Calithera Biosciences, Inc.

Thank you for standing by and welcome to Calathera Biosciences' fourth quarter 2021 earnings call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's call is being recorded. Should you require any further assistance, please press star 0. I would now like to hand the call over to Stephanie Wong, Chief Financial Officer. Please go ahead.

Thank you, Operator. Good afternoon, everyone. Welcome to our fourth quarter and full year 2021 conference call. Joining me today are Susan Molyneux, Founder, President, and CEO, and Emil Kuryakov, Chief Medical Officer. Earlier this afternoon, we issued a press release which included an overview of our fourth quarter and full year 2021 financial and operational results which can be accessed through our website at calathera.com. Before we begin, I would like to remind you that today's discussion will include statements about our future expectations, plans, and prospects that constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in the risk factors section of our periodic filings with the SEC. In addition, forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change. Please note that this call is being recorded. And with that, I'll turn the call over to Susan.

Thanks, Stephanie. Good afternoon, everyone, and thank you for joining us for today's conference call. 2021 was a transformational year at CalFERA as we took several critical steps to transition the company's focus and core programs to developing therapies for biomarker-specific patient populations while continuing to leverage the company's deep expertise in clinical development for targeted small molecule cancer therapies. In October, we announced the acquisition of two clinical stage assets from Takeda, Myvovotinib and Cepanasertib. Myvovotinib is a spleen tyrosine kinase, or SICK, inhibitor that targets the constitutively activated B-cell receptor pathway in diffuse large B-cell lymphoma and other Nod Hodgkin's lymphomas. In completed Phase I-II clinical trials, Myvovotinib showed promising single-agent responses with deep and durable activity in unselected patients with DL-BCL. Our initial development will be in ABC, or activated B cell, DL-BCL, where BCR signaling and sick activation are central drivers. Myvovotinib showed a substantially higher response rate in ABC compared to GCB-DL-BCL, with a 53% ORR, or overall response rate, in ABC compared to a 22% ORR in GCB. DL-BCL, in a retrospective analysis of completed trials, had this data, and in addition, recent preclinical studies have shown enhanced sick activity and sensitivity to sick inhibition in DL-BCL and other non-Hodgkin's lymphomas harboring mutations in MITEI-88 and or CD79. They comprise a distinct genetic subset of ABC-DL-BCL known to have poor outcomes with standard of care therapy. Approximately 50% of all ABC-DL-BCL tumors have one or both of these mutations. Myvovotinib has the potential to be the first to market therapy for patients with a genetically defined subset of DL-BCL. The compelling single agent overall response rate in ABC-DL-BCL and potential for further enrichment of single-agent activity in the genetically defined subset of ABCDL-BCL with MiD88 or CD79 mutations, we believe provides a well-defined, efficient development path to a potential single-agent accelerated approval in these populations. Sipanacertib is a dual mTORC12 inhibitor that targets a key survival mechanism in KEEP1 or Nrf2-mutated tumors. Cipanacertib has demonstrated promising single-agent activity in patients with relapsed or refractory Nrf2-mutated squamous non-small-cell lung cancer. It is a differentiated molecule from other mTOR inhibitors and is the only inhibitor to have strong single-agent activity in Nrf2-mutated squamous non-small-cell lung cancer venagraft. Nrf2 mutations occur in approximately 15% of squamous non-small cell lung cancer and confer a poorer prognosis for these patients. We believe Cepamacertib has the potential to address a substantial underserved patient population and has the potential to be the first treatment for Nrf2-mutated squamous non-small cell lung cancers. We plan to initiate Phase II studies of both the Panacertib and Mivivotinib in the first half of 2022. We also presented data from our Phase Ib trial of CB280 for the treatment of cystic fibrosis at the North American Cystic Fibrosis Conference in November of last year. The data showed that CB280 was well tolerated, demonstrated linear pharmacokinetics, and showed complete and continuous target inhibition in plasma at doses at or above 100 milligrams. CD280 also demonstrated robust pharmacodynamic effects with rapid and significant dose proportional increases in plasma arginine, the key driver of nitric oxide production. Enrollment and analysis of all four cohorts is now complete, and evaluation of next steps is ongoing. Turning to our preclinical pipeline, we have continued to advance our internally discovered preclinical pipeline of synthetic lethality targets. VPS4A and VPS4B are paralog genes, and loss of one or the other paralog in cancer cells is synthetically lethal. Our VPS4 program is the most advanced synthetic lethality program we have, and we recently announced that we will be presenting a poster on the discovery of novel VPS4A small molecule inhibitors at the upcoming AACR meeting in April. I will pass the call over to Emil now to go into additional details on our clinical program. We're excited to realize the potential of Mivovotinib and Sabanacertib in biomarker-defined populations. By focusing on well-characterized genetic vulnerabilities with molecules that have already shown single-agent activity, we believe we will be able to generate Phase II data with targeted, efficient study designs. We plan to share data from these studies by the first quarter of 2023. Thank you, Susan.