BIOTECH’S CONUNDRUM IN IMMUNO- ONCOLOGY ......BIOTECH’S CONUNDRUM IN IMMUNO-ONCOLOGY: WEIGHING...
Transcript of BIOTECH’S CONUNDRUM IN IMMUNO- ONCOLOGY ......BIOTECH’S CONUNDRUM IN IMMUNO-ONCOLOGY: WEIGHING...
BIOTECH’S CONUNDRUM IN IMMUNO-ONCOLOGY: WEIGHING HOT VERSUS COLD TUMORS, CPI-NAÏVE VERSUS CPI-EXPERIENCED PATIENTS
Jeffrey M. Bockman, PhDExecutive Vice PresidentOncology Practice HeadDecember 4th, 2019
PANELISTS
MODERATOR
3CHBC-CRI Immuno-Oncology Webinar© Cello Health BioConsulting 2019
Background on Cello Health BioConsulting, Previously Defined Health
We consult with the world’s most innovative biopharma companies, applying our strategic insight to early-stage platforms and programs. Our advice reduces development and commercial risk and increases stakeholder value.
Our Strategic Advice, given early in development (pre-PoC), drives value along the development continuum and influences ultimate outcome.
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Introductory Slides on Immuno-Oncology
6CHBC-CRI Immuno-Oncology Webinar© Cello Health BioConsulting 2019
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WW Oncology Products Sales:IO vs. Non-IO
Non-IO IO
Non-IO CAGR (2013-2024): 8%
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100120140160180
Sale
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US Oncology Products Sales:IO vs. Non-IO
Non-IO IO
Non-IO CAGR (2013-2024): 11%IO CAGR (2013-2024): 29%
IO CAGR (2013-2024): 30%Total Oncology CAGR (2013-2024): 14%Total Oncology CAGR (2013-2022): 11%
♦ Not just growth off a small base but tremendous uptake due to the clinical value being provided.♦ Total sales of IO assets in 2024 are estimated at $37B in US and $63B WW.
EvaluatePharma; DH Analysis
Immuno-Oncology Products Still Represent a Minority of the Overall Branded Cancer Market, but They Are Forecasted to Grow Strongly with US CAGR of 29% Through 2024
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Phase 1 Phase 2 Phase 3 Pre-registered Registered Marketed
Num
ber o
f Age
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Phase of Development
US IO Pipeline by Highest WW Phase and Mechanism
Viral vaccine and/or oncolytic
Other IO (ADC)
Other Cell Therapy
Innate Immunity (antagonist)
Innate Immunity (agonist)
Immuno-metabolism
Cytokine
Costim
Checkpoint
CAR-T cells
Cancer vaccine
Bispecific (IO Redirecting)
Adis R&D Insight; Clarivate Analytics Cortellis; company websites; clinicaltrials.gov; CHBC Analysis
The Clinical Pipeline Reflects a Diverse Set of MOAs & Therapeutic Modalities: Reflecting a Richness of Targets But Perhaps Insufficient Translational Insights
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Clinical Development Activity Across Liquid and Solid Tumors Varies by Therapeutic Modality, CPIss Cluster in Solid Tumors and ACT in Liquid Ones
Adis R&D Insight, Clarivate Analytics Cortellis, CHBC Insight, *NOTE: Assets designated for multiple indications are double-counted.
Indication Distribution – Top 20 Pharma Clinical Activity in Cell Tx, CPI, and OV by Count of Assets
Heme Malignancies Solid Tumors GC
MOA –Asset Count AL
L
AML
BPDC
N
CLL
CML
CTCL
/PTC
L
DLBC
L
Hem
e M
alig
nanc
ies
HL Lym
phom
a
Mul
tiple
mye
lom
a
NHL
Bilia
ry C
ance
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Blad
der C
ance
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Brea
st C
ance
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Canc
er M
etas
tase
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Cerv
ical
Can
cer
Colo
rect
al C
ance
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Esop
hage
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Fallo
pian
Tub
e Ca
ncer
Gal
lbla
dder
Can
cer
Gas
tric
Can
cer
Gas
troi
ntes
tinal
Can
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GBM
/Glio
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HCC/
Live
r Can
cer
Head
And
Nec
k Ca
ncer
Mel
anom
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Mer
kel C
ell C
arci
nom
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Mes
othe
liom
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NSC
LC
Ost
eosa
rcom
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Ova
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Canc
er
Panc
reat
ic C
ance
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Peni
s Tum
or
Perit
onea
l Can
cer
Pros
tate
Can
cer
RCC/
Rena
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cer
Sarc
oma
SCLC
Soft
Tis
sue
Sarc
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Solid
Tum
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Squa
mou
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cino
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Gen
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Can
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TOTA
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Cell Tx 10 10 1 2 1 2 6 1 16 7 1 1 1 3 1 3 2 1 3 3 2 1 1 2 1 8 27 117
CPI 1 2 1 2 2 4 4 3 2 16 4 1 3 9 3 1 3 8 10 24 3 17 2 2 1 2 12 1 6 29 4 19 201
OV 1 1 1 1 1 2 2 1 6 6 22
TOTAL 10 11 1 4 1 1 4 8 4 5 19 7 2 17 4 1 4 10 3 1 1 4 1 4 9 11 26 3 3 21 1 5 5 1 2 4 13 1 8 1 43 4 52 340
Asset Count Key
15 301
Legend
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CRI Analysis - Nature Reviews Drug Discovery, 04 November 2019
Hence the Rapid Increase in Combination Studies of Anti-PDx Agents With a Diverse Range of IO and Non-IO Approaches as Shown by the Most Recent CRI Analysis
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CRI, Nature Reviews Drug Discovery Sept 27, 2019
CRI’s Analysis Also Shows the IO Pipeline Growth Is Driven Mostly by Approaches That Are Well-Trodden
Fig. 1 | Overview of all 3,876 active IO agents in the current global drug development pipeline. In the past 2 years, 1,846 new agents have been added to the immuno-oncology (IO) pipeline, an increase of 91%.
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HOTTER TUMORS
COLDER TUMORS
Source: CHBC Analysis: ESMO, ASCO, AACR, ASH abstracts; prescribing information; company press releases; N Engl J Med 2017; 377:2500-2501*Efficacy data is weighted by the number of patients per trial, total number of patients across all trials and number of trials represented are in y-axis label
Advances with CPIs, While Dramatic in Selected Settings, Remain Incremental and/or Limited in Many Others, But Nevertheless Are Raising the Bar Across an Increasingly Diverse Set of Indications & Settings
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BCIQ; CHBC Analysis; FierceBiotech *Note: All counts include undisclosed and missing deal values
129 117 129
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No.
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eals
Non-IO vs IO Licensing and M&A Deals: 2016 to 2019Q3 (n=792)
Non-IO
IO
IO Deals Slowing with Less Than 50% in 2019 IO – Is This Maturing Understanding and a Higher Bar, or Just Fatigue Along with a Rise of New Non-IO Options?
RISKY again?
Overall Licensing and M&A deals have decreased 63% from 2018 to 2019Q3
Oncology has decreased 58% from 2018 to 2019Q3, suggesting oncology is still holding strong even with the global deals decreasing.
Expected Q4 deals
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BCIQ; CHBC Analysis
*Note Left graph = All counts include undisclosed and missing deal values, while right graph excludes them
75 Bn
48 Bn
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IO Non-IO
USD
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Total Combined Licensing Deal Values: 2016-2019Q3(n= 182)
IO
Non-IO
But While the Number of Deals Are Slowing, the Dollars Going into IO Is Still Phenomenal
3943
IO Vs Non-IO Licensing Deals Distribution: 2019Q3 (n=82)
IO Non-IO
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70%
30%
2018 Venture (Seed & Series A) Financing Distribution
$2.23B Total Raised in 2018
IO Non-IO
24%
76%
2019 To-Date Venture (Seed & Series A) Financing Distribution
$0.73B Total Raised in 2019
IO Non-IO
BCIQ; CHBC Analysis.
Funding for IO Newcos Dropped This Year, With Non-IO Fundings Taking a Larger Share
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In Fact There Were Significantly Less Early Investments into IO Companies this Year Compared to 2018
BCIQ; CHBC Analysis.
3831
2018 Venture (Seed & Series A) Financing Distribution by IO vs. Non-IO Companies
(n=69)
IO Non-IO
1417
2019 To-Date Venture (Seed & Series A) Financing Distribution by IO vs. Non-IO
Companies(n=31)
IO Non-IO
1.9B
0.8B
IO Non-IO
2018 Distribution by Amount Raised ($)
0.2B
0.6B
IO Non-IO
2019 Distribution by Amount Raised ($)
50M
26M
IO Non-IO
2018 Distribution by Financing Average per
Company ($)
13M
33M
IO Non-IO
2019 Distribution by Financing Average per
Company ($)
16CHBC-CRI Immuno-Oncology Webinar© Cello Health BioConsulting 2019
One Third of Biotech Pipeline in Companies <$100 mm Essentially Worthless Regardless of Development Phase
BCIQ, Reuters
Cash Higher vs Market
Cap33%Cash Lower
vs Market Cap67%
Cash vs Market Cap for Small Public US Biotech Companies (MC <$100M, n=203)
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Number of Small Public US Biotech Companies By Lead Product Status (MC <$100M, n=203)
Cash Higher vs Market Cap Cash Lower vs Market Cap
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Nearly 3 of 4 Companies From IPO Class of 2014 Have Lost Value
Current Share Price Below IPO
Share Price71%
Current SharePrice Above IPO
Share Price29%
Active 2014 IPO Companies (n=50)*Share Price Comparison – IPO Share Price vs Current Share Price
BCIQ
* Companies that had an IPO in 2014, but are currently inactive, were removed from this analysis (n=23)
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Platform DevelopmentEven Spectacular Science Requires Early-Stage Strategy to Manage Risk and Drive Valuation
There is inherent value in early science or platform technology that promises to generate multiple clinical programs, often targeting a ranging of opportunities from large patient groups with an established SOC to orphan populations with high unmet need.The decision to enter the clinic and how is of paramount importance as cash burn and risk increase exponentially.Strategic vision/thinking needs to see the product through to the market, not just to a partnering event mid-stage, to drive valuation and create optionality for the company.
• The first and most critical decision: Which disease(s) do you choose as your first target?• What are subsequent indications, and when is enough, enough (i.e., unfocused deployment of capital)? • What factors drive these decisions (e.g., strength of biological rationale/competitive differentiation; trial duration/
time to value inflection, size of patient population/expected commercial spend)?• Does your choice de-risk the program from a scientific, clinical/regulatory, and commercial perspective?
Key Questions at
this Stage
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Pre-Clinical & Early Clinical ProgramsDefining a Target Product Profile that Passes the Proof-of-Relevance Test (Early Relevance Profile)
The ultimate goal of developing a drug through the clinical/regulatory process is maximizing value, not just FDA approval. Clinical failure cannot always be predicted or prevented, but commercial failure often can and should be considered at an early stage with critical decisions are made to de-risk and drive value.It is imperative that R&D and Commercial objectives are aligned and that early-stage product profiles focus on value (Early Relevance Profile), outlining attributes that meaningfully differentiate the product in the future competitive landscape to all key stakeholders.
Value and Relevance Drivers:• What specific patient segment will derive the most value?• What product label will define competitive positioning in the treatment algorithm?• Which clinical endpoints will clearly establish clinical value and clearly differentiate from the competition?• How do these factors change as intrinsic (product-related) and extrinsic (market-related) factors evolve over time?• What are the key market access issues and barriers that will influence level of access to product?
Key Questions at
this Stage
20CHBC-CRI Immuno-Oncology Webinar© Cello Health BioConsulting 2019
Early Relevance ProfileTPP for an Early-Stage Program that Focuses on Value to Key Stakeholders
Early Relevance Profiles focus on key considerations associated with key stakeholders
Physician Payer
Partners
• Patient segment that will derive the most value
• Journey to treatment
• Dosing/administration requirements
• Level of access to treatment
• Impact of out of pocket expense
• Clear value proposition and position in treatment algorithm
• Label indication
• Strength of data/evidence
• Safety/tolerability profile
• Clear differentiation from alternative treatment options
• Requirements for access
• Level of unmet need (e.g. how many substitutable alternatives can be “step-edited” in front of candidate)
• Indication severity (where does it fall on continuum between fatal and cosmetic)
• Strength of evidence (trial comparator, structure)
• Duration of treatment (chronic, short-term)
• Medical benefit or pharmacy benefit
• Credibility and ease-of-access metrics for value-based contracts
• Patient financial assistance program relative to competitor’s programs
Patient
Other Stakeholders
21CHBC-CRI Immuno-Oncology Webinar© Cello Health BioConsulting 2019
PoR: A Strategic Concept Arising from Earlier Tough Times Was Initially a Survival Strategy –Now It Has Become a Proactive Value-Inflection Strategy
PoR =ProofofRelevance
To survive, biotech companies must embark on clinical programs that go beyond scientific proof-of-concept (demonstrating that the science is applicable to the disease) to prove that its approach provides a clinically and commercially relevant value proposition that makes the program attractive to all stakeholders
22CHBC-CRI Immuno-Oncology Webinar© Cello Health BioConsulting 2019
Acknowledgements to the Great Oncology Consultants & Analyst Team at Cello Health BioConsulting (previously Defined Health)
Sonam Sharma, MS, Sr Research Analyst
Armand Avetisian, Research Analyst
Adam Kaufman, Research Analyst
Olivia Dineen, Research Analyst
Brian Caffrey, Research Analyst
James Lee, PhD, Associate Principal, Oncology Team Leader
Mike Rice, MS, MBA, Principal
Joel Sandler, PhD, Associate Principal
Thanks!Questions???