investor reception ash 2015 - morphosys ag · the morphosys pipeline 25 clinical product...
TRANSCRIPT
Agenda
MorphoSys AG - Investor Event ASH - December 7, 2015 2
8:00 Simon Moroney, D.Phil., CEO
Welcome & Introduction
8:05 Arndt Schottelius, MD, Ph.D., CDO
MOR208 – Results of phase 2 with MOR208 monotherapy in NHL
8:15 Jennifer Woyach, MD
Assistant Professor of Internal Medicine, Ohio State University, USA
MOR208 in CLL
8:35 Prof. Dr. Heinz Ludwig
Director of the Wilhelminen Cancer Research Institute, Vienna, Austria
MOR202 – Results of ongoing phase 1/2a study in MM
8:50 Q&A
Closing Remarks
Food, Drinks
Safe Harbor
MorphoSys AG - Investor Event ASH - December 7, 2015
This presentation includes forward-looking statements.
Actual results could differ materially from those included in the forward-looking statements due to
various risk factors and uncertainties including changes in business, economic competitive
conditions, regulatory reforms, foreign exchange rate fluctuations and the availability of financing.
These and other risks and uncertainties are detailed in the Company’s Annual Report.
3
MorphoSys AG - Investor Event ASH - December 7, 2015 4
The MorphoSys Pipeline
25 Clinical Product Candidates, 104 Total
Program Partner Target Disease Area Discovery Preclinic Phase 1 Phase 2 Phase 3
Bimagrumab (BYM338) Novartis ActRIIB sIBM (musculoskeletal)
Guselkumab (CNTO1959) Janssen IL23p19 Psoriasis
Gantenerumab Roche Amyloid-ß Alzheimer’s disease
MOR208 - CD19 ALL, CLL, NHL
MOR103/GSK3196165 GSK GM-CSF Inflammation
MOR202 - CD38 Multiple myeloma
BHQ880 Novartis DKK-1 Multiple myeloma
CNTO3157 Janssen - Inflammation
CNTO6785 Janssen - Inflammation
LFG316 Novartis C5 Eye diseases
LJM716 Novartis HER3 Cancer
BPS804 Mereo/Novartis Sclerostin Brittle bone syndrome
Tarextumab (OMP-59R5) OncoMed Notch 2 Solid tumors
VAY736 Novartis BAFF-R Inflammation
MOR209/ES414 Emergent PSMA/CD3 Prostate cancer
Anetumab Ravtansine (BAY94-9343) Bayer Mesothelin (ADC) Solid tumors
BAY1093884 Bayer TFPI Hemophilia
BI–836845 BI IGF-1 Solid tumors
NOV–7 Novartis - Eye diseases
NOV–8 Novartis - Inflammation
NOV-9 Novartis - Diabetic eye diseases
NOV-10 Novartis - Cancer
NOV-11 Novartis - Blood disorders
PF-05082566 Pfizer 4-1BB Solid tumors
Vantictumab (OMP-18R5) OncoMed Fzd 7 Solid tumors
MOR106 Galapagos - Inflammation
MOR107 (LP2) - AT2-R Fibrosis
Immuno-oncology program Merck Serono - Cancer
Immuno-oncology program Immatics - Cancer
6 MOR programs - - Various
90 Partnered Programs
13 MOR Programs
1 Outlicensed Program
Most advanced development stage
In addition, 26 partnered programs in pre-clinic, and 43 partnered programs in discovery
The MOR Portfolio
MorphoSys AG - Investor Event ASH - December 7, 2015 5
Program Indication Target Discovery Preclinic Phase 1 Phase 2 Phase 3
Unpartnered
MOR208 NHL
CD19CLL
ALL
MOR202 Multiple myeloma CD38
MOR107 Fibrosis AT2-R
Immuno-oncology program(Immatics)
Cancer Various
6 Programs Various Various
Co-development & co-promotion
MOR209/ES414 (Emergent)
Prostate cancer PSMA / CD3
MOR106(Galapagos)
Inflammation Undisclosed
Immuno-oncology program(Merck Serono)
Cancer Undisclosed
Outlicensed to GSK
MOR103/GSK3196165
RA/handosteoarthritis
GM-CSF
FTD, orphan status US & EU
Orphan status US & EU
Phase 2a study of single-agent MOR208 in
patients with relapsed or refractory B-cell
non-Hodgkin’s lymphoma
Dr. Arndt Schottelius
MorphoSys AG - Investor Event ASH - December 7, 2015
MOR208
Introduction
MorphoSys AG - Investor Event ASH - December 7, 2015 7
MOR208 is an Fc-engineered humanized monoclonal antibody that targets CD19
CD19, a B-lymphocyte lineage specific surface antigen, is the earliest and most broadly expressed
of the selective B-cell markers, and is highly expressed in most B-cell NHLs1,2
Consequently, a CD19 antibody may have clinical utility as a new therapeutic approach to treat B
cell malignancies
A phase I study has shown MOR208 to be generally safe and well-tolerated, with encouraging single-
agent activity in patients with CLL
Recommended intravenous dose, 12 mg/kg, weekly3
1 Wang K, et al. Exp Hematol Oncol 2012;1:362 Schuurman HJ, et al. Am J Pathol 1988;131:102-11
3 Woyach JA, et al. Blood 2014;124:3553-60CLL, chronic lymphocytic leukemia;
NHL, non-Hodgkin’s lymphoma
MOR208 - Phase 2 in R/R NHL
Objectives of the Study
MorphoSys AG - Investor Event ASH - December 7, 2015 8
Primary
Antitumor activity of single-agent MOR208 in adult patients with R-R NHL who had received at least
one prior therapy containing the CD20 antibody, rituximab
Primary endpoint: objective response rate
Secondary
Duration of response and PFS
Safety and tolerability
Potential immunogenicity
Pharmacokinetics and pharmacodynamics
PFS, progression-free survival; R-R, relapsed or refractory
MOR208 - Phase 2 in R/R NHL
Baseline Characteristics: Heavily Pre-treated Patients
9MorphoSys AG - Investor Event ASH - December 7, 2015
CharacteristicDLBCL*
n=35
FL/iNHL*
n=45
MCL
n=12
Total
n=92
Median age, years 71 66 64.5 66.5
Male, n (%) 24 (69) 21 (47) 11 (92) 56 (61)
Ann Arbor stage, n (%) I–II 4 (11) 5 (11) 1 (8) 10 (11)
III–IV 30 (86) 40 (89) 11 (92) 81 (88)
Missing 1 (3) 0 0 1 (1)
ECOG PS, n (%) 0-1 32 (91) 44 (98) 11 (92) 87 (95)
2 3 (9) 1 (2) 1 (8) 5 (5)
Prior lines of therapy, n (%) 1 15 (43) 17 (38) 3 (25) 35 (38)
2 8 (23) 7 (16) 1 (8) 16 (17)
≥3 12 (34) 21 (47) 8 (67) 41 (45)
Last rituximab dose <6 months, n (%) 14 (40) 6 (13) 1 (8) 21 (23)
Prior stem-cell transplant 2 (6) 7 (16) 1 (8) 10 (11)
Data cutoff November 11, 2015
* DLBCL and FL cohorts expanded leading to an overall enrollment of 92 patients; Other iNHL cohort not expanded as response was
deemed too heterogeneous between different lymphoma subtypes; data are presented for the combined FL/other iNHL cohort
Advanced Stage, Heavily Pre-treated Patients.
Jurczak W et al., #1528 ASH 2015
MOR208 - Phase 2 in R/R NHL
Promising Efficacy Results in DLBCL, FL, iNHL
10MorphoSys AG - Investor Event ASH - December 7, 2015
Best overall response,* n (%)DLBCL
n=35FL/iNHL n=45
MCL
n=12
Total
n=92
Complete response 2 (6) 5 (11) 0 7 (8)
Partial response 7 (20) 7 (16) 0 14 (15)
Stable disease 5 (14) 21 (47) 6 (50) 32 (35)
Progressive disease 11 (31) 7 (16) 5 (42) 23 (25)
Not evaluable‡ 10 (29) 5 (11) 1 (8) 16 (17)
ORR (all patients) 9 (26%) 12 (27%) 0 21 (23%)
ORR (evaluable patients§) 9 (36%) 12 (30%) 0 21 (28%)
*Investigator assessed
Encouraging Single-agent Activity for MOR208 in NHL
‡Post-baseline response assessment not performed/data unavailable §n = 25, 40, 11 and 76, respectively
ORR (CR + PR), objective response rate
Jurczak W et al., #1528 ASH 2015
MOR208 - Phase 2 in R/R NHL
Long Duration of Responses in DLBCL, FL/iNHL
11MorphoSys AG - Investor Event ASH - December 7, 2015
0.0 5.0 10.0 15.0 20.0 25.0
Months
Pati
en
ts w
ith
CR
or
PR
Duration of response
DLBCL, n=9
Indolent NHL,* n=12
Time to response, n=21
Ongoing response, n=9
The longest response duration observed so far exceeded 20 months in both DLBCL and FL
FL/iNHL, n=12
Jurczak W et al., #1528 ASH 2015
MOR208 - Phase 2 in R/R NHL
Adverse events
12MorphoSys AG - Investor Event ASH - December 7, 2015
Grade 3/4,* n (%)DLBCL
n=35
FL/iNHL
n=45
MCL
n=12
Total
n=92
Hematological
Any 9 (26) 4 (9) 1 (8) 14 (15)
Neutropenia 6 (17) 2 (4) 0 8 (9)
Anemia 3 (9) 0 0 3 (3)
Thrombocytopenia 2 (6) 1 (2) 1 (8) 4 (4)
Non-hematological
Dyspnea 2 (6) 1 (2) 1 (8) 4 (4)
Fatigue 1 (3) 1 (2) 0 2 (2)
Hypokalemia 1 (3) 1 (2) 0 2 (2)
Pneumonia 2 (6) 0 0 2 (2)
MOR208 12mg/kg was well tolerated with favorable safety profile
Infusion-related reactions reported in only 9 (10%) of 92 patients
Treatment emergent adverse events reported in ≥2 patients
Jurczak W et al., #1528 ASH 2015
Conclusions
MorphoSys AG - Investor Event ASH - December 7, 2015 13
Encouraging single-agent activity for MOR208 in NHL
Promising objective response rates observed; 36% in the DLBCL cohort and 30% in the combined
FL/iNHL cohort (evaluable patients)
2 complete responses in the DLBCL cohort
5 complete responses in the combined iNHL cohort
Longest duration of response to date is 20.3 months for DLBCL and 20.3 months for iNHL (both
ongoing)
MOR208 was well tolerated — infusion-related reactions reported only in 10% of patients and were
typically grade 1/2
Favorable pharmacokinetic profile and very low immunogenicity
Protocols are being developed for trials which combine MOR208 with other anti-lymphoma therapies
(e.g. lenalidomide and bendamustine)
MOR208
Comprehensive Clinical Development Plan
14MorphoSys AG - Investor Event ASH - December 7, 2015
Indication 2015 2016 2017 2018
NHL
DLBCL
CLL
ALL
Phase 2
Phase 2/3
IIT: Investigator-initiated trial
MOR208 (12mg/kg) + lenalidomide; 2nd line R/R; N=80
Safety evaluation leading into anticipated pivotal study
MOR208 (12 mg/kg) + bendamustine; 2nd line R/R; N~320
MOR208 (12mg/kg) + idelalisib; BTKi-failures; N=120
MOR208 (9mg/kg) + lenalidomide; R/R, naive & Richter’s Transformation; MOR208 + ibrutinib in ibrutinib
failures; N=80 (Ohio State Univ. IIT)
MOR208 (12mg/kg) + NK cells; pediatric ALL; N=13 (St Jude’s IIT)
MOR208 (12 mg/kg); N=92
A Phase II Study of the Fc Engineered CD19
Antibody MOR208 in Combination with
Lenalidomide for Patients with Chronic
Lymphocytic Leukemia (CLL)
Jennifer Woyach, MD
Assistant Professor of Internal Medicine, Ohio State University
MorphoSys AG - Investor Event ASH - December 7, 2015
Open-label, multi-dose, single-arm, dose escalation study
Enrolled 27 heavily pretreated high risk patients suffering from relapsed or refractory CLL
Primary objective: safety, tolerability, pharmacokinetic profile
Secondary objective: anti-tumor activity
Dosing in 6 cohorts:
Dosing Scheme:
MOR208 in Clinical Development
Phase 1 in R/R CLL – Study Design
MorphoSys AG - Investor Event ASH - December 7, 2015 16
A Phase 1 Study of MOR208 to Evaluate the Safety, Tolerability, and Pharmacokinetics in Patients With
Relapsed or Refractory Chronic Lymphocytic Leukemia (R/R CLL)
d1 d4 d8 d15 d1 d8 d15d22 d22
cycle 1
maintenance with 4 monthly infusions
offered to patients with at least SD in phase I
cycle 2
Dose (mg/kg)0.3
mg/kg
1
mg/kg
3
mg/kg
6
mg/kg
9
mg/kg
12
mg/kg
No of patients (total n = 27) 1 1 3 3 316
(including P2a expansion)
MOR208 - Phase 1 in R/R CLL
Safety Overview: MOR208 is Well Tolerated
MorphoSys AG - Investor Event ASH - December 7, 2015 17
Treatment-related adverse Events0.3 mg/kg
(N=1)
1 mg/kg
(N=1)
3 mg/kg
(N=3)
6 mg/kg
(N=3)
9 mg/kg
(N=3)
12 mg/kg
(N=16)Total (%)
Any Event 1 1 3 3 2 14 24 (88.9%)
Grade 3/4 Toxicities
Grade 4 Neutropenia lasting ≥ 7 days with febrile
neutropenia (DLT)1 1 (3.7%)
Neutropenia 1 1 2 (7.4%)
Thrombocytopenia 2 2 (7.4%)
Tumor Lysis Syndrome 1 1 (3.7%)
Increased AST 1 1 (3.7%)
Grade 1/2 Toxicities Occurring in >10% of patients
Infusion Reaction 1 1 1 2 2 11 18 (66.7%)
Increased ALT 2 1 2 5 (18.5%)
Increased AST 1 2 1 4 (14.8%)
Fever 1 1 1 1 4 (14.8%)
Thrombocytopenia 1 2 3 (11.1%)
Chills 1 1 1 3 (11.1%)
Peripheral Sensory Neuropathy 1 2 3 (11.1%)
Infusion reactions (IRR) of grade 1 or 2 were the most common related AEs.IRR occurred only during 1st infusion and no grade ≥3 IRR were reported.
The rate of infections was very low. MTD was not reached. Woyach et al, Blood 2014
MOR208 - Phase 1 in R/R CLL
High Single Agent Overall Response Rate
MorphoSys AG - Investor Event ASH - December 7, 2015 18
Best Response, n (%)
0.3 - 9 mg/kg
(N=11)
12 mg/kg
(N=16)
Total
(N=27)
Response by IWCLL 2008 criteria (CT scan)
Complete Response 0 0 0
Partial Response 2 (18%) 6 (38%) 8 (30%)
Stable Disease 7 (64%) 10 (62%) 17 (63%)
Progressive Disease 2 (18%) 0 2 (7%)
ORR in 12mg/kg (recommended phase 2 dose): 38% (IWCLL2008)
Responses by NCI96 criteria (physical exam)
Complete Response 0 0 0
Partial Response 6 (55%) 12 (75%) 18 (67%)
Stable Disease 5 (45%) 4 (25%) 9 (33%)
Progressive Disease 0 0 0
MOR208 shows encouraging single-agent efficacy
Woyach et al, Blood 2014
MOR208 - Phase 1 in R/R CLL
Encouraging ORR in Subgroup Analysis (IWCLL 2008)
MorphoSys AG - Investor Event ASH - December 7, 2015 19
Best Response
(IWCLL2008), n (%)
N
(all)
ORR
(all patients)
N
(12 mg/kg)
ORR
(12 mg/kg)
Overall 27 30% 16 38%
Del17p 10 30% 3 67%
Del11q 8 38% 5 40%
Largest LN > 5 cm 9 11% 5 20%
Largest LN ≤ 5 cm 18 39% 10 50%
MOR208 also shows promising efficacy in high risk patients
Woyach et al, Blood 2014
Phase 1 in R/R CLL
Best ALC Reduction and Tumor Shrinkage
MorphoSys AG - Investor Event ASH - December 7, 2015 20
Median absolute lymphocyte count reduction from baseline: 91%Pronounced nodal size reduction from baseline by CT scan
ALC: absolute lymphocyte count
-100
10
0
-10
-20
-30
-40
-50
-60
-70
-80
-90
1.0 mg/kg
9.0 mg/kg
3.0 mg/kg12.0 mg/kg
0.3 mg/kg
6.0 mg/kgDose
% C
hange f
rom
Base
line
Woyach et al, Blood 2014
40
20
0
-20
-40
-60
-80
-100
Best ALC Reduction from Baseline Tumor Shrinkage (Lymph Nodes)
Phase 1 in R/R CLL
Long Progression-Free Survival
MorphoSys AG - Investor Event ASH - December 7, 2015 21
Patients within the 12 mg/kg extended dosing (up to 6 cycles) show impressive PFS
Median, 420 days 14 months
12 mg/kg expansion cohort (N=8)
Max. MOR208 treatment period
Woyach et al, Blood 2014
MorphoSys AG - Investor Event ASH - December 7, 2015 22
MOR208 ranks highest among various α-CD19 & α-CD20 antibodies
38%24% 30%
23%13%
MOR20812m g /k g( n =16 )
MED I - 551ph a se I / I I 12m g /k g
( n =26 )
Ob in u t u zu mab ph a se I I( n =20 )
O f a t u m um abph a se I I I( n =196 )
R i t u x im a b( n =110 )
Single-agent Antibodies in R/R CLL*
MEDI-551 data source: Poster ASCO 2013, 12mg/kg dosing group
Obinutuzumab data source: GAUGUIN study, Cartron et al, Blood 2014
Ofatumumab data source: control arm in ibrutinib vs. O phase III trial (RESONATE, ASCO 2014)
Rituximab data source: Late breaking abstract #6, ASH 2013
Criteria: Hallek et al 2008 (including CT)
ORR
PD
SD
α-CD19 mabs α-CD20 mabs
*IWCLL2008 criteria
**14 months within expansion cohort;
NR: not reported
Non-evaluable/
info not available if SD or PD
PFS:(months)
NR** 10.7 5.5814**
Best
ORR:
Phase 1 in R/R CLL
MOR208 is Superior to Other CD19 & CD20 MAbs
MOR208 in CLL: Ongoing Activities
MorphoSys AG - Investor Event ASH - December 7, 2015 23
Investigator sponsored trial (IST) - PI Jennifer Woyach, OSU
Single center, open-label, single arm study in CLL patients < 80 years of age
4 cohorts, recruiting ~80 pts:
A. Combination with lenalidomide in previously untreated patients, ineligible for approved chemo-
and/or immunotherapy options
B. Combination with lenalidomide in R/R disease
C. Combination with lenalidomide in Richter’s disease
D. Combination with ibrutinib in pts with R/R disease under ibrutinib
Address preclinical synergy of MOR208 & Lenalidomide in CLL patients
Cycle 1
MOR208 1 mg/kg D1
MOR208 9 mg/kg D2,8,15,22
+
Lenalidomide 2.5 mg po D9-28
Cycle 2-12
MOR208 9 mg/kg D1
+
Lenalidomide 2.5 mg po D1-28
(dose escalation to 10mg)
Cycle 13+
Optional
lenalidomide
alone until
progression
Woyach et al, #2953 ASH2015
Phase 2 IST in R/R & Treatment Naïve CLL
MOR208 Combo with Lenalidomide
MorphoSys AG - Investor Event ASH - December 7, 2015 24
Characteristic Previously Untreated
n (%)
Relapsed/Refractory
n (%)
Total Patients 7 9
Median Age (range) 67 (44-75) 70 (62-74)
Gender
Male 6 (86) 8 (89)
Female 1 (14) 1 (11)
Median number of prior therapies
(range)
0 3 (1-8)
IgVH Unmutated 6 (86) 7 (78)
Complex Stimulated Karyotype 1 (14) 7 (78)
Interphase Cytogenetics
del(13q14.3) 4 (57) 6 (66)
Trisomy 12 3 (43) 0
del(11q22.3) 1 (14) 3 (33)
del(17p13.1) 1 (14) 1 (11)
Patient Characteristics
Woyach et al, #2953 ASH2015
Phase 2 IST in R/R & Treatment Naïve CLL
MOR208 Combo with Lenalidomide
MorphoSys AG - Investor Event ASH - December 7, 2015 25
Relapsed/Refractory Cohort (B)
Toxicities Occurring in >2 Patients, n (%)
Previously Untreated Cohort (A)
Toxicities Occurring in >1 Patient, n (%)
Grade 3+ Grade 3+
Hematologic Toxicities
Neutropenia 6 (66.7) 1 (14.3)
Non-Hematologic Toxicities
Hyperglycemia 2 (22.2) 0
Infusion reaction 0 1 (14.3)
Upper respiratory infection 0 1 (14.3)
Hypertension 2 (22.2) 2 (28.6)
The combination of MOR208 and lenalidomide has been well tolerated.
Toxicities Grade 3/4 Without Regard to Attribution
Woyach et al, #2953 ASH2015
Phase 2 IST in R/R & Treatment Naïve CLL
MOR208 Combo with Lenalidomide
MorphoSys AG - Investor Event ASH - December 7, 2015 26
Preliminary Efficacy Evaluation
T r e a tm e n t N a iv e C o h o r t
P a tie n t
Ch
an
ge
in
Ly
mp
h N
od
e D
iam
ete
r
1 2 3 4
-1 0 0
-8 0
-6 0
-4 0
-2 0
0
6 m o n th e va lu a tio n
1 2 m o n th e va lu a tio n
Patient Best
Response
08* PR
09* PR
10* PR
14* PR
11 NE+
12 NE+
17 NE++
So far 3/9 patients with R/R disease and 4/7 patients with treatment naïve disease responded to therapy. Responses deepened over time.
R e la p s e d /R e fr a c to r y C o h o r t
P a tie n t
Ch
an
ge
in
Ly
mp
h N
od
e D
iam
ete
r
1 2 3 4 5
-1 0 0
-5 0
0
5 0
6 m o n th e va lu a tio n
1 2 m o n th e va lu a tio n
R e la p s e d /R e fr a c to r y C o h o r t
P a tie n t
Ch
an
ge
in
Ly
mp
h N
od
e D
iam
ete
r
1 2 3 4 5
-1 0 0
-5 0
0
5 0
6 m o n th e va lu a tio n
1 2 m o n th e va lu a tio n
R/R = relapsed/refractory, PU = previously untreated; NE = Non-evaluable
Patient Best
Response
01 PR
02* PR
03* PR
06 SD
07 SD
04 PD
05 PD
18 NE**
20 NE**
R e la p s e d /R e fr a c to r y C o h o r t
P a tie n t
Ch
an
ge
in
Ly
mp
h N
od
e D
iam
ete
r
1 2 3 4 5
-1 0 0
-5 0
0
5 0
6 m o n th e va lu a tio n
1 2 m o n th e va lu a tio n
Previously Untreated Relapsed/Refractory
* Still on therapy
** Have not yet reached first response evaluation
+ Discontinued due to infusion reaction
++ Discontinued due to unrelated toxicity
Woyach et al, #2953 ASH2015
Phase 2 IST in R/R & Naïve CLL
MOR208 Combo with Lenalidomide / Ibrutinib
MorphoSys AG - Investor Event ASH - December 7, 2015 27
The combination of MOR208 and lenalidomide has preliminary activity in relapsed/refractory and
treatment-naïve CLL
This combination has been well tolerated, although escalation of lenalidomide above 2.5 mg has been
difficult
Responses have generally deepened over time. 5 patients have completed 12 cycles of therapy, and
2 of these remain on lenalidomide
Correlative studies to evaluate T and NK cell number and function are underway
Cohorts are currently being accrued to evaluate this combination in Richter’s transformation as well as
adding MOR208 to ibrutinib in patients undergoing molecular relapse
Conclusions
Woyach et al, #2953 ASH2015
Ibrutinib Treatment in CLL
Incidence of Discontinuation
MorphoSys AG - Investor Event ASH - December 7, 2015 28
Maddocks et al, JAMA Oncol. 2015 Apr;1(1):80-7
Ibrutinib Treatment Failures
MorphoSys AG - Investor Event ASH - December 7, 2015 29
Maddocks et al, JAMA Oncol. 2015 Apr;1(1):80-7
Overall Survival in PatientsDiscontinuation after AEs (days)
Overall Survival in Patients Discontinuation after Progression on
ibrutinib (months)
Planned Phase 2 Study in CLL
MOR208 in Combination With Idelalisib
MorphoSys AG - Investor Event ASH - December 7, 2015 30
A Phase II, Single Arm, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of
MOR208 Combined with Idelalisib in Patients with Relapsed or Refractory CLL/SLL Previously
Treated with Bruton’s Tyrosine Kinase (BTK) Inhibitor
Primary endpoint: ORR
N = 120
Patients: R/R CLL/SLL not responding or not able to tolerate BTK-inhibitor Tx (e.g. ibrutinib)
MOR208 12mg/kg: 3 cycles qw -> q2w until progression
Idelalisib 150 mg BID: continuously up to max. 24 cycle
Planned Start in Q1 2016
MOR202
A Novel CD38 mAb in Multiple Myeloma
Univ. Prof. Dr. Heinz Ludwig
Director of the Wilhelminen Cancer Research Institute
Vienna, Austria
MorphoSys AG - Investor Event ASH - December 7, 2015
MOR202 Mechanisms of Action:
High ADCC and ADCP Activity
32
MOR202
Fully human
monoclonal IgG1
antibody directed
against CD38
MOR202 induces
potent immune
effector mechanisms:
ADCC and ADCP
MorphoSys AG - Investor Event ASH - December 7, 2015
ADCC: Antibody-Dependent Cell-Mediated Cytotoxicity
ADCP: Antibody-Dependent Cell-Mediated Phagocytosis
CDC: Complement-Dependent cytotoxicity
no CDCCDC is suspected to be a
major contributor to
infusion reactions*
*Tawara et al. J Immunol 2008
MOR202 shows similar ADCC activity
on MM cells, but spares NK cells
MorphoSys AG - Investor Event ASH - December 7, 2015 33
In vitro ADCC activity profile of MOR202, surrogates of Daratumumab and Isatuximab and a variant
of MOR202
% s
pecific
killin
g
MOR202
Daratu
mumab
Isatuximab
Afucosylated .
MOR202
Daratu
mumab
Isatuximab
Afucosylated
0
10
20
30
40
50
60 AMO-1 NCI-H929
% s
pe
cif
ic N
K c
ell k
illin
g
MOR202 Daratumumab Isatuximab Afucosylated0
5
10
15
20
25
30
35
40
45
50
55
60
65
70
variant of MOR202Surrogate Surrogate
CD38 high expressing MM cell lines CD38 low expressing NK cells
Boxhammer et al, #3015 ASH 2015
CD38 mAbs in MM
MOR202 - Best-in-class Infusion Tolerability
MorphoSys AG - Investor Event ASH - December 7, 2015 34
MOR202 Daratumumab Isatuximab
ADCC (max) +++ +++ +++
ADCP (max) +++ +++ ?
CDC (max) - +++ +
NK cell sparing +++ + +
Infusion volume 250 ml 500-1000 ml ?
Speed of infusion 125 ml / hStart at 50 ml /h**
If IRR: restart with 25 ml/h?
Infusion time 2h6,5 h (1st infusion)
3,5 h (3rd infusion)4-6 h
IRRs
(with Steroids)+ 6% 70 / 77% 52%
MOR202: Raab et al. IMW 2015Daratumumab: Lokhorst et al. NEJM 2015
Isatuximab: Martin et al. ASCO 2014** Moreau @ Janssen Symposium IMW 2015+ Even without Steroids, MOR202 shows IRRs of only 40%
MOR202
Phase 1/2a in Relapsed / Refractory MM
MorphoSys AG - Investor Event ASH - December 7, 2015 35
Study design
Phase 1/2a multicenter, open-label, dose escalation study
3+3 design plus expansion cohorts
11 sites in Germany and Austria
Patient population
Patients with relapsed/refractory myeloma
for MOR202 +/- dex and combo with pomalidomide/dex: failure of ≥ 2 prior therapies
MOR202 combo with lenalidomide/dex: failure of ≥ 1 prior therapy
Outcome measures
Determination of MTD, recommended dose, regimen
Safety profile
Immunogenicity
Pharmacokinetic
Preliminary efficacy
Raab et al, #3035 ASH 2015
MOR202 - Phase 1/2a General Study
Design
Part A Cohorts 1–8
0.01 0.04 0.15 0.5 1.5 4.0 8.0 16.0
mg/kg q2w
Dose-escalation cohorts
3 + 3 scheme, 2-hour IV infusion
Confirmatory cohorts
at RP2D
Part B
4.0 mg/kg weekly
Part C
4.0 8.0 16.0 mg/kg weekly + DEX*
MOR202 +/- DEX
at RP2D/schedule
MorphoSys AG - Investor Event ASH - December 7, 2015 36
MO
NO
Part D
8 16 mg/kg weekly/DEX* + POM
Part E
8 16 mg/kg weekly/DEX* + LEN
MOR202/DEX + POM
MOR202/DEX + LEN
Available Data as of November 2015
CO
MBO
* 20mg DEX for patients >65 years, 40mg DEX for patients <65 years
MOR202 – Phase 1/2a Patient Characteristics of Clinically Relevant Cohorts
MorphoSys AG - Investor Event ASH - December 7, 2015 37
Schedule
MOR202 dosing
Patient number
q1w + Dex
4–16 mg/kg
n=10
q1w + POM/Dex
8 mg/kg
n=3
q1w + LEN/Dex
8 mg/kg
n=4
Median age, years 68 64 59
Gender, %
Male
Female
60
40
67
33
75
25
Karnofsky PS, %
Median 90 100 95
Lines of prior therapy, n
Median 4 3 2
Prior ASCT, % 80 33 75
Prior therapies, %
Bortezomib
Lenalidomide
Cyclophosphamide
Melphalan
Doxorubicin
Thalidomide
Pomalidomide
Carfilzomib
Panobinostat
100
100
90
80
60
50
10
10
0
100
100
33
100
0
0
0
0
0
100
25
100
75
50
0
0
0
25
Raab et al., #3035 ASH 2015
MOR202 – Phase 1/2a
Safety of Clinically Relevant Cohorts
MorphoSys AG - Investor Event ASH - December 7, 2015 38
Most frequently reported treatment emergent adverse events
Schedule
Patient number
q1w + Dex
n=10
q1w + POM/Dex
n=3
q1w + LEN/Dex
n=4
TEAEs, n (%) Grade ≥3 Any ≥3 Any ≥3 Any
Haematological
Lymphocyte count decreased
Neutrophil count decreased
WBC count decreased
Thrombocytopenia
Anaemia
2 (20%)
2 (20%)
0
1 (10%)
1 (10%)
3 (30%)
3 (30%)
2 (20%)
3 (30%)
2 (20%)
1 (33%)
2 (67%)
0
0
1 (33%)
1 (33%)
2 (67%)
1 (33%)
1 (33%)
1 (33%)
2 (50%)
1 (25%)
1 (25%)
1 (25%)
1 (25%)
2 (50%)
1 (25%)
3 (75%)
1 (25%)
1 (25%)
Non-haematological
Fatigue
Back pain
Diarrhoea
Hyperuricaemia
Insomnia
Polyneuropathy
0
0
0
0
0
0
5 (50%)
3 (30%)
0
2 (20%)
3 (30%)
2 (20%)
0
0
1 (33%)
0
0
0
1 (33%)
1 (33%)
1 (33%)
0
0
1 (33%)
0
0
0
1 (25%)
0
0
0
0
2 (50%)
1 (25%)
0
0
Only 3/52 patients (6%) discontinued due to AEs with a suspected relationship to MOR202
No treatment-related deathsRaab et al, #3035 ASH 2015
MOR202 – Phase 1/2a
Infusion-related reactions (IRRs)
39
Data from patients treated with the clinically relevant dose regimens who received ≥ 1 dose of
MOR202.
Dex, dexamethasone; LEN, lenalidomide; POM, pomalidomide; IRR, infusion-related reaction.
MOR202 q1w + Dex No IRR IRR Grade 1
4 & 8mg/kg + Dex
16 mg/kg + Dex
8 mg/kg + POM/Dex
8 mg/kg + LEN/Dex
7
2
3
4
0
1
0
0
Total; n (%) 16 (94 % ) 1 (6%)
MorphoSys AG - Investor Event ASH - December 7, 2015
Raab et al, #3035 ASH 2015
MOR202 – Phase 1/2a
Best maximum change in M-protein*
40
Data from patients treated with the clinically relevant dose regimens who received > 1 treatment
cycle
*Updated data from 23 November 2015. Serum M-protein data are shown.
In case serum M-protein is not available urine M-protein data are used (S, serum; U, urine)
MorphoSys AG - Investor Event ASH - December 7, 2015
Raab et al, #3035 ASH 2015
MOR202 – Phase 1/2a
Time on study and best response*
41
Data from patients treated with the clinically relevant dose regimens who received > 1 treatment
cycle.
* Updated data from 23 November 2015. **Not confirmed yet.
Dex, dexamethasone; LEN, Lenalidomide; MR, minor response; POM, Pomalidomide; PD, progressive disease; PR, partial
response; q1w, weekly; SD, stable disease; VGPR, very good partial response.
MorphoSys AG - Investor Event ASH - December 7, 2015
Raab et al, #3035 ASH 2015
MOR202 – Phase 1/2a
Summary of Preliminary Efficacy Data
MorphoSys AG - Investor Event ASH - December 7, 2015 42
Outcome of Single Agent MOR202 (weekly + Dex)
VGPR and PR: 3/9 evaluable patients
SD: 6/9 evaluable patients
ORR of 30%
Outcome of combo of MOR202 with ImiDs
VGPR and PR: 3/6 evaluable patients
MR: 1/6 evaluable patients
Responder Analysis (all patients)
Rapid decrease in M-Protein
Improvement in quality of remission with
longer treatment duration
Ongoing responses: 5/6 patients
Best stabilization: 52+ weeks (12+ months)
DoR 2+, 3, 3+, 3+, 4+, 8+ monthsData from patients treated with the clinically relevant dose
regimens who received > 1 treatment cycle.
* Updated data as of 23 Nov 2015.
** Not confirmed yet.
Raab et al, #3035 ASH 2015
Conclusion
MorphoSys AG - Investor Event ASH - December 7, 2015 43
HuCAL IgG1 antibody binding unique epitope on CD38
One of only three CD38 antibodies in clinic
Main mode of action: ADCC and ADCP
Potent killing of MM cells
Low killing of healthy/effector cells
Active as single-agent therapy (ORR of 33%)
Active in combination with LEN/DEX or POM/DEX (clinical benefit rate of 67%)
Further cohorts will evaluate MOR202 16 mg/kg q1w in combination with LEN/DEX and POM/DEX
Excellent safety profile with only 7% IRR
MOR202 doses up to 16 mg/kg can be safely administered as a 2-hour IV infusion
Questions & Answers
MorphoSys AG - Investor Event ASH - December 7, 2015 44
Simon Moroney, D. Phil.
Arndt Schottelius, M.D., Ph.D.
Steffen Heeger, M.D., Ph.D.
Jennifer Woyach, MD
Assistant Professor of Internal Medicine
Ohio State University
Prof. Dr. Heinz Ludwig
Director of the Wilhelminen Cancer Research Institute,
Vienna, Austria
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Dr. Claudia Gutjahr-Löser
Head of Corporate Communications & IR
Phone +49 (0)89 / 899 27-122
Fax +49 (0)89 / 899 27-5122
Email [email protected]
Thank You
www.morphosys.com