Good afternoon, ladies and gentlemen. Thank you for standing by, and welcome to the Corvus Pharmaceuticals 4th Quarter 2019 Business Update and Financial Results Webcast. 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 and instructions will follow at that time.
It is now my pleasure to turn the call over to Zach Kubo of Pure Communications. Please go ahead, sir.
Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corbus Pharmaceuticals Q4 2019 business update and financial results conference call. On the call to discuss the results and business highlights for the Q4 2019 are Richard Miller, Chief Executive Officer Blake Lee, Chief Financial Officer and Murdadmal Vacher, Chief Medical Officer. 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' quarterly report on Form 10 Q filed with the SEC on October 29, 2019, 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 Laith Lee. Laith?
Thank you, Zach. I will begin with
a quick overview of our Q4 full year 2019 financials and then we'll turn the call over to Richard for a business update. At December 31, 2019, Cordless had cash, cash equivalents and marketable securities totaling $78,000,000 as compared to $114,600,000 at December 31, 2018. Research and development expenses in the Q4 2019 totaled $8,900,000 compared to $8,400,000 for the same period in 2018. The increase of $500,000 is primarily due to an increase in outside CPI-six and CPI-eight eighteen program costs, partially offset by reduced outside sulfuricamic costs. Research and development expenses for the full year of 2019 totaled $38,000,000 compared to $38,600,000 in 2018.
The decrease of $600,000 was primarily due to reduced ciforaden costs, partially offset by an increase in CPI-six and CPI-eight eighteen program costs and personnel costs. I would like to note that we continue to carefully manage our expenses and currently expect full year 2020 net cash used in operating activities to be between $39,000,000 $42,000,000 compared to $37,000,000 in 2019.
The net loss for the
Q4 of 2019 was $11,000,000 compared to a net loss of $10,500,000 for the same period in 2018. The net loss for the full year 2019 was 46 $700,000 compared to a net loss of $46,900,000 in 2018. Total stock compensation expense for the Q4 and full year 2019 was $1,700,000 $7,300,000 respectively compared to $1,800,000 $7,100,000 in 2018. I will now turn the call over to Guenther.
Thank you, Leif, and good afternoon, everyone. Thank you for joining us today for our Q4 and full year 2019 business update. In 2019, we made substantial progress enrolling patients in our studies and advancing our pipeline of precisely targeted oncology therapies. The progress provides more clarity defining 3 areas that our product candidates address. Number 1, adenosine pathway inhibition and ATA receptor blockade and inhibition of adenosine production by anti CD73 number 2, immunomodulation of immune cells, particularly B cells and 3, modulation of T cell function through the kinase ITK.
The key highlights from the year include the following. We continue to report encouraging data from the Phase IbII clinical trial of cifiradmins in combination with atezolizumab in patients with advanced refractory renal cell cancer. Ciforadenant is the most advanced candidate in development across the landscape of adenosine CoA receptor antagonists with more than 300 patients receiving treatment to date. We reported the first data for CPI-six, our novel first of its kind anti CD73 antibody, demonstrating that it may provide a new immuno oncology approach both via the activation of immune cells and through the inhibition of adenosine production. The data indicates CPI-six has potential as a monotherapy and as a combination medicine in a variety of tumor types.
In addition, we continue to develop the Adenosine gene signature, which we believe will be an important predictive biomarker for ciforabiant and for CPI-six. Our work in the adenosine pathway was reinforced by multiple independent studies from industry and academia over the course of the year, adding to our confidence that our programs are positioned for success. Outside of the adenosine pathway, at the recent American Society of Hematology meeting, we presented initial data from the dose escalation portion of our Phase I study for CPI-eight eighteen, our small molecule ITK inhibitor, making it our 3rd program in the clinic. This continued in January with additional clinical data presented at the T Cell Lymphoma Forum in San Diego. In 2020, we will continue advancing our clinical studies for Cifiradmim for CPI-six and CPI-eight eighteen.
I will begin with an update on the recent work with Cifiradmant and the Adenosine Gene Signature that gives us increasing confidence in the outlook and trajectory of our lead program. In the January 2020 issue of Cancer Discovery, our peer reviewed article was published on ciforadenant and the Adenosine Gene Signature authored by Doctor. Larry Fong of UCSF, one of Corvus' clinical trial investigators. The article presents the safety and efficacy results from 68 patients with advanced refractory renal cell cancer and for the first time in publication, describe the identification and the potential to use the adenosine gene signature as a biomarker for predicting response to therapy with cifiratinib and potentially Adenosine blockade in general. This study and the venison gene signature were recently highlighted at the ASCO Genitourinary Symposium meeting in San Francisco in February.
Briefly, here are some of the key facts related to the Adenosine gene signature. The signature has now been confirmed by other academic and industry groups. The signature appears to identify a subtype of renal cell cancer that has a poor prognosis, a group of patients that is unresponsive to anti PD-one therapies with a very low response rate and extremely poor PFS of less than 3 months even in first line setting. Patients with high adenosine signature were generally low for an angiogenesis signature. The angiogenesis signature is an established biomarker, which predicts response favorable response to angiogenesis inhibitors.
What this means is that the adenosine signature identifies a group of renal cell cancer patients. We estimate that this is about 50% of patients that do poorly with current therapies. The signature identifies a myeloid cell population in the renal cell cancer tumor microenvironment that functions as an immunosuppressive cell. This now highlights this myeloid cell population as a potential new target for immunotherapy, that is targeting the myeloid component of the tumor microenvironment. The cancer discovery article demonstrates that in patients with high levels of adenosine gene signature expression, there was a statistically significant association with tumor regression with cifurabine treatment.
Adenosine Signature positive patients achieved a 17% response rate by resist versus 0% in Signature negative patients. These patients also demonstrated more durable progression free survival with a tail on the curve for the Adenosine Signature positive patient. The data indicate that the Adenosine Gene Signature may be useful as a predictive biomarker to select patients more likely to respond to ciforadenant and that resistance to anti PD-one may be reversed by ciforadenant in these patients. It also suggests that the signature can identify patients with low expression of the angiogenesis gene signature, which can predict poor response to anti angiogenesis agents. This double enrichment gives the adenosine gene signature exciting potential as a biomarker that identifies patients that will be better with ciforadenant and have unfavorable outcomes with standard of care TKIs, tyrosine kinase inhibitors.
The article was further highlighted in the journal's editorial by Doctor. Lucia Zitkowski, Professor of Immunology at Northeastern University. In addition to acknowledging the pioneering research, he noted that the anti tumor activity was seen in highly resistant patients. We have already enrolled approximately 25 additional renal cell cancer patients with the goal of confirming the value of the Adenosine Signature. We are also working on refining the signature and very good progress is being made in that area.
We intend to update both the clinical and biomarker data at the ASCO Annual Meeting in June. With these additional data, we feel we will be positioned to initiate a late stage trial based on the Adenosine gene signature in second, third or later line renal cell cancer There remains an unmet need for these patients and we anticipate that the signature will be capable of identifying a patient group that is likely to do better with ciforadenib compared to standard therapies. We also presented data on ciforadenib in prostate cancer at the ASCO GU Cancer Symposium in February. We are in the very early stages of this trial with a median follow-up of only 3.2 months. The highlights from that data include, as mentioned, median follow-up of about 3.2 months.
There was one partial response by RECIST. This patient had a PSA drop from 98 to less than 1. 10 additional patients had tumor regression, not yet meeting the criteria for partial response. And 7 patients have confirmed stable disease exceeding 6 months. Many of these patients with minor response in stable disease are continuing on therapy, and it is possible that their responses may deepen.
We intend to update this data at ASCO in June. One other important finding reported in this presentation was gene expression profiling of tumor biopsies demonstrated a statistically significant correlation of tumor CD73 expression with the adenosine gene signature. This correlation supports the relevance of adenosine in prostate cancer, its production by CD73 and the expression of adenosine induced immunosuppressive gene. Let me turn now to CPI-six, our anti CD73 antibody. We continue to be enthusiastic about this novel immunomodulatory antibody.
We most recently presented data from the Phase I1b study at the Society of Immunotherapy of Cancer meeting in November. Similar to prior results presented at ASCO, we are seeing activity in renal cell, prostate and non small cell lung cancers with an acceptable safety profile. We also continue to see dramatic effects on circulating immune cells with B cell and T cell mobilization and redistribution. B cells are specifically activated into antibody producing cells, both in vitro and in vivo. And these are facts are adenosine independent and are related to the immunomodulatory agonistic properties of the antibody.
We are not aware of any other agent, antibody or small molecule targeting CD73 that has exhibited these properties. It should be noted that interest in the role of B cells in immunotherapy has intensified. Recent papers in Nature have shown that tumor infiltration with B cells are an important predictor of response to immuno oncology therapies. This gives us added confidence and interest in CPI-six. Recently, we have found evidence that some of our patients are producing antibodies to their tumor following therapy with CPI-six.
Although preliminary, this is a very exciting and important finding. In terms of the ongoing study, we have now selected the optimum dose of 18 milligrams per kilogram every 3 weeks for monotherapy and in combination with cifuradimant. We recently opened the CPI-six in combination with pembrolizumab arm of the study, and we expect to soon open the last arm of the study, which is CPI-six plus ciforadenine plus pembrolizumab, a triplet regimen. Finally, a quick update on CPI-eight eighteen, our ITK inhibitor. As mentioned in my opening remarks, we presented the first data on this program at ASH in December and at the T cell lymphoma forum in January.
We have now reached a dose that substantially inhibits the target, so we are now positioned to evaluate potential efficacy. The Phase I portion of the study has met our expectations as we have determined safety, PK, receptor occupancy and we have selected a dose. Early signs of antitumor activity have been observed. In summary, we continue to believe Corvus is well positioned with worldwide commercial rights to 3 unique candidates in the clinic and a leadership position in the adenosine pathway. In addition, the further characterization and confirmation of the adenosine gene signature increases our confidence that we can identify the patients most likely to benefit from therapy with ciforadenant.
We intend to share meaningful updates on this program at ASCO in June. I will now turn the call back over to the operator for questions and answers. Operator?
Thank We'll first take Tommi Butler from ROTH Capital Partners. Please go ahead.
Yes. Thanks a lot. Richard, two questions really.
One is around the antibodies produced in patients that you've been able to cultivate patients treated with 6. Question is, have you found any common antibodies among those patients to date? And can you say anything about the antigens? That's number 1. And number 2, when will we actually see up and you may have said this, so forgive me if that I missed it.
When will we see updates with the R06 data set? Thank
you. Okay. Let me take your first question on the antibodies. So we have observed low titer antibody responses in a few of these patients. In one patient, we've been able to identify the antigen.
And it is I'd rather not say what the antigen is right now, but it is a bona fide known tumor antigen, something that you would be very familiar with. So what we need to be doing now, of course, is serially monitoring these patients and trying to figure out what happens to their titer of this antibody. Now in addition to that, we, like many others, are isolating B cells from patients and looking at individual B cells and trying to dissect out what these antibodies might be reacting with. As I think you're aware, the Nature papers back a month ago or so highlighting the importance of B cells infiltrating tumors as being more important in terms of predicting the response in this area. And as you know, I'm a former antibody guy, so I love antibodies.
And they seem to work pretty well in a lot of different things. So we're really excited about the potential importance of the uneural immunity part of the IO therapy. But really, it's very early in this work. And so we don't have a lot of information yet as to what the importance of those antibodies are and what they might do. Now in terms of data on 6, ASCO is going to be I did mention ASCO is going to be mostly about 444 in renal and the biomarker.
I think 6 work will wait till 50 in November.
Thanks, Rich. Appreciate it.
Thank you. We'll next go with Mara Goldstein from Mizuho. Please go ahead.
Great. Thanks for taking the question. Just two questions. And the first is really on the adenosine Signature. I'm just understanding how you will incorporate that into the clinical trials that are ongoing and how you see that from a clinical practice perspective?
And then just on 818, I apologize, but can you confirm the dose that you're settled on?
Okay. Let's take the first question. So as I mentioned in my remarks, we've already enrolled an additional approximately 25 patients, which have the aim of confirming what we described in the cancer discovery paper. And so far, we don't have all the data in on those 25 patients. It appears to be holding up very nicely.
We're now meeting with KRLs and lots of good thought leaders in the renal cell cancer area. Probably in a few months, we'll be in a position where we'll talk about how we will incorporate this biomarker into our clinical trial plans. But I can tell you, Mara, that it will be a very important part of our clinical trial.
Okay.
Now your question on 818, we've recently enrolled patients at 600 milligrams BID. We've just gotten through the DLT period on that. We don't see any dose limiting toxicity at that dose. We've confirmed very substantial receptor occupancy, and we're following those patients now. I think that this does we have a few other measurements we have to make in addition to receptor engagement, some other functional assays that we'll be looking at.
And also, even though you make it through the DLP period, it's nice to get a little bit more follow-up on these patients because you don't want to see side effects beyond the DLT period. But I think that a dose of I think that we have a dose of around 400 or 600.
Okay. Thank you. I appreciate it. Thank you. We'll next go with Jeet Mukherjee from Jefferies.
Please go ahead.
Yes. Hey, guys. This is Jeet on for Biren. Richard, just wanted to maybe get a little bit more color on those 25 additional RCC patients you said you had. Just was wondering if you had any details in terms of maybe how these patients compare to the existing patients that we've already seen?
And I have a couple of follow-up questions.
Well, I mean, pretty much the same kind of patients. We did restrict the number of prior therapies a little more because, of course, in our original 68 patients being a Phase I study, and thank you for raising this point, there were all kinds of typical Phase I patients in this. So we did try to get a little better patients. And of course, the other big thing in these additional 25 patients was that you had to have failed an IO and a TKI. And the reason we did that is obvious in the last year or 2.
It has now become standard practice to give a TKI and IO either first line or first and second line. So those are the differences.
Got it. That's helpful. And then just two other questions that I had was heading into ASCO, how many more patients worth of data could we expect for cifuradenant in prostate cancer? I believe on the ASCO GU poster, and it said that there was perhaps some follow-up planned at the 2020 ASCO meeting. So wanted to know maybe how many more patients we can expect there for that indication?
And will these patients be stratified by adenosine signature, gene signature?
Okay. Prostate cancer patients, I think they were, what, 33 or 35 patients on our GU ASCO poster. I mentioned the follow-up was short. I mean, our main goal now is we're following those patients and trying to get more follow-up. We did not stratify for adenosine signature in that.
Obviously, we're going to be looking at that. I mentioned this relationship of CD73 in the adenosine signature, which is an interesting observation, but doesn't get exactly to your point. So but it does seem that since CD73 makes adenosine and adenosine generates the adenosine gene signature, it all fits together very nicely. But basically, I think what you're going to see at ASCO in our prostate cancer is a little bit more biology and more follow-up.
Okay. Got it. And then just my last question was on 6, when do you anticipate opening the combination dosing arm with pembro?
It's open.
It's open. Okay. Thank you very much.
Yes.
All right. Any other questions?
We'll head to our next question from Swayampakula Ramakanth from H. C. Wainwright. Please go ahead.
Thank you. This is RK from H. C. Wainwright. Thanks, Mr.
For taking my question. Most of my questions have been asked, but recently
we've
been we noted that from clinicalcloud.gov. There is a new study of cipolla death in hand as a single agent and also as a combination with daratumumab in the actual effect of multiple myeloma. Can you give us a little bit of a background and an update on that?
Yes. Thank you for that question because I often neglect talking about that. So the rationale for that study, which is being conducted at Johns Hopkins Medical School, which is perhaps one of the best myeloma groups in the world. The rationale is that daratumumab, of course, is anti CD38 antibody. CD38 turns out to be another important source of adenosine.
And there are I won't go into the biochemistry, but NAD is broken down and one of the byproducts of that is adenosine. And so the strategy is simply to combine adenosine antagonist like our ciforadenant with daratumumab in patients who have failed Dara. So this is a really nice study where patients who are growing through Dara will get our A2A inhibitor added to it initially as a monotherapy because remember our A2A antagonist as opposed to everyone else's has demonstrated monotherapy activity, single agent activity in many tumors. So we want to look at myeloma cells, and we have some in vitro evidence for that. And then I think within a month, they come in with daratumumab.
And the idea there is you're trying to restore responsiveness to an otherwise resistant patient. And of course, we're looking at bone marrow biopsies and blood and looking at the adenosine Signature and all the usual things. So the rationale is basically CD38 is a good source of agronizine and we want to come at that 2 ways. There's very nice publication on that that showed I think it was out of MD Anderson in various animal models that what they showed is that if you block ATA receptor, the ATA receptor together with anti CD38, you get a synergistic response in mouse tumors. They also looked at gene expression in patients, in human biopsy samples and found that in CD38 resistant patients, there was an increase in A2AR A2A receptor expression.
So that's the scientific rationale. We're excited about that study because it gives us a lot of potential things that we can measure and give us a lot of good information.
Thank you. Thank you for that elaborate answer. Appreciate that.
We'll next go with Tony Butler from Roth Capital Partners. Please go ahead.
Richard, sorry for the follow-up. The expanded 25 patients in the 4th study, my apologies, but they will be patients who have not previously seen the IOUs and VAIs or who have.
Tony, it's hard to hear you, but the 25 patients I mentioned, they have seen, they have failed TKI and IO.
Okay. They have failed, so they have seen. Yes. Okay. Perfect.
We have Just want to make sure.
Yes. We're clearly focusing in on the patient population. Look, our strategy is very simple. We're going to go late line in resisting patients where endpoints can be obtained presumably faster and so forth and then, of course, move up earlier as we get more experience. Now the interesting thing is that with the success of IO first line renal and second line, there are many, many more patients who are surviving to see second, third, fourth line.
So that is definitely becoming as we predicted, by the way, it is becoming a new entity or a serious patient population with unmet need.
Thank you.
All right. It appears that there are no questions at this moment. I'd like to give the conference back over to the moderators for any additional closing remarks.
Okay. This is Richard Miller. Thank you all for participating in this call, and thank you for those great questions. I look forward to updating you on future calls and of course, hopefully, see you at our ASCO meeting. Thank you very much.