UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): June 5, 2017
CORVUS PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 001-37719 | 46-4670809 | ||
|
(State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification Number) |
863 Mitten Road, Suite 102
Burlingame, CA 94010
(Address of principal executive offices, including Zip Code)
Registrant’s telephone number, including area code: (650) 900-4520
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Indicate by check mark whether the registrant is an emerging
growth company as defined in Rule 405 of the Securities Act of 1933(17 CFR §230.405) or Rule 12b-2 of the Securities Exchange
Act of 1934 (17 CFR §240.12b-2). Emerging growth company [ X ]
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for
complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. [ X ]
Item 8.01 Other Events.
On June 5, 2017, Corvus Pharmaceuticals, Inc. (“Corvus” or the “Company”) issued a press release announcing interim results demonstrating anti-tumor activity of CPI-444 in renal and lung cancer patients resistant or refractory to prior PD-(L)1 treatment. The full text of the press release is filed as Exhibit 99.1 hereto and is incorporated herein by reference.
Item 7.01 Regulation FD Disclosure.
On June 5, 2017, the interim data discussed above was presented in an oral presentation at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting in Chicago by Lawrence Fong, M.D., study investigator and Professor in Cancer Biology and Leader of the Cancer Immunotherapy Program at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. A copy of the presentation, including a slide setting forth certain cautionary language intended to qualify the forward-looking statements included in the presentation, is furnished as Exhibit 99.2 to this Current Report and is incorporated herein by reference.
The information in this Item 7.01 of this Current Report on Form 8-K shall not be deemed “filed” for purposes of Section 18 of the Securities Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that Section, or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits.
Reference is made to the Exhibit Index attached hereto.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| CORVUS PHARMACEUTICALS, INC. | ||
| Date: June 5, 2017 | By: |
/s/ Leiv Lea |
| Leiv Lea | ||
| Chief Financial Officer | ||
EXHIBIT INDEX
EXHIBIT 99.1
Corvus Pharmaceuticals Announces Interim Results Demonstrating Anti-Tumor Activity of CPI-444 in Renal and Lung Cancer Patients Resistant or Refractory to Prior PD-(L)1 Treatment
-- Clinical Data from Company’s Ongoing Phase 1/1b Study in Expansion Cohorts Presented in Oral Presentation at American Society of Clinical Oncology (ASCO) 2017 Annual Meeting –
-- Criteria Met for Second Expansion of Renal Cell Cancer Cohort Treated with Combination Therapy –
BURLINGAME, Calif., June 05, 2017 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, today announced interim safety and efficacy results from the renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) expansion cohorts in its ongoing Phase 1/1b study. The data showed that treatment with CPI-444 as a single agent and in combination with atezolizumab (Tecentriq®) resulted in anti-tumor activity in patients resistant or refractory to prior treatment with anti-PD-(L)1 antibodies and patients with PD-L1 negative tumors. CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. Atezolizumab, developed by Genentech, a member of the Roche Group, is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1).
The interim data were presented today in an oral presentation at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting in Chicago by Lawrence Fong, M.D., Professor in Cancer Biology and Leader of the Cancer Immunotherapy Program at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.
“These preliminary results from the CPI-444 clinical trial show that targeting this novel immunosuppressive pathway can lead to both anti-tumor immune responses and clinical responses in patients who have progressed on anti-PD-(L)1 therapies,” said Dr. Fong. “Lung and renal cell cancer patients who do not respond to treatment with PD-(L)1 therapies typically continue to progress rapidly and have very few options to manage their disease, creating a significant unmet need in cancer therapy. These data suggest that CPI-444, both as a single agent and in combination with atezolizumab, may induce tumor regression or disease control in these difficult-to-treat populations.”
“The anti-tumor activity and durability of responses and disease control seen to date are encouraging, especially in patients who are resistant/refractory to prior anti-PD-(L)1 therapy and have PD-L1 negative tumors. No therapies are currently approved that can overcome resistance to anti-PD-(L)1 therapies and few, if any, immunotherapies in development have reported benefit in the PD-1 resistant/refractory setting,” said Richard A. Miller, an oncologist and co-founder, president and chief executive officer of Corvus. “In addition to our previously announced cohort expansions, based on data reported here, we have met the pre-defined criteria for the second expansion to the maximum number of 48 patients in the RCC cohort receiving combination therapy. We look forward to continuing to evaluate patients with lung and renal cell cancer enrolled in the multiple expansion cohorts, as we believe that targeting the adenosine pathway could lead to new treatment options for patients in this setting.”
Key Patient Demographic Data
Interim safety and efficacy data on 75 patients with RCC (n=30) or NSCLC (n=45) enrolled in the Phase 1/1b study to date were presented. Of these, 73 percent of RCC patients and 82 percent of NSCLC patients were resistant or refractory to prior therapy with anti-PD-(L)1 antibodies. Of the RCC (n=19) and NSCLC (n=28) patients with archived samples available, 95 percent and 54 percent of patients, respectively, had PD-L1 negative tumors.
Key Study Results in RCC Patients
An infographic accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/f1df88e4-d3f5-4ed3-8e30-ae3f87467abe
· Best tumor response data for RCC patients are shown in a “waterfall” plot (Figure 1). There were two confirmed partial responses (PR) out of 22 evaluable patients.
- One PR was in a patient treated with single agent CPI-444 who was resistant/refractory to prior anti-PD-(L)1 therapy and was PD-L1 negative.
- One PR was in an anti-PD-(L)1 treatment-naïve patient treated with combination therapy. The PD-L1 status of this patient treated in combination was not available at the time of the presentation.
- The duration of PRs, which are ongoing in these two patients, exceeds eight months and three months.
· 16 patients achieved stable disease, with six of these patients experiencing minor regressions (MR). Four of the patients that achieved an MR were resistant/refractory to prior anti-PD-(L)1 therapy. The remaining patients had progressive disease or progressed before their first CT scan was obtained.
- Six patients have had disease control for more than six months (range: 6-12 months), with five of these six patients continuing on therapy (three single agent, two combination).
· For RCC patients with stable disease, an analysis of tumor growth kinetics demonstrated that several patients with documented tumor growth prior to study enrollment, had stabilization or regression of their tumors while receiving treatment with CPI-444, suggesting that treatment altered the behavior of tumor growth.
Key Study Results in NSCLC Patients
An infographic accompanying this announcement is available at http://www.globenewswire.com/NewsRoom/AttachmentNg/518f7b87-042d-42f7-84d1-29caad3e0006
· Best tumor response data for NSCLC patients are shown in a “waterfall” plot (Figure 2). There were two partial responses (PR) out of 34 evaluable patients.
- One confirmed PR was in a patient treated with combination therapy who was resistant/refractory to prior anti-PD-(L)1 therapy and is PD-L1 negative. The PR is ongoing at six months.
- One unconfirmed PR is in a patient who received the combination, was resistant/refractory to prior anti-PD-(L)1 therapy, is PD-L1 positive, and is ongoing at two months.
· 22 patients achieved stable disease. Four of the stable disease patients, all of whom were were resistant/refractory to prior anti-PD-(L)1 therapy, had MRs. The remaining patients had progressive disease or progressed before their first CT scan was obtained.
· Four patients with NSCLC, three of whom were resistant/refractory to prior anti-PD-(L)1 therapy, experienced disease control exceeding six months (two single agent, two combination). All of the patients continue on therapy.
Safety Data
CPI-444 continues to be well tolerated to date, with observed adverse events similar to previous reports. For single-agent CPI-444 cohorts, the following Grade 1 and 2 adverse events occurred in 5 percent or more of patients: fatigue, nausea, pruritis, constipation, dizziness, hypertension and fever. For combination therapy cohorts, the following Grade 1 and 2 adverse events occurred in 5 percent or more of patients: fatigue, nausea, pruritis, rash and increase in liver enzymes. In the combination cohort, one patient developed reversible Grade 3 immune-related toxicities.
Phase 1/1b Trial Design
The Phase 1/1b trial is designed to select the dose, assess the safety and examine the activity of CPI-444 as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody, in multiple histologies known to be sensitive to immuno-oncology agents. Patients with non-small cell lung cancer, melanoma, renal cell cancer, triple-negative breast cancer (TNBC), MSI-H colorectal cancer, head and neck cancer, bladder cancer and prostate cancer who have failed standard therapies are eligible. The efficacy endpoints of the study are response rate and disease control rate, which is defined as complete response, partial response (reduction of >30 percent tumor volume) or stable disease (change in tumor volume of between 20 percent growth of tumor and 30 percent reduction of tumor volume). Patients with minor tumor regressions are those with changes in tumor volume of 0 to ≤30 percent reduction in tumor volume. Patients are treated until disease progression or evidence of Grade 3 or 4 toxicity.
The dose-selection part of the study included four cohorts of 12 patients each (N=48) – three cohorts treated with single agent CPI-444 (100 mg twice daily for 14 days; 100 mg twice daily for 28 days; 200 mg once daily for 14 days) and one cohort treated with the combination (CPI-444 50 mg or 100 mg twice daily for 14 days combined with atezolizumab). A treatment cycle is 28 days. Based on biomarker analyses showing sustained, complete blockade of the adenosine A2A receptor in peripheral blood lymphocytes, and evidence of immune activation in circulating lymphocytes, an optimum single agent and combination dose of 100 mg twice a day for 28 days was selected for the second part of the study. As defined in the protocol, patients in the dose-selection stage of the trial receiving the dose and schedule selected for evaluation in the second part of the study are included in the disease-specific cohort efficacy analysis.
The second part of the study is evaluating CPI-444 as a single agent in five disease-specific cohorts (NSCLC, melanoma, RCC, TNBC and a category of “other” that includes MSI-H colorectal cancer, bladder cancer and prostate cancer) and CPI-444 in combination with atezolizumab in five additional matched disease-specific cohorts. Each of the 10 cohorts is initially enrolling 14 patients, but may be expanded based on efficacy. To date, RCC and NSCLC, both single agent and combination cohorts, have met the initial criteria for expansion to 26 patients. Recently, the combination cohort of patients with renal cell cancer met the second criteria for expansion to 48 patients.
About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company focused on the development and commercialization of small molecule and antibody agents that target the immune system to treat patients with cancer. These agents block or modify crucial immune checkpoints and reprogram immune T-cells. Corvus’ lead product, CPI-444, is a checkpoint inhibitor that is designed to disable a tumor’s ability to subvert attack by the immune system by inhibiting adenosine in the tumor microenvironment. CPI-444 is a small molecule that is taken orally. CPI-444 is currently being evaluated in a multicenter Phase 1/1b clinical trial in patients with various solid tumors. This successive expansion cohort trial is examining the activity of CPI-444 both as a single agent and in combination with Genentech’s atezolizumab, an anti-PD-L1 antibody. Corvus is conducting the trial with Genentech, a member of the Roche Group, under a clinical trial collaboration the two companies entered into in October 2015. For more information, visit www.corvuspharma.com.
Tecentriq® (atezolizumab) is a registered trademark of Genentech.
Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-444, both as a single agent and in combination with anti-PD-1, anti-PD-L1, or other therapies, the Company’s ability to develop and advance product candidates into and successfully complete clinical trials, including the Company’s Phase 1/1b clinical trial of CPI-444, the basis for any future clinical trials with CPI-444, the utility of biomarker data collected and the suitability of the dosing regimen selected for the Company’s Phase 1/1b clinical trial of CPI-444. 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 Quarterly Report on Form 10-Q for the three months ended March 31, 2017, filed with the Securities and Exchange Commission on May 4, 2017, 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 evidence of efficacy and safety for CPI-444 during its Phase 1/1b clinical trial; the results of early clinical trials may not be predictive of future results; the unpredictability of the regulatory process; and regulatory developments in the United States and foreign countries. 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.
UC Disclaimer
The information stated above was prepared by Corvus Pharmaceuticals, Inc., and reflects solely the opinion of the corporation. Nothing in this statement shall be construed to imply any support or endorsement of Corvus, or any of its products, by The Regents of the University of California, its officers, agents and employees.
Investor Contact:
Jason Coloma
SVP, Chief Business Officer
Corvus Pharmaceuticals, Inc.
+1-650-900-4511
JColoma@corvuspharma.com
Media Contact:
Julie Normart
Pure Communications
+1-415-946-1087
jnormart@purecommunications.com
Exhibit 99.2
Abstract #: 3004 Safety and clinical activity of adenosine A2a receptor (A2aR) antagonist, CPI - 444, in anti - PD1/PDL1 treatment - refractory renal cell (RCC) and non - small cell lung cancer (NSCLC) patients Presenter: Lawrence Fong, M.D . Leader, Cancer Immunotherapy Program Co - Director , Parker Institute of Cancer Immunotherapy @ UCSF University of California, San Francisco
This presentation contains forward - looking statements, including statements related to the potential safety and efficacy of CPI - 444, both as a single agent and in combination with anti - PD - 1 and anti - PD - L1, and the Company’s ability to develop and advance product candidates int o and successfully complete clinical trials, including the Company’s Phase 1/1b clinical trial of CPI - 444. 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 uncert ainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially fro m 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 Quarterly Report on Form 10 - Q for the three months ended March 31, 2017, filed with the Securities and Exchange Commission on May 4, 2017, as well a s other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the fol lowing factors, among others, could cause results to differ materially from those expressed or implied by such forward - looking statements: the C ompany’s ability to demonstrate evidence of efficacy and safety for CPI - 444 during its Phase 1/ 1b clinical trial; the results of early clinical trials may not be predictive of future results; the unpredictability of the regulatory process; and regulatory developments in the United States and foreign cou ntries. 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 re vise publicly any forward - looking statements, whether as a result of new information, future events or otherwise. Additional information may be a vailable in press releases or other public announcements and public filings made after the date of this presentation. This presentation concerns products that have not yet been approved for marketing by the U.S. Food and Drug Administration (“ FDA ”). No representation is made as to their safety or effectiveness for the purposes of which they are being investigated. 2 Forward Looking Statements Forward Looking Statements
Safety and clinical activity of adenosine A2a receptor (A2aR) antagonist, CPI - 444 in anti - PD(L)1 treatment - refractory renal cell (RCC) and non - small cell lung cancer (NSCLC) patients Lawrence Fong, Patrick Forde , John Powderly II, Jonathan Goldman , John Nemunaitis , Jason Luke , Matthew Hellmann , Shivaani Kummar, Robert Doebele, Daruka Mahadevan, Shirish Gadgeel , Brett Hughes , Ben Markman, Matthew Riese, Joshua Brody , Leisha Emens, Ian McCaffery, Richard Miller and Ginna Laport University of California, San Francisco, San Francisco, CA; Johns Hopkins Kimmel Cancer Center and Bloomberg - Kimmel Institute for Cancer Immunotherapy, Baltimore, MD; Carolina BioOncology Institute, Huntersville, NC; David Geffen School of Medicine at UCL A, Los Angeles, CA; Mary Crowley Cancer Research Centers, Dallas, TX; University of Chicago, Chicago, IL; Memorial Sloan Kettering Cancer Center, New York, NY; Stanford University School of Medicine, Stanford, CA; University of Colorado Anschutz Medical Campus, A uro ra, CO; The University of Arizona, Phoenix, AZ; Karmanos Cancer Institute/Wayne State University, Detroit, MI; Royal Brisbane Hospital, Chapel Hill, Australia; Monash Health and Monash University, Melbourne, Australia; Med Coll of Wisconsin, Milwaukee, WI; Icahn School of Medicine at Mount Sinai, New York, NY; The Johns Hopkins University, Baltimore, MD; Corvus Pharmaceuticals, Burlingame, CA Ph I CPI - 444 Trial 2 2
Background • Anti - PD - (L)1 antibodies are approved for treatment of RCC and NSCLC but a small proportion of patients benefit. • No approved agents overcome resistance to anti - PD - (L)1 with few reporting benefit in PD - 1 resistant/ refractory setting. • Converting tumors devoid of T cell infiltration (“cold tumors”) into T cell inflamed tumors (“hot tumors”) could improve response to immunotherapies. • Adenosine is a mediator of immunosuppression within the tumor microenvironment. • CPI - 444 is an oral small molecule antagonist of the adenosine A2A receptor ( A2AR) ( Emens , AACR 2017). Ph I CPI - 444 Trial 4 4 (Sharma et al. Cell, 2017) 2
Adenosine Suppresses Immunity and is a Potential Mechanism of Resistance to PD - (L)1 Therapy CD73 expression in baseline tumor biopsies from the CPI - 444 phase 1 trial Adenosine in the tumor microenvironment Tumors can generate adenosine in response to anti - PD - (L)1 (Beavis et al, Can Immunol Res 2015) Adenosine A2AR ATP AMP CD73 Tumor T Cell CD39 T Cell PD1 PDL - 1 Anti - PD - (L)1 N=17 10 CD73 Expression (mRNA) p=0.001 Anti - PD - 1 Naive 100 1,000 10,000 Anti - PD - 1 Resist/Refract N=19 Ph I CPI - 444 Trial 5 5 T cell inhibition 3
Phase 1/1b Clinical Study with Oral Drug CPI - 444 Expansion cohorts: renal cell and non - small cell lung cancer CPI - 444 Monotherapy Dose Selection 100 mg BID or 200 mg QD, 14 or 28 days Cohort Expansion 100 mg BID 28 days CPI - 444 with atezolizumab (anti - PD - L1) Dose Selection 50 mg BID or 100 mg BID + 840 mg atezo Q2W Cohort Expansion 100 mg BID 28 days + 840 mg atezo Q2W • Tumor types: RCC, NSCLC, Melanoma, TNBC, Others • Prior anti PD - (L)1 allowed • Resistant: SD or better > 3 months of treatment • Refractory: progression within 3 months • Must have progressive disease on prior therapy • No selection for PD - L1 expression Eligibility 6 6 4
CPI - 444 Blocks A2A Receptor Signaling 50mg BID 100mg BID 200mg QD pCREB cAMP A2AR Adenosine CPI - 444 CD4+ T cell Ph I CPI - 444 Trial 0 5000 10000 15000 0 50 100 150 CPI-444 (ng/mL) A 2 A R P a t h w a y A c t i v i t y ( % R e l a t i v e t o B a s e l i n e ) Analysis of pCREB by flow cytometr y Adenosine (NECA) stimulation ex vivo 7 7 CPI - 444 Plasma CPI - 444 (ng/ml) 5
Patient Characteristics Non - Small Cell Lung Cancer (N=45) Renal Cell Cancer (N=30) Prior anti - PD - (L)1 exposure Naïve Resistant/Refractory 8 (18%) 37 (82%) 8 (27%) 22 (73%) PD - L1 Negative* 54% 95% Median time since IO agent , months (range) 2.8 (0.6 – 24) 1.7 (1 – 71) Histology 28 (62%) Non squamous 17 (38%) Squamous 28 (93%) Clear cell 2 (7%) Papillary Median age, years (range) No. of patients single agent / No. of patients combination Median number prior therapies 70 (41 - 85) 22/23 2 (1 - 5) 65 (44 - 76) 14/16 3 (1 - 5) *Archive samples d ata available on 19 RCC and 28 NSCLC patients based on FDA - approved test 8 8 6
Treatment - Related Adverse Events Grade > 3 AEs: • Single a gent: none • Combination CPI - 444 + atezolizumab • One patient with Gr 3 immune related hepatitis, pneumonitis, mucositis and dermatitis Adverse Events (Gr1/2) > 5% Frequency (n=75) Single Agent (%) Combination (%) Fatigue 11 15 Nausea 6 8 Pruritus 8 5 Constipation 6 --- Dizziness 6 --- Hypertension 6 --- Pyrexia 6 --- Rash --- 5 AST increased --- 5 ALT increased --- 5 9 9 7
Phase 1/1b Trial with CPI - 444: Disease Control in NSCLC Partial responses can be seen in anti - PD - 1 progressors 10 (%) Change from Baseline Patients CPI - 444 Combination (CPI - 444+atezolizumab) Disease Control Duration Treatment (Months) Resistant/refractory to prior IO Naïve to prior IO PD - L1 Positive / Negative - + - + - - + - - - + + + - + - + + - 8
Phase 1/1b Trial with CPI - 444: Disease Control in Renal Cell Cancer Partial responses can be seen in an anti - PD - 1 progressing and naïve patients Resistant/refractory to prior IO Naïve to prior IO Treatment (Months) - - - - - - - - - - - - - - PD - L1 Positive / Negative + - CPI - 444 Combination (CPI - 444+atezolizumab) (%) Change from Baseline Patients Disease Control Duration 9
Tumor Growth Kinetics in “ Stable ” RCC Patients Days 12 12 -100 100 200 300 -80 -60 -40 -20 20 101001 SLD R e l a t i v e T a r g e t L e s i o n ( s ) S i z e Days -400 -200 200 400 -30 -20 -10 10 20 103101 SLD R e l a t i v e T a r g e t L e s i o n ( s ) S i z e Days -600 -400 -200 200 -30 -20 -10 10 20 100410 SLD R e l a t i v e T a r g e t L e s i o n ( s ) S i z e Days -100 100 200 -30 -20 -10 10 20 103210 SLD R e l a t i v e T a r g e t L e s i o n ( s ) S i z e Days -100 100 200 300 400 -30 -20 -10 10 20 101501 SLD R e l a t i v e T a r g e t L e s i o n ( s ) S i z e Days CPI - 444 Single Agent CPI - 444 in Combination with Atezolizumab Anti - PD - 1 Naïve Nivolumab Refractory Pembrolizumab Resistant Nivolumab Refractory Anti - PD - 1 Naïve Anti - PD - 1 Naïve Prior to CPI - 444 On CPI - 444 Percent Change in Target Lesion(s) -150 -100 -50 50 100 150 -40 -20 20 10
Tumor Regression in Nivolumab Refractory Renal Cancer Single Agent CPI - 444 Pre - treatment 3 months of treatment Five prior regimens including TKIs, mTOR inhibitor, and nivolumab Pre - treatment Post Dose (8w) 14% >70% H&E CD8 IHC Ph I CPI - 444 Trial 13 13 11
CPI - 444 Induces CD8 T Cell Infiltration and Th1 Gene Expression in Tumor Tissues 14 14 Log Fold Change Gene Expression Post vs pre biopsies (N=14) Immune Gene Expression (paired biopsies) CD8 T Cell Change (IHC) NSCLC RCC Median 95% CI Pre - dose NSCLC Post - dose RCC Post - dose Pre - dose C D 8 0.1 1 10 C D 8 R a t i o ( P o s t / P r e b i o p s y ) SD PR -2 -1 0 1 2 1 2 3 4 5 Log Fold Change Gene Expression - l o g P v a l u e CXCL10 GZMB PD-L1 OPG CXCL11 CXCL16 GZMA CCL17 TEFF_SIG PD-L2 ICAM1 NFATC4 IL2RA EOTAXIN CCL13 CD44 IL7R CXCL9 CD8A 12
CPI - 444 Expands New T Cell Clones in Blood and Tumor Treatment induces expansion of identical T cell clones in blood and tumor Post treatment Pre - treatment Blood Tumor Biopsy 0.01 0.1 1 10 0.01 0.1 1 10 Screen Biopsy P o s t d o s e B i o p s y 15 15 • RCC patient with PR on single - agent CPI - 444 • T cell receptor (TCR) sequencing of blood and tumor biopsies pre - and post - treatment • T cell clonotypes can be matched between blood and tumor Pre - treatment Post treatment 13
Phase 1/1b Trial with CPI - 444: Summary • CPI - 444 is well - tolerated as a monotherapy and in combination with atezolizumab • CPI - 444 has clinical activity alone and in combination with atezolizumab • Anti - tumor activity seen in: – Patients who have progressed on prior anti - PD - (L)1 – Patients with PD - L1 negative tumors • CPI - 444 can induce CD 8 T cell infiltration and expression of T cell activation genes within the tumor microenvironment • CPI - 444 induces new T cell clonotypes in the blood, which are capable of migrating to tumors • Accrual of patients into the expansion cohorts for NSCLC and RCC is ongoing 16 16 14
Acknowledgements • The patients and their families • Participating Centers: British Columbia Cancer Agency, Carolina BioOncology Institute, Cleveland Clinic, Columbia University Medical Center, Cross Cancer Institute, Emory University, Georgetown University, Indiana University, Johns Hopkins University, Juravinski Cancer Centre, Karmanos Cancer Center, Mary Crowley Cancer Research Centers, Massachusetts General Hospital, Medical College of Wisconsin, Memorial Sloan Kettering Cancer Center, Monash Health, Mount Sinai School of Medicine, Ohio State University, Ottawa Hospital Cancer Centre, Peter McCallum Cancer Center, Royal Brisbane and Women’s Hospital, Rush University, Stanford University, University of California at Los Angeles Medical Center, University of California at San Francisco Medical Center, University of Arizona Medical Center, University of Chicago Medical Center, University of Colorado Cancer Center, University of Nebraska, University of Pittsburgh, University of Washington, UT Southwestern, Washington University at Saint Louis, Yale University • C olleagues at Corvus • Colleagues at Roche Genentech Ph I CPI - 444 Trial 17 15