Download Agenus JP Morgan 2017 1-6

January 2017
Forward-looking statements
This presentation contains forward-looking statements. These forward-looking statements
are subject to risks and uncertainties, including the factors described under the Risk
Factors section of our Quarterly Report on form 10-Q filed with the Securities and
Exchange Commission on November 9, 2016 and made available on our website at
www.agenusbio.com. When evaluating Agenus’ business and prospects, careful
consideration should be given to these risks and uncertainties. These statements speak
only as of the date of this presentation, and Agenus undertakes no obligation to update or
revise these statements. This presentation and the information contained herein do not
constitute an offer or solicitation of an offer for sale of any securities.
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Broad I-O portfolio: enabling optimal combos
3
Broad I-O portfolio: opportunistic
4
Agenus Five Year Growth Plan:
balancing low & high risk initiatives
• Advance on most rapid path to BLA
•
•
Develop, register, and launch anti-PD-1/CTLA-4 mAb combinations in validated
indications
Pursue novel breakthrough indications to expedite market entry
• Leverage novel targets for market expansion
• Pursue optimal I-O mAb and vaccine combinations with anti-CTLA-4 +/- anti-PD-1
• Progress partnered programs (GITR, OX40, TIM-3, LAG-3) towards registration
• Advance Ab programs against innovative undisclosed targets to the clinic
• Engage in strategic partnerships
5
Current partnerships
• QS-21 Stimulon®: adjuvant for Shingrix®
• GSK filed for registration in U.S., Canada and Europe
• Royalties and milestones partly monetized
• 1 undisclosed target
• Lead selection completed
• Up to $100 million in milestones
•
•
•
•
Pre-clinical: LAG-3, TIM-3, 3 undisclosed
Clinical: GITR, OX40
50/50 cost and profit share*
Royalty rates are generally 6-12 %** and up to $350 million
in milestones across the 4 programs
* Specific to the OX40, GITR and two undisclosed programs
** Specific to the TIM-3, LAG-3 and one undisclosed program
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Clinical Strategy
New clinical development paradigm compressed
Risk
AGEN1884 /
AGEN2034
+
Novel CPM
(A, B, C)
AGEN1884 /
AGEN2034
+
Vaccine
AGEN1884 /
AGEN2034
Solid Tumors
Efficacy
unknown
AGEN1884 /
AGEN2034
Solid Tumors
Efficacy proven
AGEN1884 = anti-CTLA-4 mAb
AGEN2034 = anti-PD-1 mAb
CPM = checkpoint modulator
10 years
Conventional time to BLA
8
anti-CTLA-4 + anti-PD-1:
first clinically validated I-O mAb combo
• anti-CTLA-4 (low dose) combined with anti-PD-1/PD-L1 is the only
validated mAb combination with improved efficacy and safety profile
•
Near doubling of clinical response - from ~25% to 40% in NSCLC(1,2)
•
Control of CTLA-4 + PD-1/PD-L1 targeted therapies could offer a pricing advantage
•
Provides a foundation for mAbs against novel checkpoints that are yet to show
efficacy in the absence of CTLA-4 antagonism
1. 2016 ASCO Annual Meeting; CheckMate -012 study; abstract no. 3001
2. BMS press release 06/04/2016
*Anti-CTLA-4 antibody AGEN1884 is partnered with Recepta for certain South American territories
9
Targeting PD-1 has clinical benefit but
combining with CTLA-4 antagonism works better
• anti-CTLA-4 (low dose) combination with anti-PD-1/PD-L1
reduces development risk and expands markets
•
anti-CTLA-4 and anti-PD-1 mAb combination is already approved in
metastatic melanoma & almost doubles clinical benefit in 1L NSCLC(1,2)
•
CTLA-4 + PD-1/PD-L1 antagonists +/- mAbs targeting novel checkpoints have
shown compelling data in preclinical models
1. 2016 ASCO Annual Meeting; CheckMate -012 study; abstract no. 3001
2. BMS press release 06/04/2016
*Anti-CTLA-4 antibody AGEN1884 is partnered with Recepta for certain South American territories
10
Metastatic virally induced malignancies*:
appealing target for Agenus
• Clinical development:
• SOC marginally changed after the approval of Avastin in combination with chemo in 1L
• No effective treatment options in 2L
• Clinical activity of other anti PD-X in virally induced and HPV driven malignancy (HNSCC HPV+)
suggests that AGEN1884 administration could lead to an ORR ~ 15% in all comers, > 20% in PD-L1+
•Regulatory:
• US: Possibility of applying for Breakthrough Designation, assuming hypotheses are backed up by
clinical data, Accelerated Approval possible
• EU: Possibility of applying for conditional marketing authorization
• Commercial:
• Potential niche opportunity with most of the patients from Japan and South Korea where premium
prices for unmet medical needs are commonly given and where there is no off-label use reimbursed
* Anticipated in cervical cancer
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AGEN2034 (anti-PD-1): projected clinical inflection points
2017
Q1
Q2
Q3
2018
Q4
Q1
Q2
Q3
2019
Q4
Q1
Q2
Q3
2020
Q4
Q1
Q2
Q3
2021
Q4
Q1
Q2
Q3
Q4
First patient for dose
escalation
Phase 1
n = 30
Dose is established
US filing
US approval
* *n = 200
2L Virally-induced Cancer
US filing
**
Phase 3 Virally-induced Cancer
PD-1 vs PD-1 + CTLA-4 vs SOC
* Anticipated in cervical cancer
n = 700
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AGEN2034 for 2L advanced virally induced malignancy:
potential value
• Could provide a unique registration opportunity for one of our agents
as a monotherapy within the next 5 years
• Unmet medical need
• Opportunity to validate the PD-1 element of our PD-1/CTLA-4 plans
• Establish commercial presence in ~ 4 years of development
• Multiple regulatory designations possible including Sakigake and
Breakthrough Designation that could provide external government
issued program validation
• Acceptable technical and regulatory risk
13
Preclinical data
Shaping the immune response to cancer:
targeting coordinated nodes of immune regulation
* Antibodies partnered with Incyte: GITR, OX40 (agonists);TIM3, LAG3 (antagonists) and three undisclosed targets
** Antibodies partnered with Recepta for certain South American territories
^^ ASV: AutoSynVax™, PSV: PhosphoSynVax™
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Integrated antibody discovery technologies, combined with
immunology expertise
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Agenus anti-CTLA-4 mAb improves primate
vaccine response
Antibody
Anti-CTLA-4 antibody AGEN1884
+
Hepatitis B surface antigen (HBsAg) vaccine
Vaccine
Cellular Response
2 ,0 0 0 ,0 0 0
Is o ty p e c o n tro l
C o n tr o l (N = 6 )
400
300
6
1 ,5 0 0 ,0 0 0
AG EN1884
500
A G E N 1 8 8 4 (N = 6 )
S F U /1 x 1 0 P B M C
A n ti-H B s A g Ig G (U /m L )
Humoral Response
1 ,0 0 0 ,0 0 0
5 0 0 ,0 0 0
0
200
100
0
-7
15
29
43
59
69
-4
0
8
15
22
29
36
43
50
57
67
A d m in is tra tio n s o f a n tib o d y
o r v e h ic le (c o n tr o l)
p lu s H B s A g v a c c in e
Internal data (unpublished)
D a y s A fte r In itia l D o s in g
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AGEN2034: Anti-PD-1 antagonist antibody
PD-1 inhibits TCR-induced signaling to impair
T cell effector function
Response rates observed with an PD-1 antagonist in a range of
solid and hematological tumor settings
AGEN2034 binds to PD-1 with high affinity (nM)
and potently inhibits PD-1 binding to PD-L1/2
P D -L 2
50
300
A G EN 2034
is o t y p e
A G EN 2034
is o t y p e
IL - 2 ( p g /m l)
P D -L 1
b in d in g ( % )
P D -L 1 o r P D -L 2
100
AGEN2034 enhances T cell responsiveness to
suboptimal TCR activation
A G EN 2034
I s o ty p e
200
100
0
0
-5
-4
-3
-2
-1
0
1
A n t ib o d y ( lo g µ g / m L )
Internal data (unpublished)
2
-7 -6 -5 -4 -3 -2 -1
0
1
2
A n t ib o d y ( lo g µ g / m L )
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AGEN1884 combines in primary T cell assays with PD-1:PD-L1
blockade (as well as LAG-3)
Isotype
Pembrolizumab
Internal data (unpublished)
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Business
Projected milestones
2016
2017
2018
Accomplishments
Clinical Deliverables
Clinical Activity & Readouts
• Three CPM mAbs in clinic
• CTLA-4 antagonist (AGEN1884)*
• GITR agonist (INCAGN1876)**
• OX40 agonist (INCAGN1949)**
• Clinical trials
• Initiate Ph 1 for PD-1 antagonist
(AGEN2034)* monotherapy
• Initiate virally-induced cancer+ trial (2L)
• Initiate Ph 1b with AGEN1884* +
AGEN2034*
• Initiate Ph 1 with AutoSynVax™
• Complete enrollment for 2nd line
virally-induced cancer+ cohort
• Clinical Development team with I-O
development success on board
• QS-21 Stimulon® containing
Shingles vaccine filed for regulatory
approval
•
Clinical results
• Optimal monotherapy dose for
AGEN2034*
• Optimal combination dose of AGEN2034*
+ AGEN1884*
•
Clinical responses
• Results from 30 patients in the virallyinduced cancer+ cohort (2L)
• Initial immune biomarker data from 6patient Ph 1 ASV proof-of-mechanism trial
• INCY collaboration expanded
* Partnered with Recepta for certain South American rights
** Partnered with INCY
+ Anticipated in cervical cancer
• Top line data for the virallyinduced cancer+ cohort:
• Response rate
• Duration of response
• Safety and tolerability
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Management Team
•
Garo Armen, PhD, Chairman & CEO
Elan Corporation, plc, Protagenic Therapeutics, Founder - Children of Armenia Fund (COAF)
•
Robert Stein, MD, PhD, President, R&D
Incyte Pharmaceuticals, Ligand Pharmaceuticals, Dupont/Merck, Roche, KineMed, Merck, Sharp & Dohme
•
Jennifer Buell, PhD, VP Research & Development Operations
Harvard Clinical Research, Bristol-Myers Squibb
•
Christian Cortis, PhD, VP Business Development
Synta Pharmaceuticals, Advanced Technology Ventures, Columbia University
•
Jean-Marie Cuillerot, MD, VP & Global Head of Clinical Development
EMD Serono, Bristol-Myers Squibb, University Louis Pasteur
•
Alex Duncan, PhD, Chief Technology Officer
Actigen, Affitech A/S, Astra Zeneca, Cambridge Antibody Technology
•
James Gorman, MD, PhD, VP Corporate Development and Strategy
Abbott Laboratories, Harvard University
•
Christine Klaskin, VP Finance
Arthur Andersen, George Washington University
•
Michelle Linn, VP Corporate Communications
Linnden Communications, Ogilvy PR/Feinstein Kean, Chair of Women In Bio Boston Chapter
•
Karen Valentine, JD, Chief Legal Officer & General Counsel
Palmer and Dodge LLP
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