M7824 - Driving a paradigm shift in the treatment of cancer - Merck Group
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M7824 - Driving a paradigm shift in the treatment of cancer Merck & GlaxoSmithKline Dr. Stefan Oschmann, Chairman of the Executive Board and CEO Dr. Marcus Kuhnert, Member of the Executive Board and CFO Dr. Belén Garijo, M.D., Member of the Executive Board and CEO Healthcare Darmstadt, Germany – February 5, 2019
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2 Merck & GSK Global Alliance | February 5, 2019
Healthcare Strategy
Continuing to deliver on our strategic roadmap
2012-2015 2016-2018 2019-2022
Turnaround Fully leverage
Efficiency First pipeline
program in Healthcare
launches
pipeline potential Maximize our pipeline
potential:
Above-
1. Ramp up of Bavencio and Mavenclad
Portfolio
3 strong market growth sales (9M 2018: €106 m)
optimization
pillars Portfolio in Life Science
in LS and PM
management
2. Solid growth of core business
Sigma
integration
over 29 quarters
3. Diligent development and
Leadership Digital management of the pipeline
in Performance business models (e.g. Evobrutinib, Bavencio RCC 1L,
Materials New applications
beyond displays TGF-ß Trap)
3 Merck & GSK Global Alliance | February 5, 2019 | Acronyms: RCC = Renal Cell Carcinoma
Healthcare Strategy
Actively managing portfolio for value maximization
Merck’s key pipeline compounds1
Full pipeline requires regular
prioritization and de-risking
decisions Strategic Self
Asset’s fit with Merck’s R&D strategy
partnerships
Mavenclad
Bavencio Tepotinib
• Merck continuously monitors all pipeline
candidates TGF-ß Trap DNA Damage
Evobrutinib Response
• Regular assessment of their potential is based
on clinical data, strategic fit and financial criteria
• Merck then decides on how to best develop
the assets going forward Externalization
Evaluate
• Strategic partnerships and external Atacicept
financing are key to de-risk the pipeline and Abituzumab
maximize its value IL-17
Asset’s fit for Merck’s resources
4 Merck & GSK Global Alliance | February 5, 2019 | 1: Assessment may change due to regular review
M7824 Bintrafusp alfa1
A bifunctional fusion protein with significant potential
First-in-class bi-functional fusion protein, targeting both TGF-β
and PD-L1
Demonstrated superior anti-tumor activity in pre-clinical study
compared to anti-PD-L1 alone, and anti-PD-L1 and TGF-β given in
M7824 combination as separate agents
Great excitement in IO community about M7824 uniquely addressing
TGF-ß biology widely accepted as key resistance factor for anti-PDx
therapies
• Tested in 14 Phase Ib expansion cohorts across >700 patients in
more than 10 tumor types
Clinical • Shown clinical anti-tumor activity across multiple hard-to-treat cancers including
Development advanced NSCLC, biliary tract cancer, HPV-associated cancers, and gastric cancer
Achievements • PhII study M7824 monotherapy versus pembrolizumab 1L, advanced NSCLC
high PD-L1-tumor expressers started in October 2018
Clinical • Eight high priority immuno-oncology clinical development studies ongoing or expected to
commence in 2019, including pivotal registrational studies in non-small cell lung and biliary
Development tract cancers
Plans • Further plans to be communicated at a later stage
5 Merck & GSK Global Alliance | February 5, 2019 | 1: proposed International Nonproprietary Name (INN) | Acronyms: NSCLC = non-small cell lung cancer
Choice of Partner
Joining forces with a strong partner committed to advancing M7824
Selection criteria GlaxoSmithKline1
Global pharma player with strong Impressive global footprint & leadership with
capabilities in the development and deep development and commercial oncology
commercialization of blockbuster drugs expertise
Strong commitment to oncology reflected by:
Committed to advancing the • Leading industry talent
development of M7824 • Cutting edge portfolio
• Recent acquisition of Tesaro
M7824 has potential for synergies with several of
GSK's portfolio assets
Aligned on future development plans Fully aligned on current clinical development plan,
including decisions made prior to partnership
6 Merck & GSK Global Alliance | February 5, 2019 | 1: Partnering approach complimentary to Merck/Pfizer alliance
Choice of Partner
Leveraging collective strengths and an aligned vision
MeRck GSK
• Strong commitment to oncology
• Proven track record of • Strong industry talent
Proven collaborative R&D, with roughly • Proven track record in collaborative
development 50% of the pipeline developed R&D
commitment through collaborations • Rapid growth including Tesaro
acquisition
• M7824: the only TGF-ß / anti-PD-L1 • Several potential combination
Complementary therapeutic, discovered in-house assets including ICOS, TLR4, STING
oncology pipelines and others
• DDR portfolio
• Established Oncology footprint • Global commercial footprint and
Commercial growing oncology presence
strength
7 Merck & GSK Global Alliance | February 5, 2019 | Acronyms: ICOS = Inducible T-cell costimulator, STING = Stimulator of interferon genes, TLR4 = toll-like receptor 4
Alliance Development Plan
Exploring M7824‘s potential in difficult-to-treat cancers
Explorative Registrational
1L NSCLC all-comers 1L NSCLC in PD-L1 high vs
(CT combo) pembrolizumab (mono)2
NSCLC
Stage III unresectable NSCLC 2
(CRT combo)2
BTC 2L Biliary Tract Cancer
Additional studies and settings (mono)
(incl. Gastric, 1L BTC, TNBC and
HPV related cancers) to be
communicated at a later date
Others
Not yet started1 Started / ongoing Registrational intent
8 Merck & GSK Global Alliance | February 5, 2019 | 1: all studies shown to be commenced in 2019 | 2: randomized controlled trials | Acronyms: CT = chemotherapy,
CRT = chemoradiotherapy, NSCLC = non-small cell lung cancer, BTC = biliary tract cancer, TNBC = Triple-Negative Breast Cancer
Deal Structure
Attractive payment terms rewarding developmental success
Total deal volume: €3.7 bn
Milestone payments: €3.4 bn
Upfront & Upfront
Milestone payment: Development
Approval Commercial
Payment €300 m (up to €500 m)
Structure
Development milestones: Up to €500 m triggered by data from the M7824
lung cancer program
Profit & Cost • Profits & Costs: Shared equally on a global basis
sharing • Sales: Merck to recognize sales in the United States, GSK to recognize sales ex-US
9 Merck & GSK Global Alliance | February 5, 2019
Deal Structure
Upfront – and milestone payments recognized as
Other Operating Income
Payment type Amount (in €) Accounting treatment1
Around €100 m anticipated to be recognized as other operating income
Upfront payment 300 m in 2019 and remaining portion expected to be recognized until
~mid-2021
• Majority deferred and recognized as part of other operating income over
Development
Up to 500 m the remaining development term starting from the day on which the
milestone
milestone is achieved
Approval milestones
• Recognized as part of other operating income as soon as the relevant
Up to 2.9 bn
Commercial success criteria are met
milestones
• Merck to recognize sales in the US
Sales n/a
• GSK to recognize sales ex-US
Costs n/a • Reconciled to ensure 50/50 share
Profits n/a • Reconciled to ensure 50/50 share
Effective date Approx. second half of March following anti-trust clearance
10 Merck & GSK Global Alliance | February 5, 2019 | 1: Accounting treatment subject to confirmation by the Group AuditorsMerck and GSK
Driving a paradigm shift in the treatment of cancer
Innovative first-in- Strong partner truly
class bi-functional committed to
molecule co-developing M7824 and
(TGF-β plus PD-L1) leading the exploring synergies with
TGF-β immuno-oncology field their oncology portfolio
Eight high priority
Attractive deal immuno-oncology
terms rewarding clinical development
developmental, regulatory studies ongoing or expected
and commercial success to commence in 2019
11 Merck & GSK Global Alliance | February 5, 2019Constantin Fest SVENJA BUNDSCHUH ALESSANDRA HEINZ
Head of Investor Relations Assistant Investor Relations Assistant Investor Relations
+49 6151 72-5271 +49 6151 72-3744 +49 6151 72-3321
constantin.fest@merckgroup.com svenja.bundschuh@merckgroup.com alessandra.heinz@merckgroup.com
Annett Weber AMELIE SCHRADER
EMAIL: investor.relations@merckgroup.com
WEB: www.investors.merck.de
Institutional Investors / FAX: +49 6151 72-913321
Institutional Investors /
Analysts Analysts
+49 6151 72-63723 +49 6151 72-22076
annett.weber@merckgroup.com amelie.schrader@merckgroup.com
Eva Sterzel PATRICK BAYER
Retail Investors / AGM / Institutional Investors /
CMDs / IR Media Analysts
+49 6151 72-5355 +49 6151 72-5642
eva.sterzel@merckgroup.com patrick.bayer@merckgroup.comAppendix
Appendix
M7824 is a first in class TGF-β targeting bifunctional fusion protein
TGF-β targeting overcomes poorly addressable tumor biology
TGF-β Trap
2
1 3
anti PD-L1
14 Merck & GSK Global Alliance | February 5, 2019Appendix
Co-localization of two highly synergistic pathways
M7824 is superior to co-administration of TGF-β trap and anti-PD-L1
MC38 Colorectal Cancer
15 Merck & GSK Global Alliance | February 5, 2019 | Lan et al, Sci Transl Med, Jan 2018Appendix
Ongoing phase I signal-finding studies treated >670 patients
with M7824
Study design (NCT02517398)
1 Phase I, open-label, multiple-ascending dose trial
Study design 001 Indications: Locations:
Subjects with HCC 2L NSCLC PDx Sites in America, Asia,
HCC 2L NSCLC 2L
metastatic or locally Expansion Failure Europe and Oceania
advanced solid tumors Pancreatic >2L CRC >2L
Adeno
SCCHN
Esophageal >2L
and expansion to
selected indications TNBC >2L
Melanoma PDx
Cervical >2L GBM >2L
Failure
Study design (NCT02699515)
2 Phase I, open-label, multiple-ascending dose trial
Study design 008 Locations:
Subjects with Sites in Asia
metastatic or locally
advanced solid tumors Sq. Esophageal Biliary tract 2L Gastric 3L
with expansion to
selected indications in
Asian subjects
16 Merck & GSK Global Alliance | February 5, 2019Appendix
Non-small cell lung cancer (NSCLC 2L)
Impressive durable responses seen across all PD-L1
expression levels
1200 mg
Efficacy According to Independent Read, RECIST 1.1 (data cut off 23 July 2018)
85.7%
80 (6/7)
Keynote 010 M7824
60 Keynote 001
44%
ORR (%)
37%
(10/27)
40 25%
27% 29% (10/40)
19% 18%
20
0
All PD-L1+* PD-L1 All PD-L1+* PD-L1
high* high*
* TPS ≥50% with 22C3 comparable to ≥80% with EMD 001 assessments
17 Merck & GSK Global Alliance | February 5, 2019Appendix
Biliary tract cancer (BTC) - Update on Clinical Results
ORR of 20% with long durability in allcomer population - IRC read
Biliary Tract Cancer (Asian patients, 2nd line after platinum based 1st line)
RECIST 1.1, Independent Central Read
Change in target lesions from baseline
N=30 N INV % IRC (%)
Objective responses 7 23.3 6 (20.0)
CR 1 3.3 1 (3.3)
PR 6 20.0 5 (16.7)
DCR (conf CR/PR/SD) 11 36.7 12 (40.0)
DoR Median not reached, 6/6 ongoing for 8.3+ to
13.9+ months
PFS Median 2.6 months 1.3-5.6
PFS12 23.6% 9.7-40.8
OS Median 12.7 months 6.7-not
OS12 52% reached
32.8-68.2 Best change in target lesions from baseline
SOC Efficacy BTC 2L (ASAN Medical Center, Lamarca
2014)
ORR 7.5% (Lamarca 2014)
Pembrolizumab BTC cohort in PD-L1 ≥1%*
ORR 5.8%
data cut off date: 23 July 2018
18 Merck & GSK Global Alliance | February 5, 2019 | * Keynote 158, n=104 pts, 6.6% ORR in PD-L1 pos, 2.9% ORR in PD-L1 negAppendix
HPV-associated cancers – A potential pan-tumor therapy
M7824 produced strong responses in these cancers,
especially those HPV+
• Data shown is from dose escalation portion of
the Phase 1
• HPV is associated with almost all anal and
cervical cancer, and some SCCHN1-3
• Anti–PD-1 monotherapies have shown clinical
activity but response rates remain in the range
of 17–26%4-7
• Analyses of HPV+ cervical and SCCHN tumor
samples from TCGA and Oncomine
demonstrate frequent dysregulation of TGF-
βR1 signaling, suggesting this pathway plays a
role in HPV-mediated carcinogenesis BOR, n (%) N=17 N=12
(all HPV associated tumors) (all HPV-positive)
CR 2 (11.8) 1 (8.3)
1. De Vuyst et al. Int J Cancer. 2009;124:1626–36;
2. Ihloff et al. Oral Oncol. 2010;46:705–11; PR 4 (23.5) a 4 (33.3) a
3.
4.
Mehanna et al. Head Neck. 2013;35:747–55;
Bauml et al. J Clin Oncol. 2015;33(suppl; abstr TPS3094);
SD 4 (23.5) 1 (8.3)
5. Ferris et al. N Engl J Med. 2016;375(19):1856; PD 7 (41.2) 6 (50.0)
6. Frenel et al. J Clin Oncol. 2017;35(36):4035;
7. Ott et al. Ann Oncol. 2017;28(5):1036;
8. Levovitz et al. Cancer Res. 2014;74(23):6833 ORR 6 (35.3) 5 (41.7)
DCR 10(58.8) 7 (50.0)
a1patient had an unconfirmed PD per RECIST prior to durable PR (assumed
pseudoprogression)
19 Merck & GSK Global Alliance | February 5, 2019Appendix
Gastric Cancer (Asian patients, 3L+) – A promising monotherapy in allcomers
Long durability and response rates nearly twice as PDx
RECIST 1.1, investigator read Efficacy According to Investigator-Assessed RECISTv1.1:
Tumor Regression from Baseline
N=31 n INV % IRC (%)
ORR (confirmed CR+PR) 7 22.6 5 (16.1)
CR 2 6.5 1 (3.2)
PR 5 16.1 4 (12.9)
SD 5 16.1 2 (6.5)
PD 17 54.8 21 (67.7)
NE 2 6.5 2 (6.5)
DCR (CR+PR+SD) 12 38.7 7 (22.6)
All comer population has been enrolled in this trial
Nivolumab Pembrolizumab
Trial ONO-4538 KEYNOTE-059
Phase III vs. Plc II
Line of Therapy 3L+ 3L+ mono
Patient (n) 493 143
ORR 11.2% 13% (PD-L1 pos)
20 Merck & GSK Global Alliance | February 5, 2019You can also read
