Sunitinib Malate

PLYMOUTH, Mass.--( BUSINESS WIRE )--IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to developing and commercializing precision therapeutics for the treatment of cancers with well-characterized biology and significant unmet medical need, today announced updated clinical data from StrateGIST 1, the company’s ongoing Phase 1/1b trial of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST). These data continue to demonstrate promising anti-tumor activity of IDRX-42 in patients with advanced GIST and will be highlighted today in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting, being held November 13-16, in San Diego, CA. IDRX-42 is an investigational oral, small molecule, tyrosine kinase inhibitor (TKI) designed to selectively target the most prevalent KIT mutations that either drive the growth, proliferation, and survival of tumor cells (activating mutations in exons 9 and 11), or confer resistance to currently available therapies (resistance mutations in exons 13 and 17). “ In patients living with GIST, the therapeutic potential of KIT targeted TKIs has been limited by drug resistance caused by an inability to target the spectrum of the most prevalent KIT mutations, and poor tolerability,” said Suzanne George, M.D., Chief, Division of Sarcoma at the Dana-Farber Cancer Institute. “ These updated data from StrateGIST 1 are highly encouraging with respect to the clinical activity observed in later-line patients with a variety of KIT activating and resistance mutations. I am excited by the potential of IDRX-42, with its differentiated clinical profile demonstrated to date, to help meet this critical need for GIST patients.” “ We are particularly excited about the emerging durability data from StrateGIST 1. These data, together with the continued strengthening of response rate and tolerability data, underscore the potential for IDRX-42 to improve outcomes for GIST patients and support our plans to move IDRX-42 into late-phase development,” said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. “ With FDA alignment now in place, we plan to conduct StrateGIST 3, a randomized, Phase 3 registrational trial which will evaluate the efficacy and safety of IDRX-42 as compared to sunitinib in second-line GIST patients. We remain steadfast in our commitment to transform the lives of patients with GIST, including in early-line settings, where the standards of care have remained unchanged for almost 20 years and a significant unmet need remains.” Presentation Highlights As of the data cut-off date of September 30, 2024, 89 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 1200 mg total daily dose (600 mg twice daily (BID)). All 89 patients had KIT -mutant GIST. 87 patients were evaluable for efficacy as of the data cut-off date. The two non-evaluable patients were recently enrolled and remain on treatment, awaiting their first post-baseline tumor assessment. While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has been completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300 mg in tablet formulation, which has comparable steady-state plasma exposure to a dose of 400 mg in capsule formulation. Patients were heavily pretreated overall, with a median of four prior lines of therapy. 17% (15/89) patients had received one prior line of therapy (IDRX-42 evaluated as second-line). 11% (10/89) patients had received two prior lines of therapy (IDRX-42 evaluated as third-line). 72% (64/89) patients had received three or more prior lines of therapy (IDRX-42 evaluated as ≥ fourth-line). 28% (25/89) received three or more prior lines of therapy that did not include ripretinib. As of the data cut-off date, 63% (56/89) of patients remained on study treatment, and the median duration of treatment was 6.6 months. The ORR by modified RECIST v1.1 in the total efficacy evaluable population was 29% (25/87) treated across all lines of therapy, including one complete response (CR) and 24 partial responses (PRs). Two of the PRs were awaiting confirmation at the time of the data cut. At the 400 mg capsule/300 mg tablet QD recommended Phase 1b dose (RP1bD), the ORR was 26% (10/38) in the total efficacy evaluable population. The ORR in second-line patients was 53% (8/15) including one CR and 7 PRs. At the RP1bD or below, the ORR was 50% (7/14) across second-line patients. In second-line patients (n=15), the 6-month PFS was 85%, and the median was not yet reached. The median PFS in third- or later-line patients both at the RP1bD (n=25) and across all doses (n=72) was 9.2 months. The median PFS in third-line patients overall (n=10) was 12.9 months. The median PFS in fourth- or later-line patients who had not previously received ripretinib (n=25) was 9.2 months, and at the RP1bD (n=10) was 11 months. IDRX-42 was generally well-tolerated and treatment-related adverse events (TRAEs) were mainly low grade at the RP1bD. The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue. An 8% dose reduction rate due to TRAEs was observed at RP1bD, with no TRAEs leading to dose discontinuation. The Phase 1b portion of StrateGIST 1 commenced enrollment in May 2024 and includes a first-, second-, and two later-line cohorts. The second- and two later-line cohorts are nearly fully enrolled. IDRx has aligned with the FDA on fundamental elements of the trial design, dose, and statistical analysis for StrateGIST 3, a global, randomized, Phase 3 registrational trial which will evaluate IDRX-42 as a second-line therapy in patients diagnosed with metastatic and/or unresectable GIST with disease progression on, or intolerance to, imatinib, the current first-line standard of care for GIST patients. Presentation Details Title: The Novel KIT inhibitor IDRX-42 Shows Promising Activity in Second- and Later-Line Gastrointestinal Stromal Tumors (GIST): Results from a Phase 1 Trial (StrateGIST 1) Presenter: Suzanne George, M.D. Abstract Number: P 10 Presentation Type: Oral Abstract Session Time: Thursday, November 14, 10:30 a.m. – 11:30 a.m. PST Location: Harbor Ballroom, Manchester Grand Hyatt, San Diego, CA About GIST Gastrointestinal stromal tumor (GIST) is the most common subtype of soft tissue sarcoma occurring in the gastrointestinal tract. Between 4,000 to 6,000 people are diagnosed with GIST in the United States each year. Approximately 80% of all GIST cases are driven by mutations in the KIT gene. An estimated 90% of patients who receive imatinib, the current standard of care for GIST, will experience disease progression related to the emergence of KIT resistance mutations. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Despite the widespread availability of tyrosine kinase inhibitors approved for GIST, first-line and second-line standards of care have remained unchanged for almost 20 years and significant unmet need remains. 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 anti-tumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after progression on 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., United Kingdom, Belgium, the Netherlands, France, Germany, Italy, Spain, South Korea, and China. The Phase 1b portion commenced enrollment in May 2024 and includes four exploratory cohorts based on defined lines of prior tyrosine kinase inhibitor therapy, including first-, second-, third- and later-line therapies. About IDRX-42 IDRX-42 is an investigational oral, small molecule KIT tyrosine kinase inhibitor in clinical development as a monotherapy for the treatment of gastrointestinal stromal tumors (GIST). IDRX-42 is designed to selectively target the most prevalent forms of KIT mutations that either drive the initial growth, proliferation, and survival of tumor cells, or confer resistance to currently available therapies. In pre-clinical studies, IDRX-42 demonstrated superior anti-tumor activity as compared to imatinib, the current first-line of therapy, in tumors associated with both exon 9 and 11 KIT mutations. IDRX-42 was also shown in pre-clinical studies to have strong inhibition activity against the most prevalent KIT resistance mutations in exons 13 and 17, suggesting that IDRX-42 could prevent or substantially delay the emergence of such mutations. 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 StrateGIST 1, a first-in-human Phase 1/1b trial. IDRX-42 has been granted Fast Track and Orphan Drug designations by the U.S. Food and Drug Administration for the treatment of GIST after disease progression on imatinib. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to developing and commercializing precision therapeutics for the treatment of cancers with well-characterized biology and significant unmet medical need. 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 patients’ response to therapy. IDRx’s lead program is IDRX-42, which is designed to selectively target the most prevalent forms of KIT mutations and has the potential to improve outcomes for gastrointestinal stromal tumor (GIST) patients as a first- or second-line therapy, where the standards of care have remained unchanged for almost 20 years and significant unmet need remains. 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 www.idrx.com and follow us on LinkedIn .

Top-line results from registration-directed SUMMIT, PEAK and APEX trials expected in 2025 Phase 1 trial initiated for CGT-4859, a reversible, potent, selective, FGFR2 inhibitor SUMMIT and APEX clinical presentations at upcoming ASH annual meeting Strong cash position of $346 million sufficient to fund operations into late 2026 WALTHAM, Mass. and BOULDER, Colo., Nov. 12, 2024 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today reported recent business highlights and financial results for the third quarter ended September 30, 2024. “We made significant progress across our pipeline over the last quarter, including completing enrollment in our Phase 3 PEAK trial in Gastrointestinal Stromal Tumor (GIST) patients, accelerating enrollment in SUMMIT, our registration-directed trial with bezuclastinib in Nonadvanced Systemic Mastocytosis (NonAdvSM) and initiating our first Phase 1 trial with our FGFR2 inhibitor,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “Additionally, we recently presented new preclinical data from our research pipeline that demonstrated potential best-in-class attributes of our pan-KRAS inhibitor and our H1047R PI3Kα inhibitor. As we head into 2025, we are well positioned as we prepare to deliver top-line data from three registrational clinical trials.” Business Highlights & Milestones Completed enrollment in PEAK, a randomized, open-label, global Phase 3 trial evaluating bezuclastinib in combination with sunitinib vs sunitinib alone in patients with imatinib-resistant gastrointestinal stromal tumors (GIST). Based on strong global patient interest, a total of 413 patients were enrolled in the trial. The primary endpoint is median progression free survival (mPFS). In addition, Cogent completed a pre-planned interim futility analysis and the Independent Data Monitoring Committee (IDMC) recommended continuing the PEAK study without modification. This pre-specified analysis was based on an assessment of progression-free survival (PFS) as determined by independent central review and did not include the option for early stopping due to efficacy. Cogent will present updated clinical data from both SUMMIT and APEX clinical trials at the upcoming ASH annual meeting in December. There will be an investor webcast on December 9 at 8:00 a.m. ET to review the SUMMIT and APEX data. To register and listen please visit: https://investors.cogentbio.com/events Poster presentation highlighting long term follow-up from patients who participated in the Open Label Extension (OLE) portion of SUMMIT at the ASH annual meeting on Monday, December 9, 2024. SUMMIT is a randomized, global, multicenter, double-blind, placebo-controlled, multi-part Phase 2 trial evaluating bezuclastinib in patients with NonAdvSM.Oral presentation of long term follow-up from patients in Part 1 of the ongoing APEX study to be presented at the 2024 ASH annual meeting on Sunday, December 8, 2024. APEX is a global, multi-part Phase 2 trial evaluating bezuclastinib in patients with Advanced Systemic Mastocytosis (AdvSM). During the quarter, Cogent initiated a Phase 1 study of CGT4859, a reversible, selective FGFR2 inhibitor in patients with FGFR2 mutations, including advanced cholangiocarcinoma. The trial will explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well tolerated dose for further clinical investigation. Preliminary results from this trial are expected in 2025. Announced the addition of a potent and selective KRAS inhibitor to the pipeline. Preclinical data from this program as well as the Company’s H1047R mutant-selective PI3Kα clinical candidate were presented at the 2024 EORTC-NCI-AACR International Symposium on Molecular Targets and Cancer Therapeutics. Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The first poster presented described Cogent’s internally-developed pan KRAS(ON) inhibitor with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations without the potential liabilities of molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. Lead optimization of CGT6737 is ongoing.The second poster highlighted Cogent’s clinical candidate CGT6297, a potent allosteric inhibitor of PI3K, with 25-fold selectivity over PI3Kα WT. CGT6297 has high oral bioavailability and low clearance across species, providing robust inhibition of downstream signaling and efficacy in animal models. Importantly, when compared to a clinically relevant dose of a currently approved therapy in a mouse tumor model, CGT6297 demonstrated superior efficacy with no increase in insulin. IND-enabling studies are expected to be initiated in 2025. Anticipated Upcoming Milestones Complete enrollment in SUMMIT Part 2 in the first quarter of 2025 and deliver top-line results in the second half of 2025. Deliver top-line results from APEX in mid-2025. Deliver top-line results from PEAK by the end of 2025. Upcoming Investor ConferencesA live webcast of the following events can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the events and will be archived for up to 30 days. Guggenheim Healthcare Innovation Conference, today, Tuesday, November 12, 2024 at 10:30 a.m. ET. Jefferies London Healthcare Conference on Wednesday, November 20, 2024 at 12:30 p.m. GMT (7:30 a.m. ET). Piper Sandler 35th Annual Healthcare Conference on Tuesday, December 4, 2024 at 9:30 a.m. ET. Third Quarter 2024 Financial Results Cash Position: As of September 30, 2024, cash, cash equivalents and marketable securities were $345.5 million, as compared to $389.9 million as of June 30, 2024. The company believes that its cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements well past top-line results from SUMMIT, PEAK, and APEX registration-directed trials and into late 2026. R&D Expenses: Research and development expenses were $63.6 million for the third quarter of 2024 as compared to $50.1 million for the third quarter of 2023. R&D expenses include non-cash stock compensation expense of $4.8 million for the third quarter of 2024 compared to $4.0 million for the third quarter of 2023. Increases resulted from costs associated with the acceleration of enrollment in PEAK, SUMMIT and the continued development of our research pipeline. G&A Expenses: General and administrative expenses were $11.8 million for the third quarter of 2024 as compared to $9.5 million for the third quarter of 2023. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $5.6 million for the third quarter of 2024 compared to $4.8 million for the third quarter of 2023. Net Loss: Net loss was $70.6 million for the third quarter of 2024 as compared to a net loss of $55.4 million for the same period of 2023. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on November 6, 2024, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grant of “inducement” equity awards to three new employees under the company’s 2020 Inducement Plan with grant dates of November 6, 2024 and November 11, 2024. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 132,350 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. 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, PI3Kα and KRAS. 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 potential for the company’s pipeline programs targeting KRAS and PI3Kα to produce best-in-class assets; the expectation to deliver preliminary results from the company’s Phase 1 study of CGT4859 in 2025; the expectation to initiate IND-enabling studies for CGT6297 in 2025; the expectation to complete enrollment in SUMMIT Part 2 in the first quarter of 2025 and deliver top-line results in the second half of 2025; the expectation to deliver top-line results from APEX in mid-2025; the expectation to deliver top-line results from PEAK by the end of 2025; the company’s anticipated cash runway into late 2026 and planned presentations at upcoming scientific and investor conferences. 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 September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Operating expenses: Research and development$63,614 $50,127 $170,613 $125,036 General and administrative 11,800 9,453 31,592 24,866 Total operating expenses 75,414 59,580 202,205 149,902 Loss from operations (75,414) (59,580) (202,205) (149,902) Other income: Interest income 4,779 4,198 14,229 9,207 Other income, net 1 — 44 950 Change in fair value of CVR liability — — — 1,700 Total other income, net 4,780 4,198 14,273 11,857 Net loss$(70,634) $(55,382) $(187,932) $(138,045) Net loss per share attributable to common stockholders, basic and diluted$(0.64) $(0.64) $(1.85) $(1.79) Weighted average common shares outstanding, basic and diluted 110,165,580 86,165,951 101,435,402 77,274,580 COGENT BIOSCIENCES, INC.SELECTED CONDENSED CONSOLIDATEDBALANCE SHEET DATA(in thousands)(unaudited) September 30, 2024 December 31, 2023 Cash, cash equivalents and marketable securities$345,548 $273,170 Working capital$288,480 $232,603 Total assets$384,016 $313,437 Total liabilities$69,357 $55,635 Total stockholders’ equity$314,659 $257,802 Contact: Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653