Advancing the Treatment of Cancer Through Targeted Therapeutics

Transcription

1 Reaching new heights in cancer treatments Innovative approaches for a wide range of cancers Advancing the Treatment of Cancer Through Targeted Therapeutics MARCH 2018

2 Disclaimer 2 When used anywhere in this presentation, whether oral or written, the words expects, believes, anticipates, estimates and similar expressions are intended to identify forwardlooking statements. Forward-looking statements may include statements addressing future financial and operating results of Cotinga Pharmaceuticals (Cotinga). Cotinga bases these forward-looking statements on its current expectations about future events. Such statements are subject to risks and uncertainties including, but not limited to, the successful implementation of Cotinga s strategic plans, the acceptance of new products, the obsolescence of existing products, the resolution of potential patent issues, competition, changes in economic conditions, and other risks described in Cotinga s public documents such as press releases and filings with the Toronto Stock Exchange and the Ontario Securities Commission. All forward-looking statements are qualified in their entirety by the cautionary statements included in this document and such filings. These risks and uncertainties could cause actual results to differ materially from results expressed or implied by forward-looking statements contained in this presentation. These forward-looking statements speak only as of the date of this presentation.

3 Company and Pipeline Synopsis 3 Clinical stage biotech company focused on the development of novel therapeutics for the treatment of cancers and other unmet medical needs Lead drug candidate is COTI-2, targeting p53 Completed dose escalation portion of Phase 1 trial for the treatment of gynecological malignancies Promising safety, tolerability, PK, and PD readouts Initiated expansion arm of Phase 1 trial for the treatment of head and neck squamous cell carcinoma (HNSCC) Second drug candidate is COTI-219, targeting KRAS Currently in IND-enabling studies IND filing expected in 2018 Pipeline-generating CHEMSAS platform in silico high throughput screening for molecule assessment Publicly traded company TSX-V: COT OTCQB: COTQF

4 Cotinga Pipeline: Internally Discovered & Owned 4

5 COTI-2: Potential Best-In-Class Therapy Targeting p53 in Multiple Oncology Indications

6 COTI-2: Halting Mutant p53 Carcinogenesis 6 In response to cellular stress, wildtype p53 induces cell cycle arrest and/or apoptotic cell death Mutant p53 promotes tumor formation (loss of tumor suppressor function) Mutant p53: single most important cancer-causing gene mutation known Most frequently mutated gene in human cancer implicated in >50% of all human cancers COTI-2 induces a wildtype-like conformational change in the p53 mutant protein thus restoring wildtype functional activity Oral small molecule Low preclinical toxicity Active as a mono or combination therapy Phase I in gynecological malignancies complete, initiated in head and neck cancer Drug Drug mutp53 Sequence-specific transactivation defective mutp53 Conformational change to a wild-type configuration mutp53 Restoration of sequence-specific transcriptional activity Apoptosis, growth arrest, senescence

7 Mean Fluorescence Intensity (Arbitrary Units) Mean Fluorescence Intensity (Arbitrary Units) COTI-2 Specifically Targets Mutated p53 Mechanism 7 Conformational change of mutant p53 to wildtype-like No effect on wildtype p53 protein levels Wildtype p53 Levels in the Presence/Absence of COTI-2 Mutant p53 Levels in the Presence/Absence of COTI TOV-112D Cell Line H460 Control COTI TOV-112D Cell Line H460 Control COTI-2 COTI-2 induces a wildtype-like conformational change in mutant p53 R175H in TOV-112D ovarian cancer cell line but has no effect on p53 WT conformation in H460 NSCLC cell line Similar results with multiple p53 mutant proteins in other constructs from HCT-116 colorectal cancer cell line

8 Tumor Volume (mm 3 ) Tumor Volume (mm 3 ) Significant Tumor Growth Inhibition as a Single Agent 8 Effect of IV Treatment on OVCAR-3 Tumor Volume Study Day Group 1 = Vehicle IV Group 2 = COTI-2 20mg/kg IV Group 3 = COTI-2 40mg/kg IV Effect of PO Treatment on OVCAR-3 Tumor Volume Study Day Group 4 = Vehicle PO Group 5 = COTI-2 75mg/kg PO Group 6 = COTI-2 100mg/kg PO COTI-2, administered IV and PO, produced a significant tumor growth inhibition as a single agent in an OVCAR-3 ovarian cancer xenograft model

9 Tumor Volume (mm 3 ) Tumor Volume (mm 3 ) Target Specific Tumor Growth Inhibition as a Single Agent Effect of Treatment on HCT-116 (p53 G245C) Tumor Volume Study Day Vehicle Control COTI-2 (30 mg/kg) COTI-2 (75 mg/kg) Effect of Treatment on HCT-116 (GFP) Tumor Volume Study Day Vehicle Control COTI-2 (75 mg/kg) Oral COTI-2 administration produced significant tumor growth inhibition in the HCT-116 p53 G245C colorectal cancer cell line construct No effect in a HCT-116 (GFP) construct without p53 mutation

10 COTI-2 Phase 1 in Gynecological Malignancies 10 Gynecological malignancies: ~100,000 patients are diagnosed with gynecological cancer per year; disease affects ~1.2M women in total (US) Mutant p53 occurs in ~50% of recurrent disease (~15-20,000 patients per year) and in ~96% of high-grade serous ovarian cancer Current standards of care (surgery, radiation, chemotherapy) associated with increased morbidity and high toxicity COTI-2 Gynecological Malignancies Clinical Trial Design: Primary objectives: Evaluate the safety and tolerability of COTI-2 Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of COTI-2 Secondary objective: Evaluate pharmacokinetics, clinical activity, and response duration of COTI-2 Exploratory objectives: Determine if baseline molecular aberrations correlate with activity of COTI-2 Evaluate pharmacodynamic markers of COTI-2 activity

11 COTI-2 Phase 1 Primary Objective: Safety & Tolerability 11 Evaluate the safety and tolerability of COTI-2 24 patients were enrolled with ovarian, fallopian tube, endometrial or cervical cancers for which no effective or curative measures existed, with a median age of 60 and a median of 5 previous courses of chemotherapy COTI-2 was safe and well tolerated at increasing dose levels between mg/kg Most common drug-related Adverse Events (AEs) were nausea and vomiting, fatigue and abdominal pain Determine Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of COTI-2 MAD of 1.7 mg/kg and MTD/RP2D of 1.0 mg/kg established (based on 5 days/week, oral dosing)

12 Secondary Objective: Pharmacokinetics 12 COTI-2 PK parameters by cohort Cohort t 1/2 (hr) T max (hr) C max (ng/ml) AUC 0-t (ng hr/ml) AUC 0- (ng hr/ml) Highest concentrations of COTI-2 approximately 1 hour after dosing T 1/ hours; substantially longer than other treatments targeting mutant p53 No evidence of long-term drug accumulation Washout in approximately one week after last dose

13 Exploratory Objective: Pharmacodynamics patients were enrolled with ovarian, fallopian tube, endometrial or cervical cancers for which no effective or curative measures existed, with a median age of 60 and a median of 5 previous courses of chemotherapy 15 patients were evaluated for Secondary and Exploratory outcome measures, including signals of efficacy using RECIST 1 criteria. 11 of the 15 patients had ovarian cancer 12 of the 15 patients were genetically-profiled, and 9 of the 12 exhibited p53 mutations 1 of the 15 patients was determined to have overall stable disease 4 of the 15 patients were determined to have progressing disease but stable target lesions 5 of the 15 patients were determined to have progressing disease but stable non-target lesions 1 patient was observed to have a decrease in Cancer Antigen-125 (CA-125) levels in her blood

14 COTI-2 Phase 1 Trial in Head and Neck Cancers Initiated 14 COTI-2 Phase 1 HNSCC trial: Clinical trial site MD Anderson Cancer Center Initial safety and tolerability trial initiated: first cohort started at 1.0 mg/kg Primary (cohort 1-3) readout expected in Q Head and Neck Small Cell Carcinoma (HNSCC): ~65,000 patients are diagnosed with head and neck squamous cell carcinoma (HNSCC) per year; disease predominantly affects men, with approximately 447,000 patients identified (US) ~40-50% HNSCC associated with mutant p53 Current treatments include surgery, radiotherapy and chemotherapy Approximately 13,000 deaths from HNSCC in the US per year, representing a clear unmet need for additional treatment options

15 Robust in vitro Data for COTI-2 Combination in HNSCC 15 Isobolograms for two PCI13 cell lines show strong synergy for COTI-2 + cisplatin combination data points all below additive curve lines

16 Significant Tumor Growth Inhibition in Combination Chemotherapy 16 (p53 G245D) COTI-2, as a single agent and in combination with cisplatin, produced significant tumor growth inhibition relative to untreated controls in the PCI13 p G245D head and neck cancer xenograft models Cisplatin treatment alone did not yield significant tumor growth inhibition

17 Synergistic Tumor Growth Inhibition in Combination with Radiotherapy 17 COTI-2, whether as a single agent (75 mg/kg PO) or in combination with radiation, produced tumor growth inhibition relative to untreated controls in PCI13 p G245D, the p53- mutated head and neck cancer cell line COTI-2 + radiation (2 Gy) has better tumor suppression and tumor cure effect compared with COTI-2 or radiation alone Tumor growth regression was as follows: COTI-2 alone (1/6), radiation alone (1/6), COTI-2 + radiation (4/7)

18 COTI-2 Combinations in Multiple Indications 18 normalizing p53 function is expected to synergize with chemotherapy + platins vs. SCLC + taxanes vs. SCLC, endometrial, pancreatic + nucleoside analog (gemcitabine) vs. pancreatic + mtor inhibitor vs. glioblastoma + EGFR inhibitors (erlotinib, cetuximab) vs. colorectal PLoS One Jan 24;13(1). PMID: Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not induce resistance or exhibit cross-resistance in human cancer cell lines.

19 COTI-2 Effective in Resistant Cancer Cells 19 multiple chemo-resistant cell lines are sensitive to COTI-2 with repeated exposure, SCLC and NSCLC cells acquired resistance to platins and taxanes but not to COTI-2 SCLC and NSCLC cell lines with resistance to taxanes or platins were still sensitive to COTI-2 PLoS One Jan 24;13(1). PMID: Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not induce resistance or exhibit crossresistance in human cancer cell lines.

20 COTI-2 Best-in-Class Potential 20 Novel p53-dependent mechanism of action High oral bioavailability demonstrated in the patient population Low toxicity in preclinical and early clinical development High preclinical efficacy demonstrated Opportunity for single agent and combination therapy No drug resistance observed Sensitization to radiation therapy Granted FDA orphan drug status for ovarian cancer Strong IP protection in place - 8 U.S. patents issued - 1 Japanese, 1 Canadian and 1 EU patent issued - Additional patents pending

21 COTI-219: Therapy Targeting KRAS in Multiple Oncology Indications

22 COTI-219: Inhibits Oncogenic KRAS Over-Activation 22 KRAS proteins are signal switch molecules that regulate cell fates by coupling receptor activation to downstream effector pathways Over-activation of RAS occurs in ~30% of human cancers KRAS mutations are prevalent in pancreatic, colorectal, endometrial, biliary tract, lung and cervical cancers Malignant activation of KRAS promotes carcinogenesis COTI-219 prevents the activation of KRAS Oral small molecule Low preclinical toxicity Currently in preclinical development GEF COTI-219 Prevents Activation of KRAS Quiescence Cell Death KRAS-GDP OFF KRAS-GTP ON Proliferation Survival Angiogenesis GAP

23 COTI-219 Inhibits KRAS Activation 23 HeyA8 Cell Line OVCAR8 Cell Line CELL LINE HeyA8 DURATION OF COTI-219 EXPOSURE (days) IC 50 (nm) 1 10, COTI-219 inhibits KRAS activation CELL LINE OVCAR8 Inhibition is time- and concentration-dependent DURATION OF COTI-219 EXPOSURE (days) This inhibitory effect is also evident in downstream targets IC 50 (nm) 1 10,000 3 N/A

24 Tumor Volume (mm 3 ) COTI-219 Significantly Inhibits Mutant KRAS Tumor Growth 24 Effect of Treatment on Tumor Volume TGI~80% * All animals died Test Compound COTI-219 demonstrates single agent efficacy greater than standard chemotherapeutics in SHP-77 (KRAS G12V ) mouse xenograft model COTI-219 significantly inhibits tumor growth in the SHP-77 cells relative to vehicle control

25 COTI-219 Best-in-Class Potential 25 KRAS-dependent mechanism of action (effective against mutant KRAS) Orally bioavailable and effective at low dose Low toxicity in preclinical development Opportunity for single agent and combination therapy No drug resistance observed Strong IP protection in place 5 patents in the U.S., Canada, Japan and select EU countries

26 Corporate Update

27 Corporate Objectives COMPLETED CORPORATE Opened US office Raised ~$4M CDN Recapitalized equity structure Rebranded from Critical Outcome Technologies to Cotinga Pharma COTI-2 Entered into first-in-human clinical trial Completed dose escalation portion of Phase 1 trial in gynecological malignancies at MDACC and NWU Published two scientific articles on COTI-2 Launched HNSCC expansion arm in Phase 1 dose escalation trial Announced promising safety, tolerability, PK and PD data from Phase 1 trial in gynecological malignancies, including MTD and R2PD COTI-219 Designated COTI-219 as next clinical candidate for development Initiated GMP manufacturing and IND-enabling studies UPCOMING CORPORATE Strengthen the balance sheet to execute on corporate strategies Opportunistically pursue regional or codevelopment partnerships for COTI-2, pipeline programs and other technologies COTI-2 Complete additional exploratory endpoint data analysis for dose escalation portion of Phase 1 trial in gynecological malignancies Complete Phase 1 dose escalation trial in HNSCC Initiate combination trials with COTI-2 Initiate p53 basket trial with COTI-2 Initiate breast cancer trial with COTI-2 COTI-219 File IND in 2018 Launch first-in-human trial in 2018

28 Robust Scientific Advisory Board 28 Dr. Gordon Mills from the University of Texas MD Anderson Cancer Center, Houston, TX, Chairman Dr. Douglas Levine from the Memorial Sloan-Kettering Cancer Center, New York City, NY Dr. David Parkinson from New Enterprise Associates, Menlo Park, CA Dr. Marshall Strome from the Center for Head and Neck Oncology at Roosevelt St. Luke's Hospital, New York City, NY Dr. Nancy Chang, President, Apex Enterprises, Inc, and adjunct professor at the Departments of Medicine and Genetics at Baylor College of Medicine, Houston, TX

29 Experienced Leadership 29 MANAGEMENT TEAM Alison Silva, MSc President & CEO Co-founder, former EVP & COO, Synlogic Co-founder & Principal, The Orphan Group Richard Ho, MD, PhD Chief Scientific Officer EVP R&D, Marina Biotech Director, Disease Simulation, J&J PRD Gene Kelly Chief Financial Officer Kowthar Salim, PhD, MBA Vice President, Development Debi Sanderson, MBA Director, Resourcing and Operations DIRECTORS John Drake, LLB, Chairman Chairman, Whippoorwill Holdings Limited Alison Silva, MSc, President & CEO Douglas Alexander, CPA, CA Chairman, Hydrogenics Corporation Dave Sanderson, LLB Co-founder and President, Red Jacket Capital Inc. John Yoo, MD FRCPC Professor of Oncology and Professor of Otolaryngology Head and Neck Surgery at Western University; Co-chair of Cancer Care Ontario Head and Neck Disease Site

30 Key Company Facts Trading TSX Venture (2) COT Recent closing price (3) $ week range (3) $ Market capitalization (3) $16,019,489 Capital Cash (4) $1.25 M Basic shares outstanding (3) 16,686,968 Options outstanding (3) 1,433,368 Warrants outstanding (3) (5) 3,824,242 Fully diluted shares outstanding (3) 21,944,578 Board & management control (3) (6) 12.3% (1) All $ amounts in CAD (2) COTI also trades on the OTCQB as COTQF but amounts are for the TSXV only (3) As of the close of business Jan 17, 2018 (4) As at Oct 31, 2017 consisting of cash, cash equivalents and investments (5) Includes warrants accounted for as warrant liabilities under IFRS (6) On a fully diluted basis

31 Contact: Alison Silva President & CEO Office: (519) Mobile: (860) Richard Ho Chief Scientific Officer Office: (858) Mobile: (619)