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Corvus Corporate Presentation March 2020
Corvus Corporate PresentationMarch 2020
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Forward-Looking Statements / Safe Harbor
This presentation and the accompanying oral presentation contain “forward‐looking” statements, including statements related to the potential safety and efficacy of CPI-006, ciforadenant and CPI-818, the Company’s ability to identify and utilize the adenosine gene signature for purposes of its clinical trials, including the Company’s Phase 1b/2 clinical trial of ciforadenant, the Company’s ability to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1b/2 clinical trial of ciforadenant, the Company’s ability to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1b/2 clinical trial of ciforadenant, and the Company’s Phase 1/1b clinical trials of CPI-006 and CPI-818, the suitability of dosing regimen selected for clinical trials, and expected cash needs and operating expenses for 2020. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2019, filed with the Securities and Exchange Commission on March 9, 2020, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company’s ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of ciforadenant, CPI-006 and CPI-818; the accuracy of the Company’s estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials; the Company’s ability to utilize biomarker data and select a suitable dosing regimen; the results of preclinical studies may not be predictive of future results; the unpredictability of the regulatory process; regulatory developments in the United States and foreign countries; the costs of clinical trials may exceed expectations; and the Company’s ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. Such products are currently limited by Federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.
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Product Candidates DiseasesD E V E L O P M E N T S T A T U S
Lead Optimization IND-Enabling Phase 1/1b Phase 1b/2
A2AR Inhibitor• Renal Cell• Prostate• Colon• Other
Anti-CD73Immuno-Modulator
ITK Inhibitor • T-Cell Lymphoma
Anti-CXCR2 • Multiple cancers
A2BR Inhibitor • Fibrosis
An Expanding PipelineRapidly advancing programs across multiple indications
CPI-935
CPI-182
Ciforadenant Monotherapy
CPI-006 Monotherapy
Ciforadenant + Anti-PDL1 Combination
CPI-006 + Ciforadenant Combination
CPI-006 + Pembrolizumab Combination
CPI-006 + Ciforadenant + Pembrolizumab
CPI-818
Ciforadenant + Daratumumab Combination
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Lead Clinical Products with Unique MOA & Diverse Indications
Check point inhibitorBiomarker enriched patients
CIFORADENANT
Pre TreatmentJuly 2017
Post TreatmentSeptember 2019
Immuno-modulator & adenosine production blockade
CPI-006
CPI-006Control
Pre Treatment Post Treatment
ITK inhibitor
CPI-818
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Cancer Discovery January 2020 - Publication & Editorial
“Fong and colleagues describe… tumor regression, disease control, and survival of patients with otherwise refractory renal cell cancer with progressive disease after treatment with the conceptually novel…. ciforadenant.”
“Fong and colleagues are among the first clinical development teams that aimed to block not only the immunologic negative regulators, but also the powerful A2A-adenosinergic negative regulators of antitumor immunity.”
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Ciforadenant: Efficacy in Biomarker RCC PatientsAdenosine Signature identifies patients with tumor response
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RCC Treated Patient Ciforadenant + AtezoConfirming AdenoSig biomarker
Pre Post
• Failed Nivo, TKIs• Increasing pulmonary mets and pleural effusion• Began treatment with cifo/atezo April 2019• Reached PR with complete resolution of effusion after 9 mo of therapy• Adenosine Signature positive
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Durable PFS Observed in Adenosine Signature High PatientsPlateau on the curve
ADENOSINE SIGNATURE BIOMARKERConfirmation from multiple sources
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Myeloid SignatureHigh (AdenoSig) Poor Response to AtezoMcDermott et al Nature Med 24:749, 2018
• Randomized trial in 1st line RCC, N=305, Sutent vs. Atezo vs. Atezo+Avastin• Median PFS 2.9mo in myeloidhigh patients
Atezo poor PFS in MyeloidHigh
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AdenoSig Survival in RCC from TCGAPoor survival in High vs Low
AdenoSig NegAdenoSig Pos
• AdenoSig positive patients have a worse OS• Patients in TCGA database receiving various therapies
p = E-4.53
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Biomarker Provides Double Enrichment (Selection)
• Positive patients are an unfavorable group and less likely to benefit from standard therapy
• They are more likely to respond to ciforadenant
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Prostate Cancer Patient Treated with Cifo/Atezo ComboPSA and CT scans
Treatment Start (May-2017)
Last dose (Oct-17)
Before (5.7cm)
After (1.71cm)Visit
PSA
Resu
lt
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Responding Abdominal Masses and PSA in Prostate CancerTreatment with ciforadenant and atezolizumab
Pre-Treatment On-Treatment, Post 2 Cycles• 68 yr. male with mCRPC• Metastases in lymph nodes• Received external beam
radiation and progressed on Xtandi/Eligard, etc.
• Started on ciforadenant + atezolizumab
0
5
10
15
20
11-Feb 18-Apr 6-Aug 4-Sep 2-Oct
PSA
leve
l
C1D1 C2D C3
Treatment
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Cifo+Atezo in Refractory mCRPCGU ASCO Data Feb 2020
Patient Characteristics:• Median age 68• Visceral metastases 43%• Hormone refractory 96%• Chemo failures 16%
AdenoSig and CD73Correlation
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Lead Clinical Products with Unique MOA & Diverse Indications
Check point inhibitorBiomarker enriched patients
CIFORADENANT
Pre TreatmentJuly 2017
Post TreatmentSeptember 2019
Immuno-modulator & adenosine production blockade
CPI-006
CPI-006Control
Pre Treatment Post Treatment
ITK inhibitor
CPI-818
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CPI-006 is an Anti-CD73 with Unique PropertiesInduces B cell differentiation: isotype switching & immunoglobulin secretion in vitro
• CPI-006 activates B cells, resulting in morphological and surface marker changes consistent with B cell differentiation and isotype class switching
• Comparison to adenosine blocking anti-CD73 antibody (CPX-016) demonstrates unique CPI-006 property
CPI-006Day 2
Isotype Control CPI-006
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Increasing Importance of B Cells in Tumor Immunotherapy
NATURE articles published online 15 Jan 2020
“…B cells…could be potentially contributing to the anti-tumour response...”“…these data support…sub-sets of B cells at different stages of B cell development, and their role in the response to immune checkpoint blockade…”“…this work…unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision making and treatments…”
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CPI-006-001 Clinical Trial Design
Design• Phase 1/1b dose escalation/dose expansion • CPI-006 every 3 weeks; fixed dose of
ciforadenant
Eligibility• Cancers progressed on 1-5 prior therapies• CD73 expression: required in expansion, not in
dose escalation • Adenosine gene signature not used to select
patients
Objectives• Primary: Safety and tolerability• Secondary: PK/PD, efficacy, biomarkers
Biomarker Assessments• Tumor markers, cytokines, etc.• Humoral immune response
Dose Escalation
Dose Expansion
CPI-006
24 mg/kg18 mg/kg12 mg/kg
6 mg/kg3 mg/kg1 mg/kg
CPI-006 + Ciforadenant
18 mg/kg12 mg/kg
6 mg/kg3 mg/kg
1 mg/kg
CPI-006 + Ciforadenant + Pembrolizumab
18 mg/kg12 mg/kg
CPI-006 + Pembrolizumab
18 mg/kg12 mg/kg
NSCLCmCRPC RCC Others
Doses explored to date & planned doses
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Responding Pulmonary Metastases in RCC PatientCPI-006 6 mg/kg ciforadenant combination
• 36 year old male presented in 2015 with renal mass and bone metastases
• Failed TKI, nivo and nivo/ipiwith increase pulmonary mets
• Regression of multiple biopsy proven pulmonary metastases on CPI-006 + ciforadenant
Pre-treat
Post 3 cycles
Pre-treat
Post 3 cycles
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Colon Cancer Response Treated with Sequential CPI-006 followed by chemoradiotherapy
CT scan upon progression (May) CT after XRT (mid-late June) CT November 2019 (s/p Chemo)
• 51yo female metastatic colon cancer failed multiple chemotherapies including FOLFOX, FOLFIRI, Leucovorin/5FU
• Treated CPI-006 monotherapy followed by XRT, 5FU, Vectibix
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CEA Levels in Responding PatientColon cancer patient treated with CPI-006
CPI-006RadiationLUQ mass
sFU + panitumumab
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Lead Clinical Products with Unique MOA & Diverse Indications
Check point inhibitorBiomarker enriched patients
CIFORADENANT
Pre TreatmentJuly 2017
Post TreatmentSeptember 2019
Immuno-modulator & adenosine production blockade
CPI-006
ITK inhibitor
CPI-818
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CPI-818: ITK and BTK are Homologous KinasesFounding scientists of Corvus pioneered covalent kinase inhibition with Ibrutinib
• B cell activation• Migration/homing• Proliferation
• T cell activation• Migration/homing• Proliferation• Th1 skewing
PNAS 2010
B cellsBCR
CD79SY
K BTKP PL
Cγ
PI3K
PIP2 PIP3
Src-family
PKCβ
IKK
NF -kB
Ibrutinib
A BPtdIns(4,5)P2
DAG + InsP3
TCRCD4
PIP2 PIP3
CPI-818
T cells
Src-family
LCK
PI3K
ITKP PL
Cγ
PtdIns(4,5)P2
DAG + InsP3
PKCβ
IKK
NF -kB
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CPI-818 Ph 1/1b Clinical Trial Design in T cell LymphomasFirst company to evaluate ITK inhibition in humans
DOSE EXPANSION - STAGE 1(N=11 PER COHORT)
If ≥2 responses observed in a disease cohort
DOSE EXPANSION - STAGE 2(N=17 PER COHORT)
PTCL AITL OthersCTCL
Design• Phase 1/1b open label, 3 + 3 dose escalation/dose
expansion• CPI-818 PO BID every 3 weeks
Eligibility• Subjects with R/R T cell lymphoma
Objectives• Primary: Safety/tolerability and dose finding• Secondary: PK/PD, efficacy, biomarkers
Biomarker Assessments• T cell kinase occupancy in peripheral blood T cells• Tumor markers: tumor gene expression, histology,
malignant cell frequency• Immune function: T cell subset abundance, circulating
cytokines, serum immunoglobulin levels
DOSE ESCALATION
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CTCL/SS Patient on 200mg Cohort with Nodal CR
• 60 y.o. female with SS
• FDG avid adenopathy in cervical, axillary, inguinal nodes bilaterally
• Enrolled in 200mg BID cohort
• Screening PET: Mediastinal (paratracheal, subcarinal, hilar) and mandibular lymph nodes with moderate FDG avidity
• After 2mo. reduction in the mediastinal nodes with no focus of FDG activity
• mSWAT stable, Sézary cells stable Pa
ratr
ache
alSu
bcar
inal
Pre-Treatment Post-Treatment(C4D1)
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Financials
0 20 40 60 80 100 120
$39-$40MM
29MM
$78.0MM
Outstandingshares
Cash utilizationforecast 2020
Total cash (Dec 31, 2019)
(MM)
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Near-Term Milestones and Value-Drivers
Cifo + Atezo Ph2 RCC & mCRPC
CPI-818-001 Phase 1/1b T cell Lymphoma Study
CPI-006 + Ciforadenant Combination
CPI-006 + Pembrolizumab CombinationSITC
CPI-006 Monotherapy
ASH
CPI-006 + Ciforadenant + Pembrolizumab Triplet
2020 2021Q2 Q3 Q4 Q1 Q2 Q3 Q4
Ciforadenant data ASCO June 2020
SITC
CPI-818 ITKi data ASH Dec 2020
CPI-006 mono / cifo combo data SITC Nov 2020
ASCO
