immuno-oncology partnering: tipping point, or tip of the ... · immuno-oncology partnering: tipping...
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Immuno-Oncology Partnering: Tipping Point, or Tip of the Iceberg? Jeffrey M. Bockman, PhD Vice President Defined Health Defined Health Insight Series Webinar December 13, 2016
Page 2 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
BioEurope Spring 2017 March 20 – 22, 2017
Barcelona, Spain www.therapeuticinsight.com
Defined Health is pleased to present:
Defined Health will also be participating in the following industry events:
Biotech Showcase | January 9 - 11, 2017 | San Francisco, CA | https://ebdgroup.knect365.com/biotech-showcase/ JP Morgan Healthcare Conference | January 9 - 13, 2017 | San Francisco, CA
Immuno-Oncology 360° | February 1 - 3, 2017 | New York, NY | http://theconferenceforum.org/conferences/immuno-oncology-360/2017-sponsors-exhibitors/
Biocom's Global Life Science Partnering Conference | March 1 - 2, 2017, La Jolla, CA | https://www.biocom.org/s/EventDetail?event=Biocom_Partnering_Conference_2017
2nd Annual Neuroscience BioPartnering & Investment Forum | March 27, 2017 | New York, NY | http://www.sachsforum.com/2nbpi-about.html
5th Annual Cancer BioPartnering & Investment Forum | March 28, 2017 | New York, NY | http://www.sachsforum.com/5cbpi-about.html
28h Annual Cancer Progress Conference March 7 - 8, 2017
The Westin New York at Times Square www.cancerprogressbyDH.com
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♦ Deal making in the Immuno-Oncology (IO) space has been intense over the past two years. As first movers strategically took on more targets and modalities to broaden and deepen their pipelines (including numerous collaborations), follow-on players ventured out into new platforms, and those on the sidelines were compelled to participate by placing early bets in potential next wave therapies. With any stumble, pundits proclaim the bubble is about to burst, and yet, with the advent of more data, some of it only incremental but much quite meaningful, the so-called frenzy becomes reinvigorated. This talk will look at the analytics around deals and pipeline, providing Defined Health’s perspective on IO strategies: what is driving deals, such as franchise and/or MOA synergies; what are late entry follow-on (“me, too”) companies doing to potentially compete; what are the hot new areas? Finally, what can the partnering in IO tell us about the state of the industry?
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The information in this report has been obtained from what are believed to be reliable sources and has been verified whenever possible. Nevertheless, we cannot guarantee the information contained herein as to accuracy or completeness. All expressions of opinion are the responsibility of Defined Health, and though current as of the date of this report, are subject to change.
The opinions and information set forth herein are expressed solely for the benefit of the addressee and only for the purpose(s) for which the report was produced. Without the prior written consent of Defined Health, this report may not be relied on in whole or in part for any other purpose or by any other person or entity, provided that this report may be disclosed where disclosure is required by law.
This report may contain information provided by third parties such as Thomson Reuters, Wolters Kluwer, EvaluatePharma; DH analysis, Datamonitor, Informa Healthcare, IMS Health and others with a proprietary interest in the data provided herein. Please note that you are not permitted to redistribute any such third party information without consent from the originator company.
© Defined Health, 2016
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What Does the IO Market Look Like?
Page 6 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
0
20
40
60
80
100
120
140
160 Sa
les (
$B)
US Oncology Products Sales: IO vs. Non-IO
Non-IO IO
Non-IO CAGR (2012-2022): 12%
IO Assets Are Still a Fraction of the Overall Oncology Market, But Growth Far Outweighs That of Non-IO Cancer Drugs
EvaluatePharma; DH Analysis *analysis includes products marketed and in development
IO CAGR (2012-2022): 43% Total Oncology CAGR (2012-2022): 15%
♦ Total sales of IO assets in 2022 are estimated at $20B in US and $35B WW. • The CAGR of IO products from 2012-2022 is projected to be 43% in US.
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0
5
10
15
20
25
30
35
Sale
s ($B
) US IO Sales by Modality
IO Antibody Cell therapy Vaccine or Onc Virus
Small molecule Cytokine or Chemokine
IO Antibody Revenues Driven by Checkpoint Inhibitor Antibodies Continue to Dominate IO Modalities
EvaluatePharma; DH Analysis *analysis includes products marketed and in development
♦ Antibodies (Opdivo, Keytruda, Tecentriq, Yervoy) are the fastest growing modality within IO sales, driven by checkpoint inhibitors.
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Checkpoint Inhibitors are Driving Sales, Primarily in Selected Launched Indications: Melanoma, NSCLC, and Bladder Cancer
EvaluatePharma; DH Analysis *analysis includes products marketed and in development
0
2000
4000
6000
8000
10000
12000
14000
16000
1 2 3 4 5 6 7 8 9 10 11
Multiple myeloma
Glioma
Ovarian cancer
Hodgkin lymphoma
Stomach cancer
Small cell lung cancer (SCLC)
Solid tumour indications
Head & neck cancers
Non-Hodgkin lymphoma (NHL)
Renal cell carcinoma (RCC)
Melanoma
Bladder cancer
Non-small cell lung cancer (NSCLC)
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022
Dolla
rs (0
00s)
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But Why is IO All the Rage?
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Just to Make Sure We Are All on the Same Page
Oncotarget. 2014 Dec 30;5(24):12472-508; http://www.cancerresearch.org/news-publications/our-blog/april-2015/whatever-happened-to-coleys-toxins
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Nivolumab Demonstrated Not Just an ORR Better Than Chemotherapy But a Meaningful Percentage of Patients Experienced Durable Remissions
Robert C, et al. N Engl J Med. 2015;372:320-330.; Clinical Care Options
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And Nivolumab Plus Ipilimumab Demonstrated a Significant Improvement Over Ipi Alone – Especially in Patients With Low PD-L1 Expression
xxx.; Clinical Care Options
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And Now, First-Line in NSCLC, Pembrolizumab Has Bested Cytotoxic SOC
N Engl J Med 2016; 375:1823-1833
KEYNOTE-024: International, randomized, open-label, phase 3 trial compared pembrolizumab (administered at a fixed dose of 200 mg every 3 weeks) with the investigator’s choice of cytotoxic chemotherapy as first-line therapy for patients with advanced NSCLC and a PD-L1 tumor proportion score of 50% or greater.
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A Lot of Key Events (Requires Updating Almost Daily)
Adis R&D Insight, Clarivate Analytics Cortellis
2015 Pre-2015 2016 2017/2018
Provenge Apr, 2010 (Prostate)
Yervoy Mar, 2011 (Melanoma)
Keytruda Sept, 2014 (Melanoma)
Opdivo Dec, 2014 (Melanoma)
Blincyto Dec, 2014 (ALL)
Opdivo Mar, 2015 (NSCLC squamous)
Keytruda Oct, 2015 (NSCLC)
Opdivo Oct, 2015 (NSCLC Non-squamous)
Opdivo + Yervoy Oct, 2015 (Melanoma)
Imlygic Oct, 2015 (Melanoma)
Opdivo (RCC)
Approvals Recent or Expected Approvals
Atezolizumab (Bladder)
Avelumab (Merkel Cell)
CTL019 (ALL)
Durvalumab (H&N)
Atezolizumab (RCC) (NSCLC, 2nd line)
Keytruda (Bladder)
Opdivo + Yervoy (GBM)
Opdivo (H&N)
Durvalumab (NSCLC)
Recent and Near-Term I/O Approvals Timeline
Approved Oct 18, 2016
Keytruda (NSCLC, 1st line)
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Efficacy Benchmarks: Checkpoints
NEJM 2015 Jan 22; 372:320-330; NEJM. 2015 Jun 25; 372(26):2521-2532; J Clin Oncol 34, 2016 (suppl; abstr 9505); NEJM 2015 July 9; 372(2):123-35; NEJM. 2015 Oct 22; 373:1627-1639; Oncologist 2016; 21(5):643-650; Tecentriq PI; NEJM 2015; 373:1803-1813; Lancet Oncology 2016 July; 17(7):956-965; J Clin Oncol 2016; 34 (suppl abstract 7535); J Clin Oncol 2016; 34 (suppl 2S; abstract 355)
Efficacy Benchmarks: Marketed Checkpoint Inhibitors
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Efficacy Benchmarks: Checkpoints
NEJM 2015 Jan 22; 372:320-330; NEJM. 2015 Jun 25; 372(26):2521-2532; J Clin Oncol 34, 2016 (suppl; abstr 9505); NEJM 2015 July 9; 372(2):123-35; NEJM. 2015 Oct 22; 373:1627-1639; Oncologist 2016; 21(5):643-650; Tecentriq PI; NEJM 2015; 373:1803-1813; Lancet Oncology 2016 July; 17(7):956-965; J Clin Oncol 2016; 34 (suppl abstract 7535); J Clin Oncol 2016; 34 (suppl 2S; abstract 355); *squamous and non-squamous NSCLC trials averaged
Efficacy Benchmarks: Marketed Checkpoint Inhibitors (circle=ORR; diamond=mOS)
Keytruda, ORR 33% vs. Yervoy, 12%
Opdivo, ORR 40% vs. dacarbazine, 14%
Opdivo/Yervoy, ORR 58% vs. Yervoy, 19%, Opdivo, 44%
Opdivo vs. Everolimus, (ORR 25% vs. 5%; mOS 25 vs. 19.6 mo)
Tecentriq vs. docetaxel (ORR 15% vs. 15%; mOS 12.6 vs. 9.7 mo)
Opdivo vs. docetaxel (ORR 19.5% vs. 10.5%*; mOS 10.7 vs 7.7 mo*)
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But There Have Been Other Trials That Have Failed or Had Marginal Data, Just Among Checkpoints, Let Alone Other Modalities (Like Vaccines)
Clinicaltrials.gov; DH Analysis
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HL
Brea
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CRC
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Nivolumab 2 3* 1/2 M 3 M* M M 1/2 1/2
Pembrolizumab 1 1 2 2* 2* 1/2 2 M M 2 M 1 2* 2 1/2* 1 2 1 2
Durvalumab 2 1/2 1/2* 1/2
Avelumab 1 1/2 1 2 1 1 1 1
Atezolizumab 1 1 3 1 M
Efficacy Negative Positive
Numbers Represent Trial Phase or Market
*Represents a Combo Trial
If there are combination therapies that are earlier but have higher efficacy than monotherapy, the combo therapy is represented
Page 18 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
And Major Setbacks, For Example with CHECKMATE-026, While Striking a Major Blow to BMS, Have Not Noticeably Dampened the Fervor
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To Understand Deal-making, One Needs to Appreciate Immuno-Oncology Clinical Development Activity
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Hot & Cold Tumors
Citibank
Page 21 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Combination Trials Across the Various IO Platforms are Where the Industry (& Academia) Are Focused
Clinicaltrials.gov, Adis R&D Insight, Clarivate Analytics Cortellis, DH analysis
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This Focus Reflects the Significant Clinical Needs for Both Cancers Showing Good Responses/Outcomes As Well As Those Not as Yet Showing Benefit
Checkpoint Antagonists and Costimulatory Agonists Lead the Way for Combinations, seeking to amplify the outcomes in settings like melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and bladder cancer.
Clinicaltrials.gov, Adis Insight, Clarivate Analytics Cortellis, DH analysis
Checkpoint/Costim trials with 1 trial each:
41BB/KIR 41BB/PD-L1 CCR4/41BB CCR4/PD-1
CD27/CTLA4 CD27/PD-1 CD27/PD-L1 CD40/CTLA4 CD40/PD-L1 CSF1R/PD-1 CSF1R/PD-L1
CTLA4/PD-1/KIR CXCR4/PD-1 GITR/PD-1 IDO/CTLA4 KIR/CTLA4 KIR/PD-1
OX40/PD-1 OX40/PD-L1/CTLA4
PD-1/KIR PD-1/PD-1 TIM3/PD-1
LAG3 LAG3/ACT
NKG2A
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PD-1/L1 Make Up a Significant Proportion of Checkpoint Inhibitors in Clinical Development, GITR, OX40, and CD40 Are Key Costim Agonists
Adis R&D Insight, Clarivate Analytics Cortellis; DH analysis
9
5
3 3
2
2
2
1 1
1 1
1 1 1
US Checkpoint Programs by Target (n=33)
PD-1
PD-L1
CTLA4
LAG3
KIR
PD-L2
TIM3
CD276
NKG2A
PD-1/TGFb
PD-L1/VISTA
TIGIT
Undefined
VISTA
5
5 4
2
1
1 1
US Costim Programs by Target (n=19)
GITR
OX40
CD40
41BB
CD27
CD70
ICOS
Page 24 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Large Portion of IO Pipeline is in in Early Development and Focused on Cancer Vaccines, Cell Therapies, and Cytokines
228
44
187
4 34
4 4 28
US IO Pipeline by Highest Phase (n=533)
Phase 1
Phase1/2
Phase 2
Phase2/3
Phase 3
Pre-registration
Registered
Marketed
Adis R&D Insight, Clarivate Analytics Cortellis; DH Analysis
228
76
52
46
37
33
21 21 19
US IO Pipeline by IO Category (n=533)
Cancer vaccine
Other cell therapy
Cytokine
CAR-T cells
Other IO
Checkpoint
Innate Immunity
Oncolytic virus
Costim
Page 25 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
PD-1/L1s Combinations
0 5 10 15 20 25 30 35
Chemokine/Antisense Chemokine/Chemotherapy
CTLA4/Cytokine Other PD1/L1
Radiation Other Checkpoint/Kinase Inhibitor
Antibody (ADC) Oncolytic virus
Other Checkpoint PARP Inhibitor
SOC Undefined
Chemokine TLR Agonist
Costim CSF1R
Epigenetic modulator IDO inhibitor
Antibody 3+ Agents Combined Together
Other targeted therapy Vaccine
Chemotherapy Kinase Inhibitor
CTLA4
Clinical Trial Count
Anti-PD1/L1 Combination Trials (Lg Pharma PD1/L1, Industry Only, P1/2+, n=140)
Phase 1/2
Phase 2
Phase 3
Clinicaltrials.gov; DH analysis *Trials evaluating two different combinations (X+Y vs. X+Z) are noted with a “/”
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Overall PD1/L1 Clinical Trials Indication Analysis P1+ Show Activity in a Variety of Indications
PD-1/L1 Therapies
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Pembrolizumab 1 1 4 1 1 18 17 5 1 12 1 2 3 8 5 3 4 3 20 6 48 1 3 7 1 1 38 9 5 1 5 9 4 3 62 1 1 2 1 Nivolumab 1 1 5 1 1 4 2 7 1 1 2 1 2 1 5 10 1 4 6 4 6 1 1 37 2 1 2 43 2 4 1 9 4 36
Durvalumab 1 2 8 2 3 1 3 2 3 2 1 6 2 2 2 5 16 3 7 1 2 1 33 Atezolizumab 8 7 2 1 4 1 3 1 2 22 2 1 3 2 1 19
Avelumab 1 2 1 1 2 3 2 2 3 PDR001 1 1 1 7
REGN2810 1 1 1 1 MSB0011359C 2
LY3300054 1 AMP514 1 1
PF6801591 1
Clinicaltrials.gov; DH analysis
Key P1 P1/2 P2 P2/3 P3
*Agents may be double counted if more than one PD-1/L1 agent per trial
• Pembrolizumab has the farthest reach to different indications, contributed by the great proportion of their trials being academic
• A significant number of trials are still early, looking at multiple solid tumor indications • The greatest activity among PD-1/L1 therapies exists in the marketed indications • Interestingly, the new-comer PD-1/L1 therapies are not targeting too many indications
that are not already being investigated
Phase Heat Map (Academic+Industry, Mono+Combo, P1+)
Page 27 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Non-IO Still Dominates the Pipeline, But IO Agents are Making Rapid Inroads
♦ While IO shows strong market growth and an increasing presence in oncology treatment, Non-IO compounds still constitute the majority of the overall oncology pipeline.
♦ Within the oncology pipeline, Non-IO and IO compounds are split by approximately two-thirds to one-third, respectively (~1200 Non-IO and ~550 IO agents total).
Adis R&D Insight; Clarivate; DH analysis
Oncology Pipeline: IO vs. Non-IO (%) N=1759
Oncology Pipeline: IO vs. Non-IO (Count) N=1759
Page 28 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Most IO Agents Are Biologics, While Most Non-IO Agents are Small Molecules
♦ The oncology pipeline is split almost 50/50 between biologics and small molecules, with 893 vs. 852 agents, respectively. A small percentage of the pipeline is other/undefined.
• ~60% of biologics are IO agents, and ~98% of small molecule agents are Non-IO.
Adis R&D Insight; Clarivate; DH analysis
IO vs. Non-IO Biologics N=893
IO vs. Non-IO Small Molecule N=852
IO vs. Non-IO Other N=14
Page 29 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Small Molecule
Once Barely on Radar, Biologics Now Dominate Leading Products and Will Increase in Dominance in the Future
EvaluatePharma
Top 10 Selling Products (WW) Percent by Category
2005 vs 2015 vs est. 2022
Biologic
2005
2015
Small Molecule
Small Molecule
Small Molecule
Biologic
Biologic
Biologic
Regenerative, etc. ????
2022
Small Molecule
Biologic
Page 30 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
The Number of Immuno-Oncology Combination Trials Continues to Grow – Combinations with Checkpoints or Costims Doubled from 2014 to 2015
♦ The number of combination trials involving checkpoint inhibitors or costimulatory agonists more than doubled from 2014 to 2015 (92 trials in 2014, 229 in 2015).
♦ Checkpoint/costim combination trials in 2016 are poised to surpass 2015, with 184 trials from January 2016 – July 2016.
Clinicaltrials.gov; DH analysis
Checkpoint/Costim Combination Trials By Year First Received in clinicaltrials.gov, N=603
Jan - July
Page 31 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Strategic Mapping of Checkpoint Inhibitors and Costimulatory Agonists Among Major BioPharma: What I Call Combinatorial Optionality
Clinical Stage Immuno-Oncology Assets
NVS AZN BMS ROC CELG JNJ MRK PFE AMG GSK MRK KGaA SNY LLY TAK BAY ABV
Checkpoint II III M M III† I M III I III II I
Costim II I/II II I I II I
Oncolytic virus I M
Cancer vaccine I/II III II II I I III M
Other Cell Therapy II I I** I
CAR-T Cells II II
Innate Immunity I I
Cytokine M II M M M M M II M
Other IO I I II I I M I I M
Adis R&D Insight, Clarivate Analytics Cortellis; DH analysis
NVS, Novartis; AZN, AstraZeneca/MedImmune; BMS, Bristol-Myers Squibb; ROC, Roche/Genentech; CELG, Celgene; JNJ, Johnson & Johnson; MRK, Merck & Co; PFE, Pfizer; AMG, Amgen; GSK, GlaxoSmithKline; MRK KGaA, Merck KGaA; SNY, Sanofi/Regeneron; LLY, Eli Lilly; TAK, Takeda; BAY, Bayer; ABV, Abbvie
Page 32 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Majority of Phase 2+ Trials are Examining Relapse/Refractory Patients, Followed Closely by Those Targeting Front-Line Use
Clinicaltrials.gov; DH analysis
29
18
15
5 4
3 2 1 1
Specific Patient Population - Phase 2+ CTs - Combo (n=78)
1st Line R/R Advanced Chemo-Naïve Chemo-refractory 2nd Line CPI-Naïve 3+ Line All Lines
32
20 11
10
4 3 2 2 2 1 1
Specific Patient Population - Phase 2+ CTs - Mono (n=88)
R/R Chemo-refractory Advanced 1st Line 3+ Line CPI-Naïve 2nd Line Maintenance All Lines CPI-Refractory Chemo-Naïve
50
39 26
24
6 5 5 5 3 2 1
Specific Patient Population - Phase 2+ CTs - Combo/Mono (n=166) R/R 1st Line Advanced Chemo-refractory Chemo-Naïve 2nd Line 3+ Line CPI-Naïve All Lines Maintenance CPI-Refractory
Page 33 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Many Approved PD-1/L1 Gained Breakthrough Designation or Accelerated Approval and Bypassed Phase 2 and 3; or Skipped From Phase 1 to Phase 3
♦ Almost all the indications that were approved for Keytruda were able to get approval based on Phase 1 data, except for the checkpoint-naïve patient approval that skipped Phase 2 and went straight to a Phase 3 registrational trial.
Clinicaltrials.gov
Melanoma (ipi-refractory) Melanoma (CPI-naïve) NSCLC (PD-L1+/post-platinum) HNSCC (post-platinum r/r)
Keytruda Phase 1, Accelerated Approval (NCT01295827)
Phase 1 (NCT01295827) Phase 3 (NCT01866319)
Phase 1, Breakthrough and Accelerated Approval (NCT01295827)
Phase 1b, Accelerated Approval (NCT01848834)
Melanoma (BRAF V600 WT untreated)
Melanoma (BRAF V600 MUT)
NSCLC (squamous, post-platinum)
NSCLC (non-squamous, post-platinum)
RCC (post-angiogenic r/r)
HD (r/r post-HSCT and Adcetris)
Opdivo
Phase 1 (NCT00730639) and (NCT00441337) Phase 3 (NCT01721772)
Phase 1 (NCT00730639) and (NCT00441337) Phase 3, Accelerated Approval (NCT01844505)
Phase 1 (NCT00730639) and (NCT00441337) Phase 3 (NCT01642004)
Phase 1 (NCT00730639) and (NCT00441337) Phase 3 (NCT01673867)
Phase 1 (NCT00730639) and (NCT00441337) Phase 2 (NCT01354431) Phase 3, Breakthrough Designation (NCT01668784)
Phase 2, Breakthrough Designation (NCT02181738)
♦ For Opdivo, only RCC required the complete Phase 1 2 3 progression, while others skipped Phase 1 or 2.
Melanoma (untreated)
Opdivo + Yervoy
Phase 2 (NCT01927419) Phase 3 (NCT01844505)
Bladder (post-platinum r/r)
Tecentriq
Phase 1 (NCT01375842) Phase 2, Accelerated Approval (NCT02108652)
♦ Bladder cancer, being a first indication for Tecentriq, required a Phase 1 and 2, with accelerated approval at Phase 2
Page 34
Deals, Deals, Deals
Page 35 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Deals Galore: Research Collaborations, Licensing & Outright Acquisition – Especially in IO, & As We Will See, Especially at an Early Stage
MedCity News, Datamonitor Healthcare
Between 2011 and 2015, Big Pharma and Mid Pharma immuno-oncology transactions were worth $6 billion upfront, $33 billion in milestones and $46 billion in aggregate deal value, according to Datamonitor Healthcare. Bristol-Myers Squibb dominated the activity: Of the 50 immuno-oncology partnerships sealed by BMS between 2011 and 2015, 70 percent (35) were aimed at evaluating a combination treatment…
Page 36 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Top 2015 Oncology Deals: Almost All of These Top Deals Are IO
EvaluatePharma, Defined Health
Page 37 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Deal Highlights Underscore the Overall Intensity of Activity, Deals Are Still Being Done to Access Checkpoints; Many Deals are Early Stage
Apr 2015 Undisclosed CART/PDL1
P1
Apr 2015 $1.28B NKG2A
P1/2
Apr 2015 $555M
IDO/TDO Research
Apr 2015 Undisclosed
PD-L1 P3
June 2015 Undisclosed CART/TCR Research
May 2015 $360M
TCR Research
Oct 2015 Undisclosed IO Bispecifics
Preclinical
Oct 2015 Undisclosed
CSF1R P1/2
Dec 2015 $1.775B
Undisclosed CPs Preclinical
Apr 2015 Undisclosed
Undisclosed CP Research
May 2015 Undisclosed CART/TCR Research
May 2015 $132M CAR T
Research
May 2015 $737M
CART/TCR Research
July 2015 $2.67B LAG-
3/PD1/GITR PC/P1
Sept 2015 $795M
PD-1 P1
Oct 2015 Undisclosed
PD1 Research
Nov 2015 Undisclosed
CAR T Preclinical
Dec 2015 Undisclosed
CART Research
Dec 2015 Undisclosed
CTLA-4 Research
Dec 2015 Undisclosed
CART Preclinical
2015
EvaluatePharma, BCIQ, Company Press Releases, Defined Health
Page 38 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
EvaluatePharma, Company Websites, Defined Health; BCIQ
2016
Deal Highlights Underscore the Overall Intensity of Activity, Deals Are Still Being Done to Access Checkpoints; Many Deals are Early Stage
Apr 2016 $685M
LRRC32/GARP PC
May 2016 $740M
CD3 Research
Jun 2016 $2.55B
CD3/CD123 PC
Jun 2016 $200M
mRNA vaccine Research
Jul 2016 $520M
IL8 P1/2
Jan 2016 $400M
IDO1/TDO2 PC
Jul 2016 $977M
PD-1 PC
Jul 2016 Undisclosed
Oncolytic Virus
PC
Jul 2016 $2.56B ICOS /
Other CP P1/2
Aug 2016 Undisclosed
BCMA PC
Sep 2016 $250M CTLA4
PC
Jan 2016 Undisclosed
Undisclosed IO Targets Preclinical
Jan 2016 Undisclosed
mRNA Research
Jan 2016 Undisclosed TCR mimics
Research
Feb 2016 $1.7B CAR T
Research
Mar 2016 Undisclosed
PD-1 Research
MabQuest
Mar 2016 Undisclosed
CART Research
Page 39 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Combinations Are Key to Almost Every Deal, Even for New Modalities (Such as the NeoAg Sub-Fervor): Leading to Acquisitions
MedCity News
Page 40 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Combinations Are Key to Almost Every Deal, Even for New Modalities (Such as the NeoAg Sub-Fervor): Leading to Acquisitions
FierceBiotech
Page 41 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Or Accessing Combination Partners Through Research Collaborations
FierceBiotech
Page 42 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Or Accessing Combination Partners Through Research Collaborations
Yahoo Finance
Page 43 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
And Expanding the Therapeutic Modalities: NeoAntigens & Oncolytic Viruses Are the Latest Craze
FierceBiotech
Page 44 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
And Expanding the Therapeutic Modalities: NeoAntigens & Oncolytic Viruses Are the Latest Sub-Craze
FierceBiotech; Advaxis website
Page 45 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
And Expanding the Therapeutic Modalities: NeoAntigens & Oncolytic Viruses Are the Latest Sub-Craze
FierrceBiotech
Page 46 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Deal-Making in a Sellers Market Where the Number of Assets Is Increasing Every Day: Targets, Targets Everywhere – The Cancer Immunity Cycle
Immunity. 2013 Jul 25;39(1):1-10
Page 47 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
IO Deals Constitute a Majority of Oncology Deals
Evaluate Pharma; DH Analysis
2016 IO vs Non-IO Licensing Deals
Page 48 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
While the Majority of Oncology Deals Remain Non-IO, Total Immuno-Oncology Deal Values Edged Out Non-IO Deals
91
155
IO Vs Non-IO Distribution (n=246)
IO
Non-IO
Evaluate Pharma; DH analysis
$16.6 $15.7
$0.0
$2.0
$4.0
$6.0
$8.0
$10.0
$12.0
$14.0
$16.0
$18.0
IO Non-IO
USD
(bln
)
Total Combined Deal Value (2015-2016)
Page 49 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
2 1 2
7 9
13
37
20
Phase Distribution IO Assets (n=91)
Marketed
Approved
Filed
Phase III
Phase II
Phase I
Pre-clinical
Research project
21 4
11
18
19 19
46
17
Phase Distribution Non-IO Assets (n=155)
Marketed
Approved
Filed
Phase III
Phase II
Phase I
Pre-clinical
Research project
Preclinical and Research Project Deals Made Up the Majority of IO Deals, Whereas Clinical Deals Made Up the Majority of Non-IO Deals
Evaluate Pharma; DH analysis
63% Preclinical/ Research Project Deals
60% Phase 1+ Project Deals
Page 50 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
$5
$284
$601
$190 $345
$223
$408
$7 $66
$516
$102 $231 $177
$62 0
5
10
15
20
25
$0
$500
$1,000
$1,500
$2,000
$2,500
Marketed Approved Filed Phase III Phase II Phase I Pre-clinical Research project
Num
ber o
f Dea
ls
Aver
age
Tota
l Dea
l Val
ue (U
SD)
IO vs Non-IO: Average Total Deal Value
IO Non-IO Non-IO Deal Range # of IO Deals # of Non-IO Deals
The Average Total Deal Value Was Highest in Phase 3 Deals for Non-IO and Highest in Phase 2 Deals for IO
Evaluate Pharma; DH Analysis
Page 51 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
IO Upfront Deal Value Is Significantly Higher Than Non-IO Deals (Through Phase II)
$6
$75
$130
$166
$36 $60 $68
$15
$82
$13 $18 $13 $4 0
2
4
6
8
10
12
14
16
18
20
$0
$50
$100
$150
$200
$250
$300
$350
$400
$450
Marketed Approved Filed Phase III Phase II Phase I Pre-clinical Research project
Num
ber o
f Dea
ls
Aver
age
Tota
l Dea
l Val
ue (U
SD)
IO vs Non-IO: Average Upfront Deal Value
IO Non-IO Non-IO Deal Range # of IO Deals # of Non-IO Deals
Evaluate Pharma; DH analysis
The higher frequency of Non-IO
deals in later clinical stages is consistent with the fact that most IO agents are in earlier clinical stages, driven by the hope and frenzy for the IO MOA.
Page 52
Wrap-Up
Page 53 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Combinations Have Always Been the Hope for Managing Cancer (Gleevec in CML are the Exceptions), But Now With IO-Based Regimens, There May Be a Real Chance for a Cure in a Substantive Portion of Patients
https://www.elsevier.com/connect/two-major-cancer-therapies-may-work-better-together-say-researchers-at-md-anderson
Improved Overall Survival as a Result of Combination Therapy. Depiction of Kaplan-Meier survival curve with genomically targeted agents (blue line) as compared to standard therapies (purple line), indicating an improvement in median overall survival but lack of durable responses; improved median overall survival and durable responses in a fraction of patients treated with immune checkpoint therapy (green line); possibility for improved median overall survival with durable responses for the majority of patients in the setting of combination treatment with genomically targeted agents and immune checkpoint therapy (red line). (Source: Sharma, Allison: Cell, April 2015)
Page 54 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
Already the Dreams of Many, Going Back 100 Years, Are Coming True, for Researchers, and Most Importantly for Patients
http://www.notable-quotes.com/s/science_fiction_quotes.html
In science, we dream, too
Page 55
Acknowledgements
Page 56 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
The Defined Health Oncology Team & Support Staff
♦ James Lee, PhD, Consultant ♦ Samuel Leyens, Senior Research Analyst ♦ Eva Dixon, Senior Research Analyst ♦ Akash Katakam, Research Analyst ♦ Joel Sandler, PhD, Senior Consultant ♦ Mike Rice, MS, MBA, Senior Consultant
Page 57 DH Insight Series IO Webinar – 12/13/2016 © Defined Health, 2016
BioEurope Spring 2017 March 20 – 22, 2017
Barcelona, Spain www.therapeuticinsight.com
Defined Health is pleased to present:
Defined Health will also be participating in the following industry events:
Biotech Showcase | January 9 - 11, 2017 | San Francisco, CA | https://ebdgroup.knect365.com/biotech-showcase/ JP Morgan Healthcare Conference | January 9 - 13, 2017 | San Francisco, CA
Immuno-Oncology 360° | February 1 - 3, 2017 | New York, NY | http://theconferenceforum.org/conferences/immuno-oncology-360/2017-sponsors-exhibitors/
Biocom's Global Life Science Partnering Conference | March 1 - 2, 2017, La Jolla, CA | https://www.biocom.org/s/EventDetail?event=Biocom_Partnering_Conference_2017
2nd Annual Neuroscience BioPartnering & Investment Forum | March 27, 2017 | New York, NY | http://www.sachsforum.com/2nbpi-about.html
5th Annual Cancer BioPartnering & Investment Forum | March 28, 2017 | New York, NY | http://www.sachsforum.com/5cbpi-about.html
28h Annual Cancer Progress Conference March 7 - 8, 2017
The Westin New York at Times Square www.cancerprogressbyDH.com