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Building a Leading Oncology FranchiseWells Fargo Securities Healthcare ConferenceSeptember 4, 2019
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; 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
Two Drug Candidates in Studies to Support FDA Approval
Building a Leading Oncology Franchise
Clinical Pipeline of Four Independent & Partnered Programs
3*As of June 30, 2019, MEI had $79.8 million in cash, cash equivalents, short-term investments, and common stock proceeds collectible, with no outstanding debt.
Candidates Targeting Multiple Pathways Fuel Combination
Therapy Opportunities
Cash position of ~$80 million to Advance Programs*
PROGRAM INDICATION COMBINATIONS CLINICAL PROOF
OF CONCEPT
MARKETING APPROVAL
STUDY
COMMERCIAL
RIGHTS
ME-401PI3Kδ Inhibitor
Follicular Lymphoma
Relapsed/refractorySingle agent
Japan
B-Cell Malignancies
Relapsed/refractory
• Single agent
• Rituxan®(rituximab)
• Zanubrutinib
MEI RoW
VoruciclibCDK Inhibitor
B-Cell Malignancies & AML
Relapsed/refractory
• Single agent
• Venclexta® (Venetoclax)2 MEI Worldwide
ME-344Mitochondrial Inhibitor
HER2- Breast Cancer***
Treatment-naïve, early
stage
Avastin® (bevacizumab)MEI Worldwide
Late-Stage, Diversified, Clinical Pipeline
1. Phase 2 study intended to support an accelerated approval marketing application with FDA. 2. Amended protocol to evaluate voruciclib in combination with venetoclax subject to FDA approval.
PracinostatHDAC Inhibitor
Acute Myeloid Leukemia Vidaza® (azacitidine)
Myelodysplastic SyndromeVidaza® (azacitidine)
Phase 3 Pivotal Trial
Phase 2 Accelerated Approval Trial1
Clinical Collaboration
4
Combinatorial Potential with Other Major Oncology Drug Classes Across MEIP Pipeline
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 Malignancies*
• >100K new CLL / NHL U.S. cases in 2018
• ~ 5% of cancers in the US
AML**
• ~20K new U.S. cases 2018
• 32% of adult leukemias
MDS**
• ≥ 10K U.S. cases annually
• 30% of MDS → to AML
HER2- Breast Cancer***
• 200K New U.S. cases annually
MEI Retains Commercial Rights to Majority of Programs
Opportunities to Address Significant Unmet Needs
6
$1B+ Markets
*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# **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/ ***https://www.breastcancer.org/symptoms/understand_bc/statistics; https://ww5.komen.org/BreastCancer/TumorCharacteristics.html. All citations accessed June 2, 2019.
Chronic Lymphocytic Leukemia
& Small Lymphocytic Lymphoma 7,000
Mantel Cell Lymphoma 2,000
DLBCL 20,000
Marginal Zone Lymphoma 6,000
~50,000 Addressable Patients
Across Multiple Indications
Focus on Select B-Cell Malignancy Indications
7Company estimates
Follicular Lymphoma 15,000
ME-401: Differentiated PI3Kδ Inhibitor with Potential Best-in-Class Profile
ME-401
Distinct
Structural
Class
Best-in-Class Potential
Differentiated Pharmaceutical Profile
PI3Kδ Target Significance
ME-401: A Differentiated Next-generation Candidate for a New Chapter in PI3Kδ Inhibition
9
Opportunities:
✓ Utility across B-
cell malignancies
✓ Multiple unmet
needs
✓ Many combination
possibilities
ME-401
10
PI3Kδ Inhibition: A Mechanism at a Crossroads of B-cell Malignancy Signaling
• Mechanism relevant to
multiple indications
• Axis for potential benefit via
monotherapy or combination
• Potential to achieve deep
and durable responses
PI3Kδ: Central to B-Cell
Signaling
ME-401
Rapid Tissue
Distribution
Penetrates
Tumor Cells
Accumulates
in Tumor
Cells
Selectively
Binds
PI3Kδ
Tightly and
Stably Binds
to PI3Kδ
High Potency at
Low Plasma
Concentrations
11
• Dose schedule flexibility providing potential to maintain clinical benefit while minimizing adverse events of special interest common to other PI3Kδ agents
• Versatility for combination therapy opportunities
ME-401: A Next-generation PI3Kδ Inhibitor with Potential to Redefine the Class
ME-401
ME-401: A Distinct Chemical Class of PI3Kδ Inhibitor with Optimal Pharmacologic Profile
ParsaclisibIncyte
UmbralisibTG Therapeutics
DuvelisibVerastem
IdelalisibGilead
ME-401MEI Pharma
12
ME-401
ME-401 Phase 1b Study: Patient Characteristics
13
FL (N = 54) CLL/SLL (N = 17)
Total
(N = 71)
CS
(n = 31)
IS
(n = 23)
CS
(n = 9)
IS
(n = 8)
Age, in years
Median (range)
≥65 years
65 (47-81)
17 (55%)
61 (38-82)
9 (39%)
60 (50-79)
3 (33%)
72 (46-80)
7 (88%)
65 (38-82)
36 (51%)
Sex: Male / Female, % 71 / 29 69.6 / 30 78/22 87/13 73/ 27
Prior anti-lymphoma therapy
Median prior therapies (range)
≥2 prior lines of therapy
Prior anti-CD20 antibody
2 (1-10)
17 (55%)
30 (97%)
2 (1-6)
18 (78%)
22 (95%)
1 (1-2)
2 (22%)
7 (78%)
1 (1-3)
3 (37.5%)
5 (62.5%)
2 (1-10)
40 (56%)
64 (90%)
ICML 2019
ME-401
High Rate of Responses Across Patient Groups
14
Evaluable PatientsFL
(N = 50)
CLL/SLL
(N = 14)
Total
(N = 64)
All groups 40/50 (80%) 14/14 (100%) 54/64 (83%)
By treatment arm
ME-401 monotherapy
ME-401 + rituximab
30/38 (79%)
10/12 (83%)
11/11 (100%)
3/3 (100%)
41/49 (84%)
13/15 (87%)
By schedule
IS group
CS group
15/20 (75%)
25/30 (83%)
5/5 (100%)
9/9 (100%)
20/25 (80%)
34/39 (87%)
Disease assessment at end of Cycle 2, 6 and then every 6 months
Lugano criteria for FL and iw-CLL for CLL/SLL
ICML 2019
ME-401
Progression Free Survival: Median Not Yet Reached
FL: Progression-Free Survival (N=54) CLL/SLL: Progression-Free Survival (N=17)
15
6 FL (IS x4 and CS x2) and 2 CLL/SLL (CS x2) responders and continuing
therapy after reverting from IS to CS due to PD on IS were censored
IS (N=23)
CS (N=31)
IS (N=8)
CS (N=9)
ICML 2019
ME-401
Intermittent Dosing Schedule Demonstrates Improved Tolerability Compared to Continuous Dosing Schedule
16
Drug Related Adverse
Events of Special Interest
(AESI
Grade 3
CS Group
(N = 40)
IS Group
(N = 31)
Diarrhea/colitis 8 (20.0%) 3 (9.7%)
Rash, all types 4 (10.0%) 0
ALT/AST increased 3 (7.5%) 1 (3.2%)
Mucositis 1 (2.5%) 0
Pneumonia/Pneumonitis 5 (12.5%) 1 (3.2%)
ICML 2019
ME-401
Time to Grade 3 Drug-Related Adverse Events of Special Interest Improved on IS
17
Group Patients with Gr 3 AESI
CS 15 (38%)
IS 5 (16%)
Time to Grade 3 Adverse Event
ICML 2019
IS (N=23)
CS (N=31)
ME-401
Monotherapy Treatment Paradigm for R/R FL: The TIDAL Phase 2 Study Accelerated Approval Approach
Open Label
All subjects
ME-401 60mg qd
(CS) X 2 cycles
N=150
Group AME-401 60mg qd (CS)
until toxicity or PD (N=75)
Group BME-401 60mg qd, 1 wk on / 3wks off (IS)
until toxicity or PD (N=75)
Screening (28 Days)
Randomized (within
2 Days of Day1)
Disease assessments on
Day 1 of cycles 3, 5 and 7
Disease assessments approximately every 12
wks. on Day 1 of cycle 10,13,16,19,22 and 25
CS = Continuous Schedule IS = Intermittent Schedule 18
At toxicity:
Change to IS
At PD:
Discontinue
At toxicity: Re-challenge
at resolution with IS
At PD:
Change to CS
ME-401
The Near-Term Opportunity: Relapsed/Refractory FL, a Significant and Expanding Addressable Market
19
~9,000 U.S. Patients
With Relapsed/Refractory
Follicular Lymphoma
$1B: Potential
Addressable
Market
~15,000 diagnosed with follicular
lymphoma in 2018 (U.S.)
>50% relapse after each
remission
100K: U.S. follicular
lymphoma prevalence
Company estimates
ME-401
EFFICACY
SAFETY
DURABILITY
OF RESPONSE
High Response Rate:83% ORR in CLL/FL (n=54 evaluable)
Differentiated AE Profile:10% AESI
Durable Responses:Median DOR has not been reached;
Median follow-up >9 months
Opportunities for:
• Multiple indications
and lines of
treatment
• Combinatorial
treatments
20ICML 2019
ME-401: A Next-generation PI3Kδ Inhibitor with Potential to Redefine the Class
Voruciclib: A CDK Inhibitor
Voruciclib
CDK9: A Potential High Impact Target Regulating Two Important Proteins
• CDK9 inhibits:
⎼ MCL-1 (myeloid leukemia
cell differentiation protein,
an anti-apoptotic protein)
and
⎼ MYC (regulator of
proliferation, apoptosis,
differentiation and
metabolism.)
22
Voruciclib
Voruciclib: Potential to Overcome Venetoclax Resistance
• Combination opportunities across multiple indications, including:
⎼ AML, CLL & DLBCL
231 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 not MCL1Voruciclib inhibits MCL1
via CDK9 inhibition
Increased MCL1 is an established venetoclax
resistance mechanism1
Voruciclib
Voruciclib/Venetoclax Synergy Supported by MultiplePre-clinical Studies Including: AML, CLL and DLBCL*
24
Luedtke, D.A., et. al., Voruciclib, an Oral, Selective CDK9 Inhibitor, Enhances Cell Death Induced by the Bcl-2 Selective Inhibitor Venetoclax in Acute Myeloid Leukemia. Poster presented at: American Society of Hematology Annual Meeting, December 1-4, 2018; San Diego, CA. Paiva et al. Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. 2015 Nov 25;10(11):e0143685. . Dey 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 StudyA
ve
rag
e T
um
or
Vo
lum
e (
mm
3)
Vehicle
Voruciclib 200MPK
ABT-199 10MPK
ABT-199 10MPK + Voruciclib 200MPK
V2
AML DLBCL
U 9 3 7 ( 2 4 h )
C
o
n
tr
o
l
A
B
T
5
0
0
n
M
A
B
T
1
0
0
0
n
M
A
B
T
2
0
0
0
n
M
F
L
V
2
5
n
M
F
L
V
5
0
n
M
F
L
V
1
0
0
n
M
A
B
T
1
0
0
0
+
F
L
V
5
0
A
B
T
2
0
0
0
+
F
L
V
5
0
A
B
T
1
0
0
0
+
F
L
V
1
0
0
A
B
T
2
0
0
0
+
F
L
V
1
0
0
V
O
R
5
0
0
n
M
V
O
R
1
0
0
0
n
M
V
O
R
2
0
0
0
n
M
A
B
T
1
0
0
0
+
V
O
R
1
0
0
0
A
B
T
2
0
0
0
+
V
O
R
1
0
0
0
A
B
T
1
0
0
0
+
V
O
R
2
0
0
0
A
B
T
2
0
0
0
+
V
O
R
2
0
0
0
0
2 0
4 0
6 0
8 0
1 0 0
A n n V + / P I +
A n n V + / P I - C I < 0 . 8 5
* * *
* * *
* * ** * *
C I < 0 . 3 0
* * *
* * *
* * * * * *
An
nexin
V
+ cells (%
)
V2
Voruciclib
Voruciclib Phase 1 Study
• Study population⎼ Relapsed/Refractory B-cell Malignancies
⎼ AML After Treatment with Standard Therapy
⎼ Standard 3-6 patients/group (3+3)
• Endpoints⎼ Safety and Tolerability
⎼ Pharmacokinetics
⎼ Biologic Correlative Studies
⎼ Objective response rates/MRD negativity (B-cell malignancies)
⎼ CR/Cri rate
25
Voruciclib single agent
Dose escalation
Venetoclax + Voruciclib dose
escalation
50
mg
100
mg
150
mg
200
mg
250
mg
50
mg
100
mg
150
mg
200
mg
250
mgV2
• Multiple preclinical model systems demonstrate V2 activity at ~ 0.5 to 1.5 mM*• Phase I PK results suggest active steady state plasma levels achievable at 150-200mg daily; MTD=350mg** Luedtke, D.A., et. al., Voruciclib, an Oral, Selective CDK9 Inhibitor, Enhances Cell Death Induced by the Bcl-2 Selective Inhibitor Venetoclax in Acute Myeloid Leukemia. Poster presented at: American Society of Hematology Annual Meeting, December 1-4, 2018; San Diego, CA. Paiva et al. Cyclin-Dependent Kinase Inhibitor P1446A Induces Apoptosis in a JNK/p38 MAPK-Dependent Manner in Chronic Lymphocytic Leukemia B-Cells. 2015 Nov 25;10(11):e0143685. . Dey 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.
ME-344: A Novel Tumor Selective Mitochondrial Inhibitor
ME-344
ME-344 In Combination with Bevacizumab in Her2-negative Breast Cancer Patients Demonstrates Anti-tumor Activity
27
-60
-40
-20
0
20
40
60
-60
-40
-20
0
20
40
60Arm A Arm B Arm A Arm B
All Patients Patients with Vascular Normalization (PET)
Ab
so
lute
(%
) K
i67 C
han
ge (
days 0
-28)
Ab
so
lute
(%
) K
i67 C
han
ge (
days 0
-28)
ASCO 2019 ME-344 Poster
Pracinostat: Potential Best-in-Class Phase 3 HDAC Inhibitor
Pracinostat
….... In Two Ongoing Studies in AML and MDS
• 75+ w/ newly
diagnosed AML
• Unfit for intensive
chemo
Phase 3AML 500 patients:
Pracinostat (60 mg) + Aza
vs. Aza monotherapy
Primary
endpoint:
Overall Survival
Enrollment
expansion:
60 pts
Pracinostat + Aza
≤ 40 patients:
Pracinostat (45
mg) + Aza
Primary endpoints:
Overall Response
&
One Year Survival
Updated Interim Review: 9%:
discontinuation due to early AE
(N=55) (ASH 2018)
• High/Very high risk
• No prior HMA’s
Phase 2MDS
29
Key Upcoming Milestones Across Portfolio
• ME-401
⎼ Data updates from Phase 1B combination studies in B-cell
malignancies
⎼ Accelerated approval study in R/R follicular lymphoma
• Voruciclib
⎼ Phase 1B study initiation in combination with Venetoclax
⎼ Phase 1 data updates
• ME-344
⎼ Evaluate development opportunities leveraging demonstration
of anti-tumor activity published at ASCO 2019
• Pracinostat
⎼ Phase 2 data from MDS dose-optimization study
30
Building a Leading Oncology FranchiseWells Fargo Securities Healthcare ConferenceSeptember 4, 2019