NASDAQ: MEIP
Building a Leading Oncology Franchise17th Annual Needham Healthcare ConferenceMarch 27, 2018
Forward-Looking StatementsThis 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
• 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
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DRUG CANDIDATE INDICATION / COMBINATION PRE-CLINICAL CLINICAL PROOF-OF-CONCEPT PIVOTAL
PracinostatHDAC Inhibitor
Acute Myeloid LeukemiaUnfit for intensive chemotherapyVidaza® (azacitidine)
Myelodysplastic SyndromeHigh & very high risk Vidaza® (azacitidine)
ME-401PI3K Delta Inhibitor
Follicular Lymphoma & CLL Relapsed/refractorySingle agent
Indolent Lymphoma & DLBCLRelapsed/refractoryRituxan® (rituximab)
VoruciclibSelective CDK Inhibitor
B-Cell MalignanciesRelapsed/refractory Single agent
ME-344Mitochondrial Inhibitor
HER2- Breast Cancer*Treatment-naïve, early stageAvastin® (bevacizumab)
* Investigator-sponsored study
REGISTRATION STUDY
Diverse Clinical Pipeline
Multiple Near-Term MilestonesSignificant 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)
5Pracinostat, ME-401, voruciclib and ME-344 are investigational agents and have not been approved for commercial use in the U.S.
ME-401: Differentiated PI3K-dInhibitor with Potential Best In Class Pharmaceutical Properties
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ME-401: Differentiated PI3K-d Inhibitor to Meet Unmet Medical Need in R/R Follicular Lymphoma
71. 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)
• High unmet need in R/R FL1
• Fractured R/R FL treatments denote inadequate options1,2
• Differentiated efficacy valued by physicians2
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
Will Physicians Value a 2nd Generation PI3K-d Inhibitor? R/R Follicular Lymphoma Still an Unmet Medical Need
Low Low to
Moderate
Moderate Moderate to
High
High
4% 4% 28% 48% 16%
Current unmet need in relapsed/refractory FL
Low Low to
Moderate
Moderate Moderate to
High
High
0% 16% 68% 16% 0%
Overall satisfaction with drugs currently available to treat R/R FL
MEI Pharma Primary Market Research; n=25 U.S. and EU Physicians 8
>3/4:Physicians report low to moderate
satisfaction
~2/3: Physicians report high to moderate
unmet need
What is Most Important to Physicians? Prescribing Decisions Primarily Driven by Efficacy in 3L FL1
20%
25%
30%
35%
40%
45%
50%
55%
50% 60% 70% 80% 90%
Pre
fere
nce
Sh
are
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
IdelalisibGilead
DuvelisibVerastem
UmbralisibTG Therapeutics
N
O
N
F
HN
N
N
HN
N
XZ
Y NHN
N
O
N
R2
R4
R1
R3
HN
N
HN
N
N
N
O
C
Cl
H2N
N
NN
N
C
O
O
F
F
F
O
N
N
N
N
R6
R5
R4
R3
R2
H2N
INCB50465Incyte
ME-401MEI Pharma
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Pharmacodynamic Properties Suggest Potential for Improved Outcomes
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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
Distinct Structural Attributes
• Superior on target residence time
• t1/2 ~ 28 hours supports daily dosing
• Large Volume of Distribution
• Preferential cellular accumulation
Phase Ib Study in Follicular Lymphoma and CLL
Key objectives:• Efficacious Dose•Maximum Tolerated Dose (MTD)•Minimum Biologically Effective Dose
Dose EscalationStart at 60 mg
Cohort ExpansionIf no DLTs and ≥ 2 responses in 6 patients, then expand cohort to 12
Dose escalate to MTDSingle-Agent
Registration StudyCombination Studies
InitiatedTo Initiate: H2 2018
Dose escalation complete•All 3 dose levels achieved >50% efficacy• Efficacious dose determined
mBEDEfficacious Dose
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Phase 1b Study in Follicular Lymphoma and CLLEmerging 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
• No dose limiting toxicities noted (DLT assessed at d56)
• Safety and efficacy data submitted for presentation at scientific meeting in Q2 2018
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Voruciclib: A Selective CDK Inhibitor
Clinical-Stage Oral CDK Inhibitor Differentiated by MCL1 Suppression
Oral CDK inhibitor differentiated by potent
inhibition of CDK9
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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
Voruciclib: Potential to Overcome Venetoclax Resistance
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Voruciclib inhibits CDK9, 4,6 &1 at low nM concentrations
1 Blood. 2016 Jun 23;127(25):3192-201
Increased MCL1 is an established venetoclax1
resistance mechanism
Venetoclax inhibits BCL2 but not MCL1
Voruciclib inhibits MCL1 via CDK 9 inhibition
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 samples1
• Phase 1 PK results suggest steady state levels >1.5 μM achievable with 150mg daily dosing
171 PLoS One. 2015 Nov 25;10(11):e0143685
Voruciclib, μM
Voruciclib/Venetoclax Synergy Confirmed in Pre-clinical in vivo Studies*
18* U2932 diffuse large B-cell lymphoma (DLBCL) model
Voruciclib and venetoclax
synergy supports opportunities
across multiple indications
Voruciclib + Venetoclax Not Only a CLL Story: Opportunities in Double-Hit Lymphoma
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• 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 models2
1 J Clin Oncol. 2017 Mar 10;35(8):826-833; 2 Sci Rep. 2017 21:7(1): 18007
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
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Voruciclib single agentDose escalation
Venetoclax +Voruciclib dose escalation
50 mg
100 mg
150 mg
200 mg
250 mg
50 mg
100 mg
150 mg
200 mg
250 mg
ME-344: A Novel Tumor Selective Mitochondrial Inhibitor
ME-344: A Novel Mitochondrial Inhibitor with the Potential to Exploit Antiangiogenic Escape
• Single agent activity in Phase 1 dose-escalation study in refractory solid tumors4
• Investigator-sponsored study of ME-344 with Avastin® in HER2-negative breast cancer
221J PharmacolExpTher. 2016 Aug;358(2):199-208; 2Cell Rep. 2016 Jun 21;15(12):2705-18; 3Am J Cancer Res. 2015 Jan 15;5(2):689-701; 4Cancer. 2015 Apr 1;121(7):1056-63;
Targeting the metabolic escape
path would open an important therapeutic
opportunity
Antiangiogenics resistance is a major challenge in cancer therapeutics
VEGF inhibition can shift tumor glycolytic reliance towards
mitochondrial dependence1,2
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
Clinical Study in HER2-Negative Breast Cancer*
Interim data review supported study continuation
• 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
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Biopsy / Analysis
Group A (N=20)ME-344 + Avastin®
Group B (N=20)Placebo + Avastin®
Biopsy on Day 28 / Analysis
* Sponsored by Spanish National Cancer Research Centre
Interim data expected Q2
2018
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
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Unmet Needs in AML & MDS
AML:Treating older AML patients challenged by difficulty in predicting risk and benefit
MDS:Limited reliable options to treathigh and very high risk MDS
Potential Class Leading Survival Benefit in AML Breakthrough Therapy Designation by FDA
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
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Endpoint Pracinostat + Azacitindine (N=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)
Phase 2 Study: Pracinostat + azacitidine in elderly patients with newly diagnosed AML, not candidates for induction chemotherapy
Pivotal Phase 3 Study in AML: First Patient Dosed in July 2017
• 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: Newly diagnosed AML patients ≥ 18 years who are unfit to receive intensive remission induction chemotherapy due to age (≥ 75 years) or comorbidities
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Group A (N=~250)Pracinostat + Azacitidine
Group B (N=~250)Placebo + Azacitidine
Newly Diagnosed AML Patients Unfit to Receive Induction Therapy
Phase 2 Dose-Optimization Study in MDSPotential Expansion to a second indication
• Two-stage study: 12-15 sites in stage 1; approximately 25 sites in stage 2
• Primary objectives: Safety and tolerability; overall response rate (ORR)
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Stage 2: Group A (N=40)Pracinostat + Azacitidine
Stage 2: Group B (N=40)Placebo + Azacitidine
Stage 1 (N~32)Pracinostat (45 mg) + Azacitidine
If rate of discontinuation (for reasons other than progressive disease) in first 3 cycles ≤ 20%, proceed to Stage 2
Patients with High and Very High Risk MDS Previously Untreated with Hypomethylating Agents
Multiple Near-Term MilestonesSignificant 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)
29Pracinostat, ME-401, voruciclib and ME-344 are investigational agents and have not been approved for commercial use in the U.S.
NASDAQ: MEIP
Building a Leading Oncology Franchise17th Annual Needham Healthcare ConferenceMarch 27, 2018