Corporate Overview William D. Schwieterman, MD President and Chief Executive Officer June 2017 Filed pursuant to Rule 433 Registration Statement No. 333-217904 June 19, 2017
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Company Overview Biopharmaceutical company developing vascular disrupting agents (VDAs) for treatment of cancer VDAs selectively disrupt abnormal blood vessels that sustain tumors Focusing on orphan oncology indications Clinical development candidates CA4P (fosbretabulin) OXi4503 Presenting clinical data throughout 2017 Ticker (OTCQX) MATN Price (6/07/2017)$0.55 Market Cap~$15 million Average Daily Trading Volume~80,000 Market Data
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; University College London Matthew Loar Chief Financial Officer KineMed; Neurobiological Technologies; Osteologix; Genelabs Technologies Jeff Nelson VP Program Management Axsome Therapeutics; Chelsea Therapeutics; Ladenburg Thalmann; Cobalt Laboratories Management Team
Board Member Experience William Schwieterman, MD Chairman of the Board Perceptive Advisors; Chelsea Therapeutics; FDA – Chief of Immunology and Infectious Disease Branch, CBER David Chaplin, PhD Aventis; Rhône-Poulenc Rorer; Cancer Research United Kingdom; University College London Simon Pedder, PhD Athenex; Cellectar Biosciences; Chelsea Therapeutics; Hoffman-LaRoche; University of Saskatchewan Donald Reynolds Wyrick, Robbins, Yates, & Ponton; Furiex Pharmaceuticals; Salix Pharmaceuticals Bobby Sandage, Jr., PhD Euclises Pharmaceuticals; Cultivation Capital; Southern Illinois University Edwardsville; Coronado Biosciences; Indevus Pharmaceuticals Board of Directors
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 Investigator-sponsored Mateon-sponsored
2017 Upcoming Milestones Jul Oct Nov Aug CA4P FOCUS Interim Analysis #2 Dec CA4P FOCUS Interim Analysis #4 Sep CA4P FOCUS Interim Analysis #3 OXi4503 AML Cohort 5 Data
Vascular Targeted Therapies Mechanism of Action
Direct anti-vascular effect Reversibly binds tubulin Changes endothelial cell structure Occludes tumor blood supply 10-30 times more selective for tumor vasculature VDAs: Mechanism of Action VDAs: vascular disrupting agents Tozer et al. Cancer Res. 1999 Apr 1;59(7):1626-34.
CA4P: Eliminates Tumor Vasculature Untreated After CA4P Malcontenti-Wilson et al. Clin Cancer Res. 2001;7(4):1052-60.
VDAs: Selectively Target Tumor Vasculature Pericyte (support cell) Immuno-fluorescence Vascular Cast Normal Pericyte support Tumor No pericyte support VDAs: vascular disrupting agents McDonald DM, Choyke PL. Nat Med. 2003;9(6):713-25.
VDA Monotherapy VDA treatment leads to significant central tumor necrosis Tumor rim cells rely on surrounding normal blood vessels After treatment necrotic area can be re-vascularized by angiogenesis Untreated 1 day post CA4P 3 days post CA4P Murine Adenocarcinoma CaNT Model VDA: vascular disrupting agent Chaplin DJ and Hill SA. Int J Radiat Oncol Biol Phys. 2002;54(5):1491-96.
Enhances Anti-vascular Effect VDA + Anti-angiogenic Therapy Indirect anti-vascular mechanism of anti-angiogenic therapy complements the direct anti-vascular mechanism of VDAs Green = Hypoxia; Blue = Perfusion Untreated VEGFR Ab Monotherapy VDA Monotherapy Combination VDA: vascular disrupting agent Shaked Y et al. Science. 2006;313(5794):1785-7.
FACT N=75 GOG-0186I n=81 FALCON n=57 Triple therapy shows best response rates Response Rates in Previous Trials Recurrent OC and NSCLC studies are rates in patients with measureable disease/confirmed response. CA4P + Bev + C/P CA4P + Bev C: carboplatin; P: paclitaxel; Bev: bevacizumab; ATC: anaplastic thyroid cancer, OC: ovarian cancer; NSCLC: non-small cell lung cancer CA4P + C/P
US Ovarian Cancer Landscape PFS: progression-free survival; OS: overall survival; psOC: platinum-sensitive ovarian cancer; prOC: platinum-resistant ovarian cancer Source: Markman, M, Bookman, M, Second-line treatment of ovarian cancer. The Oncologist 2000, Locust Walk Partners interviews and analysis. Epithelial Ovarian Cancer 20,000– 21,000 Stage I Stage IV Stage III Stage II Surgery + Chemo (taxane + platinum) 17,000 - 18,000 Surgery Advanced Disease (85%) Localized Disease (15%) Surgery + Chemo Recurrence detected by: Physical/pelvic examination Imaging: ultrasound, computed tomography (CT) Second-look operation CA-125 blood plasma test Remission psOC prOC 3,000+ Refractory 80-85% Recurrence 13,000 - 15,000 20-25% More Favorable Prognosis Less Favorable Prognosis
Large Unmet Need in Ovarian Cancer Market Patients with prOC have few treatment options, low survival rates Potential annual sales of a branded therapeutic in prOC are ~$500 Million in US, ~$200 Million in EU/Japan1 Platinum-sensitive market is ~50-100% larger Bevacizumab is approved for both psOC (Dec 2016) and prOC (Dec 2014) Expands potential market opportunity for CA4P prOC: platinum-resistant ovarian cancer; psOC: platinum-sensitive ovarian cancer 1 Estimated 2020, assumes 100% penetration at ~$10k per month in the US
GOG-0186I Study Design Randomized, controlled, open-label Phase 2 study Funded by National Cancer Institute, conducted by Gynecologic Oncology Group Primary endpoint: Progression free survival (PFS) Secondary endpoints: Objective response rate (ORR), Overall survival (OS) Patient Population: recurrent ovarian cancer Minimum of 1, maximum of 3 prior therapies Both platinum-sensitive and platinum-resistant Treatment Regimens Bevacizumab 15 mg/kg+CA4P 60 mg/m2 IV q3 weeks (n=54) Bevacizumab 15 mg/kg IV q3 weeks (n=53) N=107 (67 sites) Monk BJ et al. J Clin Oncol. 2016;34(19):2279-86.
Progression-free Survival (ITT) GOG-0186I Results: Primary Endpoint Analysis Months on Study 1.0 0.8 0.6 0.4 0.2 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Proportion Progression-Free Events N Median (mos) CA4P + Bev 41 54 7.3 Bev 47 53 4.8 Treatment Comparison HR* 90% Cl 1-sided P Value Active vs. Control 0.685 [0.47, 1.00] 0.049 *Hazard Ratios of the experimental level to the reference level of the treatment comparison were stratified by measurable disease status (Yes/No), prior bevacizumab use (Yes/No), and platinum sensitivity (>12 months/≤ 12 months) using a Cox proportional hazards model. 53 54 1 2 6 9 0 1 ITT: intent-to-treat; Bev: bevacizumab; mos: months; HR: hazard ratio, CI: confidence interval Monk BJ et al. J Clin Oncol. 2016;34(19):2279-86.
Progression-free Survival (Platinum-resistant) GOG-0186I Results Events n Median (mos) CA4P + Bev 10 13 6.7 Bev 13 14 3.4 Treatment Comparison HR* Log-rank P Value Active vs. Control 0.57 0.01 *Hazard Ratio of the experimental level to the reference level of the treatment comparison were stratified by measurable disease status (Yes/No) and prior bevacizumab use (Yes/No), using a Cox proportional hazards model. The CI is questionable and therefore not available, which may be due to the small number of patients within some strata. Months on Study 1.0 0.8 0.6 0.4 0.2 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 Proportion Progression-Free 14 13 1 2 0 1 1 Bev: bevacizumab; mos: months; HR: hazard ratio; CI: confidence interval Monk BJ et al. J Clin Oncol. 2016;34(19):2279-86.
Progression-free Survival (Measurable Disease) GOG-0186I Results 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 File. Months on Study Events n Median ( mos ) CA4P + Bev 40 42 9.8 Bev 38 39 6.1
Overall Survival (Measurable Disease) GOG-0186I Results Nov2015 Treatment Comparison HR 95% Cl Log-rank P Value Active vs. Control 0.777 [0.44, 1.36] 0.377 42 39 Active Control 28 21 16 11 38 33 4 3 1 0 Months on Study # at Risk Bev: bevacizumab; mos: months; HR: hazard ratio, CI: confidence interval Mateon Data on File. Events n Median ( mos ) CA4P + Bev 24 42 26.8 Bev 25 39 21.2
FOCUS Study Data April 2017
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 Bev: bevacizumab (Avastin); PCC: physicians choice chemotherapy; ORR: objective response rate Regular interim analyses to detect efficacy and test powering assumptions Part 2 triggered based on interim analyses ü ü
Interim Analysis 1 FOCUS Results: Demographics Active (CA4P) N=9 Control N=11 Age (years) 66.3 59.7 ECOG Status 0 44% 73% 1 56% 27% Mean Baseline Tumor Size (cm) 14.0 14.1 Number Prior Treatments 1 33% 37% 2 11% 46% 3 44% 0 ≥4 11% 18%
Interim Analysis 1 FOCUS Results: Adverse Events >1 patient, more in active than control Active (CA4P) N=9 Control* N=10 Blood pressure increased 8 (89%) 2 (20%) Hypertension 5 (56%) 3 (30%) Fatigue 4 (44%) 2 (20%) Constipation 4 (44%) 1 (10%) Nausea 4 (44%) 1 (10%) Vomiting 4 (44%) 0 ( 0%) Abdominal pain 3 (33%) 1 (10%) Cough 3 (33%) 1 (10%) Dyspnoea 3 (33%) 1 (10%) Mucosal inflammation 3 (33%) 1 (10%) Anaemia 3 (33%) 0 ( 0%) Abdominal distension 2 (22%) 1 (10%) Pruritus 2 (22%) 1 (10%) Asthenia 2 (22%) 0 ( 0%) Dysphagia 2 (22%) 0 ( 0%) Insomnia 2 (22%) 0 ( 0%) Intestinal obstruction 2 (22%) 0 ( 0%) *One control patient has no AE data available at interim analysis AE: adverse event
Interim Analysis 1 FOCUS Results: Adverse Events Grade 3-5 Active (CA4P) (N=9) Control (N=10) Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5 Blood pressure increased 44% 0% 0% 10% 0% 0% Hypertension 22% 0% 0% 30% 0% 0% Hyponatraemia 11% 0% 0% 10% 0% 0% Abdominal pain 11% 0% 0% 0% 0% 0% Anaemia 11% 0% 0% 0% 0% 0% Fatigue 11% 0% 0% 0% 0% 0% Intestinal obstruction 11% 0% 0% 0% 0% 0% Sepsis 11% 0% 0% 0% 0% 0% Vomiting 11% 0% 0% 0% 0% 0% Choking 0% 11% 0% 0% 0% 0% Septic shock 0% 0% 0% 0% 0% 10% COPD 0% 0% 0% 0% 10% 0% Ascites 0% 0% 0% 10% 0% 0% GGT increased 0% 0% 0% 10% 0% 0% Hand-foot syndrome 0% 0% 0% 10% 0% 0% Headache 0% 0% 0% 10% 0% 0% Large intestinal obstruction 0% 0% 0% 10% 0% 0% Urosepsis 0% 0% 0% 10% 0% 0%
Interim Analysis 1 FOCUS Results: Objective Response Rate Numerical benefit in favor of CA4P in ORR Magnitude of tumor response better in CA4P arm CA4P patients with PRs had reductions of 76% and 64% versus 46% in Control PFS data immature, currently favors CA4P Active (CA4P) N=9 Control N=11 Partial Response (PR) 2/9 (22%) 1/11 (9%) Stable Disease (SD) 4/9 (44%) 6/11 (55%) Progressive Disease (PD) 2/9 (22%) 2/11 (18%) Non-Evaluable 1/9 (11%) 2/11 (18%) ORR: objective response rate; PFS: progression-free survival
Interim Analysis 1 FOCUS Results: Per Patient Performance* PD /Death Withdrew *Preliminary data as of Apr 14th; subject to continuing analyses Scan Scan shows PD PR SD Scan Not done
CA4P Safety Summary CA4P is generally well tolerated, more than 475 patients dosed to date Adverse events of interest Acute post-infusion blood pressure increase (HTN) 30-89% of patients Transient (resolves in 2 - 6 hrs), consistent with PK (t½ = 2 hrs) On average ~20 mmHg; can be managed with anti-HTN agents Due to BP effects, CA4P may not be appropriate for use in patients with significant underlying cardiovascular morbidity Tumor pain: mild to moderate within 48 hours of infusion HTN: hypertension; BP: blood pressure; AEs: adverse events
Summary of Efficacy Data CA4P shows activity in multiple tumor types Maximum efficacy in combination with anti-angiogenic agents CA4P + bevacizumab improves PFS in recurrent ovarian cancer Greatest effects in patients with larger tumors Measurable disease Platinum-resistant disease Trends showing improvement in overall survival Studies GOG-0186I and FACT Initial efficacy data from FOCUS favors CA4P PFS: progression-free survival
CA4P - Many Potential Indications Mechanism of action based on tumor vasculature, not tumor type Focus on ovarian cancer is based on clinical indication with most data Other potential orphan indications include: Cervical cancer Gastric cancer Glioblastoma multiforme Hepatocellular carcinoma Metastatic melanoma Neuroendocrine tumors Renal cell carcinoma
CA4P-induced tumor necrosis may enhance antigen presentation Combination with Immuno-Oncology Agents Three additional studies provide evidence that CA4P may enhance anti-CTLA4, anti-PD1, and anti-PD-L1 antibody activity Data from OX-2015-005
Active Forms of Lead Products Cytotoxic properties Catechols are easily oxidized to ortho-quinones Second phenolic moiety in CA1 compared to CA4 combretastatin A4 (active form of CA4P) combretastatin A1 (active form of OXi4503) Folkes LK et al. Chem Res Toxicol. 2007;20(12):1885-94.
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. Total Cells By Phase G0/G1 - Dormant S Phase – cytarabine susceptible G2/M – anthracycline susceptible KG1 KG1 + BMEC KG1 + BMEC + OXi4503
Combination with Cytarabine OXi4503: Preclinical Data in AML Enhanced killing of AML with OXi4503 (CA1P) plus cytarabine (AraC) FSC: forward scatter (parameter in flow cytometry) Bosse K et al. Exp Hematol. 2016;44(5):363-377. FSC Human CD45
UF4503 Phase 1 Monotherapy Study Investigator-sponsored, single site study in patients with relapsed/refractory AML and MDS OXi4503 given as a monotherapy Preliminary evidence of effect 1 of 19 patients (5.3%) experienced a complete remission 1 of 19 patients (5.3%) experienced blast reduction Dual mechanism of action is a novel approach in AML Vascular disruption exposes AML cells to chemotherapy Cytotoxic in myeloid lineage cells AML: acute myeloid leukemia; MDS: myelodysplastic syndromes
OX1222 Study Data
Relapsed/Refractory AML and MDS Patients (OX1222) OXi4503 Phase 1b/2 Combination Study Phase 1 Phase 2 Will only initiate with a partner, following sufficient efficacy 3.75 mg/m2 4.68 mg/m2 6.25 mg/m2 9.76 mg/m2 7.81 mg/m2 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
OX1222 Summary of Results Duration of complete remission 3.75 mg/m2: 12 months, then patient withdrew from study 4.68 mg/m2: 5 months, then progressed 6.25 mg/m2: 5 months, ongoing Cohort N CR% In Active Treatment Ongoing Response Progressed 3.75 mg/m2 6 17% 0 1 5 4.68 mg/m2 4 25% 0 0 4 6.25 mg/m2 4 25% 0 1 3 7.81 mg/m2 3 0% 0 0 2 9.76 mg/m2 Enrolling CR: complete remission
($/000s) March 31, 2017 Cash and Short-term Investments $ 8,344 Total Current Assets 10,134 Total Assets 10,175 Short-term Liabilities $ 1,393 Long-term Debt -- Stockholders’ Equity 8,782 Total Liabilities and Stockholders Equity 10,175 Quarterly Cash Burn < $4 million Common Shares Outstanding* 26,545 Financial Highlights and Capitalization * Fully diluted shares outstanding would include an additional 9.8 million warrants with a weighted average price of $2.58 and 5.9 million options with a weighted average price of $1.11.
Key Takeaways Anti-vascular approach to targeting solid and hematological cancers Our drug candidates have largest effect in larger tumors New management team and Board of Directors with deep experience formed over last 2 years Meaningful data on both clinical candidates expected throughout remainder of 2017 Initial efficacy data from FOCUS favors CA4P Initial efficacy data from AML study shows complete remissions in 3 patients to date Multiple opportunities for additional indications for drugs in pipeline AML: Acute myeloid leukemia
2017 Upcoming Milestones Jul Oct Nov Aug CA4P FOCUS Interim Analysis #2 Dec CA4P FOCUS Interim Analysis #4 Sep CA4P FOCUS Interim Analysis #3 OXi4503 AML Cohort 5 Data