Building a Leading Oncology Franchise · research and development and market data; risks and...

NASDAQ: MEIP

Building a Leading Oncology FranchiseAnalyst and Investor ReceptionOmni Hotel, San DiegoDecember 3, 2018

Forward-Looking Statements

• This presentation contains, and our officers and representatives may from time to time make, statements that are “forward-looking

statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Examples of

forward-looking statements include, among others, statements regarding our development strategy; potential advantages of our

product candidates; the initiation and completion of preclinical and clinical studies and the reporting of the results thereof; the timing of

regulatory submissions and actions; the sufficiency of our existing cash; and all other statements relating to our plans, objectives,

expectations and beliefs regarding future performance, operations, financial condition and other future events (including assumptions

underlying or relating to any of the foregoing).

• These forward-looking statements rely on a number of assumptions concerning future events and are subject to a number of risks,

uncertainties, and other factors, many of which are outside of our control. Important factors that could cause our actual results and

financial condition to differ materially from those indicated in forward-looking statements include, among others: uncertainties relating

to the initiation and completion of preclinical and clinical studies; whether preclinical and clinical study results will validate and support

the safety and efficacy of our product candidates; the outcome of regulatory reviews of our product candidates; varying interpretation of

research and development and market data; risks and uncertainties relating to intellectual property and the other factors discussed

under the caption “Item 1A. Risk Factors” in our most recent annual report on Form 10-K and our most recent quarterly report on Form

10-Q.

• Any forward-looking statement made by us in this presentation is based only on information currently available to us and speaks only

as of the date on which it is made. In addition, we operate in a highly competitive and rapidly changing environment, and new risks

may arise. Accordingly, you should not place any reliance on forward-looking statements as a prediction of actual results. We disclaim

any intention to, and undertake no obligation to, update or revise any forward-looking statement. You are urged to carefully review and

consider the various disclosures in our most recent annual report on Form 10-K, our most recent Form 10-Q and our other public

filings with the SEC since the filing of our most recent annual report.

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Building a Leading Oncology Franchise

Multiple Near-Term Milestones

Four Clinical-Stage Programs

~$90M Cash to Achieve Key Milestones Across

All Programs (09/30/18)

Targeting Multiple Oncology Pathways

3

Proven Strategic Approach Efficiently Builds Value

Paradigms

with clear medical

needs

Differentiated

clinical-stage

candidates

Apply expertise to

validate

expeditiously

Optimize

commercial value

via optionality

We pursue straight-

forward programs that

set a high bar,

build value for

stakeholders

and deliver patient

benefit beyond what is currently

achieved through

existing therapies.

4

ASH 2018

Clinical Pipeline with Diverse Mechanisms

DRUG CANDIDATE INDICATION / COMBINATION PRE-CLINICALCLINICAL

PROOF-OF-CONCEPT

MARKETING APPROVAL

STUDY

ME-401PI3K Delta Inhibitor

Follicular LymphomaRelapsed/refractory

Single agent

B-Cell MalignanciesRelapsed/refractory

• Single-agent

• Rituxan® (rituximab)

• Zanubrutinib**

VoruciclibSelective CDK Inhibitor

B-Cell MalignanciesRelapsed/refractory

Single agent

ME-344Mitochondrial Inhibitor

HER2- Breast Cancer***Treatment-naïve, early stage

Avastin® (bevacizumab)

* Phase 2 study intended to support an accelerated approval marketing application with the FDA

**Study arm to be initiated under clinical collaboration with BeiGene, Ltd.

***Investigator-initiated study

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PracinostatHDAC Inhibitor

Acute Myeloid LeukemiaUnfit for intensive chemotherapy

Vidaza® (azacitidine)

Myelodysplastic SyndromeHigh & very high risk

Vidaza® (azacitidine)

Phase 3 Pivotal Trial

Phase 2 Accelerated Approval Trial*

FULLY PARTNERED PROGRAMS

(Japan)

ME-401: Highly Active PI3Kδ Inhibitor With Best-in-Class Potential

• Best early-stage clinical data for any PI3Kδ inhibitor⎼ 76% ORR in FL (n=38)⎼ Differentiated AE profile

• Innovative dosing strategy to optimize utility⎼ Expand utility into broad set of potential indications

• Single agent• Combination

• Dosing strategy supported by Phase 1b data⎼ High ORR, low irAE, maintenance of response⎼ Adding zanubrutinib combination cohort

• Phase 2 accelerated approval for r/r FL⎼ Evaluating continuous and intermittent dosing

• Significant need and opportunity⎼ 7,500 patients in r/r FL setting

Accelerated

Approval Study

in R/R FL

Planned Around

Year-end 2018

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MEI: ASH 2018

• Me-401⎼ Preliminary safety and efficacy results with an intermittent schedule of the PI3K

delta inhibitor ME-401 alone or in combination with rituximab for b-cell malignancies

• Voruciclib⎼ Voruciclib, an oral, selective CDK9 inhibitor, enhances cell death induced by the

bcl-2 selective inhibitor venetoclax in acute myeloid leukemia

• Pracinostat⎼ Planned interim analysis of a phase 2 study evaluating the combination of

pracinostat, a histone deacetylase inhibitor (hdaci), and azacitidine in patients with high/very high-risk myelodysplastic syndrome (MDS)

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Tonight’s Event – Featured Guest Speakers & KOLs

John M. Pagel, M.D., Ph.D.Evolving PI3K Landscape

Matthew S. Davids, M.D., MMScCLL & Lymphoma disease overview

and need for combinatorial approaches

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Michael K. Keng, M.D.Review of ASH 2018 MDS Phase 2

interim data poster





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interim data poster

The Evolving Landscape of PI3K Delta Inhibitors

John Pagel, M.D.

Chief of Hematologic Malignancies and Director of Hematopoietic Stem Cell Transplantation Program at the Center for Blood Disorders and Stem Cell Transplantation in the Swedish Cancer

Institute

December 3, 2018

Dr. John Pagel, MD, PhD, is Chief of Hematologic Malignancies and the Director of StemCell Transplantation at Swedish Cancer Institute in Seattle, Washington. Dr. Pagel’sresearch interests include the development and discovery of novel therapeutics, and inparticular immunotherapies, for the treatment of hematologic malignanciesl.

Dr. Pagel has served as the principal investigator of many past and current humanclinical trials. His research has resulted in over 150 publications in peer-reviewedjournals, with his work in several scientific journals, including The New EnglandJournal of Medicine, Blood, Journal of Clinical Oncology, Cancer Research, BoneMarrow Transplantation and the Proceedings of the National Academy of Sciences.

Dr. Pagel has been a consultant for:• Pharmacyclics• Gilead Sciences• Astra Zeneca• Kite Pharma

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New Options to Treat B-Cell Lymphomas and Select Leukemias Needed• Diverse collection of diseases and treatment options, and varying:

• Response

• Durability

• Toxicity

• Combinatorial opportunities

• Differing medical needs

• Indolent vs. aggressive disease

• Patient sub-sets

• Unsatisfactory late-line treatment options

• Generally, no standard approach

• Durability remains a challenge in many cases

• Need for more non-chemo combinatorial options12

Evolving Potential of PI3K Delta Inhibitors

• Improved PK/PD

• Dosing Schedule Innovations

• Optimization of PI3K delta inhibition for improved efficacy

• Differentiated adverse event profiles

• Potential to combine with other mechanisms

• New candidates may hold enhanced potential to improve clinical utility

• Current options hold sub-optimal efficacy/toxicity profile

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Preferred Profile for New PI3K Delta Inhibitor• Improved efficacy

• Better leverage potential of the MOA

• Refined toxicity• Limit to on-target AEs• Reduce grade and frequency

• Achieve and maintain deep responses• Maximization of time on therapy

• Flexibility to treat based on patient/disease profile

• Combination “friendly” profiles• Safety• Efficacy• Dosing (i.e. route and schedule)

14

New PI3K Delta Inhibitors May Provide Needed Combination Treatment Potential

• Goal of PI3K Delta Inhibition Combinations:

• Improve efficacy and limit increases in AEs

• Potential combinations:

• CD20

• BTK

• BCL2

• PD1 / PD-L1

• JAK

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ME-401 Data to Date Supports Potential Differentiated Profile • ME-401 achieves a high response rate in patients with relapsed/refractory FL and CLL/SLL

• 76% in FL and 100% in CLL/SLL

• Encouraging duration of response and failure-free survival

• Lower incidence of grade 3 irAEs observed on the intermittent dosing schedule

• Intermittent dosing can be used successfully to retreat patients with grade 3 irAEs

• Disease control maintained in most patients treated on the intermittent dosing schedule

• 72% of patients have not experienced disease progression

• Recapture of disease response in 70% of patients retreated with daily dosing after evidence of disease

progression on intermittent dosing

• Launching global, randomized, double-blind, 2-arm study in patients with R/R FL after failure of ≥ 2 prior systemic

therapies

• One arm evaluating higher dose intensity approach with continuous daily dosing,

• Mitigation of immune-related toxicity by switching to an intermittent dosing in the presence of grade ≥ 2

immune-related adverse events

• One arm evaluating a lower dose intensity approach with intermittent schedule after 2 cycles of daily dosing

• Wwitch to daily dosing if tumor regrowth

• This randomized experiment will determine which approach results in longer duration of exposure to ME-401,

maximizes disease control, and is better tolerated

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QUESTIONS?



Matthew S. Davids, M.D., MMScLymphoma & CLL disease overview

and need for combinatorial treatment

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interim data poster

Lymphoma & CLL Disease Overview and the Need for Combinatorial Treatments

Matthew S. Davids, MD, MMSc

Associate Director |Center for Chronic Lymphocytic Leukemia

Assistant Professor of Medicine | Harvard Medical School

San Diego, CA | December 3, 2018

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Disclosures for Matthew S. Davids, MD, MMSc

• Consultancy/Advisory Boards: MEI Pharma, Abbvie, Genentech, Pharmacyclics, Janssen, Astra-Zeneca, Acerta, Verastem, Gilead, Syros, Sunesis, Adaptive Biotechnologies

• Research Funding: MEI Pharma, Genentech, Pharmacyclics, TG Therapeutics, BMS, Surface Oncology, Verastem, Astra-Zeneca

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Brief bio: Matthew S. Davids, MD, MMSc• Started at DFCI in 2008

• Current Titles• Director, DFCI Lymphoma BioBank• Associate Director, DFCI CLL Center• Assistant Professor of Medicine, Havard Medical School

• Physician: active, focused practice in CLL and NHL

• Clinical Trialist: Currently PI of 15 trials including overall study chair of voruciclib phase I trial in lymphoid malignancies

• Translational Scientist: run an independent research lab at DFCI focused on CLL and NHL

• Recent accomplishments: helped develop venetoclax, first author publications in NEJM, JCO, Blood, chaired 2017 ASH Educational Program in CLL, recipient of first James O. Armitage Award in Lymphoma Clinical Investigation (2018)

• Outside the hospital: avid cyclist, this year completed my 8th Pan Mass Challenge

Matthew S. Davids, MD, MMSc

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Roberts, Davids, et al., NEJM, 2016Jones, et al., Lancet Oncol., 2018

CLL: Response rates to the Bcl-2 inhibitor venetoclax are high, but durability of response is limited

Phase 2Phase 1

ALC

SPD LN BM

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NHL: Venetoclax is active for certain subtypes, but responses are variable

Davids MS et al., 2017: J Clin Oncol 35:826-833. 23

Adapted from DeVita and Chu, Cancer Res, 2008

Combination chemotherapy can cure hematologic malignancies

CURE?

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Diverse mechanisms allow for many possible combinations

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venetoclax

idelalisib

duvelisib

ibrutinib

BCL-2

CD20

obinutuzumab

• NA + CIT

• NA + CD20 mAb

• NA-NA combos

CD20

Stromal

Microenvironment

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Deng et al., Leukemia, 2017

BTKi increases BCL-2 dependence in CLL cells, and early clinical results of combination therapy are promising

n=36 n=33 n=20 n=10 n=3

97

3925 20

3

6175 80

100

021

45

80

100

0

10

20

30

40

50

60

70

80

90

100

PR% CR/CRi % BM MRD neg %

Jain et al. ASH 2017

1L MDACC Ibrutinib + Venetoclax Cohort

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Certo et al, Cancer Cell 2006

Bcl-2 is one of several anti-apoptotic proteins, and Mcl-1 is another key target

2727

Three direct MCL-1 inhibitors recently entered the clinic and each has potential for benefit, but also limitations

Xiang et al., Onco Targets Ther, 2018 28

Voruciclib: A Potent CDK Inhibitor

• Inhibits CDK9, 4,6, and 1 at low nM concentrations

• Transcriptional regulator of MCL-1 and MYC• Orally bioavailable• Favorable safety profile in solid tumor studies

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Increased MCL1 Expression May Be an Important Venetoclax Resistance Mechanism

• Voruciclib inhibits CDK9 at low nMconcentrations

• CDK9 inhibits MCL1 and MYC

Venetoclax inhibits BCL2 but not

MCL1

Voruciclib inhibits MCL1 via CDK9

inhibition

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interim data poster

Planned Interim Analysis of a Phase 2 Study Evaluating the Combination of Pracinostat, a Histone Deacetylase Inhibitor, and Azacitidine in Patients with

High/Very High-Risk Myelodysplastic Syndrome

Michael Keng, MDDivision of Hematology/Oncology

University of Virginia Cancer Center, Charlottesville, VA, USA.

December 3, 2018American Society of Hematology 2018, San Diego, USA

Michael Keng1, Samer Khaled2, Brenda Cooper3, Erica Warlick4, David A Ramies5, Silvia Mappa6, Ehab Atallah71. Division of Hematology/Oncology, University of Virginia Cancer Center, Charlottesville, VA; 2. Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA; 3. Hematologic Malignancies Program, University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH; 4. Division of Hematology, Oncology & Transplantation, University of Minnesota Medical Center, Minneapolis, MN; 5. MEI Pharma, Inc, San Diego, CA; 6. Helsinn Healthcare SA, Lugano, Switzerland; 7. Hematologic Malignancies, Medical College of Wisconsin, Milwaukee, WI

• Keng – Advisory Board (Agios)

• Khaled: consulting (Daiichi and Alexion); Ramies: employee (MEI Pharma) and Medical Monitor of study; Mappa: employee (Helsinn Healthcare); Atallah: research funding (ADC Therapeutics)

• The remaining authors have nothing to disclose.

Disclosures

• Medical School – Michigan State University

• Residency – University of Southern California

• Fellowship – Cleveland Clinic

• Assistant Professor of Medicine at University of Virginia

• Inpatient Oncology Medical Director and Quality Director for Division of Hematology/Oncology

• Specialty – Myeloid Malignancies in the Pre-Stem Cell Transplant Setting

Biography and Practice

• Myelodysplastic Syndrome (MDS): a bone marrow cancer

• High/very high-risk patients associated with poor survival

– High rate of progression to AML

• Hypomethylating agents (HMA), such as azacitidine, are standard of care in patients ineligible for stem cell transplantation

– 30-35% response rate and typical response of median 12-14 months

• HMA failure associated with very poor outcomes

Background

Fenaux, Lancet Oncology 2009; 10: 223-32Sekeres, JCO 2017;35(24):2745-2753. Prebet, JCO 2011;29(24):3322-3327.

• Combination treatments with HMA are being evaluated as additional treatment options in higher risk MDS

– Historically disappointing due to increased toxicity leading to early discontinuations.

• Inhibition of histone deacetylation (HDAC) and DNA hypermethylation has demonstrated potential synergistic benefit

Pracinostat: An Oral HDAC Inhibitor in Development for AML and MDS

Fenaux, Lancet Oncology 2009; 10: 223-32Sekeres, JCO 2017;35(24):2745-2753. Prebet, JCO 2011;29(24):3322-3327.

• Pracinostat 60 mg/day on 3 alternate days/week for 3 weeks (with step-down dose to 45 mg) in combination with azacitidine 75 mg/m2 x 7 days in a 28-day cycle

• Toxicities resulted in early discontinuations and a reduced efficacy, with no benefit compared with azacitidine alone

Pracinostat: Prior Phase 2 Study

Garcia-Manero, Lancet 2016;17(4):496-508. Garcia-Manero G, et al. Cancer 2017.

• Pracinostat 45 mg/day on 3 alternate days/week for 3 weeks and azacitidine at 75 mg/m2 x 7 days in a 28-day cycle

• This ongoing study evaluates the efficacy of the lower 45 mg dose of pracinostat in combination with the standard dose of azacitidine with the goal of improving tolerability and reducing the number of discontinuations

Pracinostat: Current Phase 2 Study

• To determine the safety, tolerability, and efficacy of pracinostat and azacitidine

• Multicenter, open-label, two-stage design, Phase 2 study at 24 sites.

• Results from this ongoing study as of October 2018.

Objective and Study Design

Study Design

Age ≥ 18 years

High/very high risk MDS

ECOG PS 0–2

Pracinostat 45 mg

3 days/week for 3 weeks

Azacitidine75mg/m2 for 7 days

Rest for 1 week

ONE CYCLE

Study Design – Study Medications

• PracinostatDose Reductions Prohibited in Cycles 1-4

• AzacitidineDose Reduction Prohibited in Cycle 1

• Study drugs administered until disease progression, intolerable toxicity, or allogeneic stem cell transplantation (SCT)

Study Design

Enrollment

expansion: 60 pts

Pracinostat +

Azacitidine

≤ 40 patients:

Pracinostat (45

mg) + Azacitidine

Primary endpoints:

Tolerability, Overall

Response Rate &

One Year Survival

Interim Review:

• Confirm discontinuation <20%

• May 2018: 10% discontinuation

(N=20)

Patient Population

Inclusion Criteria Exclusion Criteria

• Age ≥18 years with documented MDS• High- or very high-risk MDS according to IPSS-R• CMML-1 and CMML-2 subtypes allowed• Bone marrow biopsy and/or aspirate <28 days

prior to Day 1 treatment• ECOG performance score 0–2• Previously untreated with HMA (prior therapy

with transfusions, hematopoietic growth factors, or immunosuppressive therapy is allowed) and clinical indication for treatment with azacitidine

• Adequate Organ Function

• Bone marrow blasts ≥20%• Received any investigational agent < 14 days or

5 half-lives; hydroxyurea <48 hrs; hematopoietic growth factors: erythropoietin, (G-CSF), (GM-CSF), or thrombopoietin receptor agonists ≤7 days (≤14 for Aranesp)

• Major surgery <28 days• Unstable cardiac function or uncontrolled

infection• Prior treatment for MDS with the HDAC

inhibitor or HMA

Assessments and Analysis

Primary Endpoint • Overall response rate (ORR) [complete remission, partial remission]

Efficacy Evaluation

• By Investigator assessments based on haematological and cytogenetic examination of peripheral blood and bone marrow aspirates and biopsy, and transfusions. Disease assessment according to the IWG-R criteria.

Statistical Analysis

• Pre-planned interim analysis, pre-defined discontinuation rate due to AEs of ≤10% in the first 3 cycles and an ORR ≥20% required to expand to Stage 1b

• 60-patient sample was required to detect a substantial effect on ORR compared to historical controls treated with AZA alone

• 55 Patients enrolled as of October 2018• Majority Male: 64%• Median Age: 68• Median time from diagnosis: 1 month• About evenly split between

high and very high-risk MDS

Patient Characteristics - Baseline

• Median duration on therapy is 4.7 months

(range, 0.5-13)• 25% received >6

cycles of therapy

Patient Disposition

• Manageable AE profile,

typical for the patient population

Adverse Events

• Incidence of events

leading to early

discontinuation

lower than in

prior study

Adverse Events

– Comparison

Disease Response

• This study shows that the lower dose of pracinostat 45 mg is better tolerated than the 60 mg dose evaluated in the prior study

• The incidences of adverse events that led to early discontinuation in the prior study were lower for non-hematological events and at least comparable for hematological events in the current study

– Patient in this study were higher-risk MDS than the prior study!

– A discontinuation rate due to adverse event in the first 3 months of 4% compared to rate of 26% reported in the prior study and to that reported in prior studies with azacitidinealone

Conclusions

• CR rates are encouraging (29% at cycle 2 or later and 36% at 6 cycles or more)

• Further follow-up is needed to evaluate the effect on survival

• While enrollment in this study is continuing, the initial result are promising and showing that this lower dose of pracinostat and azacitidine combination enhances tolerability, decreases early discontinuations, and improves clinical outcomes compared with the prior study in MDS.

Conclusions - continued

• Co-Investigators:

Samer Khaled, Brenda Cooper, Erica Warklick, Ehab Atallah

• MEI

• Helsinn

• Our Patients and Their Families

Thank you!

Questions ?

Q&AMEI Pharma Management Team

Key Upcoming Milestones Across Portfolio

• Pracinostat

⎼ Phase 2 dose-optimization study in MDS enrollment and data

• ME-401

⎼ Data updates from Phase 1B study in B-cell malignancies

⎼ Initiation accelerated approval study in R/R follicular lymphoma

• Voruciclib

⎼ Phase 1 study initiation R/R B-cell malignancies

⎼ Phase 1 data updates

• ME-344

⎼ Data from investigator-sponsored study with Avastin® in HER2-

negative breast cancer

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THANK YOU!

Building a Leading Oncology Franchise · research and development and market data; risks and...

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