Inducing Tumor-Specific Ischemic Necrosis to Enhance the Efficacy of Checkpoint Inhibitors and Chemotherapy

Transcription

1 Inducing Tumor-Specific Ischemic Necrosis to Enhance the Efficacy of Checkpoint Inhibitors and Chemotherapy Company Overview, September 2018

2 Safe Harbor Statement This presentation contains forward-looking statements under the meaning of the Private Securities Litigation Reform Act of These statements give our current expectations or forecasts and use words such as anticipate, estimate, "expect," believe, plan, will and other words of similar meaning. Any or all of the forward-looking statements in this presentation may turn out to be wrong. They can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties including, but not limited to, our ability to raise capital to remain in business, the efficacy and safety of our product candidates, including the results and progress of clinical trials, obtaining regulatory approvals for our investigational drug candidates and projections of potential commercial sales of our product candidates. No forward-looking statement can be guaranteed and actual results may differ materially from the forward-looking statement. Additional information concerning factors that could cause actual results to materially differ from those in the forward-looking statements are contained in our most recent reports to the Securities and Exchange Commission, including our Form 10-K, 10-Q and 8-K reports. We undertake no obligation to publicly update forward-looking statements, whether as a result of new information, future events or otherwise. 2

3 Unique, Powerful Approach Rapid Destruction of Tumor by Ischemic Necrosis Tumor Before Treatment Tumor After Treatment Plaster casts of tumor vasculature from murine hepatic adenocarcinoma model after treatment with CA4P 3

4 Our Two Clinical Programs 1. CA4P for the Treatment of Advanced Melanoma Highly Immunogenic NeoAntigen Production Enhances Checkpoint Inhibitor Therapy 2. OXi4503 for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia Released Leukemic Stem Cells Vulnerable to Chemotherapy 4

5 CA4P as Immuno-Oncology Agent for the Treatment of Advanced Melanoma

6 Defective Antigen Presentation is Cause of Resistance to Checkpoint Inhibitors in Melanoma 1. Acquired resistance to PD-1 blockade immunotherapy in patients with melanoma (is) associated with defects in antigen presentation * 2. Resistance to checkpoint blockade therapy (occurs) through inactivation of antigen presentation ** *Zaretsky et al, N Engl J Med 2016; 375: **Sade-Feldman, et al, Nature Communications volume 8, Article number 1136 (2017) 6

7 Melanoma s High Mutation Rate Results in Comparatively High Checkpoint Inhibitor Response Nevertheless over 60% of patients do not respond Adapted from Yarchoan Dec 21, 2017 N Engl J Med

8 Three Ways to Generate NeoAntigens to Increase Anti-Tumor Immune Response Adapted from Schumacher et al Science 03 Apr 2015: 348, 6230,

9 Ischemic Necrosis is a Unique Mechanism for NeoAntigen Generation Adapted from Schumacher et al Science 03 Apr 2015: 348, 6230,

10 CA4P: Induces Massive Tumor Destruction Following Rapid Ischemic Necrosis Leads to presentation of numerous tumor-specific NeoAntigens 10

11 Ischemic Necrosis is Highly Immunogenic Because it Induces Immunogenic Cell Death NeoAntigens are generated with other cellular debris (danger signals) that together induce a potent anti-tumor immune response Adapted from Immunogenic Cell Death in Cancer: From Bench Research to Bedside Reality. Edited by Garg/Agostinis. Published Frontiers in Immunology and Frontiers in Oncology 11

12 CA4P: Increases Tumor T Cells, CD8+ T Cells and Induces Widespread Tumor Necrosis In animal models when used in combination with checkpoint inhibitors 12

13 CA4P: Significant Tumor Regressions and Improved Overall Survival In animal models when used in combination with checkpoint inhibitors 13

14 Development Plan CA4P + Opdivo in Advanced Melanoma Phase 2a Open-label; treatment failures Phase 2b Randomized trial Initiate and Complete Phase 2a Dose Escalation (COSMO Study) CA4P + Opdivo in Opdivo failures Historical controls predict ~10% response rate without CA4P Data to be assessed at 40, 50 and 60 mg/m 2 MTD determination, then open label extension of 20 patients ORR, PFS, CR, PR, markers of tumor immunogenicity Clinical sites in Italy, United Kingdom Follow-up with Randomized Phase 2b Study CA4P + Opdovio vs Opdivo alone Primary endpoint = response rate Potential for Accelerated Approval 14

15 OXi4503 for the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

16 OXi4503: Mechanism-of-Action in AML Rapid tumor necrosis releases dividing and chemotherapy-vulnerable leukemic stem cells into the periphery 16

17 OXi4503: Reduced Adherence of Leukemic Stem Cells Control OXi4503 Disrupts AML-protecting BMECs Reduces expression of VE-cadherin, VCAM-1, and BCAM AML: acute myeloid leukemia; BMEC: bone marrow endothelial cells Bosse RC et al. Exp Hematol. 2016;44(5):

18 OX1222: Completed Cohort Results to Date Complete Remissions and Dose Response Clinical trial has shown initial evidence of efficacy Completed Cohort (Dose) n CR% PR Rate ORR Cohort 1 (3.75 mg/m 2 ) 6 17% 0% 17% Cohort 2 (4.68 mg/m 2 ) 4 25% 0% 25% Cohort 3 (6.25 mg/m 2 ) 4 25% 25% 50% Cohort 4 (7.81 mg/m 2 ) 3 0% 33% 33% Cohort 5 (9.76 mg/m 2 ) 4 50% 0% 50% Cohort 5 now being expanded to better assess safety and efficacy before potentially resuming cohort 6 CR: complete remission; PR: partial response; ORR: overall response rate 18

19 OX1222: Phase 1 AML/MDS Combination Study Drug-related adverse events through cohort 5 (Grades >3) Adverse Event N % Neutrophil count decreased 5 28% Platelet count decreased 5 28% Febrile neutropenia 4 22% Anemia 3 17% White blood cell count decreased 2 11% Favorable safety profile demonstrated to date through cohort 5 AML: acute myeloid leukemia; MDS: myelodysplastic syndromes 19

20 OX1222: Phase 1b Dose Escalation Study Design Relapsed/Refractory AML/MDS Patients 9.76 mg/m mg/m mg/m mg/m mg/m mg/m 2 Completed cohorts Currently expanding cohort 5 from n = 4 (50% CR) to n= mg/m 2 potentially not well tolerated OXi4503 (Days 1 and 4 of 28 day cycle) dose escalation study in combination with cytarabine (Days 1-5, 1 g/m 2 /day) NCT Number: NCT AML: acute myeloid leukemia; MDS: myelodysplastic syndromes 20

21 Development Plan OXi Cytarabine Phase 1 Dose Escalation Phase 2 Randomized Control Next Step: Complete Phase 1 Dose Escalation Expanding cohort size from n=10 Better assessment of safety and potential efficacy at 9.76 mg/m 2 Next data expected in Fall 2018 Evaluate whether to further study 12.2 mg/m 2 Second Step: Randomized Phase 2 Study OXi4503 combination vs cytarabine alone Primary endpoint = response rate Total N = ~ Potential Accelerated Approval 21

22 OXi4503: Intellectual Property and Regulatory Patent No. Type Location Expiration US EU Composition of matter US, Canada, EU 2021 (2026 with extension) US Japan EU Method for treating hematopoietic neoplasms US, Canada, Australia, Japan, EU 2028 (2033 with extension) NA Orphan exclusivity granted AML US 7 years after approval NA Orphan exclusivity granted AML EU 10 years after approval Fast Track designation (April 2017) NA: not applicable 22

23 Company Information

24 Mateon is an under-recognized Opportunity Pursuing very large initial target markets Immuno-oncology/melanoma ~$7 billion Acute myeloid leukemia ~$1.4 billion Myelodysplastic syndromes ~$2.2 billion Numerous additional opportunities if trials successful Strong scientific rationale plus favorable existing data Unique approach will help programs stand apart Recent patent filings and orphan drug protection Current market capitalization below $10 million 24

25 Potential Valuation Comparisons Market Capitalization in millions 25

26 Key financial data 41.4 million common shares outstanding No preferred stock or debt $2.0 million cash at June 30, 2018 Stock information Ticker (OTCQB) MATN Price (8/22/2018) $0.12 Market Cap ~$5 million Average Daily Trading Volume ~50, million warrants outstanding at weighted average exercise price of $1.06 and 7.3 million options outstanding at weighted average exercise price of $

27 Investment Highlights Two promising programs serving significant markets CA4P + anti-pd1 to treat relapsed/refractory melanoma Unique & promising mechanism-of-action and preclinical data Initial clinical trial being initiated Large, supportive drug safety database OXi4503 to treat acute relapsed/refractory acute myeloid leukemia & myelodysplastic syndromes Novel agent with unique, dual mechanism-of-action Signs of efficacy in clinic 50% complete remissions in trial s 5 th cohort Additional patients enrolling into 5 th dose cohort Well-tolerated through 5 th cohort Near-term data expected from both programs 27

28 (650)