[ nasdaq: meipfilecache.investorroom.com/mr5ir_meipharma/125... · health care conference march...
TRANSCRIPT
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.
3
MEI Pharma (Nasdaq: MEIP)
• San Diego-based oncology company focused on the clinical
development of three wholly owned drug candidates
Pracinostat: Oral HDAC inhibitor with clinical activity in MDS and AML
o Significant activity in combination with azacitidine in elderly AML
o Data from randomized Phase II MDS study expected in March 2015
ME-344: Novel mitochondrial inhibitor with single-agent activity
o Data from Phase Ib study expected in 2015
PWT143: PI3K delta inhibitor with compelling pre-clinical activity
o On track to enter clinic in 1H 2015
• Strong intellectual property protection extending past 2028 in US
• Management team with proven oncology drug development
experience
4
Management Team
EXECUTIVE MANAGEMENT
Daniel Gold, PhD
President & Chief Executive OfficerFormer Chief Scientific Officer & Founder, Favrille
Robert Mass, MD
Chief Medical OfficerFormer Head of Medical Affairs, BioOncology, Genentech
Thomas Zech
Chief Financial OfficerFormer Chief Financial Officer, Pacira Pharmaceuticals
David Urso, JD
SVP, Corporate Development & General CounselFormer Principal, Forward Ventures / COO, Tioga Pharmaceuticals
Karen Potts, PhD
SVP, Regulatory AffairsFormer SVP of Regulatory Affairs, Trius Therapeutics
BOARD OF DIRECTORS
Christine White, MD (Lead Director)Former Head of Global Medical Affairs, Biogen Idec
Charles Baltic, JDCo-Head of Healthcare, Needham & Co.
Leah Cann, MBATwo-time Wall Street Journal All-Star Analyst
Kevan Clemens, PhDFormer Head of Global Oncology, Roche
Nick Glover, PhDFormer President & CEO, YM BioSciences
Daniel Gold, PhDPresident & CEO, MEI Pharma
Thomas Reynolds, MD, PhDFormer Chief Medical Officer, Seattle Genetics
William RueckertFormer Chairman, Novogen Limited
5
DRUG CANDIDATE INDICATION / COMBINATION PRE-CLINICAL PHASE I PHASE II PHASE III
EP
IGE
NE
TIC
SP
RO
GR
AM
PracinostatHDAC Inhibitor
Myelodysplastic SyndromeFront Line, Int-2 & High-RiskAzacitidine (Vidaza®)
Acute Myeloid LeukemiaFront Line, ElderlyAzacitidine (Vidaza®)
Myelodysplastic SyndromeRefractory to HMAAzacitidine (Vidaza®) or
Decitabine (Dacogen®)
MyelofibrosisFront Line & Relapsed/RefractoryRuxolitinib (Jakafi®)
CA
NC
ER
ME
TA
BO
LIS
M
PR
OG
RA
M
ME-344Mitochondrial Inhibitor
Small Cell Lung CancerAdvanced or MetastaticTopotecan (Hycamtin®)
Ovarian CancerAdvanced or MetastaticTopotecan (Hycamtin®)
SIG
NA
LIN
G
PR
OG
RA
M
PWT143PI3K Delta Inhibitor
Hematologic Cancers
Clinical Development Pipeline
6
Pracinostat: A Differentiated HDAC Inhibitor
• Potent inhibitor of Class I, II and IV HDAC isoenzymes
• Well tolerated
Tested in 300+ adult and pediatric patients in multiple hematologic and
solid tumor Phase I and Phase II clinic trials
Manageable side effects consistent with drugs of this class include
fatigue and gastrointestinal discomfort
• Best-in-class pharmacokinetic profile, broadly active
Generation of SB991, the major and highly active in vivo metabolite of
Pracinostat, yields in vivo combined on target IC50 activity for HDAC1
predicted to be >24 hours
7
Pracinostat: Clinical Activity in MDS
• Evidence of activity in combination with azacitidine in intermediate-2
or high-risk myelodysplastic syndrome (MDS) 1
90% (9/10) CR/CRp rate in pilot study
o CR = 60% (6/10)
Rapid complete bone marrow responses observed
o 50% (5/10) achieved complete cytogenetic bone marrow response
o 50% (5/10) went on to bone marrow transplantation
1 Quintás-Cardama et al. Very high rates of clinical and cytogenetic response with the
combination of the histone deacetylase inhibitor Pracinostat (sb939) and 5-azacitidine in
high-risk myelodysplastic syndrome. 2012 ASH Annual Meeting
9
Intermediate Risk-2 or High Risk MDS Patients
Previously Untreated w/ HMA
Pracinostat
+
Azacitidine
Placebo
+
Azacitidine
Phase II Study in Front Line MDS (MEI-003)
• Primary Endpoint: CR
Secondary endpoints: overall response rate, hematologic improvement,
clinical benefit rate, duration of response, progression-free survival, rate
of leukemic transformation, overall survival, safety & tolerability
• 102 evaluable patients enrolled, one-to-one randomization
• 24 sites in the U.S.
• Expect to unblind study and report top-line data in March 2015
10
Phase II Study in HMA Refractory MDS (MEI-005)
• Reached clinical milestone in December 2014
• Three responses (one PR and two marrow CRs) out of first 28
patients who received Pracinostat + HMA (azacitidine or decitabine)
after progressing on the same HMA alone
Exceeded the pre-specified response rate (two out of 29) for expansion of
study enrollment
• Combination of Pracinostat + azacitidine or decitabine generally well-
tolerated in the study with no unexpected toxicities
Most common treatment-emergent adverse events: anemia, fatigue and
gastrointestinal disorders
• Study enrollment complete (39 patients); continue to follow patients
for response and survival
One additional marrow CR to date
11
Pracinostat: Clinical Activity in AML
• Evidence of single-agent activity in elderly AML1
14% (2/14) CR rate in Phase I dose-escalation study
• Significant activity in combination with azacitidine in elderly AML2
50 patients enrolled in Phase II study at 15 sites in the U.S.
Interim data from 33 evaluable patients reported at ASH
o Primary endpoint: CR/CRi/MLFS rate = 45% (15/33) as of Dec 2014
o No patient who achieved a clinical response had progressed
1 Garcia‐Manero et al. Phase 1 Study of the Oral Deacetylase Inhibitor, SB939, in Patients
with Advanced Hematologic Malignancies. 2010 ASH Annual Meeting
2 Garcia-Manero et al. Pracinostat in Combination with Azacitidine Produces a High Rate
and Rapid Onset of Disease Remission in Patients with Previously Untreated Acute
Myeloid Leukemia. 2014 ASH Annual Meeting
12
Phase II Study in Front Line AML (MEI-004)Duration on Study and Response – ASH 2014
0 50 100 150 200 250 300
Days on Study
1stLin
e E
lderly A
ML P
atients
(N
=33) Response Based on Clinical
Review of Efficacy Data
CR
CRi
MLFS
PR/PRi
Stable Disease
Progressive Disease
Clinical Benefit –
AE/Withdrew
No Clinical Benefit –
AE/Withdrew
Time to 1st BM
Assessment for
Responders
Remains on treatment
13
Phase II Study in Front Line AML (MEI-004)Duration on Study and Response – Today
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Response Based on Clinical
Review of Efficacy Data
CR
CRi
MLFS
PR/PRi
Stable Disease
Progressive Disease
Clinical Benefit –
AE/Withdrew
No Clinical Benefit –
AE/Withdrew
Time to 1st BM
Assessment for
Responders
Remains on treatment
Months on Study
1stLin
e E
lderly A
ML P
atients
(N
=33)
*
**
*
*
* Patients with improved response since presentation at ASH 2014
14
Phase II Study in Front Line AML: Conclusions
• Significant clinical activity in elderly patients w/ newly diagnosed AML
52% (17/33) have now achieved primary endpoint
o CR = 33% (11/33) to date
Majority of clinical responses occur within first two cycles
Observed response rate continues to increase with longer follow-up
Only one patient who has achieved clinical benefit (SD) has progressed
60-day mortality rate approximately 10% (3/33)
• Well tolerated in this population of elderly AML patients (≥ 65 years)
To date 12 patients on study > 6 months, reflecting long term tolerability
• Data support definitive development of Pracinostat in combination
with azacitidine in elderly AML patients
15
Elderly (Age ≥ 60 years) Patients with Newly Diagnosed AML
Unsuitable for Intensive Therapy
Pracinostat
+
Azacitidine
Placebo
+
Azacitidine
Proposed Phase III Study in Front Line AML
• Primary endpoint to support accelerated approval: CR
Endpoint for full approval: OS
• ~450 patients, one-to-one randomization
• Estimated initiation: June 2015
16
Global Market Opportunity in MDS and AML
MDS and AML are Growing Markets with
Limited Treatment Options
• HSCT is the only curative treatment;
however, the vast majority of patients are
ineligible candidates
• Many patients are also unfit for
chemotherapy
• Most patients who are high-risk and/or
can’t tolerate intensive therapy receive an
HMA (e.g. Vidaza® or Dacogen®)
• In 2013 prior to generic entrants,
combined worldwide sales of Vidaza and
Dacogen exceeded $1B
Pracinostat in combination with HMAs may
improve treatment outcomes in a large,
unmet market
MDS Prevalence
& AML Incidence
~ 130 - 150K Patients
High Risk / Int-2 MDS
& AML >60 Yrs
~ 50 - 60K Patients
HMA Treated MDS & AML
~ 18 - 23K Patients
* Evaluate Pharma# Decision Resources
Estimate ~30K Pracinostat Target
Patients in 7 Key Markets by 2021
• General & elderly population growth
• Increased Rx use in older patients
• Improved treatment options
2013 Epidemiology and Treatment Algorithm* #
G7 Markets
17
• Derived from in-house isoflavone-based technology platform
Targets Oxphos pathway resulting in rapid loss of cellular energy and
mitochondrial instability via increased ROS
Potent inhibitor of multiple human tumor cell lines, including
chemotherapy-resistant ovarian cancer stem cells
• Solid tumor dose-escalation study complete
~ 25% (5/21) experienced progression-free survival (PFS) > 2X longer
than prior anti-cancer therapy
One confirmed PR in a patient with small cell lung cancer lasting > 2 years
Dose limiting toxicity of Grade 3 neuropathy at 15 and 20 mg/kg
Generally well tolerated at 10 mg/kg weekly
ME-344: Lead Mitochondrial Inhibitor
18
Patients Eligible
for Topotecan
Small Cell Lung,
Ovarian & Cervical
Cancers
Small Cell
Lung Cancer (n=20)
ME-344
+
Topotecan
Ovarian Cancer(n=20)
ME-344
+
Topotecan
Phase Ib Trial of ME-344 Plus TopotecanFirst Patient Dosed in Cohort Expansion in Oct 2014
Confirm MTD(n=14)
ME-344(10 mg/kg weekly)
+ Topotecan(4 mg/m2 day 1,8,15)
Primary Endpoint: Safety & Tolerability of ME-344 + Topotecan
19
PWT143: Highly Selective PI3K Delta Inhibitor
• Acquired from Pathway Therapeutics in September 2013
• Expands drug development pipeline
Clinically validated target in hematologic diseases
Potential synergies with lead drug candidate Pracinostat
• Distinct chemical structure and evidence of improved pre-clinical
activity compared to other PI3K delta inhibitors in development
• IND-enabling 2-species tox studies and scale manufacturing
methods completed
• Expect to initiate first-in-human studies in first half of 2015
20
Intellectual Property
Pracinostat
• 3 issued US and 77 issued foreign patents
2 US and 8 foreign applications pending
• Composition of matter to May 2028 in US, Aug 2026 in EP
May 2033 with up to 5 years patent term restoration in US
Aug 2031 with up to 5 years Supplementary Protection Certificate in EP
ME-344
• 2 issued US and 18 issued foreign patents
3 US and 7 foreign applications pending
• Composition of matter to Sep 2025 in US and EP
Sep 2029 with up to 4 years of patent term restoration in US
Sep 2030 with up to 5 years Supplementary Protection Certificate in EP
PWT143
• 1 issued US patent
3 US and 29 foreign applications pending
• Composition of matter to Jan 2031 in US, pending in EP
21
Financial Highlights
• Cash: $78.7 million (as of December 31, 2014)
• Debt: None
• Shares outstanding: 33.3 million
22
2015 Clinical Milestones
Pracinostat
Top-line data from Phase II study in front line MDS (March)
Full data from Phase II study in front line MDS (June)
Full data from Phase II study in front line elderly AML (June)
Initiation of Phase III study in front line elderly AML (June)
ME-344
Data from Phase Ib trial in small cell lung and ovarian cancers
PWT143
Initiation of first-in-human study