Cyclacel Pharmaceuticals, Inc.

Good afternoon and welcome to the CycloCell Pharmaceuticals third quarter 2021 results conference call and webcast. At this time, all participants are in a listen-only mode. After today's call, members of the financial community will have an opportunity to ask questions. If you would like to ask a question at that time, please press star 1 on your telephone keypad. If at any point your question has been answered, you may remove yourself from the queue by pressing the pound key. In posing your question, we ask that you please pick up your handset to allow optimal sound quality. The company will also be accepting a limited number of questions submitted via email to the address ir at cyclocell.com. Lastly, if at any time during the call you should require operator assistance, please press star zero. Please note, today's call is being recorded. I would now like to turn the conference call over to the company.

Good afternoon, everyone, and thank you for joining today's conference call to discuss Cyclocell's financial results and business highlights for the third quarter ending September 30th, 2021. Before turning the call over to management, I would like to remind everyone that during this conference call, forward-looking statements made by management are intended to fall within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and Section 21E of the Securities Exchange Act of 1934 as amended. As set forth in our press release, forward-looking statements involve risks and uncertainties that may affect the company's business and prospects, including those discussed in our filings with the SEC, which include, among other things, our Forms 10-Q and 10-K. These filings are available from the SEC or our website. All of our projections and other forward-looking statements represent our judgment as of today, and CycloCell does not take any responsibility to update such information. With us today are Spiro Rombatis, President and Chief Executive Officer, Paul McBaron, Executive Vice President, Finance and Chief Operating Officer, and Dr. Mark Kirschbaum, Senior Vice President and Chief Medical Officer. Spiro will begin with an overview of our business strategy and progress on CycloCell's clinical program, and Paul will provide financial highlights for the third quarter of 2021, which will be followed by a Q&A session. At this time, I would like to turn the call over to Spiro.

Thank you, Irina, and thank you, everyone, for joining us today. for our third quarter and business update call. I would like to begin the call by providing an update on the progress we are making across our two programs, our oral CDK2-9 inhibitor, Fadracycline or FADRA, and our oral PLK1 inhibitor, CYC140 or 140. The third quarter was characterized by continued execution of our operating plan with opening of two Phase I-II studies for oral FADRA and filing an IND for a Phase I-II study of R140. We have now enrolled a total of six patients across two dosing levels in our FADRA study designated 065-101 in patients with solid tumors and lymphomas. More recently, we announced dosing the first patient in our 065-102 study of FADRA in patients with leukemia. We have also filed with FDA an IND submission for an oral 140 phase 1-2 study in patients with solid tumors. While waiting for FDA review of the IND, we are preparing to open this study, which is supported by ongoing preclinical experiments, supporting our choice of certain cancer histologies for the proof of concept part of this study. It has been a busy year for the company, but we are pleased to be on track to deliver as many as 15 outcomes, or shots on goal, from different cohorts in the two FADRA studies next year. And we are funded to deliver on these potential outcomes with cash projected through early 2023. Let me now review the FADRA program. We are building a specialized global network of world-renowned cancer treatment centers for both the solid tumor and leukemia studies. In addition, multiple preclinical collaborations are providing strong evidence in support of our choice of treatment cohorts in the proof-of-concept stages of the two Phase I-II FADRA studies. Both of these studies are registration-directed and use a streamlined design with an initial stage to determine the recommended Phase II dose, or RP2D, of oral FADRA in solid tumors and separately in leukemias. Once RP2D has been established, the studies will immediately enter into proof-of-concept cohort stage. using a SIMON2 statistical rule to assess efficacy in individual cohorts. If sufficient efficacy at tolerable doses is observed, the relevant cohort will enter an expansion prior to possible presentation of the data to regulatory authorities. In addition to seven solid tumor in 065-101 and six leukemia cohorts in 065-102, the FADRA studies contain a basket cohort in which patients can enroll based on biomarkers relevant to FADRA's mechanism of action. Initial cohorts will receive FADRA as a single agent, with subsequent cohorts designed to treat FADRA in combination with available or emerging standard of care. In total, we expect to report outcomes from 15 cohorts, or 15 shots on goal, 8 in solid tumors and lymphoma, and 7 in leukemia. In the 065-101 solid tumor and lymphoma study, we have dosed orally administered FADRA to six patients in the first two dosing levels, or DLs. Three patients were treated at the starting DL1 level at 50 milligrams BID for three days a week. In DL2, patients are being dosed at 50 milligrams BID for five days a week. We believe that daily dosing is important for drugs enabling apoptosis, like FADRA. Oral FADRA is well-tolerated thus far, and patients are being followed up for initial assessment of efficacy. As a reminder, durable partial response was observed with intravenously administered FADRA at 200 mg two days a week. We are pleased with the pace of recruitment in the 065-101 study, which is currently enrolling at City of Hope and MD Anderson Cancer Centers. Two additional internationally recognized cancer centers located in Asia and Europe, respectively, have been added to 065-101, with one already open for enrollment. Both sites were selected for their expertise with tumor types of interest to FADRA. With a total of four sites, we expect to rapidly determine RP2D and move into the cohort stage. Although expectations of clinical efficacy are low in the dose escalation stage, as specific histologies of interest are not required in the protocol, investigators are permitted to enroll patients with relevant tumor types. In the 065-102 study of oral FADRA and leukemias, we have dosed the first patient in the dose escalation part and will update our progress as dose escalation continues. Details of this study were described in our recent press release. To summarize, Similar to the solid tumor 065-101 study, the initial dose escalation stage of the leukemia trial will determine the recommended phase 2 dose, followed by a proof of concept or cohort stage. Oral FADRA will be evaluated in patients with various hematological malignancies and leukemia subtypes. These include AML, CLL, MDS, and also specific leukemia subtypes dependent on the FLT3, KIT, or MAPK pathways. In 065-102, three cohorts will receive oral FADRA as a single agent, and the rest in combination with venetoclax, or hypomethylating agent, or low-dose RSD. The basket cohort can enroll patients with biomarkers relevant to FADRA's mechanism, but diagnosed with different hematological malignancies or benign hematological conditions characterized by uncontrolled proliferation. The protocol allows for expansion of the cohort based on efficacy, which may allow for acceleration of the clinical development and registration plan for FADRA. As a reminder, encouraging anti-leukemic activity and good tolerability in AML and CLL patients were observed with the IV formulation of FADRA dosed intermittently in combination with venetoclax. Let us now turn to 140, our novel, orally available PLK1 inhibitor. Having filed the IND with the FDA, we expect to open a Phase I-II study for the treatment of solid tumors in early 2022. We will provide details of the cohorts to be included in the study at that time, along with our dosing strategy for 140 as a single agent. This strategy is strongly supported by preclinical data, which show that 140 is biologically differentiated from the other PLK1 inhibitor in development. Specifically, preclinical studies by Cyclacel and collaborating investigators have demonstrated sensitivity of certain tumor types in patient-derived specimens to 140 monotherapy given as daily oral dosing. If these findings are reproduced in the upcoming clinical studies, 140 could emerge as a promising alternative in multiple solid and liquid cancers. The expansion of clinical programs for our two lead candidates is building up to a very exciting period for CycloCell. By the end of the first quarter of 2022, we expect to have three ongoing Phase 1-2 clinical trials, which taken together should result in one of the most data-rich periods in our company's history. As these data sets begin to mature, the positioning of FADRA relative to other development stage CDK inhibitors, is worth considering. The success of first-generation CDK drugs, such as Pfizer's Ibrans, have attracted the attention of both drug developers and investors. Several new therapies are now in clinical development, targeting a variety of CDK enzymes. We thought it was important to discuss on today's call how FADRA is differentiated. effective anti-cancer drugs must be capable of durable target engagement. While our previous intravenous formulation of FADRA clearly demonstrated strong single-agent activity, we also recognized that intermittent or weekly dosing of an IV-administered drug would not be convenient for patients, especially in the midst of an ongoing pandemic. We therefore invested a considerable time and resource studying the pharmacogenetic relationship between oral and intravenous FADRA. These data were presented in October 2020 and showed that our oral formulation had similar bioavailability to the AV formulation, including half-life, maximal concentration, and area under the curve. This led us to conclude that FADRA could be optimally dosed as an oral daily schedule therapy. With a four-hour half-life and once or twice daily dosing, we believe oral FADRA is capable of durable target engagement, but with the added benefit of oral dosing convenience for patients. As a highly selective inhibitor of both CDK2 and CDK9, FADRA can help restore apoptosis within a cancer cell in two important ways. By targeting CDK9, FADRA inhibits the transcriptional regulation of anti-apoptotic proteins such as MCL1 and MYC. By targeting CDK2, FADRA addresses an escape mechanism when CDK9 is inhibited and also directly inhibits self-proliferation by preventing overexpression of cyclin E. When it is abnormally elevated, sactin E contributes to resistance of several tumor types, mostly in the women's cancers, to various anticancer therapies. We believe that FADRA's dual targeting, both within the cell cycle pathway, may confer a competitive advantage in the clinic. In the months ahead, we hope to formally present many of these exciting findings featuring our two lead drug candidates. Having reviewed the progress with our clinical programs and ongoing research activities, I would like now to turn the call over to Paul McMarron for a review of Cyclocell's third quarter financials. Paul?