Immuno-Oncology Partnering: Tipping Point, or Tip of the ... · Immuno-Oncology Partnering: Tipping...

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

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

http://www.ebdgroup.com/bpa/index.php�

https://ebdgroup.knect365.com/biotech-showcase/�

http://theconferenceforum.org/conferences/immuno-oncology-360/2017-sponsors-exhibitors/�


https://www.biocom.org/s/EventDetail?event=Biocom_Partnering_Conference_2017�

http://www.sachsforum.com/2nbpi-about.html�


http://www.sachsforum.com/5cbpi-about.html�



♦ 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?


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


What Does the IO Market Look Like?


0

20

40

60

80

100

120

140

160 Sa

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$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.


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


♦ Antibodies (Opdivo, Keytruda, Tecentriq, Yervoy) are the fastest growing modality within IO sales, driven by checkpoint inhibitors.


Checkpoint Inhibitors are Driving Sales, Primarily in Selected Launched Indications: Melanoma, NSCLC, and Bladder Cancer


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)


But Why is IO All the Rage?


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


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


And Nivolumab Plus Ipilimumab Demonstrated a Significant Improvement Over Ipi Alone – Especially in Patients With Low PD-L1 Expression

xxx.; Clinical Care Options


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.


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)


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


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*)


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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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


And Major Setbacks, For Example with CHECKMATE-026, While Striking a Major Blow to BMS, Have Not Noticeably Dampened the Fervor


To Understand Deal-making, One Needs to Appreciate Immuno-Oncology Clinical Development Activity


Hot & Cold Tumors

Citibank


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


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


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


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


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 “/”


Overall PD1/L1 Clinical Trials Indication Analysis P1+ Show Activity in a Variety of Indications

PD-1/L1 Therapies

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CRC

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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+)


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


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


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


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.


Checkpoint/Costim Combination Trials By Year First Received in clinicaltrials.gov, N=603

Jan - July


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


Majority of Phase 2+ Trials are Examining Relapse/Refractory Patients, Followed Closely by Those Targeting Front-Line Use


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


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 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

Deals, Deals, Deals


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…


Top 2015 Oncology Deals: Almost All of These Top Deals Are IO

EvaluatePharma, Defined Health


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


CTLA-4 Research


CART Preclinical

2015

EvaluatePharma, BCIQ, Company Press Releases, Defined Health


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


Combinations Are Key to Almost Every Deal, Even for New Modalities (Such as the NeoAg Sub-Fervor): Leading to Acquisitions

MedCity News


Combinations Are Key to Almost Every Deal, Even for New Modalities (Such as the NeoAg Sub-Fervor): Leading to Acquisitions

FierceBiotech


Or Accessing Combination Partners Through Research Collaborations

FierceBiotech


Or Accessing Combination Partners Through Research Collaborations

Yahoo Finance


And Expanding the Therapeutic Modalities: NeoAntigens & Oncolytic Viruses Are the Latest Craze

FierceBiotech


And Expanding the Therapeutic Modalities: NeoAntigens & Oncolytic Viruses Are the Latest Sub-Craze

FierceBiotech; Advaxis website


And Expanding the Therapeutic Modalities: NeoAntigens & Oncolytic Viruses Are the Latest Sub-Craze

FierrceBiotech


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


IO Deals Constitute a Majority of Oncology Deals

Evaluate Pharma; DH Analysis

2016 IO vs Non-IO Licensing Deals


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)


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


63% Preclinical/ Research Project Deals

60% Phase 1+ Project Deals


$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


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


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.

Wrap-Up


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)


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

Acknowledgements


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


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

http://www.ebdgroup.com/bpa/index.php�

https://ebdgroup.knect365.com/biotech-showcase/�



https://www.biocom.org/s/EventDetail?event=Biocom_Partnering_Conference_2017�





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