[ NASDAQ: MEIP ] BIO CEO & Investor Conference February 8-9, 2016

Transcription

1 [ NASDAQ: MEIP ] BIO CEO & Investor Conference February 8-9, 2016

2 Forward-Looking Statements These slides and the accompanying oral presentation contain forward-looking statements. Actual events or results may differ materially from those projected in any of such statements. Additional information concerning factors that may cause actual events or results to differ from those projected is contained in MEI Pharma s most recent annual report on Form 10-K and quarterly reports on Form 10-Q, as well as other subsequent filings with the SEC. 2

3 MEI Pharma (Nasdaq: MEIP) Late-stage oncology drug development company with three wholly owned drug candidates in the clinic Pracinostat: Oral HDAC inhibitor preparing for Phase III study in AML o Median overall survival >14 months in Phase II AML study ME-401 (formerly PWT143): Selective oral PI3K delta inhibitor o Superior clinical PK/PD profile compared to Zydelig ME-344: Novel mitochondrial inhibitor with evidence of clinical activity o Exciting pre-clinical data in combination with VEGF inhibitors Strong intellectual property protection for all three drug candidates Management team w/ proven oncology drug development experience 3

4 Management Team EXECUTIVE MANAGEMENT Daniel Gold, PhD President & Chief Executive Officer Former Chief Scientific Officer & Founder, Favrille Robert Mass, MD Chief Medical Officer Former Head of Medical Affairs, BioOncology, Genentech Thomas Zech Chief Financial Officer Former Chief Financial Officer, Pacira Pharmaceuticals David Urso, JD SVP, Corporate Development & General Counsel Former Principal, Forward Ventures / COO, Tioga Pharmaceuticals Karen Potts, PhD SVP, Regulatory Affairs Former SVP of Regulatory Affairs, Trius Therapeutics BOARD OF DIRECTORS Christine White, MD (Chair) Former Head of Global Medical Affairs, Biogen Idec Charles Baltic, JD Co-Head of Healthcare, Needham & Co. Leah Cann, MBA Two-time Wall Street Journal All-Star Analyst Kevan Clemens, PhD Former Head of Global Oncology, Roche Nick Glover, PhD President & CEO, ProNAi Therapeutics Daniel Gold, PhD President & CEO, MEI Pharma Thomas Reynolds, MD, PhD Former Chief Medical Officer, Seattle Genetics William Rueckert Former Chairman, Novogen Limited 4

5 CANCER METABOLISM PROGRAM SIGNALING PROGRAM EPIGENETICS PROGRAM Clinical Development Pipeline DRUG CANDIDATE INDICATION / COMBINATION PRE-CLINICAL PHASE I PHASE II PHASE III Pracinostat HDAC Inhibitor Acute Myeloid Leukemia Front Line, Elderly Azacitidine (Vidaza ) Myelofibrosis* Front Line & Relapsed/Refractory Ruxolitinib (Jakafi ) REGISTRATION STUDY ME-401 (PWT143) PI3K Delta Inhibitor B-Cell Malignancies Recurrent CLL or follicular NHL Single Agent, Dose Escalation ME-344 Mitochondrial Inhibitor HER2-Negative Breast* Bevacizumab (Avastin ) 5 * Investigator-sponsored studies

6 Pracinostat: Potent & Selective Oral HDAC Inhibitor Tested in 300+ patients in multiple Phase I and II clinical studies Manageable side effects consistent with drugs of this class Potential best-in-class PK profile Enhanced PK profile leads to superior potency On target IC 50 activity for HDAC1 predicted to be >24 hours Evidence of single-agent clinical activity in AML and myelofibrosis Evidence of clinical activity in combination with azacitidine (Aza) Exploratory analyses from randomized Phase II study in MDS suggest benefit for patients able to tolerate Pracinostat for at least 4 cycles Positive results from Phase II study suggest survival benefit in newly diagnosed AML patients 6

7 Pracinostat + Aza in MDS: Summary Pilot study of Pracinostat + Aza in higher risk MDS showed encouraging CR/CRi rate of 89% 1 Randomized Phase II study of Pracinostat + Aza in higher risk MDS failed to improve clinical complete remissions compared to Aza alone Pracinostat resulted in more toxicity when added to Aza, leading to more, and earlier, drug discontinuation in the Pracinostat group Exploratory analyses of patients able to tolerate combination for at least 4 cycles confirm activity of Pracinostat + Aza 7 1 Quintás-Cardama et al. ASH 2012: 3821

8 Pracinostat + Aza in MDS: Overall Survival for Patients on Study for 4 or More Cycles 1 HR = As of data lock on June 30, 2015

9 Pracinostat + Aza in MDS: Duration of Response for Patients on Study for 4 or More Cycles 1 HR = 0.48 HR = As of data lock on June 30, 2015

10 Pracinostat + Aza in AML: Introduction Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options Pracinostat has shown single-agent activity in this population 14% (2/14) CR rate in Phase I dose-escalation study 1 Phase II study of Pracinostat + Aza in front line AML designed to assess clinical activity of combination in multi-center environment 10 1 Garcia Manero et al ASH: 3292

11 Pracinostat + Aza in AML: Patient Disposition 1 50 patients have been enrolled at 15 centers FPI: December 24, 2013 LPI: November 24, 2014 n=50 (%) Number of Patients Alive Number of Patients Active Median Observation Time: 14.3 months Number of Patients Discontinued Reasons for discontinuation: Progressive Disease Adverse Event Other* 28 (56) 11 (22) 39 (50) 15 (30) 11 (22) 13 (26) 11 1 As of ASH presentation in December 2015 * Includes patient and/or physician decision

12 Pracinostat + Aza in AML: Overall Survival As of ASH presentation in December 2015

13 Pracinostat + Aza in AML: Association of Survival with CR As of ASH presentation in December 2015

14 MEI-004 vs. AZA-001: Baseline Characteristics MEI-004 AZA Azacitidine + Pracinostat (n=50) Azacitidine (n=241) Age, Years Median Min-max Male gender AML classification (by WHO) Not otherwise specified With myelodysplasia-related changes With therapy-related myeloid neoplasms With recurrent genetic abnormalities* Prior MDS Yes Secondary No * Excluding the provisional entities of AML with NPM1 and AML with CEBPA mutation (molecular data not available) 1 Dombret et al. Blood Jul 16;126(3):291-9

15 MEI-004 vs. AZA-001: Baseline Characteristics MEI-004 AZA Azacitidine + Pracinostat (n=50) Azacitidine (n=241) BM blasts Median Min-max ECOG PS Cytogenetic risk group Intermediate Intermediate, cytogenetically normal Poor Dombret et al. Blood Jul 16;126(3):291-9

16 MEI-004 vs. AZA-001: Overall Population Conventional Care Regimens AZA MEI Azacitidine Azacitidine + Pracinostat Overall Population n=247 n=241 n=50 CR rate 21.9% 19.5% 42.0% 60-day mortality rate 18.2% 16.2% 10.0% 1-year survival rate 34.2% 46.5% 62.0% Event-free survival 4.8 months ( ) 6.7 months ( ) 7.7 months ( ) Duration of response 12.3 months ( ) 10.4 months ( ) 11.2 months ( ) Median overall survival 6.5 months (95%CI: ) 10.4 months (95%CI: ) >14 months (95%CI: 10.7-NR) 16 1 Dombret et al. Blood Jul 16;126(3): Garcia-Manero et al. ASH 2015: 453

17 MEI-004 vs. AZA-001: High-Risk Population Conventional Care Regimens AZA MEI Azacitidine Azacitidine + Pracinostat High-Risk Population n=85 n=85 n=21 1-year survival estimate 14% 30.9% 57.0% Median overall survival 3.2 months 6.4 months 13.3 months 17 1 Döhner et al. ASH 2014: Garcia-Manero et al. ASH 2015: 453

18 Pracinostat + Aza: Management of Toxicities in AML Compared to MDS Patients Phase II studies of Pracinostat: Discontinuations in first two cycles due to tolerability MDS (MEI-003) MDS (MEI-003) AML (MEI-004) 1 Azacitidine (n=51) Azacitidine + Pracinostat (n=51) Azacitidine + Pracinostat (n=50) Cycle Cycle Total 4 (8%) 13 (26%) 4 (8%) 18 1 Garcia-Manero et al. ASH 2015: 453

19 Pracinostat + Aza in AML: Conclusions Combination of Pracinostat + Aza is safe and tolerable in elderly AML High response rate compared to single agent azacitidine Prolonged overall survival compared to single-agent azacitidine Apparent correlation of CR and survival in this low intensity therapy Based on these findings, plan to initiate Phase III registration study in 2 nd half of

20 ME-401: Potential Best-in-Class PI3Kd Inhibitor ME-401 (formerly PWT143) has superior pre-clinical activity compared to other PI3Kd inhibitors, including recently approved Zydelig On-target activity more than 10-fold greater First-in-human, single ascending dose study completed Superior PK/PD profile to Zydelig PK confirms once-daily dosing Expected to have excellent safety margin Phase 1b study in B-cell malignancies anticipated in Q Dose-escalation study in recurrent chronic lymphocytic leukemia (CLL) or follicular non-hodgkin s lymphoma (fnhl) 20

21 ME-401: Superior Pre-Clinical Potency Cell Line Tumor Type IC 50 (um) in Proliferation Assays ME-401 (PWT143) CAL-101 (Zydelig ) PCI (Imbruvica ) Farage DLBCL (GCB) SU-DHL-5 DLBCL (GCB) WSU-NHL DLBCL (GCB) or FL RL DLBCL (GCB) SU-DHL-10 DLBCL (GCB) no data U-2932 DLBCL (ABC) no data 21

22 ME-401: Modeling of PK/PD Data Supports Once-Daily Dosing Biomarker for inhibition of PI3K delta: Inhibition of basophil activation by FceR1 antibody PK/PD data was fit to E max Model EC50 = 0.6 ng/ml (1.0nM) EC90 = 5.2 ng/ml (8.9nM) Daily dosing of > 60 mg expected to afford continuous plasma concentrations above the EC 90 ; i.e. in the plateau of the concentration-inhibition curve 22

23 ME-401: Linear PK & T 1/2 Suitable for Once-Daily Dosing Single ascending dose study now complete: 15 healthy volunteers enrolled in 10, 30, 60, 90 & 150 mg dose levels Mean T 1/2 ~ hr. Independent of dose No reported adverse events 23

24 ME-401: Proposed Phase 1b Clinical Study Objective: Demonstrate therapeutic window in cancer patients RSD = 145 mg, but will start lower to establish MED and will dose escalate to MTD Dose-escalation study in recurrent chronic lymphocytic leukemia (CLL) or follicular non-hodgkin s lymphoma (fnhl) Naïve to phosphatidylinositol-4,5-biphosphate 3 kinase p110d subunit (PI3Kd) and Bruton s tyrosine kinase (BTK) therapies Starting dose = 60 mg q.d. Expected study initiation: Q

25 ME-344: Lead Mitochondrial Inhibitor Mechanism of action directly targets mitochondrial OXPHOS complex I 1, resulting in rapid loss of cellular energy (ATP) Evidence of single agent activity in Phase I dose-escalation study in refractory solid tumors 2 Phase 1b combination study with topotecan in relapsed refractory ovarian & small cell lung cancers demonstrated insufficient activity to warrant further development Exciting pre-clinical data in combination with VEGF inhibitors 3 Expect to initiate an investigator-sponsored combination study with Avastin in HER2-negative breast cancer in Q Lim et al. Am J Cancer Res. 2015;5(2): Bendell et al. Cancer Apr 1;121(7): Manevich et al. AACR 2015: 5409

26 Rationale for ME-344 as Combination Therapy Tumor cells can switch between glycolysis and mitochondrial metabolism for survival + VEGF INHIBITOR + ME-344 Glycolysis Mitochondria SURVIVAL VEGFi DEATH 26

27 ME TKI Inhibit Tumor Growth Synergistically* Tyrosine Kinase Inhibitors (TKI) and ME-344 synergistically modulate glycolysis and oxidative phosphorylation in cancer cells to inhibit tumor growth 1200 Spontaneous Breast Tumor Model 1 Tumor Growth Weeks Vehicle ME-344 BIBF ME TKI #1 BIBF+ME TKI #1 + ME Guy et al Mol Cell Biol 12(3): * Collaboration with Miguel Quintela-Fandino, MD, PhD, Spanish National Cancer Research Centre, Madrid

28 % of Tumor Growth Mouse Xenograft Model: Non-Small Cell Lung Cancer Growth Inhibition Xenograft PULM Vehicle ME344 BIBF BIBF+ME T0 T1 T2 T3 T4 T5 T6 T7 T8 T9 T10 T11 T12 T13 T14 T15 Time (weeks) 28

29 Intellectual Property Pracinostat 4 issued U.S. and 77 issued foreign patents 2 U.S. and 8 foreign applications pending Composition of matter to May, 2028 in U.S. May, 2033 with up to 5 years patent term restoration in U.S. ME-401 (formerly PWT143) 2 issued U.S. patent 1 U.S. and 21 foreign applications pending Composition of matter to Dec in U.S., excluding patent term restoration ME issued U.S. and 18 issued foreign patents 3 U.S. and 7 foreign applications pending Composition of matter to March, 2027 in U.S. March, 2032 with up to 5 years of patent term restoration in U.S. 29

30 Financial Highlights Cash: $53.8 million as of December 31, 2015 Debt: None Shares outstanding: 34.2 million 30

31 2016 Clinical Milestones Median overall survival in Phase II study of Pracinostat + azacitidine in elderly AML Initiation of Phase Ib study of ME-401 in CLL & fnhl (Q2) Initiation of investigator-sponsored study of ME Avastin in HER2-negative breast cancer (Q2) Initiation of Phase III registration study of Pracinostat + azacitidine in elderly AML (2H) Interim data from Phase Ib study of ME-401 in CLL & fnhl (Q4) 31

32 [ NASDAQ: MEIP ] BIO CEO & Investor Conference February 8-9, 2016