EX-99.1 2 d834776dex991.htm EX-99.1 EX-99.1
[ NASDAQ: MEIP ]
Analyst & Investor Event
December 8, 2014
Exhibit 99.1


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
Agenda
Time
Presentation
Speaker
6:00 pm
Welcome & Introduction
Daniel P. Gold, PhD
6:05 pm
Pracinostat: A Differentiated HDAC Inhibitor
Guillermo Garcia-Manero, MD
Update on MDS Pilot Study
Guillermo Garcia-Manero, MD
Review of Front Line AML Data
Guillermo Garcia-Manero, MD
6:25 pm
Next Steps for Pracinostat in AML
Robert D. Mass, MD
Preview of Front Line MDS Data
Robert D. Mass, MD
6:30 pm
Q & A
All
7:00 pm
Conclusion


4
Introductions
Guillermo Garcia-Manero, MD
Professor, Department of Leukemia, MD Anderson Cancer Center
Chief, Section of Myelodysplastic Syndromes, MD Anderson Cancer
Center
Robert D. Mass, MD
Professor, Department of Leukemia, MD Anderson Cancer Center
Chief, Section of Myelodysplastic Syndromes, MD Anderson Cancer
Center
Deputy Chair, Translational Research, MD Anderson Cancer Center
Co-Chair, MDS Clinical Research Consortium
Principal Investigator of Pracinostat studies
Chief Medical Officer, MEI Pharma
Former Head of Medical Affairs, BioOncology, Genentech


Clinical Development Pipeline
5
Pracinostat
HDAC Inhibitor
Myelodysplastic
Syndrome
Front Line, Int-2 & High-Risk
Azacitidine
(Vidaza
®
)
Acute Myeloid Leukemia
Front Line, Elderly
Azacitidine
(Vidaza
®
)
Myelodysplastic
Syndrome
Refractory to HMA
Azacitidine
(Vidaza
®
) or
Decitabine
(Dacogen
®
)
Myelofibrosis
Front Line &
Relapsed/Refractory
Ruxolitinib
(Jakafi
®
)
ME-344
Mitochondrial
Inhibitor
Small Cell Lung Cancer
Advanced or Metastatic
Topotecan
(Hycamtin
®
)
Ovarian
Cancer
Advanced or Metastatic
Topotecan
(Hycamtin
®
)
PWT143
PI3K Delta Inhibitor
Hematologic Cancers
DRUG CANDIDATE
INDICATION / COMBINATION
PHASE I
PRE-CLINICAL
PHASE II
PHASE III


Pracinostat: A Clinical Perspective
Guillermo Garcia-Manero, MD
MD Anderson Cancer Center


7
Pracinostat: A Differentiated HDAC Inhibitor
Potent inhibitor of Class I, II and IV HDAC isoenzymes
Tested in 300+ patients in multiple Phase I and Phase II clinic trials
Hematologic and solid tumor indications, adult and pediatric patients
Well tolerated
Manageable side effects consistent with drugs of this class
Best-in-class pharmacokinetic profile, broadly active
SB991, the major in vivo metabolite of Pracinostat, demonstrates higher
activity than Pracinostat
Combined on target IC
50
activity for HDAC1 predicted to be >24 hours


8
Evidence of Clinical Activity in MDS and AML
Evidence
of
single-agent
activity
in
elderly
AML
1
14% (2/14) CR rate in Phase I dose-escalation study
Evidence
of
activity
in
combination
with
azacitidine
in
MDS
2
80% (8/10) CR/CRi rate in pilot Phase II study
Rapid complete bone marrow responses observed
50% (5/10) achieved complete cytogenetic bone marrow response
50% (5/10) went on to bone marrow transplantation
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, Abstract 3821
1
2
G.
Garcia-Manero,
et
al.
Phase
1
Study
of
the
Oral
Deacetylase
Inhibitor,
SB939,
in
Patients
with
Advanced
Hematologic
Malignancies.
2010
ASH
Annual
Meeting,
Abstract
3292


9
MDS Pilot Study –
Patient Characteristics
Patient
1
2
3
4
5
6
7
8
9
10
Median (range)
Age (years)
71
71
63
57
22
70
18
71
52
66
64.5 (18-71)
Sex
F
M
F
F
F
M
M
F
F
F
% BM blasts
18
8
2
9
3
3
6
1
12
9
7 (1-18)
Hemoglobin g/dL
11
9.3
10.9
9.5
10.2
9.2
8.2
10.7
11.1
9.9
10.05 (8.2-11.1)
WBC K/uL
3.2
1.5
2.3
2.5
0.7
2.6
9.3
4.5
1.2
1.5
2.4 (0.7-9.3)
ANC K/uL
1.44
0.2
1.3
1.55
0.9
1.7
4.7
2.8
0.4
0.25
1.37 (0.2-4.7)
Platelets k/uL
29
56
130
14
27
32
269
13
92
52
42 (13-269)
Creatinine mg/dL
1.03
0.99
0.72
0.7
0.5
1
0.8
0.67
0.78
0.6
0.75 (0.5-1.03)
Bilirubin mg/dL
1.1
0.7
0.6
1.3
0.4
1
1.1
0.6
0.8
0.5
0.75 (0.4-1.3)
Cytogenetics
C
C
C
-7
-7
C
t(6;9)
-7
C
C
t-MDS
Y
Y
Y
Y
N
Y
Y
Y
Y
N
Response
CR
CRp
CR
CRp
CR
NR
CRp
CR
CR
CR


MDS Pilot Study…
Three Years Later
10


11
Stage 2 (n = 13)
Pracinostat plus Azacitidine
Three or more patients required to achieve CR/CRi/MLFS to advance to Stage 2
Stage 1 (n = 27)
Pracinostat plus Azacitidine
Elderly (Age
65 years) Patients with Newly Diagnosed AML
AML, acute myeloid leukemia; CR, complete response; CRi, complete response with incomplete blood count recovery; MLFS, morphologic leukemia-free state
Phase II Study in Front Line AML (MEI-004)


12
Pracinostat 60 mg is administered orally 3 days a week (days 1,3
and 5 of
each week) for 21 days of each 28 day cycle
Azacitidine is administered subcutaneously or intravenously on days 1-7 or
days 1-5 & 8-9 (per site preference) of each 28-day cycle
Dose Modifications:
Reductions
Treatment Regimen
Indicated for treatment related
Grade 3 non-hematologic toxicity following
maximal medical treatment
Indicated for treatment related
Grade 3 hematologic toxicity in the absence
of disease
Delays (between or within cycles)
Subsequent reduction to 45 mg of Pracinostat is allowed
Begin with Azacitidine which may be reduced to 75% of the starting dose


13
Key Inclusion:
Age
65 years
Newly diagnosed de novo, secondary, or treatment-related AML with
intermediate or unfavorable-risk cytogenetics based on the Southwest Oncology
Group (SWOG) classifications (Slovak et al, 2000).
20% bone marrow blasts
Adequate renal, cardiac and liver function
QTcF <450 ms for males or <470 ms for females
Key Exclusion:
Acute promyelocytic leukemia (FAB M3);  t(15;17), t(8;21), t(16;16), del(16q), or
inv(16) karyotype
Candidate for intensive chemotherapy (induction chemotherapy, bone marrow, or
stem cell transplant) within the next 4 months
Active central nervous system (CNS) disease
Eligibility Criteria


14
Study Evaluations
Primary Endpoint: Complete Response (CR) + Complete Response with
Incomplete Blood Count Recovery (CRi) + Marrow CR (Morphologic
Leukemia Free State, MLFS)
Secondary Endpoints:
Overall response rate (CR + CRi + partial response [PR] + PR with incomplete
blood count recovery [PRi] + MLFS)
Complete cytogenetic response (CRc) + molecular complete remission (CRm)
Duration of response
Event free survival (EFS)
Overall survival (OS)
Assess the tolerability and adverse event profile
Response assessments end of cycle 1 or 2, and then every other cycle until
CR is achieved or as clinically indicated


15
N = 41
Number of Patients Active
25
Number of Patients Discontinued
Reasons
for
discontinuation:
Progressive
Disease
Adverse Event
Other 
16
6
6
4
50 patients enrolled between December 2013 –
December 2014 at 15 sites
41 patients enrolled at data cutoff
Other –
includes patient or physician decision
Patient Disposition


16
Number of Patients at Baseline
n = 41 (%)
Age (years)
Median
76
Range
69 -
84
Gender
Male
24 (59)
Female
17 (41)
Newly diagnosed de novo
29 (71)
Secondary (AHD & treatment related)
12  (29)
0-1
33 (80)
2
8 (20)
Median
38
20-29% Range
13 (32)
30-50% Range
15 (36)
>50% Range
13 (32)
Intermediate
23 (56)
High
17 (41)
Not Evaluable
1 (3)
AHD, antecedent hematologic disorder; AML, acute myeloid leukemia; ECOG, Eastern Cooperative Oncology Group
AML Disease Status
ECOG Status
Bone Marrow Blasts at Baseline
Cytogenetic Risk Category
Baseline Characteristics


17
Treatment Emergent Adverse Events in
10%
of Patients (all causality)
All Grades (%), n=41
Grades 3-4 (%), n=41
Hematologic
Febrile Neutropenia
12 (29)
10 (24)
Thrombocytopenia
11 (27)
10 (24)
Anemia
9 (22)
4 (10)
Neutropenia
4 (10)
4 (10)
Leukopenia
4 (10)
1 (2)
Non-Hematologic
Nausea
18 (44)
2 (5)
Constipation
17 (41)
0
Fatigue
17 (41)
4 (10)
Peripheral Edema
6 (15)
0
Vomiting
6 (15)
0
Diarrhea
5 (12)
1 (2)
Dizziness
5 (12)
0
Headache
5 (12)
1 (2)
Hypokalemia
5 (12)
0
Pyrexia
4 (10)
0
Cellulitis
4 (10)
4 (10)
Rash
4 (10)
0
Hypotension
4 (10)
0
Cough
4 (10)
0
Dyspnea
4 (10)
0
QTc Prolongation*
2 (5)
1 (2)
*QTC events were seen in < 10% of patients, however are noted here


18
Treatment Emergent Adverse Events Leading
to Drug Discontinuation
AE Term
Grade
Discontinuation
(Cycle/Day)
Outcome
Peripheral Motor Neuropathy
3
3/1
Resolved
Parainfluenza
3
3/22
Resolved
Prolonged QTc/AF
3
2/15
Resolved
Subdural Hematoma
5
3/22
Fatal
Sepsis
5
2/3
Fatal
Sepsis
5
2/14
Fatal
AE, adverse event; AF, atrial fibrillation.


19
Response
Interim Response Assessment
n=33* (%)
CR/CRi/MLFS (Primary endpoint)
15 (45)
CR
9 (27)
CRi
4 (12)
MLFS
2 (6)
PR/PRi
3 (10)
Stable Disease
4 (12)
Progressive Disease
6 (18)
Clinical Benefit**
1 (3)
No Clinical Benefit
4 (12)
*All
patients
who
have
had
at
least
1
on-study
disease
assessment
OR
discontinued
study
therapy
prior
to
an
on
study
disease
assessment due to adverse event or other reasons
** Patients did not meet strict International Working Group (IWG) response criteria, but were determined to have clinical benefit
by Investigator


20
Evolution of Clinical Responses:
Interim Efficacy and Duration on Study


21
Event Free Survival


22
Overall Survival


23
Bone Marrow Response in MDS and AML
n = 27; 6 patients had no on-study BM performed
MDS Pilot Study
n = 9
Phase II AML Study
200
180
160
140
120
100
80
60
40
20
0
-20
-40
-60
-80
-100
-120
50
40
30
20
10
0
-10
-20
-30
-40
-50
-60
-70
-80
-90
-100
-110


24
Conclusions
Pracinostat in combination with azacitidine demonstrates significant
clinical activity in elderly patients with newly diagnosed AML
To date, 15 of 33 patients (45%) achieved the primary endpoint of
CR+CRi+MLFS
No patient who achieved a clinical response has progressed
Most clinical responses occur within the first 2 cycles and continue to
improve with ongoing therapy
The observed Response Rate may increase with longer follow up of
patients achieving PR or SD
The 60 day mortality rate is approximately 10% (3/33)


25
Conclusions (cont’d)
Pracinostat in combination with azacitidine was well tolerated in this
population of elderly AML patients
The most common treatment-emergent AEs included neutropenia,
febrile neutropenia, thrombocytopenia, nausea, fatigue and anemia
Adverse events resulting in dose reductions
were uncommon, and
frequently due to disease under study
Six patients to date have received study drug beyond 230 days
reflecting long term tolerability
These data support definitive development of Pracinostat in
combination with azacitidine in elderly AML patients


Pracinostat: Looking Ahead
Robert D. Mass, MD
Chief Medical Officer


27
Elderly (Age
60 years) Patients with Newly Diagnosed AML
Unsuitable for Intensive Therapy
Pracinostat
+
Azacitidine
Placebo
+
Azacitidine
Proposed Phase III AML Study Designs
Primary endpoint: CR
Secondary endpoints: OS, ORR, transfusion independency rate,
duration of response, PFS, tolerability and AE rate, PK
~450 patients, one-to-one randomization
Estimated initiation: June 2015


28
Intermediate Risk-2 or High Risk MDS Patients
Previously Untreated w/ HMA
Pracinostat
+
Azacitidine
Placebo
+
Azacitidine
Phase II Front Line MDS Study (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 topline data in March 2015


29
Phase II Front Line MDS Study (MEI-003)
Patient Demographics
Study MEI-003
(N=102)
Pub
(N=99)
Pub
(N=179)
Age
Median
<65
>65
70 yrs
29%
71%
69 yrs
NR
NR
69 yrs
32%
68%
Gender
Male
Female
69%
31%
72%
27%
74%
26%
PS
0
1
2
34%
57%
9%
NR
NR
NR
44%
48%
7%
IPSS
INT-2
High
65%
35%
11%
9%
43%
46%
1
Based on unclean data; study closed to enrollment on August 29, 2014
2
Vidaza
®
package insert, table 1 (Silverman, JCO 2002 study)
3
Vidaza
®
package insert, table 2 (Fenaux, Lancet Oncology 2009 study)
1
2
3


30
2015 Clinical Milestones
Pracinostat
Top line data from Phase II study in front line MDS (March)
Full data set from Phase II study in front line MDS (June)
Initiation of Phase III study in front line elderly AML (June)
ME-344
Data from Phase Ib trial in small cell lung & ovarian cancers
PWT143
Initiation of first-in-human study


[ NASDAQ: MEIP ]
Analyst & Investor Event
December 8, 2014
Q & A