Merck Oncology Investor Event...2021/06/06 · 20 30 40 50 60 70 80 90 100 Months PFS, % No. at...
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Merck Oncology Overview ASCO 2021
Transcript of Merck Oncology Investor Event...2021/06/06 · 20 30 40 50 60 70 80 90 100 Months PFS, % No. at...
MerckOncology Overview ASCO 2021
Agenda
• Overview of Oncology Program | Dr. Dean Li, President, Merck Research Labs
• ASCO 2021 Highlights | Dr. Roy Baynes, SVP and Chief Medical Officer, MRL
• Late-stage Pipeline | Dr. Vicki Goodman, VP of Late-stage Oncology Development, MRL
• Early-stage Pipeline | Dr. Eric Rubin, SVP of Early-stage Oncology Development, MRL
• Commercial Update | Jannie Oosthuizen, SVP of Oncology Human Health, Merck
• Q&A
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Forward-looking statement of Merck & Co., Inc., Kenilworth, N.J., USA
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This presentation of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2020 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Dr. Dean LiPresident, Merck Research Labs
Uniquely positioned to drive long-term success and oncology leadership through continued execution and momentum
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Broad oncology program with deep
pipeline of differentiated early-
and late-stage assets
World-class scientific expertise and ability to leverage KEYTRUDA’s
foundational stature
Extensive runway to advance science to
reach more patients and solve for unmet
need
Unmatched commercial expertise
to capitalize on significant
opportunities
KEYTRUDA has now demonstrated activity in more than 30 different types of cancer defined by site of origin, histology, or genetic markers
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100Gastric6
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100Mesothelioma9
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100SCLC11
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100NPC13 HCC16Esophageal12
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100Ovarian10
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100ER+/HER2– BC17 Cervical18
Thyroid19 Salivary20 Endometrial21
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100Melanoma1
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100Biliary Tract15
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100Prostate22 GBM23
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100MSI-H CRC24
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100Carcinoid25
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100pNET25
ccRCC27 nccRCC28
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100MSI-H non-CRC24
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100Merkel Cell26
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tTMB-H29
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1. Daud A et al. ASCO 2015; 2. Garon EB et al. ESMO 2014; 3. Seiwert T et al. ASCO 2015; 4. Plimack E et al. ASCO 2015; 5. Nanda R et al. SABCS 2014; 6. Bang YJ et al. ASCO 2015; 7. Moskowitz C et al. ASH 2014; 8. Zinzani PL et al. ASH 2015; 9. Alley EA et al. AACR 2015; 10. Varga A et al. ASCO 2015; 11. Ott PA et al. 2015 ASCO; 12. Doi T et al. ASCO 2015; 13. Hsu C et al. ECC 2015; 14. Marabelle A et al. ASCO 2020; 15. Bang Y-J et al. ECC 2015; 16. Zhu A et al. ASCO 2018; 17. Rugo HS et al. SABCS 2015; 18. Frenel JS et al. ASCO 2016; 19. Mehnert JM et al. ASCO 2016; 20. Cohen R et al. ASCO 2016; 21. Ott PA et al. ASCO 2016; 22. Hansen AR et al. ESMO 2016; 23. Reardon D et al. SNO 2016; 24. Diaz L et al. ESMO 2017; 25. Mehnert J et al. ESMO 2017; 26. Nghiem P et al. ASCO 2018; 27. McDermott DF et al. ASCO 2018; 28. McDermott DF et al. ASCO-GU 2019; 29. Marabelle A et al. ESMO 2019; 30. Grob JJ et al. ESMO 2019.
= cancer types with approved indications
KEYTRUDA monotherapy and in combination improved cancer outcomes in Phase 3 studies across a broad range of malignancies
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0 10 20 30 40 50 600
10
20
30
40
50
60
70
80
90
100
Months
PFS,
%
No. at Risk153 73 53154 56 14
6025
288
62
00
0 6 12 18 24 30 36 42 48 540
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk432 407 286429 379 252
384336
259224
1612
318279
00
345306
141110
0 8 16 24 32 40 48 56 64 720
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk270 148 49272 109 25
9859
4224
3623
6935
00
5827
116
0 10 20 30 40 50 600
20
40
60
80
100
Months648 509 440 410 344 86 0655 396 336 290 227 61 1
No. a t Risk
0 3 6 9 12 15 18 21 24 270
10
20
30
40
50
60
70
80
90
100
Months
EFS,
%
No. at Risk784 780 765 666 519390 386 380 337 264
00
376186
242116
7335
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0 5 10 15 20 25 30 35 40 450
10
20
30
40
50
60
70
80
90
100
Months
DFS
, %
No. at Risk496 151498 145
6156
233209
00
457436
414389
11
371341
2119
0 8 16 24 32 40 480
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk278 190 79135 84 27
12249
00
5316
162
0 6 12 18 24 30 36 42 48 54 60 660
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk637 463 304 246 100637 485 236 177 60
193131
00
10
5940
368319
156100
1912
0 12 24 36 48 60 720
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk690 333 217 148 90343 114 46 35 18
11027
113
Monotherapy
0 12 24 36 48 60 720
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk556 387 297 245278 145 103 90
00
21179
17769
KEYNOTE-006Pembro vs Ipi
Ipi-Naive Melanoma, Any PD-L1
OS
0 6 12 18 24 30 36 42 48 54 60 66 720
10
20
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40
50
60
70
80
90
100
Months
OS,
%
No. at Risk154 121 78 66 20151 108 48 35 13
6233
00
8961
5126
10680
7344
5428
03
KEYNOTE-024Pembro vs Chemo
1L NSCLC, TPS ≥50%
OS
0 5 1 0 1 5 2 0 2 5 3 0
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
M o n t h s
OS
, %
N o . a t R is k2 4 7 1 6 0 1 0 32 4 8 1 5 1 8 2
4 83 4
00
1 41 0
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KEYNOTE-040Pembro vs SOC
2L+ HNSCC, Any PD-L1
OS
KEYNOTE-042Pembro vs Chemo
1L NSCLC, TPS ≥1%
OS
0 5 10 15 20 25 30 35 40 45 50 55 600
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20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk257 197 152 92 62255 207 132 60 29
7142
00
5522
2210
126
20
11190
4016
KEYNOTE-048Pembro vs EXTREME1L HNSCC, CPS ≥1
OS
KEYNOTE-181Pembro vs Chemo
2L Esophageal, CPS ≥10
0 4 8 12 16 20 24 28 32 360
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk107 86 59 45 10115 76 48 23 9
2914
00
54
01
2114
OS
KEYNOTE-240Pembro vs Placebo2L HCC, Any PD-L1
OS
0 5 10 15 20 25 30 35 400
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk96 79 57 41 2398 80 54 36 12
00
114
11
2623
KEYNOTE-119Pembro vs Chemo
2/3L TNBC, CPS ≥10
OS
0 6 1 2 1 8 2 4 3 0 3 6 4 20
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
M o n t h s
OS
, %
N o . a t R is k9 2 6 2 5 29 0 7 0 4 2
4 52 8
00
3 21 6
1 37
40
KEYNOTE-062Pembro vs Chemo 1L Gastric, CPS ≥10
OS
KEYNOTE-045Pembro vs Chemo
2L Bladder, Any PD-L1
OS
KEYNOTE-010Pembro vs Docetaxel 2L+ NSCLC, TPS ≥1%
OS
0 6 12 18 24 30 36 420
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20
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50
60
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100
Months
OS,
%
No. at Risk307 110352 104
6246
133150
10
228297
170197
1920
KEYNOTE-361Pembro vs Chemo
1L Bladder, Any PD-L1
OS
RFS
KEYNOTE-054Pembro vs Placebo Adjuvant Melanoma
PFS
KEYNOTE-177Pembro vs Chemo
1L MSI-H/dMMR CRC, Any PD-L1
0 6 12 18 24 30 36 42 480
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Months
PFS,
%
No. at Risk270 170 116 86272 140 73 47
6935
00
6028
5226
1712
KEYNOTE-204Pembro vs BV
R/R cHL, Any PD-L1
PFS
Combinations
0 6 12 18 24 30 36 42 48 540
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60
70
80
90
100
Months
OS,
%
No. at Risk410 347 234 184 99206 149 72 55 29
12534
00
28398
14942
2810
KEYNOTE-048Pembro + Chemo vs
EXTREME1L HNSCC, Any PD-L1
0 5 10 15 20 25 30 35 40 45 50 55 600
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk281 227 169 94 70278 227 148 67 32
7847
00
6324
308
92
10
122101
4917
OS
KEYNOTE-361Pembro + Chemo vs
Chemo1L Bladder, Any PD-L1
0 6 12 18 24 30 36 420
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk351 118352 104
5646
168150
00
306297
217197
1720
OSKEYNOTE-189
Pembro + Chemo vs Placebo + Chemo
1L Nonsquam NSCLC, Any PD-L1
OS
KEYNOTE-426Pembro + Axitinib vs
Sunitinib1L RCC, Any PD-L1
KEYNOTE-407Pembro + Chemo vs
Placebo + Chemo1L Squam NSCLC, Any PD-L1
0 6 12 18 24 300
10
20
30
40
50
60
70
80
90
100
MonthsO
S, %
No. at Risk278 232 180 119 46281 246 137 91 36
43
OS OS0 3 6 9 12 15 18 21 24 27 30 33 36
0
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk373 348 68376 338 51
235200
1715
74
151108
00
295274
187147
11882
3628
21
OS
KEYNOTE-590Pembro + Chemo vs
Placebo + Chemo1L Esophageal, Any PD-L1
KEYNOTE-604Pembro + EP vs
Placebo + EP 1L SCLC, Any PD-L1
0 6 12 18 24 300
10
20
30
40
50
60
70
80
90
100
Months
OS,
%
No. at Risk228 175 60225 170 44
10289
158
10
OS
KEYNOTE-522Pembro + Chemo/Pembro vs
Placebo + Chemo/PlaceboNeoadj/Adj TNBC, Any PD-L1
EFS
KEYNOTE-355Pembro + Chemo vs
Placebo + Chemo1L TNBC, CPS ≥10
0 6 12 18 24 30 360
10
20
30
40
50
60
70
80
90
100
Months
PFS,
%
No. at Risk220 122 44103 41 12
6318
258
53
00
PFS
KEYNOTE-775 (Study 309)Pembro + Lenvatinib vs Doxorubicin or Paclitaxel
2L EC, Any PD-L1
OSKEYNOTE-581 (CLEAR)Pembro + Lenvatinib vs
Sunitinib1L RCC, Any PD-L1
OS
KEYNOTE-053Pembro vs IFN or Ipi Adjuvant Melanoma
RFS
RFS
KEYNOTE-564Pembro vs Placebo
Adjuvant RCC
Broad oncology strategy to improve outcomes for cancer patients globally
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Further establishKEYTRUDA as foundational treatment and expand to additional tumor types and to earlier stages of disease
Advance pipeline and pursue strategic collaborations and acquisitions to broaden portfolio
Identify patients most likely to benefit using biomarkers
Deepen responses and extend benefit with combinations
Industry’s broadest immuno-oncology development program aimed to advance standard-of-care and address unmet needs
Merck’s Oncology
Development Program
>1,500 Ongoing
clinical trials
>1,000 Combination
trials
>100 Registrational
trials for KEYTRUDA under way
>25 Novel
mechanisms
>50Business
development transactions
in 2020
>120Keytruda
trials in adj/neoadjuv
and earlier lines
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More than tripling the number of new indications and launches across oncology portfolio over the next eight years
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2014-2020 2021-2028
PIPELINE ASSETS
LENVIMA
LYNPARZA
KEYTRUDA
>90 potential approvals expected by 2028 with more than 50 expected by 2025
Shaping the future of oncology by leveraging our robust portfolio and pipeline…
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Further establish KEYTRUDA as a foundational anti-PD-1 cancer treatment in monotherapy and in combination regimens
Diversify through partnerships with PARPi, VEGF TKI, HER2 TKI, LIV-1 ADC
Ladiratuzumab Vedotin (LV)
HIF-2α(MK-6482/belzutifan)
BTK (MK-1026)
ROR-1 ADC(MK-2140)
Diversify through acquisitions of BTK, HIF-2α, ROR-1 ADC assets
Expand the IO-IO strategy throughcombinations with internal assets
TIGIT(MK-7684/
vibostolimab)
CTLA-4(MK-1308/
quavonlimab)ILT4
(MK-4830)
LAG-3(MK-4280/
favezelimab)
Expand into cell-based therapies & T/NK cell engagers
Dr. Roy BaynesSVP and chief medical officer, MRL
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New Phase 3 data for KEYTRUDA in Adjuvant RCC (KN-564)
New Lynparza data in adjuvant breast cancer (OlympiA)
Final analysis of OS and RFS in Phase 3 KN-053 studying adjuvant KEYTRUDA in melanoma patients
First-time presentation of KN-811 in HER2+ gastric/GEJ patients
Recent top-line from KN-522 in adjuvant and neoadjuvant TNBC
New outcomes data from KN-581 and KN-775 supporting benefit from the combination in RCC and endometrial carcinoma patients
Long-term survival data for KEYTRUDA in urothelial carcinoma based on 5-year follow-up from KN-045 and KN-052
Final analysis from KN-426 in front-line RCC
First-time presentation of Phase 1 data studying favezelimab (MK-4280) in MSS CRC patients
Additional data from belzutifan (MK-6482) in RCC and non-RCC malignancies
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ASCO 2021: new, long-term and early data from broad portfolio
New Data Including in Early-Stage Disease…
… DemonstratingPatient Benefit ...
… And Progressing Novel Mechanisms
KEYNOTE-564: new data in adjuvant RCC demonstrated clinically meaningful improvement in disease-free survival compared to placebo
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KEYTRUDA following surgery reduced risk of recurrence or death by 32% compared to placebo for patients with RCC
• Favorable trend in overall survival (OS) was observed with a 46% reduction in the risk of death with KEYTRUDA as compared to placebo (HR=0.54 [95% CI, 0.30–0.96]; p=0.0164).
• First anti-PD-1 therapy to show positive results for adjuvant immunotherapy in RCC
• Nearly half of high-risk RCC patients experience disease recurrence after surgery
0 5 10 15 20 25 30 35 40 450
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Months
DFS
, %
No. at Risk
PembroPlacebo
496 457 414 371 1 0233 21151 61498 436 389 341 1 0209 19145 56
PembroPlacebo
HR 0.68 (95% CI, 0.53–0.87); P = 0.0010a
% Events Median (95% CI)
Pembro 22.0% NR (NR–NR)
Placebo 30.3% NR (NR–NR)
Median follow-up: 24.1 (14.9–41.5) mos.
aCrossed prespecified p-value boundary for statistical significance of 0.0114.ITT population included all randomized participants. NR, not reached. Data cutoff date: December 14, 2020.
Disease-free survival in ITT population
12-mo rate85.7%76.2%
24-mo rate77.3%68.1%
OlympiA: Lynparza in adjuvant breast cancer changing survival expectations in certain early-stage patients
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Lynparza reduced risk of invasive disease recurrence or death by 42% in gBRCAm High-risk HER2- early-stage breast cancer based on Phase 3 study
• Stratified HR=0.58 (99.5% CI, 0.41 to 0.82); P<0.0001• At three years since trial initiation, 85.9% of patients
treated with Lynparza were free of invasive disease versus 77.1% on placebo (difference 8.8%; 99.5% CI 4.5%, 13.0%)
• Improvement in secondary endpoint of distant disease recurrence or death by 43% in the ITT population (HR=0.57 [99.5% CI, 0.39-0.83]; p<0.0001)
• Favorable trend in OS with a 32% reduction in the risk of death (HR=0.68 [99% CI, 0.44 to 1.05]; p=0.024)
Data cutoff: Dec. 15, 2020In partnership with AstraZeneca
921 820 737 607 477 361 276 183
915 807 732 585 452 353 256 173
Olaparib
Placebo
0 6 12 18 24 30 36 42Time Since Randomization (Months)
0
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40
60
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Inva
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Dis
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-Fre
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Olaparib (106 events)Placebo (178 events)
88.4
93.3
81.5
89.2 85.9
77.1
No. at Risk
Difference: 3-year IDFS rate8.8% (95% CI, 4.5% to 13.0%)
Favezelimab (LAG-3): ASCO data shows anti-tumor activity in MSS CRC patients; advancing into Phase 3 study as co-formulation with KEYTRUDA
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Favezelimab + PembrolizumabN = 80
PD-L1 CPS ≥1N = 36
PD-L1 CPS <1N = 35
Best response n % (95% CI) n % (95% CI)
ORR (CR + PR) 4 11 (3.1-26.1) 1 2.9 (0.1-14.9)Best overall response
CR 1 2.8 (0.1-14.5) 0 0 (0.0-10.0)
PR 3 8.3 (1.8-22.5) 1 2.9 (0.1-14.9)
SD 9 25.0 (12.1-42.2) 4 11.4 (3.2-26.7)
PD 15 41.7 (25.5-59.2) 24 68.6 (50.7-83.1)
DCR (CR+PR+SD) 13 36.1 (20.8-53.8) 5 14.3 (4.8-30.3)Median DOR 10.6 months (range, 5.6-12.5)
aNo patient receiving favezelimab alone responded; No response occurred in patients with missing PD-L1 status (N=9); bDoes not include patients with missing PD-L1 status (N=9).
CR, complete response; DCR, disease control rate; DOR, duration of response; PR, partial response; PD, progressive disease; SD, stable disease; Data cut-off date Oct 23, 2020.
Antitumor Response
High unmet need in sick patients treated at later stages with low survival rates. Limited treatment options.• Responses seen in additional tumor
types
KEYNOTE-581: outcomes data further supports benefit of combination for patients with first-line RCC
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KEYTRUDA plus LENVIMA significantly improved several health-related quality of life (HRQoL) measures compared with sunitinib in RCC patients• At ASCO GU 2021, data on the
combination was highlighted demonstrating significant improvements in PFS (HR=0.39 [95% CI: 0.32-0.49]; p<0.001), and OS (HR=0.66 [95% CI: 0.49-0.88]; p=0.005) vs sunitinib in the same patient population
KEYNOTE-775: outcomes data further supports benefit of combination for patients with previously-treated endometrial carcinoma
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KEYTRUDA plus LENVIMA shows an overall favorable benefit/risk profile compared with physician’s choice treatment in endometrial carcinoma patients based on HRQoL data• At SGO 2021, data on the combination was
highlighted demonstrating significant improvements in PFS (HR=0.56 [95% CI: 0.47-0.66]; p<0.0001), and OS (HR=0.62 [95% CI: 0.51-0.75]; p<0.0001) vs physician’s choice treatment
Changes from baseline to week 12 in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-EN24 functional scales where a higher score denotes better quality of life or function.
KEYNOTE-811: KEYTRUDA+trastuzumab+chemotherapy becomes new treatment option for HER2+ metastatic gastric/GEJ cancer
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Pembro Arm N = 124a
Any decrease 97%
Decrease of ≥80% 32%
Placebo Arm N = 122a
Any decrease 90%
Decrease of ≥80% 15%
• Results support FDA accelerated approval in May 2021• Pembrolizumab plus trastuzumab and chemotherapy provided a 74.4% ORR that resulted in a statistically significant,
clinically meaningful 22.7% improvement in ORR compared with placebo plus trastuzumab and chemotherapy• Responses to pembrolizumab plus trastuzumab and chemotherapy were deeper and more durable• Study is continuing as planned, and analyses of OS and PFS will be performed in the future in accordance with the
analysis plan
Long-term follow-up data confirm durable benefits of KEYTRUDA monotherapy or in combination across important indications
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+XX% YOY
1L RCC 1L Bladder 2L Bladder
In a final analysis of KN-426 (42 months follow-up) KEYTRUDA+axitinib continued to demonstrate clinically significant improved efficacy compared with sunitinib for previously untreated renal cell carcinoma patients (CR rate: 10% vs 3.5%)
Updated results from KEYNOTE-052 studying cisplatin-ineligible patients with untreated advanced UC after 5 years of follow-up were consistent, showing an ORR of 29% across the entire population (initial results showed an ORR of 24%)
After at least 5 years of follow-up, KEYTRUDA continued to show improved OS, ORR and DOR compared to chemotherapy in patients with advanced, platinum-resistant/refractory urothelial carcinoma
Overall survival in ITT populationOverall survival in ITT population
HR, 0.73 (95% CI, 0.60-0.88)P < 0.001
Kaplan-Meier Estimates of DOR
Dr. Vicki GoodmanVice President, Late-stage Oncology
Select assets from late-stage oncology program
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belzutifan (HIF-2α)
vibostolimab (TIGIT)
quavonlimab (CTLA-4)
favezelimab (LAG-3)
MK-1026 (BTK)
Belzutifan: continues to demonstrate efficacy in VHL-disease associated RCC and potential in other tumor types
HIF-2α
Hypoxia
MK-6482 Binds to HIF-2α and Prevents Its Heterodimerization with HIF-1β
NucleusHIF-2α
HIF-2α
Prolyl hydroxylases
Normoxia (O2)
HIF-2αHOHO
pVHL
Inactivated VHL PseudohypoxiaO2
MK-6482
HRE
HIF-1β
Updated data at ASCO showed durable responses and disease control in VHL-RCC
• Belzutifan, first-in-class HIF-2α Inhibitor under FDA priority review with Sept. PDUFA; breakthrough therapy and orphan drug designations also granted
• MHRA granted first ever Innovation Passport, part of the Innovative Licensing and Access Pathway (ILAP)
• Advanced into 3 pivotal Phase 3 studies in advanced RCC
Vibostolimab (TIGIT): advancing clinical development of co-formulation based on compelling early data
MK-7684 + Pembrolizumab Arm
• Presented vibostolimab combination data at ESMO 2020 in PD-1/L1-naïve patients; more to come
• New Phase 3 study in PD-L1+ mNSCLC patients
• New Phase 2 biomarker study in mNSCLC patients
• Additional signal-finding studies under way across multiple other tumor types
Quavonlimab (CTLA-4): encouraging co-formulation data in patients with RCC leads to late-stage development
Cell Activation by Anti-CTLA-4 mAb
Cell Activation by Anti-PD-1 mAb
• Evaluating as co-formulation with KEYTRUDA in 6 studies across 5 tumor types, including RCC, HCC, MSI-H CRC and Melanoma
• Newly posted MSI-H CRC Phase 2 study
• Exploring additional combinations with assets in late-stage pipeline, including LENVIMA and belzutifan in patients with RCC
• Encouraging data from Phase 1 studying co-formulation in patients with advanced solid tumors presented at ESMO 2019
Favezelimab (LAG-3): early encouraging co-formulation data in MSS CRC patients leads to Phase 3 advancement
MK-4280 Blocks the Interaction Between MHC Class II Receptors and LAG-3
MK-4280 Could Inhibit LAG-3 Upregulation Restoring T-cell Effector Functions Targeting Tumor Cells
aEvaluated in patients with measurable disease at baseline and ≥1 evaluable post-baseline imaging assessment (n = 18 for MK-4280 monotherapy, n = 14 for MK-4280 + pembrolizumab).Database Cutoff Date: Jun 12, 2018. 1. Lakhani N et al. Presented at SITC 2018.
• Encouraged by early data presented at SITC 2018 and most recently the data at ASCO 2021
• Advancing to Phase 3 in 2H 2021 in co-formulation with KEYTRUDA in MSS CRC
• One of three assets being studied in co-formulation with KEYTRUDA
• Responses observed in additional tumor types
MK-1026 (BTK): plans to advance into studies with registrational intent based on strong early data and optimized dose
• Encouraged by early data presented at ASH 2019
• Phase 2 under way to further understand and optimize dose and efficacy
• Planning for registrational trials is under way
• Demonstrates broader interest in hematologic malignancies
Dr. Eric RubinSVP, Early-stage Oncology
Early oncology pipeline* includes more than 25 investigational immuno-therapeutic candidates, including novel combinations with KEYTRUDA
Personalized Cancer Vaccines
Tumor Microenvironment Modulators
Therapeutic vaccines based on patients’ specific cancer could
potentially prime the immune system to recognize certain characteristics
and attack the cancer cells
Regulating the environment around tumors, including through ADCs,
may influence tumor growth and its interaction with the immune system
Phase 1 Phase 2
ImmuneAgonists
Molecules designed to stimulate immune system functions, such as
enhancing the activity of anti-tumor immune cells
STING agonist(MK-2118)
CD-27 agonist (MK-5890)
Inhibition of Negative Immune Regulators
Blocking the action of molecules that suppress the immune system may trigger a more
robust anti-tumor response
ILT-4 antagonist (MK-4830)
LAG-3 (favezelimab/MK-4280)
CTLA-4 (quavonlimab/MK-1308)
TIGIT (vibostolimab/MK-7684)
KRAS (Moderna)(V941 / mRNA-5671)
BTK Inhibitor(MK-1026)
AKT Inhibitors(MK-7075 & MK-4440)
Pre-Clinical
KRAS – Taiho/Astex
*Select compounds only
ROR-1(MK-2140)
HIF-2α Inhibitor(MK-6482/belzutifan)
RNA-based vaccine (Moderna)(V940 / mRNA-4157)
LIV-1(MK-6440)
ILT-3 antagonist(MK-0482)
ERK Inhibitor(MK-8353)
Cell-based therapies & T/NK cell engagers
Use of allogeneic T and NK cells and T/NK cell engagers to attack tumors
Cytokine derivatives (Sutro)
Cell-based therapies (A2, Artiva)
T/NK cell engagers(Janux, Dragonfly)
Select assets from early-stage oncology program
30
ILT-4 antagonist (MK-4830)
CD-27 agonist
(MK-5890)
ROR-1 ADC (MK-2140)
LIV-1 ADC (MK-6440)
MK-4830 (ILT-4 antagonist): first-time initial efficacy data from Phase 1 dose escalation study shows potential for asset in solid tumors
31Data presented at ESMO 2020
ILT-4 preliminary efficacy data showed an ORR of 24% (8/34) in patients who received MK-4830 in combination with KEYTRUDA
Among 11 patients who progressed on prior PD-1 therapy, there were 5 responses (45%)
Under evaluation in signal-finding studies in combination with Keytruda in 9 different tumor types
MK-2140 (ROR-1 ADC): promising activity in patients with previously-treated relapsed or refractory B-cell cancers
Ig (Immunoglobulin domain)CRD (Cysteine-rich
domain)
Kr (Kringle domain)
TK (Kinase domain)
PRD (Proline-rich domain)
Ser/ThrSer/Thr
ROR1Tumor cell
Change in Tumor Regression2
1. Figure reprinted with permission from Borcherding N et al. Protein Cell. 2014. 5(7):496-502.2. Wang ML et al. Presented at ASH 2020. 3. Zhang et al. Am J Pathol. 2012 Dec;181(6):1903-10.
• Deep and prolonged tumor regressions among patients with mantle cell or diffuse large B-cell lymphoma
• Phase 2 in patients with advanced solid tumors • ROR1 expression has been associated with more aggressive disease that
doesn’t respond to current therapies in hematologic malignancies and solid tumors
1
3
MK-6440 (LIV-1 ADC): anti-tumor activity demonstrated in TNBC and signal finding studies under way to evaluate in multiple other tumor types
33
• Humanized IgG1 ADC selectively binds to cells expressing LIV-1
• LV-mediated delivery of MMAE drives anti-tumor activity through cytotoxic cell killing and immunogenic cell death
Tumors LIV-1 RNA prevalence
Prostate 99-100%
Breast 84-96%
Melanoma 67-92%
Esophageal 24-47%
Head & Neck 38-78%
Squamous lung 27-75%
Stomach adeno 2-14%
Ovarian 2-19%
Non-squamous lung 12-45%
MK-6440 (LIV-1): evaluating as monotherapy and in combination with KEYTRUDA for patients with TNBC
34
Phase 1 Study of LV in solid tumorsReduction in Total Tumor Burden by Best
Overall Response – mTNBC Patients
Phase 1/2 Trial in for 1L Treatment of Patients with Unresectable Locally-Advanced or Metastatic TNBC:
KEYNOTE-721
Maximum Change in Tumor Burden
MK-5890 (CD-27 agonist): encouraging anti-tumor activity
35
MK-5890, anti-CD27Best Percentage Change From Baselinein Target Lesions
Shapira-Frommer R et al. Presented at SITC 2019 Figure reproduced with permission
• Early anti-tumor activity observed in patients with advanced solid tumors in both the monotherapy and combination arms
• Signal-finding effort in combination with KEYTRUDA in NSCLC and TNBC under way
• First companion diagnostic for NSCLC: PD-L1 on tumor cells• First companion diagnostic for gastric, cervical,bladder, esophagealand head & neck cancers: PD-L1 on
tumor and immune cells
Leader in precision medicine, identifying patients most likely to benefit from treatment
36
Our clinical trials and predictive biomarker approachesare based on strong biological hypothesesBiomarker cutoffs are defined prospectively based on threshold analyses in independent training sets
• First approval based on biomarker, agnostic to tissue/site of origin, for MSI-H Cancer• Second approval based on biomarker, agnostic to tissue/site of origin, for TMB-H Cancer with
FoundationOne Companion Diagnostic (Foundation Medicine Inc)
Increased Antigenicity Dueto High DNA Mutation Load
• Companion diagnostics for ovarian, breast, pancreatic & prostate gBRCA mutations• Companion diagnostic for BRCA mutations in ovarian tumors• Companion diagnostic for BRCA mutations and/or genomic instability in ovarian tumors• Companion diagnostic for homologous recombination repair (HRR) gene mutations in prostate• First companion diagnostic approval in Japan for US-based test
Homologous Recombination Deficiency
Exploratory Biomarkers• IHC for TIGIT, ILT-4, ROR-1, LIV-1, Trinkets• BTK and KRAS mutations and association with efficacy and resistance
PD- L1 Expression
Leading biomarker-driven strategy
In 2020, KEYTRUDA was granted two new biomarker-driven approvals:
37
TMB-H cancers based on KN-158 results demonstrating meaningful improvement in ORR
1L MSI-H CRC based on PFS results from KN-177
The PD-L1 IHC22C3 Test was the first FDA-approved companion diagnostic in immuno-oncology
Diagnostic testing for treatment decisions has become a standard and a widespread practice in NSCLC as well as other tumor types
Companion diagnostic approved in 1L/2L NSCLC, 2L cervical, 1L bladder, 2L esophageal and 1L H&N
Jannie OosthuizenPresident, Global Oncology
Unmet needs are high and pace of innovation has accelerated
39
Unmet needs remain and cancer
patients need continued innovation
The science of oncology is
accelerating, including the
advancement of precision medicines
Cost, health system capability and affordability
barriers limit access to
innovation
Strong need to demonstrate value
with data supporting clear
patient outcomes
Urgency to act now to advance standard of care
and provide more options for
patients
Driving global leadership across broad portfolio of commercial assets
40
Broad-based TKI
Foundational cancer treatment
Market-leading PARPi
40Approved
Indications
20Tumor types
+ MSI-H, TMB
>730KPatients treated with KEYTRUDA
Highly-selective small-molecule TKI
1
1. Patients treated with commercially-available product as of May 2021
• First-in-class molecule targeting a gene transcription factor, based on Nobel Prize-winning science
• Result of successful business development
• Merck’s rapid execution has resulted in speed-to-market
• First market entry (US) expected 3Q21 in VHL-associated renal cell carcinoma
• 3 pivotal clinical trials in progress assessing efficacy alone and in combination with TKI & IO in advanced renal cell carcinoma
• Expected to be a blockbuster in the medium term
Belzutifan: first-in-class molecule well positioned for success in RCC and beyond
41
2-4LMonotherapy
2-3L inCombinationwith Lenvima
and more …
1L in Combinationwith Lenvima& Keytruda
VHL-AssociatedRCC
Growth opportunities in renal cell carcinoma and beyond
Lynparza: set for sustained class leadership in women’s cancers and beyond with earlier stage disease
42
• Only PARPi approved in 7 indications across 4 different tumor types in the U.S.
• Moving into earlier lines of breast cancer treatment with OlympiA in adjuvant setting
• Lynparza has class leadership in the U.S. across ovarian cancer treatments, with ~60% of total PARPi prescriptions
• Only PARPi approved in pre-chemo metastatic castration-resistant prostate cancer beyond patients with BRCA mutations
• Additional indications with monotherapy and combinations with KEYTRUDA to drive significant growth going forward
Growth opportunities across multiple tumor types
In collaboration with AstraZeneca
Breast cancer
Pancreatic cancer
and more …
Prostate cancer
Ovarian cancer
Lenvima: establishing as TKI of choice with roll-out of new indications
43
• Combination program rolling out with new indications in 1L RCC and 2L Endometrial carcinoma –approvals expected in 3Q21
• 20 combination studies ongoing across 14 tumor types including NSCLC, HCC, Gastric, H&N and Melanoma
• Approved in markets worldwide in RCC, EC, HCC and differentiated thyroid cancer
• Significant opportunity in China given prevalence of HCC in the market
• Strong commercial collaboration sets foundation for execution in many future indications
Renal cellcarcinoma
Lungcancer
Hepatocellularcarcinoma
and more …
In collaboration with Eisai
Endometrialcarcinoma
Thyroidcancer
Growth opportunities across multiple tumor types
Well positioned for opportunity in early-stage treatment across cancer types where prevalence is significant
44
Early stage
Metastatic
Unknown
HEAD AND NECK
Early stage
Metastatic
Unknown
BLADDER
Early stage
MetastaticUnknown
BREAST
Early stageMetastatic
Unknown
LUNG
Early stage
Metastatic
Unknown
RENAL
Early stage
Metastatic
Unknown
MELANOMA
Source: SEER 2020: Cancer Prevalence by Stage in U.S.
Meaningful opportunity to improve patient outcomes with earlier diagnosis and treatment
KEYTRUDA is being explored in a broad adjuvant program with 20 registrational studies ongoing
2018 2019 2020 2021 2022 2023 2024 2025 2026+
Adjuvant Melanoma (KEYNOTE-054) APPROVED
TNBC Neoadjuvant / Adjuvant(KEYNOTE-522)
Met dual primary EP in pCR and EFS
NMIBC (KEYNOTE-057) APPROVED
cSCC Locally Advanced (KEYNOTE-629) APPROVED in recurrent or metastatic; Sept. 2021 PDUFA for locally advanced
RCC Adjuvant (KEYNOTE-564) Met primary EP of DFS
NSCLC Adjuvant (KEYNOTE-091 -Interim)
Adjuvant Melanoma (KEYNOTE-716)
HNSCC Adjuvant (KEYNOTE-412)
Locally Advanced NMIBC (KEYNOTE-676 –Interim; Final Analysis 2025)
Gastric & Esophageal Adjuvant / Neoadjuvant (KEYNOTE-585)
HNSCC Adjuvant / Neoadjuvant (KEYNOTE-689)
NSCLC Neoadjuvant (KEYNOTE-671)
Neo/adjuvant MIBC (KEYNOTE-866)
Neo/adjuvant MIBC (KEYNOTE-905)
NSCLC Stage I/IIa (KEYNOTE-867)
HCC Adjuvant (KEYNOTE-937)
Ovarian BRCAwt + chemo (KEYLYNK-001)
TNBC Adjuvant (KEYNOTE-242)
cSCC Locally Advanced (KEYNOTE-630)
ER+ / HER2-Breast Cancer Adjuvant / Neoadjuvant (KEYNOTE-756)
Timeline based on clinicaltrial.gov primary completion dates. Actual timing may vary.45
Potential for 90+ approvals across oncology portfolio through 2028
Proportion of expected indications and new launches by product
46
Other(including co-formulated assets)
Expect to be oncology market leader by 2026 driven by additional indications, earlier lines of therapy and new assets and technologies
47
Source: Evaluate Pharma (as of 2/28/2021)
2021E 2022E 2023E 2024E 2025E 2026E
Merck
• Indications expected to more than triple over next 8 yearso Earlier lines of therapy, including
adjuvant / neoadjuvanto New combinations and co-formulationso New tumor typeso New assets
• Building on leadership in lung with early stage launches and further penetration of existing indications in Europe and other markets
• Encouraged by uptake of Q6W dosing in U.S., Europe and Japan
• Excited to launch additional adjuvant indications as data becomes available
• Well-positioned with early-stage assets, co-formulations and new routes of administration to sustain success well into next decade
Dr. Dean LiPresident, Merck Research Labs
Uniquely positioned to drive long-term success and oncology leadership through continued execution and momentum
49
Broad oncology program with deep
pipeline of differentiated early-
and late-stage assets
World-class scientific expertise and ability to leverage KEYTRUDA’s
foundational stature
Extensive runway to advance science to
reach more patients and solve for unmet
need
Unmatched commercial expertise
to capitalize on significant
opportunities
Q&A
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