Oncotelic Therapeutics Inc · OTC:OTLC
Oncotelic Therapeutics — Mateon Therapeutics — IPO Roadshow (September 2017)
44 slides from Oncotelic Therapeutics's IPO roadshow presentation, Sep 11, 2017
Slide 1: Corporate Overview
Corporate Overview William D. Schwieterman, MD President and Chief Executive Officer September 2017 Filed pursuant to Rule 433 Registration Statement No. 333-217904 September 11, 2017
Slide 2: Safe Harbor Statement
Safe Harbor Statement This presentation contains forward-looking statements under the meaning of the Private Securities Litigation Reform Act of 1995. These statements give our current expectations or forecasts and use words such as “potential”, “anticipate,” “estimate,” "expect," “believe,” "can,"
Slide 3: Company Overview
Company Overview Biopharmaceutical company developing vascular disrupting agents (VDAs) for treatment of cancer VDAs selectively occlude tumor vasculature Focusing on orphan oncology indications Core development programs CA4P (fosbretabulin) for ovarian cancer OXi4503 for AML CA4P in combination wit
Slide 4: Management Team
Team Member Experience William Schwieterman, MD President and Chief Executive Officer Perceptive Advisors; Chelsea Therapeutics; FDA – Chief of Immunology and Infectious Disease Branch, CBER David Chaplin, PhD Chief Scientific Officer Aventis; Rhône-Poulenc Rorer; Cancer Research United Kingdom; Uni
Slide 5: Product Pipeline Summary
Product Pipeline Summary Program Indication Preclinical Phase 1 Phase 2 Phase 3 CA4P Platinum-resistant ovarian cancer OXi4503 Acute myeloid leukemia CA4P Combination with immuno-oncology agents CA4P Recurrent ovarian cancer CA4P Neuroendocrine tumors Phase 2/3 Phase 2 Phase 1/2 Phase 1b Investigato
Slide 6: OXi4503 for the Treatment of Acute Myeloid Leukemia
OXi4503 for the Treatment of Acute Myeloid Leukemia
Slide 7: Unmet Medical Need
Unmet Medical Need Relapsed, Refractory AML Poor prognosis Treated with chemotherapy 1-year survival after first relapse = 29% 5-year survival after first relapse = 11% No new therapies have consistently improved outcomes vs chemotherapy in over two decades Leukemic stem cells in bone marrow likely
Slide 8: Bone Marrow Endothelial Cells (BMEC) Protect Residual Disease In AML
Bone Marrow Endothelial Cells (BMEC) Protect Residual Disease In AML AML–BMEC adhesion via VCAM-1, VE-cadherin, and BCAM AML: acute myeloid leukemia Bosse RC et al. Exp Hematol. 2016;44(5):363-77. AML Cells Adhering to BMEC
Slide 9: Adherent Leukemic Stem Cells are Less Susceptible to Chemotherapy
Adherent Leukemic Stem Cells are Less Susceptible to Chemotherapy Adherence of KG1 leukemic stem cells to BMEC results in more cells in G0/G1 dormant phase BMEC: bone marrow endothelial cells Bosse RC et al. Exp Hematol. 2016;44(5):363-77. Total Cells By Phase G0/G1 - Dormant S Phase – cytarabine su
Slide 10: Adherence of Leukemic Stem Cell to BMEC Reduces Effectiveness of Cytarabine
Adherence of Leukemic Stem Cell to BMEC Reduces Effectiveness of Cytarabine BMECs also reduced the effectiveness of anthracycline and nucleoside metabolic inhibitors (NMI) BMEC: bone marrow endothelial cells; AML: acute myeloid leukemia Bosse RC et al. Exp Hematol. 2016;44(5):363-77. p < 0.001 % AML
Slide 11: OXi4503: New Mechanism for AML Treatment
OXi4503: New Mechanism for AML Treatment #1. Endothelial Cell Disruption Disrupts shape of BMECs by tubulin depolymerization Releases adherent tumor cells from BMEC Reduction of VCAM-1, VE-cadherin, and BCAM Activates the cell cycle #2. Cytotoxic Directly cytotoxic to myeloid lineage cells Cytotoxic
Slide 12: OXi4503: Dual-mechanism of Action
Endothelial cell disruption via cadherin inhibition Cytotoxic via DNA damage and apoptosis OXi4503: Dual-mechanism of Action + O2•- + O2•- OXi4503 CA1 2e/2H+ Prodrug conversion via endogenous phosphatases Peroxidases Orthoquinone
Slide 13: OXi4503: Reduces Adherence of Leukemic Stem Cells
OXi4503: Reduces Adherence of Leukemic Stem Cells OXi4503 disrupts AML-protecting BMECs OXi4503 reduces expression of VCAM-1, VE-cadherin, and BCAM Bosse RC et al. Exp Hematol. 2016;44(5):363-77. Control OXi4503
Slide 14: OXi4503 Forces AML Cells Into Active Cell Cycle
OXi4503 Forces AML Cells Into Active Cell Cycle AML: acute myeloid leukemia; BMEC: bone marrow endothelial cells Bosse RC et al. Exp Hematol. 2016;44(5):363-77. 100% 80% 60% 40% 20% 0% Total Cells By Phase G0/G1 - Dormant S Phase – cytarabine susceptible G2/M – anthracycline susceptible KG1 KG1 + BM
Slide 15: OXi4503: Enhances Efficacy of Cytarabine
OXi4503: Enhances Efficacy of Cytarabine AraC Dose = 100 mg/kg CA1P = OXi4503; AraC = Cytarabine; AML: acute myeloid leukemia; FSC: forward scatter (parameter in flow cytometry) Bosse RC et al. Exp Hematol. 2016;44(5):363-77. FSC Human CD45 SCID mice FLT-3 mutated human AML xenograft model
Slide 16: OXi4503: Efficacious as a Monotherapy
Directly Cytotoxic to Myeloid Blasts OXi4503: Efficacious as a Monotherapy SCID mice FLT-3 mutated human AML xenograft model Normal Mouse Cells Leukemic Cells OXi4503 Dose = 10 mg/kg, 3 times a week AML: acute myeloid leukemia Madlambayan GJ et al. Blood. 2010;116(9):1539-47. Control OXi4503
Slide 17: OXi4503 Clinical Studies
OXi4503 Clinical Studies MATEON THERAPEUTICS
Slide 18: UF4503: AML Phase Monotherapy Study
UF4503: AML Phase 1 Monotherapy Study Investigator-sponsored by University of Florida Patients with treatment refractory AML or MDS OXi4503 (weekly) dose escalation study 19 patients enrolled; dose range 2.5 mg/m2 to 7.81 mg/m2 One patient (5%) had complete marrow remission One patient (5%) had part
Slide 19: Bone Marrow Micrograph Showing Complete Remission
Baseline Cycle 1 Day 28 A representative micrograph of bone marrow sections from one patient showing reduction in blasts (20% to < 5%) after 4 infusions of OXi4503. (Red=CD34, Mag 60X) Bone Marrow Micrograph Showing Complete Remission OXi4503 Monotherapy in AML AML: acute myeloid leukemia Turner et
Slide 20: UF4503: Phase 1 OXi4503 in AML and MDS Adverse Events
Drug-related Adverse Events (Grades >3; N=18) UF4503: Phase 1 OXi4503 in AML and MDS Adverse Events N (%) D-dimer Elevation 15 (83) Bone Pain 7 (39) DIC 5 (28) Febrile Neutropenia 5 (28) Flu-Like Symptoms (F/C/NS) 5 (28) INR Increased 5 (28) Thrombocytopenia 5 (28) Leukopenia 4 (22) PTT prolonged 4
Slide 21: OX1222: Phase 1b Dose Escalation
Relapsed/Refractory AML and MDS Patients OX1222: Phase 1b Dose Escalation NCT Number: NCT02576301 AML: acute myeloid leukemia; MDS: myelodysplastic syndromes OXi4503 (Days 1 and 4 of 28 day cycle) dose escalation study in combination with 1 g/m2/day x 5 days cytarabine 3.75 mg/m2 4.68 mg/m2 6.25 mg/
Slide 22: OX1222 Summary of Results
OX1222 Summary of Results Cohort (Dose) n CR% PR Rate ORR Ongoing Response Cohort 1 (3.75 mg/m2) 6 17% 0% 17% 1 Cohort 2 (4.68 mg/m2) 4 25% 0% 25% 0 Cohort 3 (6.25 mg/m2) 4 25% 25% 50% 1 Cohort 4 (7.81 mg/m2) 3 0% 33% 33% 0 Cohort 5 (9.76 mg/m2) 4 50% 0% 50% 2 CR: complete remission; PR: partial res
Slide 23: Complete Remissions in High Risk Patients
Complete Remissions in High Risk Patients Cohort (Dose) Subject Age Cytogenetics Cycles* Response Cohort 1 (3.75 mg/m2) 106-004 59 inv(3), del(5) 2 Complete Remission (cytogenetic); 13 months – ongoing Cohort 2 (4.68 mg/m2) 106-006 65 Trisomy 8 2 Complete Remission (morphologic); 7 months – ongoing
Slide 24: OX1222: Most Common Adverse Events
OX1222: Most Common Adverse Events Adverse Event N % Febrile neutropenia 10 56% Pyrexia 9 50% Nausea 7 39% Anaemia 6 33% Diarrhoea 6 33% Chills 5 28% Fatigue 5 28% Hypotension 5 28% Neutrophil count decreased 5 28% Platelet count decreased 5 28% Vomiting 5 28% Hypokalaemia 4 22% Pleural effusion 4 2
Slide 25: OX1222: Grade 3+ Related Adverse Events
OX1222: Grade 3+ Related Adverse Events Adverse Event N % Neutrophil count decreased 5 28% Platelet count decreased 5 28% Febrile neutropenia 4 22% Anaemia 3 17% White blood cell count decreased 2 11%
Slide 26: OXi4503: Intellectual Property
Patent No. Type Location Expiration US 9040500 Japan 5302328 EU 2219451 Method for treating hematopoietic neoplasms US, Canada, Australia, Japan, EU 2028 (2033 with extension) US 7078552 EU 1278758 Composition of matter US, Canada, EU 2021 (2026 with extension) NA Orphan exclusivity granted – AML US
Slide 27: OXi4503: Pathway to Approval
OXi4503: Pathway to Approval Phase 2 Randomized Control Phase 1 Dose Escalation Phase 3 Randomized Phase 2 study N = ~50; OXi4503 combination vs cytarabine alone Primary endpoint = response rate Select a dose from Phase 1 study Pivotal Phase 3 study Primary endpoint = overall survival 2017 2019 2018
Slide 28: OXi4503 Summary
OXi4503 Summary Dual-mechanism of action Eliminates protective effect of endothelial cells Cytotoxic in myeloid lineage cells Initial evidence of efficacy in AML Complete Response = 5/21 (24%) relapsed/refractory AML patients including low-dose cohorts Well-tolerated to date Pathway to approval Comp
Slide 29: CA4P for the Treatment of Platinum-resistant Ovarian Cancer
CA4P for the Treatment of Platinum-resistant Ovarian Cancer
Slide 30: Progression-free Survival (Measurable Disease)
Progression-free Survival (Measurable Disease) Study GOG-0186I Nov2015 Treatment Comparison HR 95% Cl Log-rank P Value Active vs. Control 0.600 [0.38, 0.95] 0.027 42 39 Active Control 5 2 3 0 21 9 1 0 # at Risk Bev: bevacizumab; mos: months; HR: hazard ratio, CI: confidence interval Mateon Data on F
Slide 31: prOC FOCUS: Phase 2/3 Study Design
prOC FOCUS: Phase 2/3 Study Design Initiate Study Interim Interim Interim Interim Study Startup Study Complete CA4P + Bev + PCC n=178 Bev + PCC n=178 ORR Data, PFS Data ORR Data Trigger Part 2 Trigger Part 2 Bev + PCC n=40 CA4P + Bev + PCC n=40 NCT Number: NCT02641639 prOC: platinum-resistant ovaria
Slide 32: Interim Analysis FOCUS Results: Demographics
Interim Analysis 2 FOCUS Results: Demographics Active (CA4P) N=19 Control N=21 Age (years) 67.6 61.0 ECOG Status 0 63.2% 57.1% 1 36.8% 38.1% Mean Baseline Tumor Size (cm) 6.86 7.38 Number Prior Treatments 1 26.3% 33.3% 2 31.6% 33.3% 3 21.1% 14.3% ≥4 21.1% 19.0%
Slide 33: Interim Analysis FOCUS Results: Adverse Events
Interim Analysis 2 FOCUS Results: Adverse Events Note: Occurring in >3 patients, more in active than control Active (CA4P) N=19 Control N=21 BP Increased 57.9% 9.5% Hypertension 52.6% 28.6% Nausea 47.4% 19.0% Fatigue 42.1% 23.8% Vomiting 31.6% 14.3% Cough 26.3% 4.8% Abdominal distension 21.1% 9.5% C
Slide 34: Interim Analysis FOCUS Results: Grade 3+ Adverse Events
Interim Analysis 2 FOCUS Results: Grade 3+ Adverse Events Active (CA4P) (N=19) Control (N=21) Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 BP Increased 31.6% 0 0 9.5% 0 0 Hypertension 21.1% 0 0 23.8% 0 0 Dehydration 10.5% 0 0 0 0 0 Note: Occurring in >1 patient
Slide 35: Interim Analysis FOCUS Results: Efficacy
Interim Analysis 2 FOCUS Results: Efficacy PFS favored CA4P Median PFS of 202 days in CA4P treated group versus 151 days in placebo group (HR=0.68; p=0.46) PR rate of 25.0% in CA4P treated group versus 31.6% in placebo group Stable disease of 56.3% in CA4P group versus 57.9% in placebo group PFS: pr
Slide 36: CA4P - Checkpoint Inhibitors
CA4P - Checkpoint Inhibitors
Slide 37: Mechanism of Action of CA4P in Immuno-oncology
Mechanism of Action of CA4P in Immuno-oncology Rapid induction of tumor ischemic necrosis Increased release of tumor antigens Increased tumor antigen presentation to T cells Increased tumor specific T cell cytotoxicity Increased efficacy of checkpoint inhibitors
Slide 38: EMT-6 Mammary Model
Initial Tumor Volume = ~50 mg EMT-6 Mammary Model Data from OX-2015-005. Animals tumor free at study completion: 2/8 in anti-CTLA4 group vs 7/8 in CA4P plus anti-CTLA4 group
Slide 39: CT-26 Colon Model
Initial Tumor Volume = ~150 mg CT-26 Colon Model Data from OX-2017-006.
Slide 40: Summary Immuno-oncology Data
Summary Immuno-oncology Data CA4P increases the efficacy of checkpoint inhibitors Effects in both small (~50 mg) and large (~250 mg) tumors Further studies planned
Slide 41: Finances
Finances Stock traded on OTCQX Market: MATN $5 million cash at 30Jun2017 Limited cash runway into 4Q2017 Expect additional meaningful clinical data in the near term FOCUS – interim analysis 3 OX1222 – final data from cohort 5 No preferred stock or debt outstanding 26.5 million shares outstanding S-1
Slide 42: Investment Highlights
Investment Highlights Orphan oncology focused biopharmaceutical company Anti-vascular approach to targeting cancer Two compounds in active clinical development CA4P – platinum-resistant ovarian cancer (prOC) OXi4503 – acute myeloid leukemia (AML) Additional attractive indications can be pursued Opti
Slide 43: Key Near-term Milestones
Key Near-term Milestones Phase 2/3 FOCUS (prOC) study – 3rd interim analysis Phase 2/3 FOCUS (prOC) study – 4th interim analysis Phase 1b OX1222 (AML) study – Cohort 5 final data
Slide 44: www.mateon.com 650.635.7000
www.mateon.com 650.635.7000