ASDAQ: MEIP Building a Leading Oncology Franchise 17th Annual eedham Healthcare Conference March 27, 2018
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Building a Leading Oncology Franchise 4 clinical oncology programs leveraging development and oncology expertise 1 Program in Phase 3 registration Second program planned to enter registration study 2H 2018 Multiple near term milestones 3 data readouts 1H 2018 1 study initiation 1H 2018 Efficient business strategy MEI building value in wholly-owned programs Strategic partnerships support late-stage asset development Strong financial position $42M at YE 2017 3 3
Diverse Clinical Pipeline DRUG CADIDATE IDICATIO / COMBIATIO PRE-CLIICAL CLIICAL PROOF-OF-COCEPT PIVOTAL Pracinostat HDAC Inhibitor ME-401 PI3K Delta Inhibitor Voruciclib Selective CDK Inhibitor ME-344 Mitochondrial Inhibitor Acute Myeloid Leukemia Unfit for intensive chemotherapy Vidaza (azacitidine) Myelodysplastic Syndrome High & very high risk Vidaza (azacitidine) Follicular Lymphoma & CLL Relapsed/refractory Single agent Indolent Lymphoma & DLBCL Relapsed/refractory Rituxan (rituximab) B-Cell Malignancies Relapsed/refractory Single agent HER2- Breast Cancer* Treatment-naïve, early stage Avastin (bevacizumab) REGISTRATIO STUDY * Investigator-sponsored study 4
Multiple ear-term Milestones Significant value creation potential in 2018 Pracinostat Data from stage 1 of Phase 2 dose-optimization study in MDS (Q2 2018) ME-401 Data from Phase Ib study in follicular lymphoma & CLL (Q2 2018) Initiate single-agent registration study in R/R follicular lymphoma (2H 2018) Voruciclib Initiate Phase 1 study in R/R B cell malignancies (Q2 2018) ME-344 Data from investigator-sponsored study with Avastin in HER2-negative breast cancer (Q2 2018) Pracinostat, ME-401, voruciclib and ME-344 are investigational agents and have not been approved for commercial use in the U.S. 5
ME-401: Differentiated PI3K-d Inhibitor with Potential Best In Class Pharmaceutical Properties
ME-401: Differentiated PI3K-d Inhibitor to Meet Unmet Medical eed in R/R Follicular Lymphoma High unmet need in R/R FL 1 Fractured R/R FL treatments denote inadequate options 1,2 Differentiated efficacy valued by physicians 2 2018 Registration Study Initiation in R/R FL ~15,000 will be diagnosed with Follicular Lymphoma in 2018 (U.S.) 3 - Significant number advance to R/R disease 1. MEI Pharma Proprietary Primary Market Research; n=25 U.S. and EU Physicians; 2. MEI Pharma Proprietary Primary Market Research; n=60 U.S. Physicians; 3. https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html (accessed 3/22/18) 7
Will Physicians Value a 2 nd Generation PI3K-d Inhibitor? R/R Follicular Lymphoma Still an Unmet Medical eed 4% 4% 28% 48% 16% Low Low Current unmet need in relapsed/refractory FL Low to Moderate Low to Moderate Moderate Moderate Moderate to High Moderate to High High Overall satisfaction with drugs currently available to treat R/R FL 0% 16% 68% 16% 0% High ~2/3: Physicians report high to moderate unmet need >3/4: Physicians report low to moderate satisfaction MEI Pharma Primary Market Research; n=25 U.S. and EU Physicians 8
Preference Share What is Most Important to Physicians? Prescribing Decisions Primarily Driven by Efficacy in 3L FL 1 55% 50% 45% 40% 35% 30% 25% 20% 50% 60% 70% 80% 90% Overall Response Rate (ORR) 1. MEI Pharma Primary Market Research; n= 60 Physicians 9
What is Different About ME-401? Distinct Chemical Structure as Basis for Differentiated Pharmaceutical Properties ME-401 MEI Pharma ICB50465 Incyte Umbralisib TG Therapeutics Duvelisib Verastem Idelalisib Gilead F O R 3 O Cl O F O R 3 R 4 R 2 F C R 5 O C Z X R 1 H H H Y R 6 H H R 4 H 2 F H 2 R 2 O 10
Pharmacodynamic Properties Suggest Potential for Improved Outcomes Distinct Structural Attributes Superior on target residence time t 1/2 ~ 28 hours supports daily dosing Large Volume of Distribution Preferential cellular accumulation Intended Improved Outcome Superior PK/PD attributes results in high potency at low plasma concentrations Potential for significant improvement in therapeutic window Versatility for combination approaches 11
Phase Ib Study in Follicular Lymphoma and CLL Key objectives: Efficacious Dose Maximum Tolerated Dose (MTD) Minimum Biologically Effective Dose Dose escalation complete All 3 dose levels achieved >50% efficacy Efficacious dose determined Dose Escalation Start at 60 mg Cohort Expansion If no DLTs and 2 responses in 6 patients, then expand cohort to 12 Dose escalate to MTD Efficacious Dose Single-Agent Registration Study To Initiate: H2 2018 mbed Combination Studies Initiated 12
Phase 1b Study in Follicular Lymphoma and CLL Emerging Safety and Efficacy Data 41 patients enrolled 30 patients received monotherapy 12 at 60 mg, 12 at 120 mg, 6 at 180mg 11 patients received 60 mg MEI-401 in combination with rituximab Median follow-up = 4.8 mo. (range = 0.5-13.3 mo.) 30 patients receiving monotherapy evaluable for efficacy Response rate well in excess of 50% at all dose levels o dose limiting toxicities noted (DLT assessed at d56) Safety and efficacy data submitted for presentation at scientific meeting in Q2 2018 13
Voruciclib: A Selective CDK Inhibitor
Clinical-Stage Oral CDK Inhibitor Differentiated by MCL1 Suppression Oral CDK inhibitor differentiated by potent inhibition of CDK9 CDK9 suppresses MCL1, a BCL2 inhibitor resistance mechanism Tested in > 70 patients with solid tumors Phase 1/2 study in B cell malignancies and then + venetoclax (Q2 2018 start) Potential utility in multiple indications and combinations 15
Voruciclib: Potential to Overcome Venetoclax Resistance Increased MCL1 is an established venetoclax 1 resistance mechanism Venetoclax inhibits BCL2 but not MCL1 Voruciclib inhibits MCL1 via CDK 9 inhibition Voruciclib inhibits CDK9, 4,6 &1 at low nm concentrations 1 Blood. 2016 Jun 23;127(25):3192-201 16
Voruciclib Sensitivity of CLL Patient Samples at Clinically Achievable Drug Levels Voruciclib was dosed from 75-500 mg QD in Phase 1 solid tumor studies; MTD 350mg Induces apoptosis at 0.5 1 μm in >50 patient-derived CLL samples 1 Phase 1 PK results suggest steady state levels >1.5 μm achievable with 150mg daily dosing Voruciclib, μm 1 PLoS One. 2015 ov 25;10(11):e0143685 17
Voruciclib/Venetoclax Synergy Confirmed in Preclinical in vivo Studies* Voruciclib and venetoclax synergy supports opportunities across multiple indications * U2932 diffuse large B-cell lymphoma (DLBCL) model 18
Voruciclib + Venetoclax ot Only a CLL Story: Opportunities in Double-Hit Lymphoma Subtype of diffuse large B-cell lymphoma (DLBCL) characterized by rearrangements of MYC and BCL2 (most common) or BCL6 Poor prognosis, significant unmet need Voruciclib inhibits MYC protein expression (right) Low response rate to BCL2 inhibitor venetoclax as monotherapy in DLBCL (18% ORR; n = 34) 1 Voruciclib synergistic with venetoclax in multiple DLBCL models 2 1 J Clin Oncol. 2017 Mar 10;35(8):826-833; 2 Sci Rep. 2017 21:7(1): 18007 19
Phase 1 Study Initiation Q2 2018 Relapsed/Refractory B cell Malignancies Standard 3-6 patients/group (3+3) Endpoints Safety and tolerability Pharmacokinetics Biologic correlative studies Objective response rates/mrd negativity Voruciclib single agent Dose escalation 50 mg 100 mg 150 mg 200 mg 250 mg Venetoclax + Voruciclib dose escalation 50 mg 100 mg 150 mg 200 mg 250 mg 20
ME-344: A ovel Tumor Selective Mitochondrial Inhibitor
ME-344: A ovel Mitochondrial Inhibitor with the Potential to Exploit Antiangiogenic Escape Antiangiogenics resistance is a major challenge in cancer therapeutics VEGF inhibition can shift tumor glycolytic reliance towards mitochondrial dependence 1,2 Single agent activity in Phase 1 dose-escalation study in refractory solid tumors 4 Targeting the metabolic escape path would open an important therapeutic opportunity ME-344, as a mitochondrial inhibitor, induces rapid loss of cellular energy (ATP) Proof-of-Concept may support application to additional tumor types where VEGF inhibition applicable Investigator-sponsored study of ME-344 with Avastin in HER2-negative breast cancer 1 J PharmacolExpTher. 2016 Aug;358(2):199-208; 2 Cell Rep. 2016 Jun 21;15(12):2705-18; 3 Am J Cancer Res. 2015 Jan 15;5(2):689-701; 4 Cancer. 2015 Apr 1;121(7):1056-63; 22
Clinical Study in HER2-egative Breast Cancer * Interim data review supported study continuation Group A (=20) ME-344 + Avastin Biopsy / Analysis Group B (=20) Placebo + Avastin Interim data expected Q2 2018 Biopsy on Day 28 / Analysis Prospective, randomized study being conducted at 8 sites in Madrid, Spain Study Objectives: Assess ability of Avastin to shift tumor reliance from glycolysis to mitochondrial metabolism Access ability of ME-344 + Avastin to inhibit tumor proliferation compared to Avastin + placebo * Sponsored by Spanish ational Cancer Research Centre 23
Pracinostat: Potential Best-in- Class Phase 3 HDAC Inhibitor
Pracinostat: Orally Available HDAC Inhibitor with Best-in-Class Potential Ongoing Phase 3 AML registration study FDA breakthrough therapy designation Ongoing Phase 2 MDS study Improved pharmacokinetics compared to approved drugs Increased bio-availability Increased half-life Highly active primary metabolite Evaluated in >300 patients Helsinn global development and commercialization partnership Unmet eeds in AML & MDS AML: Treating older AML patients challenged by difficulty in predicting risk and benefit MDS: Limited reliable options to treat high and very high risk MDS 25
Potential Class Leading Survival Benefit in AML Breakthrough Therapy Designation by FDA Phase 2 Study: Pracinostat + azacitidine in elderly patients with newly diagnosed AML, not candidates for induction chemotherapy Endpoint Pracinostat + Azacitindine (=50) CR rate 42% 60-day mortality rate 10% Duration of Response (CR/CRi) 17.2 months (95%CI: 10.9-21.5) 1-year survival rate 62% Median overall survival 19.1 months (95%CI: 10.7-26.5) Pracinostat + azacitidine was generally well tolerated: Most common grade 3/4 treatment-emergent adverse events in 25% of patients included febrile neutropenia, thrombocytopenia, anemia and fatigue 26
Pivotal Phase 3 Study in AML: First Patient Dosed in July 2017 ewly Diagnosed AML Patients Unfit to Receive Induction Therapy Group A (=~250) Pracinostat + Azacitidine Group B (=~250) Placebo + Azacitidine Randomized, double-blind, placebo-controlled study to enroll up to 500 patients Primary endpoint: Overall survival Secondary endpoints: Morphologic CR rate, event free survival & duration of CR Inclusion criteria: ewly diagnosed AML patients 18 years who are unfit to receive intensive remission induction chemotherapy due to age ( 75 years) or comorbidities 27
Phase 2 Dose-Optimization Study in MDS Potential Expansion to a second indication Patients with High and Very High Risk MDS Previously Untreated with Hypomethylating Agents Stage 1 (~32) Pracinostat (45 mg) + Azacitidine If rate of discontinuation (for reasons other than progressive disease) in first 3 cycles 20%, proceed to Stage 2 Stage 2: Group A (=40) Pracinostat + Azacitidine Stage 2: Group B (=40) Placebo + Azacitidine Two-stage study: 12-15 sites in stage 1; approximately 25 sites in stage 2 Primary objectives: Safety and tolerability; overall response rate (ORR) 28
Multiple ear-term Milestones Significant value creation potential in 2018 Pracinostat Data from stage 1 of Phase 2 dose-optimization study in MDS (Q2 2018) ME-401 Data from Phase Ib study in follicular lymphoma & CLL (Q2 2018) Initiate single-agent registration study in R/R follicular lymphoma (2H 2018) Voruciclib Initiate Phase 1 study in R/R B cell malignancies (Q2 2018) ME-344 Data from investigator-sponsored study with Avastin in HER2-negative breast cancer (Q2 2018) Pracinostat, ME-401, voruciclib and ME-344 are investigational agents and have not been approved for commercial use in the U.S. 29
ASDAQ: MEIP Building a Leading Oncology Franchise 17th Annual eedham Healthcare Conference March 27, 2018