Item 8.01 Other Events.
On July 7, 2020, Corvus Pharmaceuticals, Inc.
(“Corvus” or the “Company”) announced that it has initiated a Phase 1 study to investigate a novel
immunotherapy approach for patients with COVID-19. The first cohort of five patients enrolled in the study was treated at
Temple University Hospital in Philadelphia, PA. The study is expected to enroll up to 30 patients at several sites in the
United States. This follows the U.S. Food and Drug Administration’s (FDA) review and acceptance of the Company’s
investigational new drug (IND) application for the COVID-19 study.
Corvus is studying an agonistic humanized monoclonal antibody, designated
as CPI-006, which has demonstrated a potential new approach to immunotherapy of infectious diseases. In both in vitro and
in vivo studies in cancer patients, CPI-006 has demonstrated binding to various immune cells and the inducement of a humoral
adaptive immune response – B cell activation and lymphocyte trafficking leading to the production of antigen-specific immunoglobulin
(IgM and IgG) antibodies. Administration of CPI-006 has also led to increased levels of memory B cells, which are the cells responsible
for long-term immunity. The similar production of antibodies and memory cells to pathogens such as severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, could provide immediate and long-term clinical benefits for patients,
including shortened recovery time and improved long-term protective immunity. To the Company’s knowledge, Corvus is the only
company exploring the potential to induce antibody production via B cell activation for the treatment of COVID-19.
To date, over 90 cancer patients have been treated with CPI-006 in
the Corvus Phase 1/1b study, with dosing as high as 24 mg/kg every three weeks. CPI-006 has been well tolerated in these
patients and evidence of B cell activation and lymphocyte trafficking was observed in patients that received doses as low as 1
mg/kg. Corvus’ study showed that CPI-006 is associated with increases in memory B cells, the emergence of new B cell clones
and, in some patients, the production of novel anti-tumor antibodies. These results have been previously reported in a presentation
at the Society of Immunotherapy of Cancer annual meeting in 2018 and 2019 and in a presentation at the American Society of Clinical
Oncology annual meeting in 2019. CPI-006 was designed to bind to an epitope on an antigen known as CD73. This antigen is known
to be involved in lymphocyte migration and activation. CPI-006 binds to a distinct region of on CD73 and behaves as an agonist
that serves as a signal to activate certain immune cells. As previously reported, binding of CPI-006 affects B cells, T cells and
antigen presenting cells. The collection of observed changes are consistent with enhanced antigen recognition and induction of
an adaptive immune response. These results are also supported further by the data set forth below from Corvus’ preclinical
and Phase 1/1b clinical trial of CPI-006.
The graph below shows results from an in vitro study designed
to compare CPI-006 to an anti-CD73 antibody in clinical development by a third party that reacts with a different epitope or region
on CD73. Using human blood lymphocytes treated in vitro, there was an increase in expression of CD69, a known marker of
B cell activation, that occurred following incubation with CPI-006 as compared to incubation with another anti-CD73 antibody, that
does not activate B cells. CD69 is the signal for B cells to traffic to lymph nodes. The middle and right panels show that CPI-006
induced markers of B cell differentiation into plasma cells (CD27, CD38 and CD138) and secretion of IgM and IgG.
In the Company’s Phase 1/1b clinical trial of CPI-006, Corvus
measured the levels of B cells at three points in time: pre-treatment, 30 minutes post treatment, and 21 days post treatment. The
plots below provide an example from a patient treated with a single dose of CPI-006. Using flow cytometry to quantitate memory
B cells, there was a reduction in total B cells at 30 minutes (middle plot), but at day 21, memory B cells represented 29% of the
total B cells, compared to approximately 10% prior to the administration of CPI-006.
The graph below plots the fold-increase of memory B cells, 30 minutes
after treatment and 21 days after treatment compared to baseline in several patients receiving 6 mg/kg or more of CPI-006. Each
dot represents a patient.
A recently enrolled patient with advanced metastatic non-small cell
lung cancer (NSCLC) was diagnosed with concomitant COVID-19 at the time of initiating CPI-006 therapy for cancer. The patient was
in a very high risk group for potential progression of COVID-19, including elderly, prior immunosuppressive therapies for cancer
and chronic obstructive pulmonary disease as comorbidities. The patient remained asymptomatic from COVID-19 following treatment
with CPI-006. Serum antibody testing demonstrated no anti-SARS-CoV-2 antibody at baseline and the development of high titers of
anti-SARS-CoV-2 IgG and IgM of >1:100,000 and 1:3,200, respectively, within six weeks of treatment with CPI-006. The patient
then tested negative for the virus. The anti-SARS-CoV-2 antibody titers seen in this patient would be considered to be high as
recovered patients with serum titers of 1:320 or higher are candidates to donate blood for COVID-19 convalescent plasma therapy.
Memory B cells in the blood increased to 30% of total B cells, from 16% previously.
About the Phase 1 Study
The open-label, Phase 1 study is expected to enroll up to 30 COVID-19
patients with mild to moderate symptoms. Patients will receive a single dose of CPI-006, with levels of 0.3, 1.0, 3.0 and 5.0 mg/kg,
escalating in four cohorts as the study progresses. Patients will receive medications, therapies, and interventions per standard
treatment protocols for COVID-19 for the duration of the study. The primary efficacy endpoint is the change in serum immunoglobulin
(IgM and IgG) anti-SARS-CoV-2 levels compared to baseline at day 28. The study will also examine safety and other clinical endpoints,
including time to resolution of symptoms and duration of hospitalization. Data from this study should be available later this year.
The objective of the study is to show that CPI-006 has the potential
to induce the patient to produce an enhanced antibody response to SARS-CoV-2. The expected benefit for patients is the potential
eradication of the virus, leading to a better clinical outcome – less severe disease, prevention of complications, and faster
recovery – and the potential for long term immunity. If the study meets its objectives, Corvus intends to work with the FDA
to initiate a broader, randomized study at a fixed dose of CPI-006 that could potentially be adapted into a pivotal study to support
a regulatory submission for FDA approval.
About CPI-006
CPI-006 is a potent humanized monoclonal antibody that reacts with
a specific site on CD73. It has demonstrated immunomodulatory activity resulting in activation of lymphocytes, induction of antibody
production from B cells and effects on lymphocyte trafficking. Other anti-CD73 antibodies are in development for treatment of cancer.
Those antibodies react with a different region of CD73 and are designed to block production of adenosine, which is not involved
in the immunomodulatory processes seen with CPI-006.
Forward-Looking Statements
To the extent that statements contained herein
are not descriptions of historical facts regarding Corvus, they are forward-looking statements, including statements related to
the potential safety and efficacy of ciforadenant, CPI-006, and CPI-818, the Company’s ability to develop and advance product
candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1 clinical
trial of CPI-006 for COVID-19, and the impact of COVID-19 and related “shelter in place” orders and other public health
guidance measures on the Company’s clinical programs and business operations. 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 quarter ended March 31, 2020, filed with
the Securities and Exchange Commission on April 30, 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 CPI-006; the accuracy of the Company’s estimates relating
to its ability to initiate and/or complete preclinical studies and clinical trials; 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; the Company’s ability to raise additional capital;
and the effects of COVID-19 on the Company’s clinical programs and business operations.