Corvus Pharmaceuticals Inc.’s success in treating a COVID-19 patient previously diagnosed with non-small-cell lung cancer (NSCLC) with CPI-006 helped boost shares (NASDAQ:CRVS) to $4.96, up $2.21, or 181%, as the Burlingame, Calif.-based company disclosed the start of a phase I study to investigate the anti-CD73 immunotherapy prospect.
The first cohort of five patients enrolled in the study was treated at Temple University Hospital in Philadelphia. Expected to enroll up to 30 patients at several sites in the U.S., the experiment with agonistic humanized monoclonal antibody CPI-006 follows in vitro and in vivo studies in cancer patients that showed binding to various immune cells. The compound induced a humoral adaptive immune response – B-cell activation and lymphocyte trafficking leading to the production of antigen-specific immunoglobulin (IgM and IgG) antibodies. CPI-006 has also led to increased levels of memory B cells, the company said.
Especially intriguing was news of a recently enrolled patient with advanced metastatic NSCLC who was diagnosed with concomitant COVID-19 and remained asymptomatic from the virus following treatment with CPI-006. CEO Richard Miller said the patient received a single dose of 18 mg/kg. “We see changes in B-cell trafficking and activation with as low as 1 mg/kg [dosed] a single time, and at 3 mg/kg, we see a very reproducible B-cell activation and associated biology. That's why the doses that we're examining in this phase I trial go from 0.3 up to 5,” he told investors during a conference call.
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 IgM and IgG anti-SARS-CoV-2 levels compared to baseline at day 28. The study also will examine safety and other clinical endpoints, including time to resolution of symptoms and duration of hospitalization. Data should be available later this year. 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 be adapted into a pivotal study to support a bid for FDA approval.
Meanwhile, company backers digested findings from the NSCLC patient. 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’s PCR viral test converted to negative along with the rising titers of antibody. Corvus noted that the anti-SARS-CoV-2 titers seen in this patient would be considered to be high, since 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 of this patient also increased to 30% of total B cells, from 16% previously. CPI-006 is undergoing work as a monotherapy and combination treatment in renal cell, prostate and other tumor types.
Jefferies analyst Biren Amin Biren wanted to know why the company started at 0.3 mg/kg in the COVID-19 effort, since “you already, I'm sure, have safety data that's available from healthy volunteers as well as from cancer patients, where you've tested higher doses? Why not go into a dose that would be a therapeutic range, like a 1 or 3 mg/kg as your dose level one?”
Miller noted that patients afflicted with COVID-19 “have very unique pathophysiology. They have coagulopathy, they have a lot of inflammation. We thought it was prudent to start with a lower dose in that kind of patient population. Remember, this is a new disease. We never faced this before. That's the first point. The second point is [that] B cells are circulating in your blood, and even though 0.3 mg/kg sounds like a low dose, that's enough antibody” to react with them. “Now, a higher dose will probably be better, but it is possible that you'll see something at a dose like that.”
H.C. Wainwright’s Swayampakula Ramakanth pointed out that “this is not the first coronavirus we have seen. There has been SARS, there's been MERS from previous times. Has anybody tried any of the B-cell treatments that we have out in the market to date? And has there been any data regarding what sort of responses that they had received with such treatments?”
Miller said that, “to my knowledge, there is no other antibody that exhibits these properties.” He and his team have been involved in work on such drugs as Imbruvica (ibrutinib, Johnson & Johnson/Pharmacyclics LLC) and Rituxan (rituximab, Roche Holding AG/Biogen Inc.) “that do the opposite, they take B cells away” rather than activating them, he said. “One of the interesting things – when you bring up MERS and SARS-CoV-1 – one of the nice things about eliciting an antibody response is that it's polyclonal, and therefore, any antigenic variation, variability from one virus to the next, could possibly be hit by the nature of the immune response,” he added. More than 90 patients have been treated with CPI-006 in the phase I/Ib cancer study, with dosing as high as 24 mg/kg every three weeks, and the drug has proved well-tolerated.
Corvus, which went public with a $70 million financing in March 2016, presented in late May at the American Society of Clinical Oncology’s virtual annual meeting data from the ongoing study evaluating another oncology candidate, ciforadenant. The drug is an oral small-molecule inhibitor of the adenosine A2A receptor, used as a monotherapy or in combination with Tecentriq (atezolizumab, Roche Holding AG) in patients with relapsed or refractory renal cell carcinoma. Among 50 evaluable patients for the biomarker adenosine gene signature, positive patients achieved a 17% (5/30) objective response rate by RECIST criteria compared to none in patients negative for the signature. The latest update “confirms ciforadenant’s antitumor activity” in patients with the biomarker, analyst Ramakanth wrote in a June 1 report.