Curis, Inc.

Good afternoon, and welcome to QRIS's first quarter 2021 earnings call. All participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After the company's prepared remarks, call participants will have an opportunity to ask questions. To ask a question, you may press star, then one on your touchtone phone. To withdraw your question, please press star, then two. Please note, this event is being recorded. I would now like to turn the conference over to the company's Chief Financial Officer, Bill Steinkraus. Please go ahead.

Thank you, and welcome to QRIS's first quarter 2021 earnings call. Before we begin, I would encourage everyone to go to the investor section of our website at www.qris.com to find our first quarter 2021 earnings release and related financial tables. I would also like to remind everyone that during the call, management will be making forward-looking statements, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and actual results may differ materially. For additional details, please see our SEC filings. Joining me on today's call are Jim Denser, President and Chief Executive Officer, and Bob Martel, Head of R&D. We will also be available for a question and answer period at the end of the call. I'd now like to turn the call over to Jim. Jim?

Thank you, Bill. Good afternoon, everyone, and thank you for joining us today. Every day at Keras, we push to develop the next generation of transformative targeted cancer therapies that will meaningfully improve and extend patients' lives. In the first quarter of 2021, we took important steps towards that goal, building upon the exciting progress we made last year and expanding into additional areas where we believe we can make a difference. Our novel small molecule IRAC4 inhibitor, CA4948, is currently being evaluated in three clinical studies. First, the Phase 1-2 monotherapy study in AML-MDS I just mentioned. Second, the Phase 1-2 study in combination with ibrutinib for patients with relapsed or refractory NHL or other hematologic malignancies. And third, the Phase 2 Lucas study evaluating CA4948 in patients with lower-risk MDS, being led by Dr. Uwe Platzbecker of the University of Leipzig. We are especially pleased with the progress of CA4948 and the exciting data update published in the European Hematology Association abstracts this morning. From our Phase I-II monotherapy study in relapsed or refractory acute myeloid leukemia, or AML, and high-risk myelodysplastic syndromes, or MDS. As many of you have been following, the long isoform of IRAC4, or IRAC4L, has been recently identified as the key driver of disease in the majority of patients with AML and MDS. We at QRIS have the first and only drug that directly targets IRAC4 to enter clinical testing for these patients. Today, I am also pleased to announce that we have amended our AML and MDS study to add both a combination dose escalation and a monotherapy dose expansion. Preclinical data supporting the combination study was published by EHOP earlier today and will be presented in a poster presentation at the EHA conference next month. We expect to begin enrollment in this portion of the study in Q3. While there has certainly been a lot of attention on our IRAC4 study, it is important to note that we have also been pleased with patient enrollment in the phase one dose escalation study of our first in-class monoclonal anti-VISTA antibody, CI8993. We look forward to reporting initial clinical data for this study later this year. All told, we opened 2021 with strong momentum following our updates in December at ASH and the successful execution of key strategic financings and partnerships with premier institutions like the NCI and the European MDS Consortium that will support the continued advancement and expansion of our clinical programs. With that, let's dig into some detail on our ongoing clinical programs, starting with the IRAC4 study in leukemia. In April, we were pleased to report that CA4948 had received orphan drug designation from the FDA for the treatment of AML and MBS. This special designation represents a significant milestone for CURUS as we work to advance CA-4948 through clinical testing and, in time, seek to make it available to the patients who need it most. In the EHA abstract published this morning, we were pleased to report that the data in our AML and MBS study continue to exceed our original expectations. showing consistent single-agent efficacy across the spectrum of late-line AML and MDS patients, despite these patients having already experienced several unsuccessful prior lines of therapy. To provide some context, in conjunction with ASH last year, we reported preliminary data from six patients as of a November cutoff showing marrow blast reductions in all six patients with two of the patients demonstrating marrow complete responses and none of the patients experiencing a dose limiting toxicity at either the 200 or 300 milligram BID dose levels. The data published today, which are from 15 patients and the February 8th cutoff, showed bone marrow blast reductions in all tested doses 200, 300, and 400 milligram BID, and in eight of nine evaluable patients with elevated blast counts at baseline. Of these, one patient experienced a full hematologic recovery CR, one patient experienced a CRI with negative minimal residual disease, and two patients had bone marrow CRs. Three of these patients presented with a U2AF1 or SF3B1 spliceosome mutation, and all three of those patients achieved a marrow CR or better, validating our belief that these spliceosome mutations are specific oncogenic drivers of the long isoform of IRAC4, which CA4948 is explicitly designed to target. We were also pleased to see that all patients with objective responses showed signs of hematologic recovery. Delving a bit deeper on this point, the blast reduction data reported in the abstract this morning provide further evidence that CA4948 is effective at reducing a patient's cancer burden. For this late line patient population, having a drug that can safely and effectively get the cancer out is the immediate goal. In first-line patients, those patients whose bone marrow has not been irrevocably damaged by cancer or by prior cytotoxic treatment, it has been shown that if given a drug that reduces the level of leukemic blasts, these patients can achieve clear and substantial hematologic recovery within a few months. For the extremely sick late line population, such as the patients in our study, it is important to remember that their cancer has progressed despite numerous prior lines of therapy. As a result, these patients often have deeply scarred dysfunctional marrow, which may delay or even prevent successful hematologic recovery. It is therefore especially encouraging that we have been able to see signs of hematologic recovery even in these late-line patients after only a few months of treatment. It underscores our optimism that CA-4948 may have both a combo therapy and a monotherapy regulatory path. Overall, we are very pleased with the progress for CA-4948, and we look forward to the EHA conference where we will provide an updated and expanded data set with a later cutoff date to include additional patients, including those enrolled in our 500 milligram BID cohort. In addition, we will provide an update on safety, pharmacodynamic data, including IREC4L expression levels, and further genomics information. We have found that the 500 milligram BID dosing regimen has exceeded the maximum tolerated dose according to protocol guidelines. We observed two patients with dose-limiting toxicities, one of whom had grade three CPK elevation or rhabdomyolysis, similar to what we saw in the NHL study, and the other experienced grade three syncope. Both patients' AEs were reversible and quickly resolved after discontinuation of dosing. Now that we have established the maximum tolerated dose, we will explore the lower dose levels to determine the appropriate recommended phase two dose. I'd like to briefly touch on the preclinical data in our other EHA abstract published earlier today. These data highlighted CA4948's synergistic anti-tumor activity in combination with azacitidine and venetoclax in leukemia cells and will be presented in a poster session at EHA next month. These data demonstrate that CA4948 potentiates anti-tumor activity in certain cell lines resistant to clinically relevant concentrations of azacitidine and venetoclax. Further, CA4948 demonstrated synergistic anti-leukemic activity in combination with venetoclax and azacytidine in AML cell lines. Even before we saw these data, we knew that CA4948 was unique. It is oral. It is disease modifying. It directly targets the key driver of disease, IRAC4L, which is a novel mechanism of action. and it has demonstrated the ability to provide clear and significant single-agent activity without significant myelosuppression, including complete elimination of detectable cancer burden. With the latest preclinical data adding a possible synergistic effect as well, we and our clinical investigators are very excited to explore the combination of CA4948 with azacitidine and venetoclax in the clinic. As I mentioned earlier, this quarter we amended the protocol of our existing study to include expansion cohorts for both monotherapy and combotherapy. The monotherapy dose expansion will begin after the recommended phase two dose is determined and will include four cohorts. Patients with spliceosome mutated MDS, that is relapsed refractory to HMA, patients with MDS without spliceosome mutation that is relapsed refractory to HMA, patients with FLT3 mutated relapsed refractory AML, and patients with FLT3 wild-type relapsed refractory AML. The combo therapy study will start dose escalation at 200 milligrams BID and will include two cohorts. CA4948 plus azacitidine for patients with AML, MDS who are naive to HMA, and a second cohort of CA4948 plus venetoclax for patients with AML or MDS who are naive to venetoclax. We hope that the design of these cohorts will help to identify the most appropriate regulatory path or paths for CA4948. we expect to begin enrolling patients in these combo therapy cohorts in Q3. We may also explore a triple combination of all three drugs of CA4948 plus azacitidine plus venetoclax. But that would of course be dependent upon the initial safety and efficacy results from the two agent combination cohorts. Before moving on from leukemia, I would like to touch briefly on the ongoing IST treating patients with lower risk MDS that we announced in February. The phase two Lucas study is being led by the co-chairman of EHA's scientific working group on MDS, Dr. Uwe Plotzbecker, who will be coordinating this study in 17 sites across Europe to evaluate CA4948 for the treatment of anemia in patients with lower risk MDS. If this study is successful, it could lead to a potential breakthrough in the MDS field. While current EPO-stimulating agents can be effective for patients with lower-risk MDS who have low serum EPO, this effect is often transient and is not disease-modifying, and it does not affect progression to AML and further disease complications. With its direct non-myelosuppressive targeting of IRAC4 and its robust safety profile, we believe CA4948 could potentially offer a safe and transformative disease-modifying alternative for patients at earlier stages of disease. Now moving to lymphoma. In an oral presentation at ASH last December, We reported expanded clinical data from our phase one dose escalation study of CA4948 for the treatment of patients with relapsed or refractory NHL or other hematologic malignancies. These data highlighted durable reductions in tumor burden in six of seven evaluable patients treated with 300 milligrams of CA4948 twice daily following a median of four prior lines of therapy. It is important to reiterate that seeing clear efficacy with a novel monotherapy agent and seeing that this efficacy is durable over such an extended period of time for these extremely sick patients is enormously encouraging and provided powerful affirmation of our intention to launch the current combination study evaluating CA4948 with ibrutinib. This combination study, which began enrolling in Q1, is expected to enroll approximately 18 patients in a 3 plus 3 design with CA4948 doses starting at 200 and escalating to 300 milligrams BID. Ibrutinib dosing will be whatever is appropriate for the patient's respective NHL subtype. We expect to provide an enrollment update for this study as well as initial safety and efficacy data in Q4. Now I'd like to turn to CI8993, our first-in-class monoclonal antibody for the treatment of patients with relapsed or refractory solid tumors. Checkpoint inhibitors that function to enhance T cell priming, such as anti-CTLA-4 antibodies, and checkpoint inhibitors that relieve T cell exhaustion, such as anti-PD1 antibodies, all have two key limitations. First, T cells stuck in a quiescent state cannot be acted upon by these checkpoint inhibitors. Second, myeloid-derived suppressor cells, or MDSCs, actively impair the effectiveness of these checkpoint inhibitors. VISTA is a primary enforcer of T cell quiescence and can sequester a large proportion of T cells in a quiescent state, preventing them from being acted upon by anti-CTLA-4 or anti-PD-1 antibodies. VISTA is also a primary driver of MDSCs. These cells function to promote T cell exhaustion and suppress pro-inflammatory tumor-associated macrophages. Finally, we know that VISTA expression can increase dramatically as a compensatory mechanism during treatment with anti-CTLA-4 or anti-PD-1 therapy. For these reasons, we believe that therapeutic targeting of VISTA will be a crucial addition to the arsenal of immune oncology therapy. We believe CI-8993 is the most advanced anti-VISTA antibody currently in clinical development and has the potential to be a game-changing cancer therapy. The clinical community has already shown a deep excitement and interest in this program, and we look forward to reporting initial clinical data later this year. To wrap up, I'd like to extend my utmost appreciation to the entire QRIS team who have made all of this progress possible. We are eager to build upon our efforts in the quarters to come and advance our next generation targeted cancer programs to help patients in need. With that, I'll turn the call over to Bill to review our financial results for the quarter. Bill?