CYT-0851 Phase 1 dose escalation results show early clinical activity and generally well-tolerated safety profile in advanced solid tumors and hematological malignancies

LEXINGTON, Mass.–(BUSINESS WIRE)–Cyteir Therapeutics, Inc. (“Cyteir”) (Nasdaq: CYT), a company focused on the discovery and development of next-generation synthetic lethal cancer therapies, today reported results from a trial of phase 1 escalating monotherapy with CYT -0851 in a poster entitled “Phase 1 Results of CYT-0851 in Patients with Advanced Solid and Hematologic Cancers” (abstract: 3084, poster: 76) at the 2022 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois.

“Data presented today from the Phase 1 dose-escalation study with CYT-0851 show that the drug performed well in patients with advanced, relapsed and/or refractory cancer : it has desirable pharmacological properties with an estimated half-life of three days, proportional to the dose. exposure and a dose-dependent, predictable and favorable safety profile. Additionally, anti-tumor activity was observed with disease stabilization and responses in patients with solid tumors and hematological malignancies, supporting the advancement of CYT-0851 as a potential first-of-its-kind drug. category, in the Phase 2 expansion cohorts as monotherapy and Phase 1 in combination with standard-of-care regimens,” said Markus Renschler, MD, President and CEO of Cyteir. “The Cyteir team continues to execute clinical development of CYT-0851 and we look forward to sharing data in the second half of 2022.”

Phase 1 Dose Escalation Results

The primary objectives of the Phase 1 dose escalation trial with CYT-0851 were to determine the recommended Phase 2 dose, to determine the maximum tolerated dose (MTD), and to assess safety and tolerability. Primary secondary objectives include determination of pharmacokinetic parameters, optimal dosing regimen, and preliminary anti-tumor activity. As of the data cutoff date of April 13, 2022, 80 patients have been enrolled in twelve dose escalation cohorts from 30 mg to 1200 mg total daily dose. Eighty patients were evaluable for safety and 65 patients were evaluable for efficacy.

The maximum tolerated dose has been determined at 600 mg once daily for solid tumors and hematological malignancies. The recommended dose for Phase 2 is 400 mg once daily, a practical and commercially attractive regimen.

Main findings

In solid tumors:

  • Forty-five patients had an evaluable response and one unconfirmed partial response (PR) was achieved in one patient with soft tissue sarcoma who was treated for almost 11 months

  • Nineteen patients (42%) had stable disease and twelve patients (27%) had a decrease in target lesion size for an overall disease control rate of 44%

  • Stable disease (42%) has been observed in patients with soft tissue sarcoma, squamous cell carcinoma of the head and neck, pancreas, ovary and breast

In hematological cancers:

  • Eighteen patients with non-Hodgkin’s lymphoma had an evaluable response

  • Responses were seen in patients with follicular lymphoma (1 complete response (CR) and 1 PR) and diffuse large B-cell lymphoma (1 PR)

  • Three patients with follicular lymphoma, one patient with diffuse large B-cell lymphoma and one patient with hairy cell leukemia achieved stable disease

  • Patients responding to CYT-0851 showed durable clinical benefit, as evidenced by more than 18 months of treatment in the patient with follicular lymphoma who achieved CR

Security:

  • To date, CYT-0851 has exhibited a generally well-tolerated safety profile, with 42% of patients reporting no treatment-related adverse events (TRAEs)

  • At the recommended Phase 2 dose or below, no patients discontinued treatment for EITRs.

  • The most common AETRs were fatigue (18%), alopecia (14%), nausea (11%), hyperuricemia (10%), constipation (8%) and anemia (8%) .

  • Dose-limiting toxicity was reversible metabolic acidosis, consistent with the drug’s mechanism of action

“Phase 1 data for CYT-0851 monotherapy demonstrated promising clinical activity with a manageable safety profile for a broad spectrum of cancers in a heavily pretreated patient population,” said Dr. Ryan C. Lynch, Professor assistant at the Fred Hutchinson Cancer Center. and first author of the study. “The broad activity coupled with the mechanistic understanding that CYT-0851 impacts cancer cell metabolism creates a promising therapeutic approach for use in a wide range of cancers.”

Knowledge about the mechanism of action of CYT-0851 has the potential to extend to other tumor types

Based on new molecular, bioinformatic and biochemical characterization research that was performed at Cyteir to elucidate the mechanism of action of CYT-0851, management believes that the observed effects of CYT-0851 on cancer cell viability are due to inhibition of the monocarboxylate transporter (MCT) and subsequent disruption of lactate transport. Monocarboxylate transporters are essential proteins in cancer metabolism, making MCTs an attractive target for cancer treatment. This new understanding of the mechanism of action of CYT-0851 could potentially accelerate biomarker development and allow expansion into additional opportunities in other tumor types.

Data from ongoing Phase 2 monotherapy expansion cohorts and combined Phase 1 study expected in H2 2022

Cyteir continues to make progress in advancing CYT-0851 into monotherapy and combination clinical studies. Recruitment is ongoing in six disease-specific Phase 2 expansion cohorts with monotherapy in hematological malignancies and solid tumors. Completion of enrollment in Stage 1 of this study is expected before the end of 2022. Recruitment is also underway in a combined Phase 1 study of CYT-0851 with three standard treatment regimens: (1) rituximab plus bendamustine ; (2) gemcitabine; and (3) capecitabine, both in hematological malignancies and solid tumors. The first safety data from this combined study are expected before the end of 2022.

About Cyteir Therapeutics, Inc.

Cyteir is a clinical-stage oncology company focused on the discovery and development of next-generation synthetic lethal therapies to treat cancer. At Cyteir, we use an integrated approach to target discovery that integrates critical evaluation of target biology with internal and external information from a variety of genetic and chemical synthetic lethality screens to power our discovery and development pipeline. of drugs. Cyteir’s 100%-owned lead compound, CYT-0851, is a selective oral investigational drug currently in Phase 1/2 clinical trials for hematological malignancies and solid tumors. Follow Cyteir on social media: LinkedIn and Twitter.

Forward-looking statements

This press release contains “forward-looking statements” about Cyteir’s strategy, future plans and prospects, including statements regarding the development of Cyteir’s compounds and potential expansion opportunities, regulatory strategy and path for compounds of Cyteir, as well as the timing and communication of expected results of preclinical and clinical studies of Cyteir. The words “anticipate”, “believe”, “continue”, “could”, “estimate”, “expect”, “intend”, “probable”, “may”, “could”, ” plan”, “potential”, “project”, “seek”, “will”, “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain such identifying words.

Actual results could differ materially from those included in the forward-looking statements due to various factors, risks and uncertainties, including, but not limited to: clinical trials of Cyteir may not adequately demonstrate the safety and efficacy of one of its drug candidates; that preclinical testing of Cyteir’s compounds may not be predictive of clinical trial results or success; that the preclinical and clinical development of Cyteir’s compounds could be delayed or otherwise take longer and/or cost more than expected; that Cyteir may not be able to initiate, enroll or complete clinical development of its compounds; that the continuing global outbreak of COVID-19 (including any resurgence or variation) may result in development or manufacturing delays, supply shortages, or shortages of qualified healthcare personnel; that synthetic lethality, as an emerging class of precision medicine targets, could result in negative perceptions of the efficacy, safety, or tolerability of this class of targets, which could impair our ability to conduct our business, to advance our drug candidates or to obtain regulatory approvals; and that Cyteir’s compounds may not receive regulatory approvals or become commercially successful products. These and other risks and uncertainties are identified under the heading “Risk Factors” in Cyteir’s most recent Annual Report on Form 10-K and in other filings Cyteir has filed and may file with the Securities and Exchange Commission (“SEC”) in the future, available on the SEC’s website at www.sec.gov.

The forward-looking statements contained in this press release are based on management’s current opinions, plans, estimates, assumptions and projections regarding future events, and the Company does not undertake and specifically disclaims any obligation to update the statements. prospective.

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