Spiro Rombotis
Analyst · Ladenburg
Thank you, Alex, and thank you everyone for joining us today for our first quarter business update call. 2019 is an exciting year for the company as we’re evaluating our three clinical stage drugs led by CYC065, our CDK 2/9 inhibitor across a total of six clinical studies, four in patients with hematological malignancies and two in patients with solid tumors. These studies are designed to deliver on our core business strategy to overcome cancer resistance. We’re also pleased to have reported data presented at last month’s 2019 AACR Annual Meeting. Let us start by explaining our scientific and business strategy. Cancer resistance proteins are central to the ability of cancer cells to invade the treatment effect of anti-cancer drugs which eventually lose their effectiveness. They are often referred to as pro-survival proteins as they help cancer cells survive anti-cancer therapy and gain an advantage over normal cells. Suppressing pro-survival proteins is therefore a promising therapeutic strategy to address the growing problem of resistance. This is particularly true for recently approved targeted drugs as emergence of resistance is a major concern in new but expensive treatment plans for patients. As new drugs stop working against cancer after early effectiveness, risk of disease progression, relapse and death increase undermining society’s return on investments. Cyclacel’s strategy addressing this problem is to target proteins whose aberrant expression correlates with the resistance. Such proteins include members of the Bcl-2 protein family such as Bcl-2 itself and Mcl-1 and also MYC and cyclin E. Mcl-1 in particular is receiving wide attention in recent medical conferences. Multiple preclinical studies show that simultaneous suppression of Bcl-2 and Mcl-1 restores sensitivity of cancer cell to the drugs that target one of these proteins and have stopped working. Venetoclax, the first approved Bcl-2 inhibitor is indicated for first or second line chronic lymphocytic leukemia, or CLL, and first line acute myeloid leukemia, or AML, in combination with a hypomethylating agent or a nucleoside analogue. Venetoclax represents an important advance, however, patients eventually stop responding. These clinical findings have attracted a lot of attention in the scientific community and a competitive race has ensued to bring to market drugs that inhibit Mcl-1 function with the aim of using them in combination with venetoclax. Cyclacel is a leader in this race having demonstrated in patients that CYC065 durably suppresses Mcl-1 at tolerable doses and recently started treating patients in a combination study with venetoclax in patients with relapsed/refractory CLL and soon also in AML and MDS. An additional strategy is to enhance the efficacy of standard of care drugs by targeting inherited mutations in DNA damage pathways such as homologous recombination deficient cancers which include those with BRCA mutations. The modest duration of clinical benefit to PARP inhibitors, the standard of care approved for BRCA mutant gynecological cancers suggest the need for novel drugs used in combination to improve the disease control and extend survival. Sapacitabine works by an HR deficient relevant mechanism that is distinct from the mechanism of action of PARP inhibitors. Sapacitabine has demonstrated activity in BRCA-positive breast cancer with one patient still on drug after six years. Recent clinical data with sapacitabine reported at the 2019 AACR have provided the rationale for an ongoing combination study of orally dosed sapacitabine and olaparib, the leading PARP inhibitor approved for breast and ovarian cancer. Let us now turn to the execution of our strategy. We have recently open for enrollment and are treating patients in two out of our studies under our collaboration with the MD Anderson Cancer Center with the other two studies to open shortly. In CYC065-02, the Phase 1 combination study of CYC065 and venetoclax in relapsed/refractory CLL, two patients have been treated at MD Anderson without dose-limiting toxicity or DLT with the approved full dose of venetoclax and intravenously administered CYC065 at a dose of 64 mgs per meter squared. The first patient is continuing on cycle 4 and has experienced an improvement in platelet levels. The second patient is on cycle 1. We have recently submitted to the IRB a protocol amendment to broaden the eligibility criteria. In parallel with MD Anderson, we’re also recruiting additional sites to join our study. In CYC140-01, the first-in-human Phase 1 study of CYC140 our PLK1 inhibitor in advanced leukemia, the first two patients have been dosed, one at the starting dose of 16 milligrams per meter squared administered intravenously and the second at 32 mgs per meter squared. No dose-limiting toxicities have been observed thus far. CYC140 is a small molecule, selective, PLK1 inhibitor that has demonstrated potent and selective target inhibition and high activity in xenograft models of human cancers. Protocols for the other two Phase 1 studies in the MD Anderson alliance have been finalized and submitted to IRB. These are CYC065-03, a combination of CYC065 and venetoclax and CYC682-11, a combination of sapacitabine and venetoclax both in patients with relapsed/refractory AML or MDS. Both are expected to open shortly for enrollment. We continue to enroll patients in Part 2 of the CYC065-01 Phase 1 trial of 065 in patients with advanced solid tumors. Part 2 is evaluating the pharmacokinetic profile of a one hour infusion of CYC065 administered over two days per week for two weeks out of a three-week cycle. 10 patients have been enrolled thus far; three at 90 milligrams per meter squared, five at 120 milligrams per meter squared and two at 160 milligrams per meter squared, respectively. As a reminder, in Part 1, CYC065 was administered over a four-hour infusion once every three weeks. We made good progress with developing the order formulation of CYC065 and capsules for oral administration are now available for clinical trial. The CYC065-01 Part 3 protocol has been amended to evaluate dosing of oral CYC065 and its pharmacokinetics. The protocol amendment is under institutional review at the Dana-Farber Cancer Institute and is expected to open for accrual shortly. Let us now turn to the Phase 1b/2 investigator-sponsored trial or IST of the combination regimen of sapacitabine and the PARP inhibitor olaparib or AstraZeneca's LYNPARZA in PARP inhibitor naïve patients with BRCA-mutant breast cancer. Three patients have been dosed in this IST sponsored by the Department of Breast Cancer at Dana-Farber. According to the investigators, the first two patients treated with 150 milligrams of sapacitabine and the approved dose of olaparib achieved tumor shrinkage with no safety concerns. These patients are continuing treatment. A third patient has recently been treated. Cyclacel and AstraZeneca are supplying sapacitabine and olaparib, respectively. With capital on hand estimated until the end of 2020, we have the resources to take us through key clinical milestones in our ongoing clinical studies. In summary, as we continue to execute on our strategy and advance our clinical development plans, our key milestones include initiate CYC065 and venetoclax Phase 1 study in patients with relapsed/refractory AML or MDS. Initiate sapacitabine and venetoclax Phase 1 study in patients with relapsed/refractory AML or MDS; report initial data from the CYC065 and venetoclax Phase 1 study in leukemias; report initial data from the CYC140 Phase 1 first-in-human study; report initial data and bioavailability from the Phase 1 study of oral CYC065. Report updated CYC065 Phase 1 data in patients with advanced solid cancers; report data from the Phase 1b/2 IST of sapacitabine-olaparib combination in patients with BRCA mutant metastatic breast cancer when reported by the investigators; and determine regulatory pathway and submissibility of sapacitabine in elderly AML. I will now like to turn the call over to Paul to review our first quarter 2019 financials. Paul?
