The 19th Annual Needham Virtual Healthcare ConferenceApril 14, 2020
NASDAQ: MEIP
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; the impact of the COVID-19 pandemic on our industry and individual companies, including
on our counterparties, the supply chain, the execution of our clinical development programs, our access to financing and the allocation of
government resources; 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.
2
Building a Leading Oncology Franchise
• 4 Clinical-Stage Oncology Programs: Focus On HemOnc
• 2 Candidates in Studies Intended to Support FDA Marketing
Approval Applications
• ME-401: TIDAL Study Supporting Accelerated Approval
Submission in r/r Follicular Lymphoma
• $104 Million to Advance Programs (as of Dec 31, 2020)
• $100M to be received from KKC Global Alliance
3
PROGRAMS INDICATION COMBINATIONCLINICAL PROOF
OF CONCEPT
MARKETING APPROVAL
STUDY
COMMERCIAL
RIGHTS
ME-401Oral P13K Delta
Inhibitor
Follicular Lymphoma
Relapsed/refractoryMonotherapy
U.S. co-promote; ex-
U.S. Kyowa Kirin
exclusive rights
B-Cell Malignancies
Relapsed/refractory
• Monotherapy
• Rituxan®(rituximab)
• Zanubrutinib2
VoruciclibOral CDK Inhibitor
B-Cell Malignancies
& AML
Relapsed/refractory
• Monotherapy
• Venclexta® (venetoclax)3
ME-344Mitochondrial Inhibitor
HER2-Breast Cancer
Treatment-naïve, early
stage
Avastin® (bevacizumab)4
Late-Stage Diversified Clinical Pipeline
1. Phase 2 study to support an accelerated approval marketing application with FDA. 2. Study arm initiated under clinical collaboration with BeiGene, Ltd. 3. Initiation of clinical studies is subject to opening of a new Investigational
New Drug Application with FDA 4. Investigator-initiated trial.
PracinostatHDAC Inhibitor
Acute Myeloid Leukemia
Treatment-naïveVidaza® (azacitidine)
Myelodysplastic Syndrome
Treatment-naïveVidaza® (azacitidine)
Phase 3 Pivotal Trial
Phase 2 Accelerated Approval Trial1
Clinical Collaboration
4
Pipeline of Compatibility Shift Towards Versatile Drugs in Potent Combinations
5
MEI Drug Candidates Select Combinations Potential Indications
FL
MCL
MZL
MDS
Solid Tumor
CLL/ SLL
AMLAzacitidine
Anti-angiogenic
BCL2i
BTKi
Anti-CD20ME-401
Voruciclib
ME-344
Pracinostat
DLBCL
B-cell Malignancies1
• >100K new CLL / NHL U.S. cases in 2018
• ~ 5% of cancers in the US
AML2
• ~20K new U.S. cases 2018
• 32% of adult leukemias
MDS2
• ≥ 10K U.S. cases annually
• 30% of MDS → to AML
MEI Retains Commercial Rights to Majority of Programs
Select Opportunities to Address Significant Unmet Needs
6
$1B + Markets
1. https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/key-statistics.html; https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/key-statistics.html; https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2018.html# 2. https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html; https://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml/statistics; https://www.cancer.org/cancer/myelodysplastic-syndrome/about/key-statistics.html; https://www.mds-foundation.org/what-is-mds/
ME-401 ± Rituximab in Relapsed/Refractory
(R/R) B-cell Malignancies
7
$582Min potential development, regulatory and
commercial milestones
KKC exclusive ex-U.S. rights, MEI to received escalating tiered royalties starting in teens
U.S. COST SHARING, KKC responsible for incremental ex-U.S. costs
AGREED ON BROAD DEVELOPMENT PLAN for B-cell malignancies
Global License, Development and Commercialization Agreement Optimizes ME-401 Value
$100M upfront to MEI
8
50/50U.S. co-promote,
MEI books U.S. sales
The Time for PI3Kδ Has Come: Target Profile to Meet B-Cell Malignancy Medical Need
9
Low G3+ TEAEs
High Responses
Oral
Administration
Durable
Responses
ME-401
Low Discontinuation
Rate
10
ME-401 Fits the Profile of a New Treatment for B-Cell Malignancies
ME-401 data is from r/r follicular lymphoma patients in an ongoing Phase 1b study. Data cutoff: September 19, 2019
79% ORR
High Response Rates
>20 months
Durable Responses to Date(Median follow-up: 10.4 mo.)
<10%Low G3
TEAEs of Special Interest
4% Low Discontinuation Rate
for any TEAE
11
ME-401: Maintaining the Promise of PI3Kδ Inhibition1
In Development
1Data on File (ORR: n=39 on IS monotherapy. Safety: n=57 pts. on IS), 2ZYDELIG (idelalisib) [prescribing information]. Foster City, CA: Gilead Sciences, Inc (n=72 FL pts), 3ALIQOPA (copanlisib) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc (n=104 FL pts), 4COPIKTRA (duvelisib) [prescribing information]. Needham,
MA: Verastem, Inc (n=83 FL pts), 5Grade 3 neutrophil laboratory abnormalities.
Approved2, 3, 4
Note: These data are based on cross-trial comparisons and not based on any head-to-head preclinical studies or clinical trials. As a result, the values shown may not be directly comparable and do not report robust comparative analyses. ME-401 data is from ongoing Phase 1b study. Data cutoff is September 19, 2019
ME-401 (IS)
Overall Response
Rate (ORR)54% 59% 42% 79%
Diarrhea/Colitis 14% 5% 23% 7%
Rash 3% 2% 9% 2%
ALT/AST 19%/12% 2%/2% 8%/6% 2%/0%
Pneumonia/
Pneumonitis16% 14% 20% 2%
Neutropenia 25% 27% 42% 11%5
Discontinuation for
AE; any grade53% 16% 35% 4%
ME-401
12
ME-401
BCL2i2
BTKi1
ME-401 Emerging Profile: Potential for Broad Acceptance Across B-Cell Malignancies & Supports Combinations with Other Modalities
Note: These data are based on cross-trial comparisons and not based on any head-to-head preclinical studies or clinical trials. As a result, the values shown may not be directly comparable and do not report robust comparative analyses. ME-401 data is from an ongoing Phase 1b study evaluating patients on the intermittent schedule as a monotherapy or in combination with Rituxan® (rituximab). Data cutoff is Sept. 19, 2019
Discontinuation Rate: TEAEs (Any Grade)
10.0% (Range: 6.5% - 10.0%)
16.0% (Range: 9% - 16%)
14.6%R22
Diarrhea/
ColitisNeutropenia Anemia Thrombocytopenia
Pneumonia/
PneumonitisHemorrhage
Atrial
Fibrillation/Flutter
Secondary
Malignancy
Tumor Lysis
SyndromeFetal Toxicity
ME-401 7% 0% 0% 0% 2% 0% 0% 0% 0% -
BTKi 0.6%-5% 23%-27% 8%-10% 7%-8% 6%-13% 2%-4% 0.6%-4% 9%-12% 0% -
BCL2i 3%-4% 45%-62% 8%-18% 20-28% 8% 0% 0% 0% 2%-13% -R2 2.8% 50% 4.5% 2.3% 2.2% 0% 0% 0% ✔
1. Includes the FDA approved BTK inhibitors: IMBRUVICA (ibrutinib), CALQUENCE® (acalabrutinib) and BRUKINSA® (zanubrutinib). Rates of TEAE are from FDA labels and relate to safety databases for IMBRUVICA (n=1,124), CALQUENCE (n=1,029) and BRUKINSA (n=629), across clinical trials evaluating patients with CLL/SLL, MCL, WM, and MZL. 2. Rates of TEAEs are from the FDA label for VENCLEXTA (Venetoclax®) as indicated for the treatment CLL/SLL (n=758). 3. Rates of TEAEs are from the FDA label for Revlimid® (lenalidomide) as indicated for the treatment of follicular lymphoma and marginal zone (AUGMENT trial: n=176).
4.0%
High Volume of
Distribution
Tumor
Penetration
Tumor
Accumulation
Selective
Binding
Stable PI3Kδ
Binding
13
Supports Dose Schedule Optimization
ME-401: A Next-generation PI3Kδ Inhibitor with Potential to Redefine the Class
➢ Intermittent dosing (1 wk on / 3 wks off) begins at month 3
following 2 months of daily dosing
• ~80% disease responses occur by month 2
• PK/PD modeling projects ~2 weeks of tumor exposure above EC90
• Intermittent dosing expected to allow Treg repopulation
ME-401
ME-401 Copanlisib(Intravenous)
Idelalisib Duvelisib Parsaclisib Umbralisib
High VSS
VSS (L) ~7001
871 23.0 28.5 ~402
N/A
Cell Penetration
Cellular Association3
In Vivo Biologic
Activity IC50 (nM)4
61%
1
68%
NA
~10%
150
~10%
115
19%
NA
--
NA
1. Assumes average body weight of 70kg. 2. Incyte reported that “PK analysis has demonstrated that Parsaclisib distributes with body water. 3. Estimated from blood/plasma ratio. 4. Inhibition of basophil activation, except for Parsaclisib
which is inhibition of pAKT formation in SUDHL5 cells after incubation in blood from patients.
ME-401: Potential Superior Volume of Distribution and Cell Penetration Offer a Differentiation Explanation
14
Sources: ME-401: Moreno, et. al. Clinical Therapeutics (2018) and Moreno et. al., Targeted Oncology (2019). Copanlisib: CDER Multi-Discipline Review; Package insert. Idelalisib: CDER Clinical Pharmacology and Biopharmaceuticals Review; CHMP assessment report. Duvelisib: CDER Multi-Discipline Review; Package insert. Parsaclisib: Torres, et. al., Blood (2019). Umbralisib: Burris, et. al., Lancet Oncology (2018).
Note: These data are based on cross-trial comparisons and not based on any head-to-head preclinical studies or clinical trials. As a result, the values shown may not be directly comparable and do not report robust comparative
analyses.
ME-401
0
20
40
60
80
Plasma B-cell Tumor
4h
24h
0
25,000
50,000
75,000
100,000
Plasma B-cell Tumor
4h
24h
ME-401: Preferential Retention in Tumors
ng/ml ng/ml
ME-401 Idelalisib
15
Preferential Retention in Murine B-cell Tumors
Moreno et. al., Targeted Oncology (2019).
ME-401 and Idelalisib 50 mg/kg.
16
ME-401 at 60 mg
daily x2 cycles (28
Days)
N = 120
ME-401 at 60 mg for 1 wk
on / 3wks off
starting at Cycle 3 until
toxicity or PD If toxicity: Re-challenge
at resolution with IS
• Histologically confirmed diagnosis of FL, Grade 1, 2, or 3a
• FL, relapsed or refractory to 2 prior systemic therapies including an anti-CD20 antibody and chemotherapy
• No prior therapy with PI3Kδ inhibitors
• No histological transformation to an aggressive lymphoma
16
If PD: Change to CS
Phase 2 TIDAL Trial to Support Accelerated Approval Marketing Application – The Initial Opportunity in r/r FL
(NCT03768505)
ME-401
Select Combinatorial Potential of ME-401
17
Select Combinations Potential Indications
FL
MCL
MZL
CLL/ SLL
BCL2i
BTKi
Anti-CD20
ME-401
DLBCL
ME-401
Chronic Lymphocytic Leukemia
& Small Lymphocytic Lymphoma
Mantel Cell Lymphoma 4,500
DLBCL 22,000
Marginal Zone Lymphoma 6,000
Focus on Select B-Cell Malignancy Indications*
18
Follicular Lymphoma 15,000
(U.S. Only)
20,000
>65,000 Addressable
Patients Across Multiple
Indications
*U.S. incidence rates: Cancer.net, Cancer.org, Lymphoma.org (accessed on November 6, 2019).
$1B+Markets
ME-401
ME-401Conclusion
19
Many
Combinatorial
Options
Across B-Cell
Malignancies
Best-in-class
Potential
Emerging Profile
to Meet Need
Across B-cell
Disease and
Supports Broad
Acceptance
ME-401: Retaining the Promise of PI3Kδ
Voruciclib: Oral CDK Inhibitor with
Potent CDK9 Activity
20
Voruciclib
• Cyclin dependent kinases (CDKs)
are a family of enzymes involved in
cell cycle and transcription control
• CDK9 activates RNA Polymerase II
which is important for the
transcription of MCL-1 and c-Myc
• Voruciclib, an oral CDK inhibitor with
low nM inhibition of CDK9, 4/6 & 1,
causes potent suppression of both
MCL-1 and c-Myc
21
Voruciclib: a Novel, Oral CDK Inhibitor
Voruciclib
Voruciclib: Potential to Overcome Venetoclax Resistance
• Combination opportunities across multiple indications, including:
⎼ AML, CLL & DLBCL
221 Blood. 2016 Jun 23;127(25):3192-201 2 J Clin Oncol. 2017 Mar 10;35(8):826-833; 3 Sci Rep. 2017 21:7(1): 18007
Venetoclax inhibits BCL2
but can lead to
stabilization of MCL1
Voruciclib inhibits MCL1
via CDK9 inhibition
Increased MCL1 is an established venetoclax
resistance mechanism1
Voruciclib
THP-1 (24 h)
Contr
ol
VEN 1
000
nM
VEN 2
000
nM
VEN 4
000
nM
VOR 1
500
nM
VOR 2
000
nM
VOR 3
000
nM
VEN 1
000
+ VOR 2
000
VEN 2
000
+ VOR 2
000
VEN 1
000
+ VOR 3
000
VEN 2
000
+ VOR 3
000
0
50
100 AnnV+/PI+
AnnV+/PI-***
***
*** ***
CI<0.61A
nn
exin
V+
ce
lls (
%)
MOLM-13 (24 h)
Contr
ol
VEN 1
2.5
nM
VEN 2
5 nM
VEN 5
0 nM
VOR 5
00 n
M
VOR 1
000
nM
VOR 2
000
nM
VEN 1
2.5
+ VOR 1
000
VEN 2
5 +
VOR 1
000
VEN 1
2.5
+ VOR 2
000
VEN 2
5 +
VOR 2
000
0
20
40
60
80
100 AnnV+/PI+
AnnV+/PI-
CI<0.41
***
***
*** ***
An
ne
xin
V+
ce
lls (
%)
Voruciclib Synergizes with Venetoclax and Enhances Apoptosis in AML cell lines
V2
23Luedtke et al. Voruciclib, and Oral, Selective CDK9 Inhibitor, Enhances Cell Death Induced by the Bcl-2 Selective Inhibitor Venetoclax in Acute Myeloid Leukemia. ASH 2018
V2
Voruciclib
Voruciclib Synergizes with Venetoclax in a DLBLC Patient Derived Xenograft Model
24Dey J, Deckwerth TL, Kerwin WS, Casalini JR, Merrell AJ, Grenley MO, et al. Voruciclib, a clinical stage oral CDK9 inhibitor, represses MCL-1 and sensitizes high-risk diffuse large B-cell lymphoma to BCL2 inhibition. Sci Rep
2017;7:18007.
Days in Study
Ave
rag
e T
um
or
Vo
lum
e (
mm
3)
Vehicle
Voruciclib 200MPK
ABT-199 10MPK
ABT-199 10MPK + Voruciclib 200MPK
U2932
V2
Voruciclib
MEI Phase 1 Study: Daily Dosing Design in R/R B-Cell Malignancies and AML
• Study population⎼ Relapsed/Refractory B-cell Malignancies
⎼ AML After Treatment with Standard Therapy
• Dose escalation with standard 3+3 design
• Endpoints⎼ Safety and tolerability
⎼ Pharmacokinetics⎼ Biologic correlative studies
• BH3 profiling, MCL-1 expression (Dana Farber)
• Molecular mutations analysis (City of Hope)
⎼ Objective response rates⎼ CR/CRi rate
25
Voruciclib single agent
dose escalation
Venetoclax + Voruciclib dose
escalation
100
mg
150
mg
200
mg
50
mg
100
mg
150
mg
200
mgV2
Key Upcoming Milestones Across Portfolio
• ME-401
⎼ Data updates from Phase 1B combination studies in B-cell
malignancies (Mid 2020)
⎼ TIDAL, accelerated approval, study in R/R follicular lymphoma,
complete enrollment (H2 2020)*
• Voruciclib
⎼ Phase 1B study initiation in combination with Venetoclax
⎼ Phase 1 data updates (End 2020)
• ME-344
⎼ Evaluate development opportunities leveraging demonstration of
anti-tumor activity published at ASCO 2019
• Pracinostat
⎼ Phase 2 data from MDS dose-optimization study (Mid 2020)
26*Timing subject to developments related to the COVID-19 pandemic
The 19th Annual Needham Virtual Healthcare ConferenceApril 14, 2020
NASDAQ: MEIP