Sunitinib Malate

SUMMIT, PEAK and APEX registration-directed clinical trial enrollment remains on track; topline results expected from all three studies in 2025 Ended 2Q 2024 with $390 million, sufficient to fund operations into 2027 WALTHAM, Mass. and BOULDER, Colo., Aug. 06, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported financial results for the second quarter ended June 30, 2024. “Cogent has made tremendous progress in the first half of 2024 and we look forward to continuing to execute on our key priorities across the portfolio,” said Andrew Robbins, the Company’s President and Chief Executive Officer. “All three of our bezuclastinib registration-directed trials remain on track and we expect to complete enrollment in our PEAK global Phase 3 trial this quarter, with topline data expected from all three trials in 2025. In parallel, our Research team continues to make excellent progress as we develop next-generation programs to build out our pipeline.” Recent Business Highlights Announced alignment with the U.S. Food and Drug Administration (FDA) on the Company’s novel patient reported outcome measure, Mastocytosis Symptom Severity Daily Diary (MS2D2), for use in Part 2 of the registration-directed SUMMIT trial evaluating bezuclastinib in Nonadvanced Systemic Mastocytosis (NonAdvSM) patients.Announced additional clinical data from SUMMIT Part 1 at the 2024 European Hematology Association (EHA) Congress. As of the cutoff date, December 18, 2023, patients in Part 1 treated at the recommended dose of 100 mg bezuclastinib demonstrated >90% reductions across all markers of mast cell burden. Additional data also showed meaningful reduction in symptom severity and objective measures of disease, including: Substantial reduction in mast cell reactions (>50%) and patients’ most severe symptoms as measured by MS2D2.Clinically meaningful reduction in all individual MS2D2 TSS symptoms and domains, as well as additional symptoms including dizziness, diarrhea severity, and brain fog. Clinically meaningful improvement in skin symptoms as well as objective reduction in skin lesions. Consistent with results previously reported, the recommended dose of 100 mg demonstrates a favorable safety and tolerability profile. Presented positive lead-in data from the ongoing Phase 3 PEAK trial at the 2024 ASCO annual meeting. As of the cutoff date, April 1, 2024, 42 patients in Part 1 had been on study for a median of 15.3 months. The median progression-free survival (mPFS) during treatment with bezuclastinib and sunitinib was 10.2 months in all patients. In a subset of patients with second-line gastrointestinal stromal tumors (GIST) with only prior imatinib, which most closely resembles patients currently enrolling in Part 2 of PEAK, the data demonstrate a mPFS of 19.4 months. In addition, the objective response rate (ORR) in all patients treated with bezuclastinib and sunitinib was 27.5% and in the subset of second-line patients the ORR was 33.3%, per investigator assessment. Combination treatment resulted in a disease control rate of 80% in all patients and 100% in patients with prior imatinib only.The combination of bezuclastinib and sunitinib does not appear to add to the severity of adverse events known to be associated with sunitinib monotherapy and is well-tolerated. The majority of treatment-emergent adverse events (“TEAEs”) were low-grade and reversible and discontinuations due to TEAEs remain limited. Announced a new Phase 2 clinical trial of bezuclastinib plus sunitinib in later line GIST patients, sponsored by the Sarcoma Alliance for Research through Collaboration (SARC) and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute. The open label, single-arm Phase 2 trial sponsored by SARC and in collaboration with The Life Raft Group and Dana-Farber Cancer Institute is designed to evaluate the mPFS as well as the safety and tolerability of bezuclastinib plus sunitinib in 40 patients with GIST who have previously progressed on sunitinib. Appointed Cole Pinnow Chief Commercial Officer. Mr. Pinnow joined Cogent from Pfizer, where he held increasing roles of responsibility, including President and Managing Director of Pfizer Canada and most recently as Global Franchise Lead, Genitourinary and Breast Cancer Business where he led a global commercial team accountable for the growth of a $5B innovative cancer portfolio in prostate, kidney, bladder and breast therapies. Prior to Pfizer, he held several leadership roles with Hospira and founded the company’s commercial development organization. Mr. Pinnow began his pharmaceutical career as a scientist at Abbott Laboratories. Initiated IND-enabling studies for the potent, selective CNS-penetrant ErbB2 program following presentation of new preclinical data at the American Association for Cancer Research (AACR) 2024 Annual Meeting. The poster described CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species.In addition, CGT4255 demonstrated 80% brain penetrance in mice and was well-tolerated at 10 fold maximally efficacious concentration, resulting in mouse tumor regression, suggesting potential best-in class performance. Anticipated Upcoming Milestones Complete enrollment in the global, Phase 3 PEAK trial in patients with GIST in Q3 2024.Provide additional safety, tolerability, and patient-reported outcomes data from the open label extension portion of SUMMIT Part 1 by the end of 2024.Complete enrollment in the registration-directed APEX Phase 2 trial in patients with Advanced Systemic Mastocytosis (AdvSM) by the end of 2024 and report top-line results by mid-2025.Complete enrollment in SUMMIT Part 2 in the second quarter of 2025 and deliver top-line results by the end of 2025.Initiate a Phase 1 trial of the first Cogent-discovered pipeline program, designed as a potent, selective, reversible FGFR2 inhibitor with best-in-class potential in the second half of 2024.Select lead candidate and initiate IND-enabling studies from ongoing PI3Kα program, designed to potently and selectively target the H1047R driver mutation, which affects >30,000 cancer patients each year. Second Quarter 2024 Financial Results Cash Position: As of June 30, 2024, cash, cash equivalents and marketable securities were $389.9 million, as compared to $435.7 million as of March 31, 2024. The company expects its existing cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into 2027 and through clinical readouts from ongoing SUMMIT, PEAK, and APEX registration-directed trials. R&D Expenses: Research and development expenses were $54.3 million for the second quarter of 2024 as compared to $38.9 million for the second quarter of 2023. The increase was primarily due to costs associated with accelerating enrollment in both SUMMIT and PEAK clinical trials, on-going APEX costs and costs related to development of the research pipeline. R&D expenses include non-cash stock compensation expense of $4.7 million for the second quarter of 2024 as compared to $3.5 million for the second quarter of 2023. In the quarter, an additional $4.5 million was incurred to support sunitinib clinical supply for the PEAK trial due to faster than expected enrollment. G&A Expenses: General and administrative expenses were $10.1 million for the second quarter of 2024 as compared to $8.2 million for the second quarter of 2023. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $5.3 million for the second quarter of 2024 as compared to $3.6 million for the second quarter of 2023. Net Loss: Net loss was $59.0 million for the second quarter of 2024 as compared to a net loss of $44.1 million for the same period of 2023. About Cogent Biosciences, Inc. Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2, ErbB2 and PI3Kα. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: the company’s anticipated cash runway into 2027, the expectation to complete enrollment in the global Phase 3 PEAK trial in the third quarter of 2024 and to report top-line results by the end of 2025, the expectation to complete enrollment in the SUMMIT Part 2 trial in the second quarter of 2025 and to report top-line results by the end of 2025, the expectation to complete enrollment in the registration-directed APEX Phase 2 trial by the end of 2024 and to report top-line results mid-2025, the expectation to provide additional safety, tolerability and patient-reported outcomes data from the open label extension portion of SUMMIT Part 1 by the end of 2024, the expectation to initiate a Phase 1 trial of the company’s FGFR2 inhibitor with best-in-class potential in the second half of 2024, the expectation to select a lead candidate and initiate IND-enabling studies from the company’s ongoing PI3Kα program. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. COGENT BIOSCIENCES, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS(in thousands, except share and per share amounts)(unaudited) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Operating expenses: Research and development$54,294 $38,871 $106,999 $74,909 General and administrative 10,093 8,214 19,792 15,413 Total operating expenses 64,387 47,085 126,791 90,322 Loss from operations (64,387) (47,085) (126,791) (90,322)Other income: Interest income 5,393 2,741 9,450 5,009 Other income, net 44 268 43 950 Change in fair value of CVR liability — — — 1,700 Total other income, net 5,437 3,009 9,493 7,659 Net loss$(58,950) $(44,076) $(117,298) $(82,663)Net loss per share attributable to common stockholders, basic and diluted$(0.59) $(0.59) $(1.21) $(1.14)Weighted average common shares outstanding, basic and diluted 99,240,030 74,753,269 $97,022,345 72,755,210 COGENT BIOSCIENCES, INC.SELECTED CONDENSED CONSOLIDATED BALANCE SHEET DATA(in thousands)(unaudited) June 30, December 31, 2024 2023 Cash, cash equivalents and marketable securities $389,904 $273,170 Working capital $329,968 $232,603 Total assets $429,935 $313,437 Total liabilities $56,712 $55,635 Total stockholders’ equity $373,223 $257,802 Contact:Christi WaarichSr. Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

Encouraging signs of activity were observed, including a 23% objective response rate (ORR) across all patients (median four prior lines of therapy) and a 43% ORR across second-line patients Favorable tolerability pro observed, consistent with use in front-line and second-line settings Data to be highlighted in an oral presentation today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting PLYMOUTH, Mass.--(BUSINESS WIRE)-- IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, today announced updated preliminary clinical data from the Phase 1 portion of the company’s ongoing StrateGIST 1 study of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST). These data will be highlighted today in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. IDRX-42 is a novel, KIT mutant-selective, tyrosine kinase inhibitor (TKI) that has potent activity against both the key activating mutations and broad coverage of the clinically relevant resistance mutations in KIT-driven GIST. IDRX-42 was designed to overcome the twin challenges of on-target treatment resistance and off-target driven adverse events, which limit the clinical benefit of currently available TKIs. “There is a significant unmet medical need for next-generation therapies for GIST patients. Current standards of care either lack the breadth of resistance mutation coverage necessary for patients to realize long durations of response or disease stabilization, or they lack selectivity, resulting in unwanted side effects, or both,” said Professor Patrick Schöffski, M.D., M.P.H., Head of the Department of General Medical Oncology at the University Hospitals Leuven. “These promising Phase 1 data support the potential of IDRX-42 to provide meaningful clinical benefit for GIST patients, with encouraging evidence of clinical activity in patients with activating KIT mutations in exons 9 and 11, as well as in patients with clinically relevant resistance mutations in KIT, importantly those in exons 13 and 17.” Updated Preliminary Clinical Data Summary As of the data cut-off date of April 28, 2024, 73 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 600 mg twice daily (BID). All 73 patients had KIT-mutant GIST. 66 patients were evaluable for efficacy as of the time of the data cut-off. Patients who were efficacy evaluable must have had at least 1 post-baseline tumor assessment or had clinical progression or death before the first post-baseline tumor assessment. While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300mg tablet formulation, which is equivalent to the 400mg capsule formulation. Patients were heavily pretreated, with a median of four prior lines of therapy. 19% (14/73) patients had received one prior line of therapy. 11% (8/73) patients had received two prior lines of therapy. 70% (51/73) patients had received three or more prior lines of therapy. 74% of patients remained on study treatment, and the median duration of treatment was 16 weeks as of the data cut-off. 100% of second line patients remained on treatment as of the data cut-off. The objective response rate (ORR) by modified RECIST v1.1 in the efficacy evaluable population was 23% (15/66) treated across all lines of therapy, of which all were partial responses (12 confirmed PRs, 3 pending confirmation). The ORR across second line patients was 43% (6/14; 4 confirmed PRs, 2 pending confirmation). In analyses of circulating tumor DNA (ctDNA), reductions in mutant allele fraction were observed consistently across KIT mutations detected in baseline samples. Reductions in mutant allele fraction, including to undetectable levels, as best response were observed in exon 9 and 11 activating mutations, and in resistance mutations exon 13, 14, and 17. IDRX-42 exhibited a favorable safety pro treatment-related adverse events (TRAEs) were mainly low grade. The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue. Gastrointestinal adverse events were Grade 1 in most patients, when they occurred. A low rate of dose modifications due to TRAEs was observed at the 400mg QD dose level, with only 6% dose reductions, 9% dose interruptions, and 0% discontinuations due to TRAEs. Dose-limiting toxicities (DLTs) were observed in 3/73 patients at doses of 600 mg, 800 mg and 1200 mg, respectively. All 3 patients elected to reduce dose and remained on study as of the data cut-off (range: >3 to >11 months); 2 of these patients have achieved a confirmed PR at a reduced dose of 400 mg QD. A flat and dose-linear pharmacokinetic pro observed. “In this dataset, IDRx has presented preliminary proof-of-concept of IDRX-42 supporting its potentially best-in-class pro patients with GIST,” said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. “Importantly, we believe these efficacy and safety data support our plan to move IDRX-42 rapidly into early lines of therapy, including second-line and front-line, where patients haven’t seen a new treatment option in over 15 years.” “We are excited for these data to be presented today, as they support all aspects of our target product profile, including evidence of potent activity against relevant activating and resistance mutations in KIT, combined with a favorable safety profile,” said David Kerstein, M.D., Chief Medical Officer of IDRx. “Across a wide dose range and in this heavily pre-treated patient population, promising signs of clinical activity have been observed, and the initial data compares favorably against approved therapies and those in clinical development. We are encouraged by the emerging safety and tolerability profile, characterized mainly by low grade, manageable gastrointestinal adverse events with a notable lack of adverse events generally associated with off-target activity, such as hand-foot skin reaction and hypertension, supporting the overall selectivity of the molecule. We would like to express our gratitude to the patients and investigators for their participation in the ongoing StrateGIST 1 study.” The Data Will be Highlighted in an Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting: Title: StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs) Presenter: Patrick Schöffski, M.D., M.P.H. Abstract Number: 11501 Presentation Type: Oral Abstract Session Session Title: Sarcoma (Sub Track Gastrointestinal Stromal Tumors) Time: 3:12 P.M. CDT About GIST Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. About the StrateGIST 1 Study StrateGIST 1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after failure of imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., Belgium, Germany and Spain. The Phase 1b portion will include expanded exploratory cohorts based on defined lines of prior TKI therapy. About IDRX-42 IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is currently being evaluated in a first-in-human Phase 1/1b study. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to transforming cancer care with intelligently designed precision therapies. IDRx aims to address the limitations of today’s precision cancer medicines with highly potent and selective targeted therapies to stop key tumor escape mechanisms and prolong response to therapy. IDRx’s lead program is IDRX-42, designed to inhibit key genetic drivers and drug-resistant mutations of KIT in gastrointestinal stromal tumor (GIST). IDRx's pipeline also includes a second KIT inhibitor, IDRX-73. Founded in 2021, IDRx’s leadership team has extensive experience in drug development and collectively has been involved in the discovery, development, and commercialization of more than 10 approved medicines. To learn more, please visit and follow us on LinkedIn. View source version on businesswire.com: Contacts 1AB Katie Engleman katie@1abmedia.com Source: IDRx, Inc. View this news release online at: