Good afternoon, ladies and gentlemen. Thank you for standing by. Welcome to the Corvus Pharmaceuticals First Quarter 2019 Business Update and Financial Results Conference Call. Today's conference is being recorded. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Instructions will follow at that time. It is now my pleasure to turn the call over to Zack Kubow of Pure Communications. Please go ahead, sir.
Thank you, operator. Good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals First Quarter 2019 Business Update and Financial Results conference call. On the call to discuss the results and business highlights for the first quarter of 2019 are Richard Miller, Chief Executive Officer; Leiv Lea, Chief Financial Officer; Mehrdad Mobasher, Chief Medical Officer, who is traveling and phoning in remotely. The executive team will open the call with some prepared remarks, followed by a question and answer period. 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's quarterly report on Form 10-Q filed with the SEC today, 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 Leiv Lea. Leiv?
Thank you, Zack. I will start with a quick overview of our first quarter financials and then turn the call over to Richard for a business update. On March 31st, 2019, Corvus had cash equivalents, and marketable securities totaling $105.8 million, as compared to $114.6 million at December 31st, 2018. Research and development expenses in the first quarter of 2019 totaled $9.4 million, compared to $12.1 million for the same period in 2018. The decrease of $2.7 million is primarily due to a decrease in sifrolimab program costs. The net loss for the first quarter of 2019 was $11.6 million, compared to a net loss of $14.3 million for the same period in 2018. Total stock compensation expense for the first quarter 2019 was $2 million, compared to $1.8 million of total stock compensation expense for the same period in 2018.
I will now turn the call over to Richard.
Thank you, Leiv, and good afternoon, everyone. Thank you for joining us today for our first quarter 2019 business update. Since this is the first quarterly call that we have hosted since becoming a public company, I want to take a few moments to highlight the significant progress we have made since our IPO and the value we are building with our product pipeline. I will then provide an update on our development programs and anticipated key milestones for the remainder of 2019. At Corvus, we like to say that we are bringing ingenuity to cancer drug development, identifying product candidates with precise mechanisms of action and advancing them through extensive preclinical testing and rigorously conducted clinical trials.
Our highly experienced team is deeply committed to this mission. As a result, we have built a leadership position in the adenosine cancer pathway with our two lead programs that have generated meaningful clinical data. We have just entered the clinic with our third program that is distinct from the adenosine pathway, focused on ITK inhibition with a novel drug that affects T-cell biology. In total, we now have three unique agents with novel mechanisms of action in clinical trials for a wide range of solid and hematologic cancers, along with a pipeline of preclinical programs that we expect to move into IND-enabling studies over time. If you have been following Corvus, you know that we are committed to providing regular data updates from our studies, which have been consistently presented at major medical meetings such as AACR, ESMO, SITC, and ASCO.
We plan to continue to have a steady cadence of new data at major medical meetings over the remainder of the year. I will now provide a more detailed update on our three clinical programs, starting with our lead program, ciforadenant, which was previously known as CPI-444. Ciforadenant is an oral, small molecule drug that is an antagonist of the adenosine A2A receptor. There are several differentiating factors that we believe make ciforadenant the leading adenosine pathway product candidate in development today. Let me discuss a few of these. First, efficacy data. Ciforadenant has demonstrated antitumor activity as monotherapy and in combination with atezolizumab in patients that have failed a median of three prior therapies. Many, over 70%, failed anti-PD-1 therapies, with some patients experiencing durable responses and disease control out to over 28 months. We have several patients who have now been on ciforadenant for more than two years.
We have seen efficacy signals in our comprehensive phase I-B study in non-small cell lung cancer and in renal cell cancer. Of note, in our 68 patients with renal cell cancer, there is an overall survival exceeding 88% at 28 months. A median progression-free survival of 5.8 months. These results are solid compared to numerous other trials with other agents in advanced refractory renal cell cancer. Multiple recurrence renal cell cancer is an unmet need, as long-term disease control has been very difficult to achieve. Although we see better results with combination therapy, our monotherapy data is also strong. Monotherapy activity is crucial to understanding and developing cancer drugs, and this is why we have focused on that. At the recent AACR meeting, AstraZeneca presented phase I data for their oral adenosine A2A receptor inhibitor, showing signs of efficacy in prostate cancer patients, including a monotherapy partial response.
We are very pleased that their data confirms the activity of A2A receptor blockade. Of note, we also have seen activity in prostate cancer patients. As it relates to efficacy, unlike some other adenosine receptor antagonists in development, an attractive feature of ciforadenant is that it is able to cross the blood-brain barrier, which we believe has important implications for treatment of cancer patients. Many cancer patients present with or develop brain metastases during the course of their illness, and it is important that a cancer drug controls disease in that vital organ, since lack of tumor control in the brain results in devastating neurologic consequences. For example, the anti-PD-1s and targeted drugs like alectinib are successful partly because they control disease very well in the brain. Second, safety pharmacokinetic and pharmacodynamic data.
To date, over 250 patients have been treated with ciforadenant, with a strong safety profile without dose-limiting adverse events. No patients have discontinued therapy due to toxicity. Our PK/PD studies have shown excellent oral bioavailability and complete A2A receptor blockade. Third, through diligent collection of biopsies and genetic analysis, we have developed ciforadenant as a precision medicine based on the identification of a predictive genetic biomarker, the adenosine signature, that was discovered by our team. The adenosine signature may provide clinicians with the ability to select patients most likely to benefit from therapy. From a biologic perspective, activation of the adenosine signature genes appears to be related to resistance to anti-PD-1 therapies. This provides a compelling rationale to use ciforadenant in combination with anti-PD-1s, as we are now doing. Taken together, we believe that ciforadenant is positioned as the leading A2A receptor inhibitor.
We are currently evaluating ciforadenant in combination with atezolizumab in a phase I-B/II clinical trial in patients with renal cell cancer. The patients in the trial have failed treatments with anti-PD-1 antibodies and tyrosine kinase inhibitors. Our recent data presentation last fall at SITC reported durable objective tumor responses and prolonged survival in a large group of biomarker unselected patients, which is very encouraging given such advanced disease. The current ongoing trial is in earlier patients who have failed less than or equal to three prior therapies. We also have a phase I-B/II study evaluating ciforadenant in combination with atezolizumab in patients with non-small cell lung cancer who have failed no more than two prior regimens. The lung cancer study is ongoing and is being conducted by Genentech as part of its MORPHEUS platform, which was established to develop immunotherapy combination therapies more rapidly and efficiently.
Our second development program is CPI-006, which is a potent humanized monoclonal antibody directed against CD73. CPI-006 is a unique anti-CD73 antibody, as has been presented at recent meetings. We selected this antibody because it possessed dual mechanisms of action. It inhibits the catalytic function of CD73, blocking production of adenosine, and it induces the activation and trafficking of immune cells to peripheral lymphoid tissues. Largely overlooked by others, the CD73 protein is known to function in immune cell activation and migration. These properties are synergistic. Removing adenosine eliminates its immunosuppressive effects, and activating lymphocytes could enhance antitumor immunity. You will hear much more about this at ASCO. We are developing CPI-006 to treat advanced cancers and are currently evaluating it in a multi-center phase I-B dose escalation study as a single agent and in combination with ciforadenant and in combination with the anti-PD-1 antibody pembrolizumab.
The trial is designed to select a dose and evaluate the safety, pharmacokinetics, immune biomarkers, and efficacy in patients with renal cell cancer, lung cancer, and several other solid tumors who have failed standard therapies. We also believe that our adenosine signature will play an important role in the development of this agent. The phase I-B study will enroll up to 350 patients and is currently enrolling in the dose escalation portion of the study for CPI-006 administered as a monotherapy and in combination with ciforadenant. Initial data from the Phase I/I-B study will be delivered in an oral presentation at ASCO on June 2nd by Dr. Jason Luke, Director of Cancer Immunotherapeutics and Associate Professor of Medicine at the University of Pittsburgh Medical Center.
This will build upon data presented in February that demonstrated early signs of immunologic activity across multiple pathways that may be important in cancer therapy. In addition to the myriad of immunologic effects, we will also present early clinical data with monotherapy and combination with ciforadenant. In addition to the oral presentation at ASCO, we will also be hosting an investor and analyst reception on Sunday, June 2nd at 6:00 P.M. Central Time, during which Dr. Luke will provide an overview of his oral presentation on CPI-006. In addition, Dr. Mehrdad Mobasher and I will provide an update on our programs, and all three of us will be available for Q&A. If you would like to receive information on attending this event, please reach out to Leiv. Our third development program is CPI-818, which is an oral, small molecule drug that has been shown to selectively inhibit ITK.
ITK is an enzyme that is expressed in T-cells and plays a role in T-cell and natural killer cell lymphomas and leukemias, as well as in normal immune function. We believe CPI-818 has the potential to be directly cytotoxic to T-cell lymphomas and also may lead to enhancement of the immune system by increasing the Th1 immune response, which could provide a therapeutic benefit for lymphomas and for solid tumors. Some of our research also indicates that this drug may be an attractive drug candidate to examine in autoimmune diseases. We are particularly excited about this program because the development of CPI-818 was based on a similar targeting strategy to that of BTK inhibitors. Members of the scientific team at Corvus, including myself, led the development of the first BTK inhibitor, ibrutinib, which is approved for the treatment of several types of B-cell lymphomas.
ITK has many biochemical and functional similarities with BTK. We believe that inhibiting ITK with CPI-818 for T-cell lymphomas could have analogous effects to the inhibition of BTK with ibrutinib in B-cell lymphomas. CPI-818 has extraordinary specificity, a feature that has been lacking in previously described ITK inhibitors. We have previously reported evidence of efficacy in dogs with spontaneous, naturally occurring T-cell lymphomas treated with CPI-818. This gives us optimism for its potential in human T-cell lymphomas. As we announced in today's press release, we have initiated patient enrollment in a global phase I/I-B study of CPI-818 in patients with T-cell lymphomas, a patient group that often has limited treatment options and a very poor clinical outcome. Looking forward, we are planning to present data from all three of our programs at medical meetings over the course of the year. I've already highlighted our CPI-006 oral presentation at ASCO.
We expect to provide updated data for ciforadenant and CPI-006 at SITC, the first CPI-818 data at the American Society of Hematology meeting. For ciforadenant, we plan to initiate a late-stage study in patients with renal cell cancer late this year. This study will utilize our adenosine signature to select patients. We believe the use of this biomarker will further improve the efficacy results in patients with renal cell cancer treated with ciforadenant. These are important catalysts for the company. We look forward to providing updates on our progress at these medical meetings and in future business update calls. I will now turn the call over to the operator for the question-and-answer session. Operator?
Thank you. If you would like to ask a question, please signal by pressing star one on your telephone keypad. Also, if you are using a speakerphone, please make sure your mute function is turned off to allow your signal to reach our equipment. Again, press star one to ask a question. We'll pause for just a moment to allow everyone an opportunity to signal for questions.
Okay.
We'll go first to Biren Amin with Jefferies.
Hi. Thanks for taking my questions, Richard. I can start with CPI-444. When can we expect next data from the RCC and non-small cell lung cohort? I guess, when do you expect to reach a time point where you can make a decision on how to proceed forward into more advanced studies?
We expect that we'll have a next update on renal cell cancer data with CPI-444, now known as ciforadenant, at the SITC meeting, which is in November. In terms of the lung cancer study with ciforadenant and atezolizumab, that study is part of the MORPHEUS program being conducted by Genentech, enrolling very nicely, actually. That's our control study that has a concomitant group of patients treated with chemotherapy TAXOTERE. I'm not sure exactly when we'll be in a position to report on that data since it's being run by Genentech, but I know we're getting a cut of the data in just a couple of months. Your next question on the subsequent studies with ciforadenant in renal. We're working right now, in fact, we have KOL meetings set up at ASCO for a very interesting trial in renal cell cancer that would start later this year. Dr.
Mobasher is working on that very hard, which will use our adenosine signature to select patients for enrollment in that study. That'll be a phase II study with opportunity to convert that into even a randomized or phase III study. That study design, very briefly, is going to be patients who failed PD-1s and TKIs. Again, because we think our adenosine signature identifies patients as we presented at recent meetings. We think it identifies patients who are likely to respond to our drug, ciforadenant. Moreover, it seems to identify patients who fail to respond to PD-1s. It's, in a sense, the perfect biomarker because it's selecting those patients who don't respond to PD-1s, presumably because they have adenosine production as a resistance mechanism, and therefore combining the PD-1 and the ciforadenant makes very good sense. I hope that answers your question. That's sort of our plans on that.
Maybe just a follow-up on the renal cell study that you're planning in patients that fail PD-1/TKI. Our recent conversations with some KOLs in the area suggest that first line seems to be PD-1/ipilimumab. Would you potentially also evaluate in that cohort of patients as well?
Possibility. As you're aware, two recent papers looked at anti-PD-1 or anti-PD-L1 combinations with axitinib. Those results were very good. They were published in the "New England Journal of Medicine" and presented at the GU meetings in San Francisco. We believe that PD-1 axitinib is probably going to move to frontline very soon. I know many physicians are still using ipilimumab/nivolumab, but there are going to be a lot of patients getting pembrolizumab and axitinib. Those results are very good. While we're on the subject of those results, although the response rates are very good, 50%, 60%, mostly partial responses, if you look at the progression-free survival curves in those studies, everybody's relapsing. The PFS curves have a continuous downward trajectory. As we predicted two years ago, the field is moving in our direction.
We predicted that PD-1s would move to frontline along with TKIs, that the perfect role for our therapies would be in those relapsed patients. We think that's playing out nicely. There'll be plenty of patients with pembro axitinib or avelumab axitinib, the Pfizer drug. There'll be plenty of those patients who relapse and are in need of subsequent lines of therapy.
Got it. Given the recent AstraZeneca data with their A2AR in prostate cancer where they saw several responses and given also your data set as well in that tumor type, are there any plans to move forward in metastatic CRPC patients that may have failed on AR therapy?
There's a lot of plans for that. Again, first of all, congratulations to AstraZeneca for doing a good study where they looked at monotherapy, you can really understand what's going on. We know those folks well, they do very good clinical research. I think three or four of their prostate cancer patients were a combination with, of course, their anti-PD-L1, and one was a monotherapy. I think they had another patient who had a drop in PSA with monotherapy. Prostate seems to be, at least based on early results, a good target for this kind of therapy. Come to our ASCO presentation, you'll hear more about prostate cancer there. Yes, we definitely have plans to look at prostate with ciforadenant and with adenosine blockade in general.
I think with AstraZeneca's work, our work and AstraZeneca work now really validates A2A receptor as a really good target.
Great. Thanks for taking my question.
As a reminder, if you'd like to ask a question, please press star one at this time. We'll take our next question from Michael Morabito with Credit Suisse.
Hi, Richard. Thanks for taking my questions. I was just looking to see if you could give us a little bit of a reminder on CPI-818 of roughly how many patients you plan to enroll per arm. If you can update how many patients have enrolled so far, how enrollment's ongoing, and if you plan to enroll the same number of patients for each lymphoma type or just as they come in.
Okay. Very good question. There's a lot there. First of all, this is a first in human clinical trial. T-cell lymphoma, as you know, is a heterogeneous group of diseases, but there's about four or five main kinds of T-cell lymphoma. The initial part of the study is the CPI-818 is delivered in a 3-by-3 dose escalation design. We're taking all patients with T-cell lymphomas, and the purpose of that is to define the dose, the safety, and of course, look at efficacy as well. We have an extensive biomarker program where we're looking at the occupancy of the target, effects on the immune system, things like that. Then once the dose is determined, the trial in an adaptive design breaks into separate parts where we look at the various principal kinds of T-cell lymphomas.
For example, those are peripheral T-cell lymphoma, which is one of the more common T-cell lymphomas, what's called angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, and then we have the category of other. Dose escalation initially in all comers, then we enroll patients in the different disease-specific cohorts, and based on response in those disease-specific cohorts, we can expand those in a disease-specific manner as appropriate. Hard to put the final number, but it could be hundreds of patients, depending on how many of those cohorts got expanded. I guess, the number of centers we have, obviously because of the track record of our group here with ibrutinib, we are very well connected in hematologic malignancies. We've worked with all the thought leaders. My group here at Corvus has worked with all the thought leaders throughout the world. We have the very best people involved in conducting this trial.
It'll be an international study, U.S., Canada, Australia, South Korea. We have sites there. The study just started. Total number of centers that will be up will probably be, I think our plan is for more than 30 centers, if I'm recalling correctly. We're not there yet, but I think that the pace of enrollment in this study is going to be very good because this is a really unique mechanism of action and a novel agent. The nice thing about ITK as a target, which by the way, stands for interleukin-2-inducible T-cell kinase. The reason that people are excited about this is because of the success with ibrutinib and BTK. I mean, BTK was a sleepy little target that nobody thought much about. Of course, our group made it one of the most important targets in oncology in the last 10 or 20 years.
We hope we're replaying that now with ITK. ITK is involved in T-cell biology. That gets you into a whole lot of other stuff. Like can you manipulate cytotoxic killer cells so that they might attack a solid tumor, not necessarily a T-cell, but a solid tumor better? Can you affect autoimmune diseases? The opportunities with an ITK inhibitor we think are really significant. Cancers are T-cell lymphomas, the sort of lowest hanging fruit. It gives us the opportunity to learn a lot about the intrinsic biology and pharmaceutical properties of the compound. There's a lot more we intend to do with it. As I mentioned in my opening remarks, the key point about this compound is its extraordinary selectivity. This really only hits ITK.
It is really difficult to do that because the similarity of the kinases, ITK, BTK, and the 11 other kinases in that family, there are very few amino acid differences, and it's difficult to get that kind of selectivity. The selectivity is crucial for the immunologic effects. I think it's a tribute to the experience and the talent of our group here, who obviously have already succeeded with their development of ibrutinib. Sorry for that long answer, you get me turned on when you talk about that.
I guess as a follow-up, is there any chance that we will see early data from this at either SITC or ASH later this year? If so, will it just be pure dose escalation data, safety data, or is there a chance that we might actually see dose expansion data?
I don't know about dose expansion data because obviously 3x3 design, you have to wait to get through your DLT periods. The good thing about our trial is that because of the extensive preclinical work we did which showed that the drug was actually quite safe, at least in animal systems, we were able to start at a reasonable dose in our phase I study, we don't have to waste a lot of time going up through a lot of low doses. My hope is that we have some data to present at the ASH meeting in December. I think we're going to have a whole lot of immunology that's never been described before. Hopefully we'll have, certainly we'll have some safety data, and hopefully have some early efficacy data. Michael, we always present.
Yeah.
You know we always present efficacy. You know that.
I just.
Unlike other companies.
I know when you would.
We're here for efficacy.
Thanks, Richard.
We'll go next to Robert Driscoll with Wedbush.
Hey, guys. Thanks for taking the questions. Again, just related to CPI-818, do you have a sense of how ITK activation or kind of overexpression varies within each T-cell lymphoma type or kind of between types? How dependent each type is on ITK signaling? Also just to add on, can you talk a little bit about the biomarker work you're doing in the study, what you're kind of trying to find out there? Thanks.
Okay. ITK is expressed differently in different T-cell lymphomas. You are correct about that. There's not a lot of information about that. We're collecting the seminal information in the field, but there is literature that says ITK is expressed a lot in peripheral T-cell lymphomas, which I mentioned is over 90% of them. Similarly for AITL. AITL, or angioimmunoblastic T-cell lymphoma, and peripheral T-cell lymphomas together are the most common, for sure. ITK expression is very common in those. In the other tumors, it's not that well-known. We do know that T-cell receptor is expressed in all of the T-cell lymphomas. Robert, I'm going to turn it around. I know you have a PhD, I'm going to turn it around on you. If I asked you which B-cell tumors overexpress BTK, the answer is none that I'm aware of.
All of them have B-cell receptor. The bet there was that B-cell receptor signaling would be involved in B-cell lymphomas, and it is in many signals. ITK is, of course, present in all T-cells and all T-cell tumors. It's just a question of what it's doing and whether or not it's overexpressed, and whether that's a critical driver in the malignant process. There's a lot that is to be learned about this. There's no question that PTCL and AITL have a lot of ITK. T-cell receptor and that pathway appears to be functioning in many T-cell lymphomas.
Got it.
In fact, I don't know the T-cell lymphoma. I'm sure somebody will find me some paper here after this call, but I don't know of a T-cell lymphoma that does not express the T-cell receptor. You have to ask yourself the question: why is that receptor so critical to the malignant process? Why is it that every T-cell cancer has that receptor? Is it by accident, or does it play a role?
Very helpful. Just quickly on the adenosine signature, I probably looked this up from the SITC presentation. Can you remind us what proportion of renal cell cancer patients might screen positive here? Any early thoughts on how that test might potentially be commercialized? Thanks.
Okay. Great question. Thank you for asking that. I can speak for hours on this. The answer to your question is, in our studies, we're finding that 60% of renal cell cancer patients express our adenosine signature. In a related study published by Genentech and coworkers in late 2018 in over 400 patients with renal cell cancer, 49% of their patients expressed what they called a myeloid signature. There's significant overlap between the myeloid signature and our adenosine signature. Most of our genes are myeloid cell-derived. It's a good number of patients. In terms of commercialization, we have done the test two ways. We do it with NanoString, and we've also done it with RNA-seq, and there's concordance in those two methods. We believe it might even to develop a immunohistochemical test for some of these markers.
By the way, this analysis is done on the tumor biopsy. It's not the blood, it's the tumor biopsy. We are now talking with at least three companies about developing a clinical diagnostic, and ultimately approved, for the detection of our adenosine signature. I don't think that development of the test for either phase III trials or commercial sale will be an impediment at all.
Great. Thanks a lot.
That concludes today's question and answer session. I'd like to turn it back over to today's management for any additional or closing remarks.
Thank you, operator. First, let me thank everyone for participating in this call. Very interesting. We look forward to speaking with you more on future calls and future updates. Hopefully, we'll see you all at ASCO. Thank you.
That concludes today's conference. Thank you for your participation. You may now disconnect.