia.nih.gov 7 7
The Root Cause of AD: Toxic Oligomers of Aβ Toxic Aβ oligomers, also known as prions, are the real root cause of AD Aβ monomers and Aβ plaque have little or no demonstrable toxicity in vitro or in vivo 1-3 Soluble Aβ oligomers show the highest degree of neurotoxicity 4 Toxicity in primary neuron cultures and brain slices 1,3,5-7 Induction of cognitive impairment in rodents 3,4 Synaptotoxicity of human Ab oligomers on hippocampal neurons 5 Plaque is not the problem that explains many previous failures 1 Shankar et al, Nature Med 2008; 2 Cleary et al, Nature Neuroscience 2005; 3 Hong et al, Science 2016; 4 Benilova et al, Nature Neuroscience 2012 - Review; 5 Lacor et al, J Neuroscience 2007; 6 Jin et al, PNAS 2011; 7 Lauren et al, Nature 2009 8
Large Pharma Clinical Results Confirm; Selectively Target Toxic Oligomers Product Clinical Results Monomer binding BAD Plaque binding BAD Oligomer binding GOOD Companion Diagnostic GOOD Aducanumab (Biogen-fully human IgG1) Solanezumab (Eli Lilly-humanized IgG1) CTAD-2 yr. efficacy confirmed dose limiting # ARIA-E Likely 2021 Approval first in class CTAD-11% efficacy; p=0.095 3 rd failed phase 3 No Yes Yes No Yes No Yes No Verubecestat (Merck-BACE inhibitor) Pivotal failed (interim futility) Depletes Monomer N/A N/A No Bapineuzumab (Pfizer-humanized IgG1) Microhemorrhage, ARIA-E No cognitive benefit Yes Yes Yes No Efficacy Killer Creates Side Effects The target Critical for best efficacy # ARIA-E: Amyloid-Related Imaging Abnormality, or neurovascular edema 9
Dr. Eliezer Maslia, new head of US National Institute of Ageing, stressed the need for therapies that target the toxic oligomer at the AAN meeting in April 2017 A common mechanism underlies the top 3 neurodegenerative disorders, including Alzheimer s: Monomers aggregate into oligomers that are toxic to synapses and propagate in a prion-like fashion. Need to target oligomers of Ab, Tau, a-synuclein [with therapy] Biogen s aducanumab is showing promise, since it targets aggregated Amyloid beta [oligomers] 10
Target Product Profile for Best in Class Aβ mabs is Clear Products meeting these criteria are likely to have better clinical data than Aducanumab s expected label NO MONOMER BINDING NO PLAQUE BINDING HIGHLY SELECTIVE BINDING TO TOXIC OLIGOMER PERSONALIZED MEDICINE WITH COMPANION DIAGNOSTIC - Monomer outnumbers oligomers 100 1000 fold - Monomer binding reduces efficacy through target distraction - Target distraction reduces efficacy - Plaque may be protective sequester oligomers - Plaque binding contributes to ARIA-E - Targets root cause of neuronal death - Must be highly selective to avoid target distraction - Any single monoclonal antibody will have non-responders due to different toxic oligomer strains 11
ProMIS Best in Class Playbook; Building the Pharmasset of Alzheimer s The three largest products in industry history were not first in class, but best in class - Solvaldi/Harvoni, Humira, Lipitor They evaluated predecessor compounds and executed scientific strategies for creating meaningful improvements Pharmasett created Solvadi, best in class therapy in Hepatitis C, and sold to Gilead after Ph2 data for $11B ProMIS is creating the Pharmasett of Alzheimer s, with clear science-based improvements over likely first in class therapy Aducanumab from Biogen ProMIS competitive advantage lies in our platform technology, patented processes that allow us to identify Disease Specific Epitopes (targets for antibody drugs and diagnostics) 12
Toxic Oligomers Spread Through Brain - Killing Neurons & Causing AD Amyloid beta (Aβ) Propagation or spreading Neurotoxic oligomers kill neurons ~100B Neurons in a Healthy Brain Neurotoxic Oligomers form 13
ProMIS Antibodies Stop Toxic Oligomers Amyloid beta (Aβ) Propagation or spreading Neurotoxic oligomers kill neurons Neurotoxic Oligomers form ProMIS antibody products disable toxic oligomers and stop them from spreading 14
Administration of PMN310 to Mice Prevents Loss of Short-Term Memory Formation Caused by Toxic Oligomers AbO +/- Mab 7 days Novel Object Recognition Assay Control mice remember a familiar object when reexposed 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 0.6 Discrimination Index 0.5 0.4 0.3 0.2 0.1 0.0-0.1-0.2 * * Vehicle # AβO PMN 310 + vehicle PMN 310 + AβO N=12 per arm *different from AβO (p < 0.05) # different from vehicle (p <0.05) Discrimination index = (Time exploring new object time exploring familiar object) / total exploration time Results press released January 9, 2017, www.promisneurosciences.com 15
PMN310 Differentiation Plan PMN310 as Best in Class vs Aducanumab Property Aducanumab PMN310 Binding pattern Binds oligomers, plaque Binds toxic oligomers only Side effects - ARIA ARIA caused by plaque binding & IgG1 effector isotype ARIA not expected: no plaque binding & IgG4 non-effector isotype Therapeutic efficacy - Positive dose-dependent signal in Phase 2 - Therapeutic window limited by ARIA (dose limiting toxicity) No dose limiting toxicity expected -> Greater levels of CNS exposure and efficacy Response rate A priori non-responders cannot be prospectively identified Detection of target in CSF/blood (companion diagnostic) to allow for selection of likely responders ARIA: Amyloid-related imaging abnormalities 16
Compelling Best in Class Data Package Creation for PMN310 Product Feature Biogen s Aducanumab PMN310 existing data PMN310 Advantage Binding Profile Toxic Oligomer and plaque AAIC 2016 Toxic oligomer only AAIC 2016 ADPD 2017,AAN 2017 PMN310 more selective for the neuron killers ARIA-E, Brain swelling side effect 55% in highest dose arm, 35% with dose titration CTAD 2016 IgG4 isotype Little or no ARIA-E expected due to IgG4 and no plaque binding Dosing Dose titration that reduced ARIA-E also reduced efficacy CTAD 2016 PMN310 likely to be able to dose higher, increasing efficacy Personalized or Precision Medicine None PMN310 selectively targets a known epitope PMN310 companion diagnostic will eliminate non responders, increase efficacy AAIC, CTAD, and ADPD are leading international Alzheimer s Disease science meetings 17
ProMIS Best in Class Therapy - Significant Progress & Key Catalysts On track for 2017 Further in vivo efficacy data on lead product PMN310 Includes both behavioral and functional outcomes Further in vivo validation of other mabs Cohort Study to assess prevalence of different strains of toxic oligomers underlining need for precision medicine Development of companion diagnostics Development of blood based screening assay Tau and TDP43: Identification & IP filings on specific epitope targets 18
PMN310: Key Steps in Development Plan to Clinical Proof of Concept (POC) q q q q q q q q 2016 Create mabs 2016 Select best candidates, In Vitro Validation 2017 In Vivo Validation 2018 Manufacturing scale-up 2018 GLP animal toxicology Late 2018 IND Submission 2019 Phase 1 Single Ascending Dose Trial 2021 Phase 2 Proof of Concept Trial Complete 19
Numerous Prior AD Programs Targeting Aβ Help Set Expectations for Path Forward GLP Tox Manufacture Ph 1 SAD Ph 2 POC - Numerous previous programs have had success, few issues in GLP toxicolgy, manufacturing or bioavailability - High odds of success - ProMIS trial to be larger than Biogen s Aducanumab (n=166) - ProMIS to develop Companion Diagnostic (CDx) to ensure patients in trial have correct oligomer strain Expectations: better data than Aducanumab 1) no ARIA-E due to no plaque binding, IgG4 isotype 2) Higher efficacy higher dose possible 3) Higher efficacy CDx, no a priori non-responders Ph1 SAD = phase 1 trial, single ascending dose Ph2 POC = phase 2 trial, proof of concept 20
ProMIS Neurosciences: Summary Developing personalized, best in class therapies targeting the root cause of Alzheimer s disease Lead product PMN310 on track to: further confirm differentiation from likely first in class aducanumab in 2017 file IND late 2018, and generate better clinical data in 2021 shortly after aducanumab anticipated approval ProMIS proprietary technology platform is generating additional differentiated products in dementia and ALS Numerous catalysts near term Cohort study, personalized medicine Lead product PMN310 functional differentiation Other portfolio positive results ProMIS pursuing NASDAQ listing, likely in 2018 21
ProMIS has very Experienced Management and Outstanding Advisory Boards Management Gene Williams, Executive Chairman - Genzyme, DART, Adheris Elliot Goldstein, CEO - Maxygen, DART, GSK Neil Cashman, Chief Science Officer - University of British Columbia Steven Plotkin, Chief Physics Officer - University of British Columbia Johanne Kaplan, Chief Development Officer - Genzyme, GSK Advisory Boards Todd Golde Scientific Adv. Bd. (SAB) - University of Florida William Mobley (SAB) - University of Cailfornia, San Diego Lary Walker (SAB) - Emory University Mara Aspinall Business Adv. Bd. (BAB) - Ventana, Genzyme Nigel Burns (BAB) - CAT, SweetSpot Michael Higgins (BAB) - Ironwood, Genzyme, Voyager 22 23
ProMIS has Successfully Raised $7.7MM CDN in Four Rounds, at Increasing Values, Since a Strategic Restart in July 2015 MKT CAP JUNE 2 $62MM $25MM Financial Status $10MM $2MM $2.5MM at $2MM Pre $1M M at $9M M Pre $1.5MM at $24MM Pre $2.7MM at $26MM Pre 201MM common shares outstanding ~240MM including options and warrants Current burn rate ~$300k due to efficient science process Restart July 2015 May 2016 Sep 2016 Feb 2017 Cash life into Q4 2017 23 24
Thank You We appreciate your interest in ProMIS Neurosciences and the exciting developments in AD therapeutics. Please feel free to contact us with any additional questions. Eugene Williams, Executive Chairman eugene.williams@promisneurosciences.com +1 (617) 460-0978 Elliot Goldstein, MD, CEO elliot.goldstein@promisneurosciences.com +1 (415) 341-5783 Website: www.promisneurosciences.com Twitter: https://twitter.com/promisinc LinkedIn: https://www.linkedin.com/company/promis-neurosciences 24