Ladies and gentlemen, thank you for standing by, and welcome to the Corvus Pharmaceuticals Second Quarter 2019 Business Update and Financial Results Conference Call. As a reminder, 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 be given at that time. It is now my pleasure to turn the call over to Zach Kubo of Peer Communications.
Please go ahead.
Thank you, operator, and good afternoon, everyone. Thanks for joining us for the Corvus Pharmaceuticals Q2 2019 business update and financial results conference call. On the call to discuss the results and business highlights for the Q2 2019 are Richard Miller, Chief Executive Officer Leif Lee, Chief Financial Officer and Mehrdad Mobasher, 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 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 Blake.
Thank you, Zach. I will begin with a quick overview of our Q2 financials and then turn the call over to Richard for a business update. At June 30, 2019, Corvus had cash, cash equivalents and marketable securities totaling $96,800,000 as compared to $114,600,000 at December 31, 2018. Research and development expenses in the Q2 2019 totaled $10,600,000 compared to $9,700,000 for the same period in 2018. The increase of $900,000 was primarily due to an increase in CPI-six program costs.
The net loss for the Q2 of 2019 was $13,000,000 compared to a net loss of $11,600,000 for the same period in 2018. Total stock compensation expense for the Q2 of 2019 was $1,900,000 compared to $1,700,000 of total stock compensation expense for the same period in 2018. I would like to note that we continue to carefully manage our expenses and currently expect full year 2019 net cash used in operating activities to be between $38,000,000 $42,000,000 with a 2019 year end cash balance between $73,000,000 $77,000,000 I will now turn the call over to Richard.
Thank you, Leif, and good afternoon, everyone. Thank you our Q2 2019 business update. During the quarter, we continued advancing all three of our clinical programs, highlighted by the presentation of the initial CPI-six clinical data in an oral presentation at ASCO in June. On today's call, I will provide a recap of the highlights from ASCO along with an update on our other development programs, including anticipated key milestones for the remainder of 2019. We had a very positive ASCO meeting, reinforcing our position as a leader in the development of adenosine pathway based therapeutics and in the development of 2nd generation immuno oncology medicines.
The initial data from our 6 clinical trial was presented in an oral presentation by Doctor. Jason Luke, Principal Investigator of the trial and Director of the Cancer Immunotherapeutics Center at the University of Pittsburgh Medical Center, Hillman Cancer Center. The presentation included data from a total of 20 patients, 12 patients who received CPI-six given intravenously as monotherapy at doses of 1, 3, 6, 12 milligrams per kilogram every 21 days and 8 patients who received the combination treatment of CPI-six at 136 milligrams per kilogram every 21 days plus a fixed dose of cifuradenant 100 milligrams twice daily. These patients all had advanced refractory disease and had failed a median of 4 prior therapies. CPI-six is a novel first of its kind anti CD73 antibody.
We created and are developing this antibody because it possesses unique immunomodulatory properties. We are pleased with the results presented at ASCO as they confirm what we set out to create with 6, an immunologically active and very selective antibody targeting CD73. The combination of immune stimulation and adenosine blockade is expected to be synergistic. Let me give a few takeaways from the presentation at ASCO. First, the clinical and laboratory results support a new immunotherapeutic approach with CPI-six via both its activation of immune cells and the inhibition of adenosine production.
6 binds to a site on the CD73 protein that blocks its enzymatic activity, blocking the production of immunosuppressive adenosine. Other antibodies to CD73 have also been described to do that of course. But our CD73 is also a co stimulatory antibody. 6 interacts with a site on the CD73 molecule that leads to its activation. It is an agonist in this regard.
This process is independent of adenosine. More specifically, we found evidence of B cell activation and effects on lymphocyte trafficking in our treated patients. Treatment induced expression of markers of immune cells associated with activation of antigen presenting cells. And these effects are specific to CD73 positive cells consistent with the exquisite selectivity of the antibody. Together, the immunologic data collected from these patients supports stimulation of the immune system and suggest the trafficking of activated cells to peripheral lymphoid tissues.
Why is that important? Because immune cells become sensitized to tumor antigens in peripheral lymphoid tissue, namely regional lymph nodes. That's where the action happens. I want to emphasize that we are not aware of any other agent, antibody or small molecule targeting CD73 that has exhibited these dual independent properties. Some companies are developing small molecule inhibitors of CD73 enzymatic activity.
It is very unlikely, actually impossible, that such agents will have these immunomodulatory effects that I just described. 2nd, the initial very early results demonstrated a dose dependent disease control in patients with advanced refractory disease when CD73 when our CPI-six was administered as a monotherapy and when it was given in combination with cifuratinib. This included a trend toward longer disease control in patients with doses in patients receiving doses of 6 milligrams per kilogram and higher and the combination therapy appear to enhance disease control. Doses of 6 milligrams per kilogram and higher achieved sustained occupancy of CD73 sites on peripheral blood lymphocytes and 12 milligrams per kilogram was shown to achieve saturation of the antigen in tumor biopsies. In short, we are zeroing in on the optimum dose.
3rd, we were very pleased to see signs of tumor control and regression occurring in patients with very advanced cancers. These patients were resistant to previous treatments. In particular, we see early signs of activity in renal cell cancer and prostate cancer. We also reported a positive safety profile as CPI-six was well tolerated at all dose levels with no dose limiting toxicities observed so far. We are delighted with the response to our ASCO data from scientists and clinicians.
The importance of the presentation was confirmed by the selection of our presentation for one of ASCO's highlight of the day sessions. For those that may not be familiar with these sessions, only a handful of papers are selected to be a highlight and they are very popular with ASCO attendees because they provide an efficient way to keep informed on the most important discoveries and findings coming out of the meeting. The highlight of the day presentation was made by Doctor. Mary Diesis, a leading oncology researcher from the University of Washington and Editor in Chief for JAMA Oncology. In the session, Doctor.
Diess has highlighted the key themes that we have been emphasizing about our approach to clinical development, starting with monotherapy to confirm single agent activity and utilizing pharmacodynamic biomarkers to enhance our understanding of the clinical results. We also hosted a well attended analyst and investor meeting during ASCO featuring Doctor. Luke to review the 6 data. If you have not had a chance to listen to this presentation, I would encourage you to listen to the replay, which is available on our website. We continue to enroll patients with advanced cancer in our Phase 1, 1b clinical trial of CPI-six with a focus on the first two arms, single agent and in combination with cirapiforadenant.
To date, we are seeing a continuation of the trends reported at ASCO, and we have been pleased that our presentation at ASCO has stimulated increased interest in our study, which is now enrolling very well. We plan to provide an update from our 6 study at the SITC meeting in November with more patients, more immunobiology and longer follow-up, both for the monotherapy and ciforadenant combination arms. I would now like to discuss ciforadenant, our small molecule drug that is an antagonist of the adenosine A2A receptor. Ciforadenant is the most advanced candidate in development across the landscape of A2A receptor antagonists with more than 250 patients receiving treatment to date. It has demonstrated anti tumor activity as a monotherapy and in combination with atezolizumab in patients that have failed a medium 3 prior therapies and the drug has exhibited strong safety PK and PD profile.
Some of our patients have experienced durable responses and disease control out to now over 30 months. Some patients have been on therapy in excess of 2.5 years. We continue to enroll patients in our Phase IbII clinical trial evaluating stifiradenant in combination with atezolizumab. This study has most recently been focused on patients with advanced refractory renal cell cancer, which is a significant unmet need. We are also enrolling patients with prostate cancer.
On our Q1 call, we noted that we have seen activity in prostate cancer and that AstraZeneca presented Phase 1 data for their oral A2A receptor inhibitor also showing signs of efficacy in prostate cancer patients including responses in patients receiving monotherapy. As part of these protocols, we are testing patients for the adenosine signature to evaluate its use as a predictive marker for future studies. To date, we have treated about 14 patients with metastatic castration resistant prostate cancer, with cifuradenant as a single agent in combination with atezolizumab or in combination with CPI-six. We plan to deepen our experience with prostate cancer for both ciforadeniz and for CPI-six going forward. Related to the adenosine pathway and with a goal to broaden our pipeline, we continue to study and advance our selective adenosine A2B receptor inhibitor through preclinical studies.
Our research has shown that inhibiting the A2B receptor does not have meaningful effects on the immune system, but it does have effects on fibrosis and other related processes. This activity has been reported by other scientists in the literature and is something we plan to continue exploring. Although reported by one group, we do not believe there is persuasive evidence to explore the dual simultaneous inhibition of A2A and A2B receptors for immunotherapy either with combinations of selected A2A and A2B drugs or for a dual or with a dual inhibitor that we have synthesized. Outside of the adenosine pathway, we are enrolling our Phase 1, 1b study of CPI-eight eighteen, our small molecule ITK inhibitor in patients with T cell lymphomas, including peripheral T cell lymphoma, cutaneous T cell lymphoma and others. We believe CPI-eight eighteen has the potential to be directly cytotoxic to T cell lymphomas and also may lead to enhancement of the immune system by increasing what is called 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 a very attractive candidate to examine in autoimmunity. As a reminder, the development of CPI-eight eighteen was based on a similar targeting strategy to that of BTK inhibitors such as Ibrutinib and members of the scientific team at Corvus including myself led the development of Ibrutinib, the first BTK inhibitor, which is now approved for the treatment of several types of B cell lymphomas. We treated the first patient in our CPI-eight eighteen study during the Q2 and this study is now open in the United States, Australia and South Korea. So far CPI-eight eighteen has been well tolerated and we are pleased with the PK and PD findings. We expect early clinical data to be presented in late 2019 or early 2020.
In summary, we continue to believe Corvus is well positioned with 3 unique candidates in the clinic. We are encouraged with the latest data presented at ASCO demonstrating that CPI-six is unique among CD73 antibodies based on its dual mechanism of action, immunomodulation and adenosine blockade. We are seeing positive early signs of antitumor activity in the CPI-six study and look forward to presenting additional more mature data later this year at the SITC meeting in November. Cifiradinib continues to demonstrate attractive pharmaceutical properties, including complete receptor blockade and high specificity for A2A. And importantly, ciforadenant and CPI-six, which are wholly owned by Corvus, appear to be complementary with attractive potential as combination therapy.
Outside of our 3 programs in the clinic, we are also advancing our pipeline assets, but the majority of our focus continues to be on our clinical work. We look forward to providing updates on our progress with our pipeline at upcoming medical meetings and in future business update calls. Let me remind everyone about SITC in November, where we anticipate presenting more clinical data and hosting an investor reception. I will now turn the call over to the operator for a question and answer session. Operator?
Thank We'll take our first question from Michael Morabito with Credit Suisse.
Hi, team. Thanks for taking my questions. I just have 2 for you. 1 on CPI-six, I was trying to find out if I heard you correctly, are you still increasing the dose beyond 12 mgs per kg in that and how many new patients should we expect roughly when the data come at CPT? And also on the OpEx guidance that you gave, you said you saw net 2019 cash use of $38,000,000 to $42,000,000 but the first half use was already $26,000,000 So I was just wondering where the savings would be coming from?
Okay. So there are 2 questions. I'll take the first one. So we have continued to increase the dose of the antibody to now 24 milligrams per kilogram, not yet seen any NPD or DLT dose limiting toxicity. 24 milligrams per kilogram is the highest dose we're going to test.
We know we're super saturating the antigen and the dose that we'll use for our expansion part of the trial will be lower than 24 milligrams per kilogram. We're still working out the details of our pharmacokinetics and pharmacodynamics. But we're at higher than the dose we expect to use in the future. And the financial question, Laithol, I can take that one.
Sure, Mike. So for the 1st 6 months, our net cash used in operating activities was $18,000,000 which is
a little bit half the $40,000,000 of the midpoint of our full year forecast.
Okay. Thank you.
Hey, Michael. And also sorry, I forgot to answer the second part of your question. How many more patients? You're going to see at least a doubling of the patients.
Okay. That's very helpful. Thanks.
We'll take our next question from Biren Amin with Jefferies.
Yes. Hey, guys. This is Ajit on for Biren. Thanks for taking our questions. Just a couple from me.
Could you just reiterate again for the prostate cancer patients that you said you're including in the Phase 1b study, could you just clarify the breakdown of those patients from monotherapy and combo? And when can we potentially expect to see the data on those patients?
I think we'll probably talk about some of that data at SITC. The breakdown, I don't have those exact numbers off the top of my head, but probably about half of them were monotherapy, Some of them were combo with atezo and some of them are combo with 6.
Okay. And just a second one for me as well. Just regarding the ciforadenantinostmallcell data from the Morpheus ongoing study. I think on the Q1 call you said that there might be a cut of the data that would be seen around about this time. Is there any update on that?
And when can we expect to see some data from that study?
So I don't have a cut on that data yet. Patients have been enrolled in the study and they're still under follow-up. We don't control that study as you know. I would expect that we'll get a look at that data later this year.
Okay. Got it. And maybe just one more from me, more of a biology one on 818. Is RLK down regulation or lack of expression a consistent observation that's been seen across human T cell lymphoma subtypes? Or is it observed in more select subtypes?
I'm just looking for more of a general trend there.
So first of all, our 818 is an ITK inhibitor, just to be clear, not RLK. But RLK is a very interesting story. The unique feature of our drug is that it inhibits ITK without inhibiting RLK. And that turns out to be biologically crucial and very difficult to do chemically. That's one of the reasons why we get this Th1 skewing.
If you block this is a long story, but if you block ITK and not RLLK, the differentiation of T cells is such that you'll bias differentiation towards the Th1, which you want in cancer therapy. Now in terms of T cell lymphomas specifically, there's very good reason to believe that many, many T cell lymphomas have overexpression of the T cell receptor signaling pathway of which ITK is a critical signaling molecule. That was the whole rationale for going after ITK, similar to the rationale we used when we went after BTK in B cell lymphomas.
Okay. Thank you so much.
We'll take our next question from Toni Butler with ROTH Capital.
Hi. This is Deborah on for Toni. Just had a quick follow-up or a confirmation here. Richard, did you say that for the combo data for CPI-four and CPI-six that you're currently at the 24 mg or is that in the monotherapy cohort?
The monotherapy is at the 24 mg per kg. The combo is just a little bit behind it. The combo is at 18.
18, okay. So you're definitely above the 12 hurdle then.
And
then just a quick follow-up. Have you enrolled anyone in the CPI-six plus KEYTRUDA combo arm?
Not yet. Our plan is to get more data on our own drugs, 6 and 444. And once we get more comfortable with that, then we'll open up the other arm.
Okay. Thank you. And just to make sure I heard this correctly, did you say that you were positive or leading more towards CPI-six plus CPI-four forty four for the prostate cancer combo? Or you're still trying to figure things out versus atezo or not?
I would say we're still trying to figure things out. We've been extremely encouraged by what we're seeing with 6 and 444. And that has caused us to pay to look much more carefully at that combination.
Thank you.
We'll take our next question from Robert Driscoll with Wedbush Securities.
Hi. This is Akshay Kumarik on for Robert. Thanks for taking my question. I just wanted a quick clarification on the new prostate cancer arm for the Phase 1b2 study. Will you be using the adenosine signature to help select for those patients?
Or will
that be more of a retrospective analysis? Thanks.
We're going to use it retrospectively for two reasons. 1, we need to also get more experience on adenosine Signature negative as well as positive. And secondly, it really helps enrollment if you allow everyone in. If you require a biopsy and then tell patients you can't go on the study, they get very irritated. So it makes the study a lot more practical.
And that concludes the question and answer session. I'd like to turn the call back over to Richard Miller for any additional or closing remarks.
All right. Thank you, operator. First of all, thanks everyone for joining us in on the call today. Appreciate everybody's interest. Again, let me remind everybody about SITC in November and hopefully you can attend our presentations and you can also attend the investor reception that we're hosting.
Thank you. Operator?
Thank you. And that does conclude today's presentation. Thank you for your participation. You may now disconnect.