Greetings, and welcome to the Corvus Pharmaceuticals Update Call. At this time, all participants are in a listen only mode. A brief question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Mr.
Zach Kubo of Pure Communications. Thank you. You may begin.
Thank you, operator, and good morning, everyone. Thank you for joining us for the Corbus Pharmaceuticals conference call to discuss the initiation of a COVID-nineteen clinical trial. This call is also being webcast with presentation slides. We encourage participants to join the webcast in order to view the slides. You can find the link to join the webcast on the Investor Relations homepage of the Corvus website.
Joining me on the call from the company are Doctor. Richard Miller, Chief Executive Officer Blaise Flea, Chief Financial Officer Doctor. Mehrdad Mobasher, Chief Medical Officer and Doctor. Stephen Willingham, Director of Translational Biology, who leads our COVID-nineteen research program. The executive team will open the call with some prepared remarks followed by a question and answer period.
Turning to Slide 2, I would like to remind everyone that comments made by management today and answers to questions will include forward looking statements. Forward looking statements are based on estimates and assumptions as of today and are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied by those statements, including the risks and uncertainties described in Corvus' most recent quarterly report on Form 10 Q and other filings the company makes with the SEC from time to time. The company undertakes no obligation to publicly update or revise any forward looking statements except as required by law. With that, I'd like to turn the call over to Richard Miller. Richard?
Thank you, Zach, and good morning, everyone. Thank you for joining us today to discuss the exciting news that we have initiated a clinical study of a novel immuno therapy for COVID-nineteen. The unique biologic features of CPI-six, our B cell activating monoclonal antibody, give it the potential to be an important treatment option for COVID-nineteen patients. Specifically, we believe it could increase production of antibodies against SARS CoV-two reducing the severity and duration of COVID-nineteen disease along with improving long term immunity. The antigen specific activation of B cells may provide a foundational immunotherapy approach that could lead to treatments or preventions for future outbreaks, including SARS CoV-two mutant variants, other coronaviruses and future pandemics.
We are proud to join others in the biopharma industry working to develop the testing, treatments and vaccines needed to address this dreadful pandemic. Our unique treatment approach has evolved over the last few years derived from our laboratory and clinical work in oncology. Much of the data supporting this work has been presented at major oncology meetings, including the Society For the Immunotherapy of Cancer, SITC, in 2018 and again in 2019 and at the American Society of Clinical Oncology, ASCO, in 2019. The agenda for today's call is shown on Slide 3. We will begin with a brief overview of Corbus for those that may be new to the story, followed by an in-depth discussion on CPI-six for COVID-nineteen.
This includes an overview of CPI-six, its mechanism of B cell activation and the preclinical and clinical evidence that provides the rationale for initiating the study, including a patient case study. We will also cover the study design and anticipated timeline and our thoughts on the long term potential for CPI-six and COVID-nineteen and other infectious diseases. We will close with a summary of the key takeaways from the call and following the prepared remarks, Laith, Mehrdad and Stephen will join me for a Q and A session. Let me start with the company overview on Slide 4. Corvus is a clinical stage biopharmaceutical company with 4 programs in human trials.
This includes the COVID-nineteen study that we announced today along with our core clinical programs in oncology. Our lead program, cifiradimant, blocks the adenosine pathway and CPI-six is an immunomodulatory antibody. Both of these agents are being evaluated in multiple cancer indications. Most recently, we presented updated clinical data at ASCO from our Phase 1btwo clinical trial of ciforadenant in patients with advanced refractory renal cell carcinoma. In addition to confirming the benefit of blocking the Adenosine 2A receptor, the new data supports and refines our predictive biomarker to identify patients most likely to respond to treatment with cifuradenant.
Based on this data, we are planning to initiate a biomarker driven pivotal trial in renal cell cancer. In addition, we plan to provide data updates on CPI-six in cancer and CPI-eight eighteen, our ITK inhibitor for T cell lymphomas and oncology meetings later this year. Corvus was started in 2015 by a group of successful industry veterans that played major roles in the discovery and development of both rituxan and IMBRUVICA, both major breakthroughs in the treatment of B cell lymphomas and autoimmune diseases. There is a common thread between these medicines and CPI-six. They are all focused on B cell biology.
Let's review some of the biology behind CPI-six. As shown on Slide 5, CPI-six is a humanized monoclonal antibody that reacts with a specific site or epitope on CD73, which is a combination of B cells and T cells. Resta and Thompson showed in 1997 that CD73 was involved in lymphocyte activation. Finding of CPI-six to naive B cells, cells that have not encountered antigen sends a signal through the cell to become activated. Activated B cells express markers that cause them to traffic to lymph nodes where they become exposed to antigen and differentiate into plasmablasts and then plasma cells.
Plasma cells are little antibody factories that pump out large quantities of specific antibodies to the antigen. One of the hallmarks of the immune system is memory. Once we have been exposed to an antigen, the next time we encounter it, we can respond faster and more briskly, limiting disease severity. This is immunity. The cells responsible for this are called memory B cells and they are induced by CPI-six.
Memory B cells are long lived. In some cases, they can persist for years. After encountering antigen, they expand and circulate throughout the body, acting as our immune surveillance system, protecting us from future reinfection and disease. As shown in the slide, the strategy behind CPI-six immunotherapy is that the antigen is the virus SARS CoV-two. The antigen is already present in the infected patient.
So we can think of this approach as therapeutic vaccination. On slide 6, we have focused on the key points. CPI-six is intended to boost antibody response to the viral antigens and enhance the generation of anti SARS CoV-two memory B cells. We believe this will result in improved clinical outcomes with increased antibody levels or titers, accelerating viral clearance, shortening recovery times and reducing the window during which a patient is contagious. Increased production of long lived memory B cells could provide long lasting immunity.
It is also possible that enhanced immune response will provide patients with increased cross protection against mutants of SARS CoV-two and other coronaviruses. Based on this mechanism of action and these potential benefits, we believe CPI-six has the potential to be a foundational therapy for treatment or prevention of COVID-nineteen and other infectious diseases. We are not aware of any other agent, antibody or small molecule targeting CD73 that has exhibited these properties. Other anti CD73 antibodies react with a different region of CD73 and are designed to block production of the CD73 protein. Adenosine plays no role in the immunomodulatory effects seen with CPI-six described here.
As far as we know, Corbus is the only company exploring the potential to induce antibody production via B cell activation for the treatment of COVID-nineteen. Approximately 90 patients have been safely treated with repeated doses of CPI-six to date in the company's Phase 1, 1b study in oncology. At ASCO 2019, Doctor. Jason Luke from the University of Pittsburgh made an oral presentation that included data demonstrating that infusions of CPI-six resulted in rapid activation and migration of B cells. And we have seen evidence of antitumor antibodies produced in some of our cancer patients treated with CPI-six.
The data on the next two slides, 78, comes directly from presentations we have made at medical meetings over the past 2 years. Slide 7 shows results from an in vitro study designed to compare CPI-six to another anti CD73 antibody that reacts with a different epitope or region on CD73. On the top left, using human blood lymphocytes treated in vitro, you can see an increase in expression B cell activation that occurs with incubation with CPI-six compared to incubation with an anti CD73 antibody from another company that is also in cancer trials that does not activate B cells. CD69 is the signal for B cells to traffic to lymph nodes. The remaining data on the slide shows that in vitro the cells begin to differentiate or transform into plasma blasts.
They begin to express markers of plasma cells such as CD27 and they begin to secrete IgM and IgG. On the bottom slide you can appreciate what this looks like under the microscope. Normal resting B cells transform into antibody producing plasma glass and plasma cells. You don't need to be a hematologist to appreciate these morphologic changes. And this happens in vivo in patients.
We've been able to study these phenomena in our cancer patients receiving CPI-six. Slide 8 highlights results from patients treated after a single dose of CPI-six in our Phase 1 oncology study. We measured the levels of total and memory B cells at 3 points in time, pre treatment, 30 minutes post treatment and 21 days post treatment. Here's an example in one patient using flow cytometry to quantitate memory B cells. In the middle plot you can see that after 30 minutes there is a reduction in total B cells.
They are trafficking to lymphoid tissues. But at day 21 B cells return to the circulation and the memory B cells now represent 29% of the total compared to around 10% previously, a threefold increase. For the experts on this call, memory cells are identified based on the lack of expression of IgD and positive expression of CD27. They are IgD negative, CD27 positive. On the right hand side of the slide, we have plotted this comparison of memory B cells 30 minutes after treatment and 21 days after treatment with CPI-six compared to baseline described by full change.
In several patients receiving 6 milligrams per kilogram or more, there is a significant increase in the number of memory B cells. The findings are very reproducible and robust. These data are consistent with the production of a humeral adaptive immune response. What this means is an antibody response to a new foreign antigen introduced into the body. The data I just reviewed demonstrating the activation, differentiation of B cells into antibody secreting plasma cells and generation of memory B cells by CPI-six came from preclinical in vitro and in vivo clinical research related to our oncology study.
In a cancer patient, we are seeking to generate anti tumor antibodies. In a COVID-nineteen patient, we would be looking for antibodies to the SARS CoV-two virus. Now I would like to describe our findings of SARS CoV-two antibody response and memory B cell production in a patient in our oncology study with concomitant COVID-nineteen. Although anecdotal, this patient provides us with very valuable information. Slide 9 is an overview of this patient case study.
This is new data that we have not shared before. In April, one of our New York sites enrolled a 68 year old African American female with advanced metastatic non small cell lung cancer in our CPI-six cancer study. The patient was diagnosed with concomitant COVID-nineteen infection on routine screening at the time of initiating CPI-six therapy for cancer. The patient was in a very high risk group for progression of COVID-nineteen due to her age, race and comorbidities such as chronic obstructive pulmonary disease, cancer and extensive prior treatment with chemotherapies. In the top table, you can see that serum antibody testing demonstrated no anti SARS CoV-two antibody at baseline and the development of high titers of anti SARS CoV-two IgG and IgM of greater than 1 to 100000 and greater than 1 to 3,200 respectively at 6 weeks.
For context, recovered patients with serum titers of 1 to 3 20 or higher are candidates to donate blood for COVID-nineteen convalescent plasma therapy. Titers of antibody binding to RBD, receptor binding domain of the virus were also very high. The patient remained asymptomatic from COVID-nineteen following treatment with CPI-six and our initial positive PCR test converted to a negative test at 6 weeks. We also measured her memory B cells. At the bottom, you can see that memory B cells in the blood increased to 30% of total B cells from 16% previously, similar to the findings we shared on prior slides.
The level of antibodies produced by this patient are very high, especially given her poor prognostic features. These titers of antibody are in the range sometimes seen with younger, more favorable COVID-nineteen patients that do not have the same adverse risk factors. On slide 10, we have included 2 charts that compare the IgG and IgM levels of the CPI-six treated patient with the levels from 10 patients that recovered from COVID-nineteen. These patients were younger and had no comorbidities. And you can see on the slide the IgG and IgM levels in the CPI-six patient were high compared to this much more favorable group of recovered COVID-nineteen patients.
Now let's look at our Phase 1 study design on Slide 11. The study will examine the safety and immunobiologic and have satisfactory blood oxygen saturation on room air or low flow oxygen. The objective of this study is to show that CPI-six improves anti SARS CoV-two antibody response. CPI-six will be administered intravenously over 10 to 15 minutes. At the highest doses, this will be a volume of about 30 to 40 cc's.
In the future, we believe we can modify the formulation to be delivered by the more convenient subcutaneous route. The dose escalation study is expected to enroll up to 30 patients in 4 cohorts receiving a dose of 0.3, 1.03.0 or 5.0 milligrams per kilogram. Patients will receive standard care for COVID-nineteen for the duration of the study. The primary efficacy endpoint is the change in serum immunoglobulin, IgM and IgG anti SARS CoV-two titers at day 28 compared to baseline. We will follow antibody levels for 6 months to assess effects on long term immunity.
The study will also examine safety and other clinical endpoints, including time to resolution of symptoms, clearance of virus by PCR testing and duration of hospitalization. The first cohort of 5 patients enrolled in the study was treated at Temple University Hospital in Philadelphia. Temple has been caring for large numbers of COVID-nineteen patients. Other sites participating in the study at this time include Mount Sinai in New York. Several other leading centers are in various stages of obtaining protocol approvals and will participate in the trial.
Since the primary study endpoint is antibody response, we expect to have meaningful data in 3 to 6 months. On slide 12, we have outlined the initial and potential future role of CPI-six in COVID-nineteen. In the future, if successful, we see this immunotherapy playing a role in later stage patients or in early stage patients in the outpatient setting and perhaps even as a vaccine adjuvant in disease prevention for use in the elderly or high risk individuals. Of course at this time we do not know the effectiveness of vaccines that are under development, but historically vaccination of the elderly and sick has been challenging. To summarize, as outlined in Slide 13, I want to emphasize several key points from our announcement today.
We believe CPI-six has the potential to be a novel immunotherapy for the treatment of COVID-nineteen. The mechanism of action is unlike any other therapies being studied for COVID-nineteen that we are aware of, stimulating the body's adaptive immune response to increased levels of anti SARS CoV-two antibodies and memory B cells. This could benefit patients by reducing the severity and duration of their infection and potentially enhancing their long term immunity to repeat infection. If successful, we believe CPI-six will be an important option for a range of COVID-nineteen patients beyond the initial study group with mild to moderate symptoms. Our clinical trial may provide proof of concept for use in future outbreaks of the current or related strains of coronaviruses or other viruses.
We are working diligently with our clinical trial sites to quickly enroll the study and collect 28 day follow-up data on antibody titers for patients. If the study meets its objectives, Corbus intends to work with the FDA to conduct a double blind placebo controlled randomized pivotal study to support a regulatory submission for FDA approval. Our plans include evaluating CPI-six in both the outpatient and inpatient setting. Outpatient treatments are of great interest as this group of patients is becoming an increasing part of the COVID-nineteen pandemic. In closing, in addition to the COVID-nineteen program discussed here, we are continuing to execute on our other clinical studies and anticipate presenting updated data from our cancer programs in the Q4 of this year.
Before I turn it over for Q and A, I'd like to, in particular, thank our employees who have exhibited extraordinary effort during this very trying time to get an IND protocol and clinical sites up and running, assays in place very expeditiously, almost flawlessly. Thank you to every one of our employees who I think sense the unprecedented medical need caused by this terrible pandemic. With that, we will now open the call for questions. Operator?
Thank you. We will now be conducting a question and answer Our first question comes from the line of Mara Goldstein with Mizuho. Please proceed with your question.
Yes. Can you hear me okay?
Okay. It seems that she's having some technical difficulties. Our next question comes from the line of Biren Amin with Jefferies. Please proceed with your question.
Yes. Hi, guys. Thanks for taking my questions and thanks for the update. Richard, if I could just start with the patient with non small cell lung cancer that received CPI-six and that showed an antibody response and was basically had increased levels of titers. What dose was given of CPI-six in that patient and how many doses were given?
That patient received a single dose of 18 milligrams per kilogram. In our data that we've presented at other meetings, we see changes in B cell trafficking and activation with as low as 1 milligram per we see very reproducible B cell activation and associated biology. So that's why the doses that we're examining in this Phase 1 trial go from 0.3 up to 5. We think that covers a range that's going to be sufficient to cause activation of B cells.
Which was
going to be my second question. Why evaluate 0.3 given 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 therapeutic range like a 1 or 3 milligram as your dose level 1?
Okay. So COVID-nineteen patients have very unique pathophysiology. As you're aware, they have coagulopathy, they have a lot of inflammation, and we thought it was prudent to start with a lower dose in that kind of patient population. Remember, this is a new disease, never we've never faced this before. So that's the first point.
The second point is, B cells are circulating in your blood and even though 0.3 milligrams per kilogram sounds like a low dose, that's enough antibody to actually react with B cells that are in the blood. Now higher dose will probably be better, but it is possible that you'll see something at a dose like that. So we're just trying to cover the range of dosing, beer in a disease that nobody's ever seen before.
Got it. Great. Well, thanks for taking my questions.
Thank you. Our next question comes from the line of Swayampakula Ramakanth with H. C. Wainwright. Please proceed with your question.
Thank you. Thank you, Richard, for the presentation. And certainly, it looks like you have some convincing anecdotal data based on that single patient. My question is a little bit more general. Obviously, 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 markets to date? And has there been any data regarding what sort of responses that they have received with such treatments?
Well, RK, I'm a little confused by your question. To my knowledge, there is no other antibody that exhibits these properties that activates these cells. Now, my personal experience and my team, we've been involved in drugs like Ibrutinib and rituxan that do the opposite. They take B cells away. This is a drug that activates B cells.
And I don't think this has ever been done before. But one of the interesting things, and you bring up MIRRORS and SARS CoV-one, 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
Thank you.
Thank you. Our next question comes from the line of Mara Goldstein with Mizuho. Please proceed with your question.
Great. Let's try this again. Can you hear me?
Yes.
Great. Thanks. Just a question on your patient 1. And can you correlate the COVID recovery with the antibody titers? Have you looked at that experience and can you talk to us about that?
And then secondarily, are you able to or would you at this point look to modify any of the current CPI-six trials for subset of patients with co infection of COVID or as a prevention for COVID infection?
All right. First of all, your first question, so the patient had a positive PCR test on nasal swab at the initiation of the 6. It was just done on a routine clinic visit for her cancer treatment. 6 weeks later, she had those enormous titers of 1 to over 100000 in IGG and 1 to over 3,200 IgM. In fact, the hospital that she was treated out, which is Mount Sinai, it was off the charts and had to redo it.
At 6 weeks, her PCR test was negative. So her test became negative at the time that we saw that high titer antibody response. Obviously, it's one patient. You can't prove that they're associated. But we feel good about it because this patient is not expected to do well given her age and comorbidities and cancer, especially lung cancer patients do very badly with COVID-nineteen.
They have a 40% mortality from COVID-nineteen in a recent Lancet article presented and also presented at ASCO recently. And titers of 1,000 to 100,000, especially an IGM titer that was still persistent at 6 weeks is very, very unusual. That's very extraordinary. So that's the answer to that question. In terms of the CPI-six, first of all, in our cancer study, we're continuing with our dosing regimen and what we've been doing in that study.
Now for the COVID-nineteen, again, study to repeat, we're going to give a single injection because we think that's sufficient to activate B cells. Remember, one beautiful thing about the immune We can give you a tiny little bit of antigen and you can amount a robust antibody response. So it just needs to be triggered and then it amplifies itself. That's the beauty of the immune system. So we have our dosing regimen now.
We've gone through the 1st cohort. We'll be measuring the antibody levels at day 7, 14, 28, etcetera. And obviously, we'll increase the dose from there. Now in terms of comparing cancer and COVID-nineteen, there's one big difference. I mean, there's obviously a lot of difference in the disease.
They're completely different etiology. But cancer patients have antigens on their tumor, but they're very subtle, very subtle. You have to work hard to show that there's any unique antigens in a cancer. And you know there are many companies and many academic laboratories that have been working 100 years on that, very subtle. Cancer cells are mostly self.
SARS CoV-two is not self. It is an extremely foreign protein, very foreign. And so we feel that the single injection at the doses we're using will be enough to trigger a more robust immune response to the foreign virus. Mara, did that answer your questions? I may have forgotten the different components.
No, that's great. Thank you. I appreciate it.
Thank you. Our next question comes from the line of Robert Driscoll with Wedbush. Please proceed with your question.
Hi, thanks. Good morning, Richard. Thanks for taking the question. Just wondering how maybe you can thinking about controlling the timing of treatment for the patients that receive 6 in the Phase 1 and maybe in subsequent studies, just assuming that the earlier the patient receives the dose, the better?
Yes. The earlier the well, I'm not sure we know that, but the protocol is written so that they have to have a positive PCR within 7 days.
Okay, got it. Thanks.
Okay. Now of course, Robert, sometimes you have a patient who might have symptoms for a couple of weeks, right, before they go in and see the doctor. So we're going to learn about that stuff. But we require a recent PCR, cannot be more than 7 days.
Got it. Thanks. Very helpful. Thanks.
Thank you. There are no further questions at this time. I'd like to turn the call back over to management for any closing remarks.
All right. Well, thank you very much everyone for getting up so early on this morning to listen to our call. We're happy to follow-up and talk with you. And I think our my system will be scheduling some meetings. The slides I believe will be up on our website.
And we look forward to presenting more data about the COVID-nineteen study really within a few months. Thank you very much.
Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a wonderful day.