thOpening Address, 26th Annual Cancer Progress Conferenceg
Jeff Bockman, PhD, VP, Defined Health
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
March 17-18, 2015New York, NY
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Cancer Progress © 2015
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
Oncology Is Still a Leading Driver of Growth i Bi Phin BioPharma
200000
Worldwide Sales by Therapeutic Area 2013-2020
160000
180000
200000
Oncology & ImmunomodulatorsBlood
100000
120000
140000
es M
illio
ns
CVCNSDermEndocrine
60000
80000
100000
$WW
Sal
e Gastro-IntestinalGenito-UrinaryMusculoskeletalRespiratorySensory Organs
0
20000
40000Sensory OrgansSystemic Anti-infectivesVarious
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
02013 2014 2015 2016 2017 2018 2019 2020
EvaluatePharma, Defined Health
Top Selling BioPharma ProductsTop Selling BioPharma Products
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma
Top Selling Oncology ProductsTop Selling Oncology Products
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma
Small Molecules Still Are the Main C t ib t t th C M k tContributors to the Cancer Market…
WW Oncology Sales by Technology Type
80%
90%
100%
68% 66%
50%
60%
70%
32% 34%20%
30%
40%
%
0%
10%
2013 WW Sales 2020 WW Sales
Biotechnology Conventional
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma, Defined Health
But, Biologics Have & Will Continue to D t t Si ifi t G thDemonstrate Significant Growth
200,000Historic and Future Growth by Technology Type
160,000
180,000
Vaccine
Small molecule chemistry
Protein extractonve
ntio
nal
Tech
nolo
gy
100,000
120,000
140,000
ales
($M
)
Plant extract
Chiral chemistry
Recombinant product
Co T
60,000
80,000WW
Sa
Other biotechnology product
Monoclonal antibody (conjugated)
Monoclonal antibody
Gene therapy
Biol
ogic
s
20,000
40,000
py
DNA & RNA therapeutics
Cell therapy
Bioengineered vaccine
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
02003 WW Sales 2013 WW Sales 2020 WW Sales
EvaluatePharma, Defined Health
The Oncology Pipeline Remains The Most A ti f A Th ti AActive of Any Therapeutic Area
Clinical Development by Therapeutic Area (Percentages)
O l &Systemic
Anti
Various2%
Oncology & Immunomod
ulators21%
Blood3%Respiratory
Sensory Organs
4%
Anti-infectives
14%
%
CV7%
GU
Musculoskeletal7%
5%
CNS13%
Derm5%
Endocrine7%
GI5%
GU7%
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
Adis R&D Insight, Defined Health
The Oncology Pipeline Remains The Most A ti f A Th ti AActive of Any Therapeutic Area
OncologyClinical Development by Phase Oncology
Clinical Development by Phase
5%3%
11%
18191
376
p y
2%37%
376
621231
26%854
16%
Registered PreregistrationPhase III Phase II/IIIPhase II Phase I/II
543
Registered PreregistrationPhase III Phase II/III
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
Adis R&D Insight, Defined Health
Phase II Phase I/IIPhase I
Phase II Phase I/IIPhase I
Number of Product Deals by Therapeutic A 2010 2014Area, 2010-2014
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
IMS Pharma Deals
Top Deals of 2014Top Deals of 2014
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015 11
Thomson Reuters
Largest Upfronts of 2014Largest Upfronts of 2014
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015 12
Thomson Reuters
The Age of Collaborative R&D Deals, Driven E i ll b I O lEspecially by Immuno-Oncology
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
IMS Pharma Deals
2015 Immuno-Oncology Deals (I d t I d t O l )(Industry-Industry Only)
Date BMS Originator Platform/Product
Phase Terms
1/5/2015 Amgen Kite ACT: CART Pre Kite to Receive a $60 Million Upfront Payment From Amgen and Eligible for1/5/2015 Amgen Kite ACT: CART Pre Kite to Receive a $60 Million Upfront Payment From Amgen and Eligible for up to $525 Million in Regulatory and Sales Milestone Payments per Amgen Program; Plus, Tiered High Single- to Double-Digit Royalties for Sales and License of Kite's Intellectual Property for CAR T Cell Products Amgen Eligible to Receive up to $525 Million in Milestone Payments per Kite Program; Plus, Tiered Single-Digit Sales Royalties
1/9/2015 Incyte Agenus Checkpoints and costims:
Pre Agenus to receive $60 million comprised of a $25 million technology and program access fee under the collaboration plus $35 million equity investmentand costims:
GITR, OX40, LAG-3 and TIM-3
program access fee under the collaboration plus $35 million equity investment in Agenus at $4.51/share Agenus eligible to receive up to $350 million in development, regulatory and commercial milestones across the four lead programs
1/12/2015 MedImmune Omnis OV -Genetically engineered strain of VSV
I ND
1/21/2015 C l Z k Bi ifi P Z k ill i i iti l f t t ll it1/21/2015 Celgene Zymeworks Bispecific Pre Zymeworks will receive an initial upfront payment, as well as an equity investment from Celgene. Zymeworks is eligible to receive clinical, regulatory, and commercial milestones on successful candidates totaling up to US $164Mper therapeutic candidate. Additionally, Zymeworks will receive royalties on worldwide net sales. Further financial details are not disclosed.
1/27/2015 Janssen Macrogenics Bispecific T-cell engager
Pre MacroGenics will receive a $50 million upfront license fee and Johnson & Johnson Innovation - JJDC, Inc. has invested $75 million with the purchase of 1 923 077 new shares of MacroGenics common stock at a price of $39 00of 1,923,077 new shares of MacroGenics common stock at a price of $39.00 per share. Janssen will be fully responsible for developing MGD011 following submission of the IND, which is planned for 2015. Assuming successful development and commercialization, MacroGenics could receive up to an additional $575 million in clinical, regulatory and commercialization milestone payments. MacroGenics may elect to fund a portion of late-stage clinical development in exchange for a profit share in the U.S. and Canada. If commercialized, MacroGenics would be eligible to receive double-digit royalties on any global net sales and has the option to co-promote the
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma, Defined Health
14
royalties on any global net sales and has the option to co-promote the molecule with Janssen in the U.S.
2015 Immuno-Oncology Deals (I d t I d t O l )(Industry-Industry Only)
Date BMS Originator Platform/Product
Phase Terms
2/11/2015 Incyte Advaxis Vaccine: ADXS-HPV
II Advaxis and Incyte will collaborate on a non-exclusive basis to evaluate the combination of ADXS-HPV with IDO1 inhibitor for the treatment of cervical cancer. The companies will collaboratively conduct and fund the study, which is expected to begin later this year. Results from the study will be used to determine whether further clinical development of this combination is warranted. Further details of the agreement were not disclosed.
2/23/2015 BMS Rigel TGF-beta kinase inhibitors
Pre Bristol-Myers Squibb will obtain exclusive, worldwide rights to develop and commercialize small molecule therapeutics derived from Rigel’s TGF betainhibitors commercialize small molecule therapeutics derived from Rigel s TGF beta library, including, but not limited to, those approved to treat cancer. Bristol-Myers Squibb will pay $30 million upfront and Rigel will be eligible to receive development and regulatory milestones that could total more than $309 million for a successful compound approved in multiple indications. Rigel will also be eligible to receive tiered royalties on the net sales of any products from the collaboration.
2/23/2015 BMS Flexus IDO1 inhibitors Pre $800 million upfront to gain control of a preclinical IDO1 immunotherapy that2/23/2015 BMS Flexus IDO1 inhibitors Pre $800 million upfront to gain control of a preclinical IDO1 immunotherapy that shows promise in treating cancer, buying out San Carlos, CA-based Flexuswith another $450 million set aside for milestones.
3/4/2015 BMS Bavarian Nordic Vaccine:Prostvac
Up to $975 million: $80 million upon exercise of the option plus additional incremental payments starting at $50 million, but with a potential to exceed $230 million should the median overall survival benefit of PROSTVACexceed the efficacy seen in Phase 2 results. Furthermore, Bavarian Nordic could receive regulatory milestone payments of $110 million, up to $495 million in sales milestones as well as tiered double-digit royalties on future sales of PROSTVAC.
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma, Defined Health
15
The History of Oncology as a Pharma Market Is Surprisingly ShortIs Surprisingly Short
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma, Defined Health
The Perfect Illustration of the Old & New O lOncology
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
The Perfect Illustration of the Old & New O lOncology
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
The Perfect Illustration of the Old & New O l (C t )Oncology (Cont.)
BMS really established the modern oncology market and th bl kb t d l t t t d h
Taxol WW Sales Opdivo WW Sales
the blockbuster development strategy, and now has repositioned itself for the 21st century…
Taxol, WW Sales Opdivo, WW Sales
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
EvaluatePharma, Defined Health
But Are We Nearing a Good or Problematic Ti i P i t?Tipping Point?
KIF11
KRASE2F1
Gl t iNeuropilinSome novel KRAS
Sphingosine
GlutaminaseFUS1
TGF-beta
NKG2AEpherins TNFRSF10B
early stage programsA whole lot
of apparent copycats
PD1
S 0
EGFR
copycats
ALK
PI3K
EGFR
VEGF/Rn
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
Defined Health, Adis R&D Insight (625 Highest Phase = Phase I)
Cancer Drugs vs. Need: Pipeline Activity vs Incidence & MortalityPipeline Activity vs. Incidence & Mortality
300,000
200,000
250,000
NuIn
divi
dual
s
100,000
150,000
Drugs in clinical …
umber of D
ruNum
ber o
f
0
50,000
New Cases
ugs
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
American Cancer Society, Leukemia & Lymphoma Society, Defined Health
We Have Come a Long Way, But Can Do –Must Do – Better StillMust Do Better Still
Colorectal cancer, five-year relative survival rate, 1997-2002 and 2004-09 (or nearest period)
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
CancerProgress.net (NCI); OECD Health Data 2011
CML Remains One of a Few Striking Successes (Not Without Controversies)Successes (Not Without Controversies)
Estimated 10-year survival in CMLincreased from less than 20% to above 80%The cost of managing CRC
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
J Clin Oncol 25:180-186, 2007; Am J Manag Care. 2011 May;17 Suppl 5 Developing:SP45-52 Am J Manag Care. 2012;18:S257-S264
Fun With Math Riddle: More Drugs Than Possible But Less Than Necessary?Possible, But Less Than Necessary?
Phase* Number of Cancer Drugs
Cancer Drugs Reaching Market – BioMedTracker**
Cancer Drugs Reaching Market - Nat Rev Drug Discov***
Number of Lung Cancer Drugs
Lung Cancer DrugsReaching Market**
Prereg-Reg
42 34 159 10 8
Phase III 145 64 50 22
Phase II 476 71 320 115 17Phase II 476 71 320 115 17
Phase I 771 69 456 35 3
Total 1434 238 935 210 50
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015 24
Adis R&D Insight, WW*Phase II/III categorized as Phase II; Phase I/II as Phase I
**BioMedTracker, BIO presentation, BIO 2011
***Nature Reviews Drug Discovery 8, 15-16 (January 2009)
Pressure – But Can Targeted Agents Allied to Stratified Patient Segments Allay the Risk?Stratified Patient Segments Allay the Risk?
• Reliance on oncology just when payers are applying more scrutiny to cancer drugs –it is no longer sacrosanct.
• Payers are starting to experiment with “clinical pathways” rather than prior authorization.
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015 25
In Vivo , May 2011, “What New Cancer Pathway Programs Mean for the Drug Industry”
To Be Addressed or Not, That Is the Question: Complexity, Heterogeneity, Q p y, g y,
Plasticity
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
How To Treat/Prevent Metastases – Moving Earlier Mo ing Smartl D T PEarlier, Moving Smartly: Dx, Tx, Px
Late Dissemination ModelModel
Early/Parallel Dissemination Model
Nature Reviews Cancer 12, 133-143 (February 2012)
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015 27Cancers 2011, 3, 298-318
Nature Reviews Cancer 9, 302-312 (April 2009)
Key Themes Running Through Cancer P 2015Progress 2015
• We open with the touchiest of topics: How to think about pricing cancer drugs and regimens – it may not be the elephant in the closet but it is still an unwieldy and wild beastelephant in the closet, but it is still an unwieldy and wild beast
• Mutations and biomarkers are important…but not enough• Learning from the outliers in extraordinary responders• Beyond DNA are other omics, but integration and validation and then implementation of the data remains to be
optimizedp• New ways to managing and bringing the data to physicians and patients are being beta tested• Cancer will likely continue to require combinations of agents hitting multiple pathways, and thinking of how and
why and when to combine brings in many scientific, clinical and market issues• We are still evolving the development and regulatory approaches with umbrella and bucket studies to better study
the drugs in their various settings and to make sure these are accessible to patients in as timely a fashion as possible
• There are still key underserved segments, such as rare and pediatric cancers• Heme malignancies such as B-cell cancers are a good surrogate of the scientific advances and of the commercial
issues like competitive dynamicsissues like competitive dynamics• The industry is diversifying in its approach to funding innovation, in discovery and development• Immunotherapy is all the rage, seems to be something distinct from what we have seen before, but still no
panacea• And finally, we will conclude the conference by taking a step back – and maybe forward – in challenging the
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015
y, y g p y g gconventional way we approach targeting cancer in light of the latest understanding of how cancers develop and evolve.
28
That Was Then…This Is When?That Was Then…This Is When?
Cancer Progress by Defined HealthNew York, NY | March 17-18, 2015