PDGFR antagonists(Platelet-derived growth factor receptor antagonists), RTK inhibitors(Receptor protein-tyrosine kinase inhibitors), VEGFR antagonists(Vascular endothelial growth factor receptor antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [4]

Active Indication

Malignant Gastric Gastrointestinal Stromal TumorIslet Cell CarcinomaRenal Cell Carcinoma+ [10]

Inactive Indication

Adrenocortical CarcinomaAdvanced breast cancerAdvanced gastric carcinoma+ [77]

Originator Organization

Pfizer Inc.

Active Organization

Pfizer Ltd.Accord Healthcare SLU

Pfizer Japan, Inc.

+ [3]

Inactive Organization

Bristol Myers Squibb Co.

Novartis Pharmaceuticals Corp.

Huizhi Pharmaceutical (Dalian) Co., Ltd.

+ [5]

Drug Highest PhaseApproved

First Approval Date

US (26 Jan 2006),

Advanced Renal Cell CarcinomaGastrointestinal Stromal Tumors

RegulationAccelerated Approval (US), Orphan Drug (JP)

Structure

Molecular FormulaC26H33FN4O7

InChIKeyLBWFXVZLPYTWQI-IPOVEDGCSA-N

CAS Registry341031-54-7

509

Clinical Trials associated with Sunitinib Malate

NCT06726421 / RecruitingPhase 3IIT

Systemic Therapy Combined with Radiotherapy Versus Systemic Therapy Alone for Oligometastatic Kidney CancER (STROKER): a Multicenter, Randomized Controlled Phase III Trial

This phase III randomized controlled trial evaluates the efficacy of stereotactic body radiation therapy (SBRT) in oligometastatic renal cell carcinoma. The study aims to determine if the addition of SBRT to standard systemic therapy prolong survival compared to the standard systemic therapy alone. In addition, the study will explore the impact of this combined modality therapy on patients' toxicity and quality of life. The researchers will compare SBRT plus standard systemic therapy to standard systemic therapy alone, which is targeted agents and immunotherapy in this case, to determine if SBRT could prolong survival.

Start Date18 Sep 2024

Sponsor / Collaborator

Sun Yat-Sen University

NCT05687123 / RecruitingPhase 1IIT

A Phase I Dose Escalation-Expansion Trial of Sunitinib Malate Plus Lutetium Lu 177 Dotatate (Lutathera) in Somatostatin Receptor Positive Pancreatic Neuroendocrine Tumors

This phase I trial tests the safety, side effects, and best dose of sunitinib malate in combination with lutetium Lu 177 dotatate in treating patients with pancreatic neuroendocrine tumors. Sunitinib malate is in a class of medications called kinase inhibitors and a form of targeted therapy that blocks the action of abnormal proteins called VEGFRs that signal tumor cells to multiply. This helps stop or slow the spread of tumor cells. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. It is also a form of targeted therapy because it works by attaching itself to specific molecules (receptors) on the surface of tumor cells, known as somatostatin receptors, so that radiation can be delivered directly to the tumor cells and kill them. Giving sunitinib malate and lutetium Lu 177 dotatate in combination may be safer and more effective in treating pancreatic neuroendocrine tumors than giving either drug alone.

Start Date14 Aug 2024

Sponsor / Collaborator

National Cancer Institute

NCT06208748 / RecruitingPhase 2IIT

A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST Who Progressed on Sunitinib Monotherapy

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

Start Date01 Jul 2024

Sponsor / Collaborator

Sarcoma Alliance for Research through Collaboration

[+3]

100 Clinical Results associated with Sunitinib Malate

100 Translational Medicine associated with Sunitinib Malate

100 Patents (Medical) associated with Sunitinib Malate

520

Literatures (Medical) associated with Sunitinib Malate

01 Jan 2025·INTERNATIONAL JOURNAL OF PHARMACEUTICS

Development of hyaluronic acid/β-cyclodextrin semi-interpenetrating network hydrogels for prolonged delivery of water-soluble sunitinib malate

Article

Author: Ma, Yingchang ; Zhou, Xintong ; Brocchini, Steve ; Waudby, Christopher A ; Williams, Gareth R ; Ju, Tian ; Yu, Ziqi

Sunitinib malate (SUM), widely used in cancer treatment for its anti-VEGF properties, has also been explored for ocular neovascular diseases. For ocular applications, sustained drug release is essential to reduce dosing frequency. Hyaluronic acid (HA)-based hydrogels are commonly used for controlled drug delivery, but their hydrophilicity leads to rapid drug diffusion, especially for water-soluble drugs like SUM. To address this, β-cyclodextrin (β-CD) polymers (2-300 kDa) were incorporated into tyramine-conjugated HA (HA-TA) (200-400 kDa) networks to extend drug release via host-guest inclusion complexes. SUM-CD intermolecular interactions were identified and characterised by ¹H NMR and FTIR spectroscopies, and NOESY spectra further confirmed a 2 SUM: 1 βCD inclusion complex. β-CD polymers (10 % w/v) were integrated into HA-TA (0.25, 0.5, 1 % w/v) networks crosslinked through enzymatic crosslinking using horseradish peroxidase and hydrogen peroxide, forming a semi-interpenetrating polymer network hydrogel. This hydrogel exhibited faster gelation, enhanced swelling behaviour, higher drug loading capacity, a denser matrix, and a longer SUM release duration compared to HA-TA hydrogels. In an in vitro flow model, post-gelation loading of SUM led to a longer release duration than pre-loading, with release continuing over 20 days. The HA-CD semi-IPN hydrogel therefore warrants further exploration for its potential ocular applications.

01 Jan 2024·Current research in toxicology

Sunitinib malate induces cell death in adult human cardiac progenitor cells

Article

Author: Papaspyros, Sotiris ; Smith, Andrew J ; Steele, Derek S ; Walmsley, Robert

Sunitinib malate is known to cause cardiotoxicity in a sub-population of patients, with heart failure seen in more severe cases. Cardiac progenitor cells (CPCs) have been identified in adult human myocardium and contribute to overall tissue maintenance, with previous work identifying negative impacts of sunitinib on these cells. This study aimed to characterise the toxic effects of sunitinib in human CPCs, applying sunitinib concentrations equivalent to clinical plasma levels to these cells in vitro. Cell viability was reduced by 26.5 ± 6.6 % by 2 μM sunitinib for 24 h (p < 0.01); this concentration also induced fold-change increases in gene expression of: calpain (3.1 ± 0.73, p < 0.05), FAS (2.3 ± 0.8, p < 0.05) and BAX (1.9 ± 0.2, p < 0.05), and a decrease in BCL-2 (3.5 ± 0.0, p < 0.001), vs. control (1.0 ± 0.0). This was affirmed by sunitinib inducing fold changes in protein expression of: calpain-1 (2.5 ± 0.5, p < 0.05); FAS receptor (2.1 ± 0.2, p < 0.05) and BAX (2.1 ± 0.2, p < 0.05) vs. control (1.0 ± 0.0). These results indicated that sunitinib induced apoptosis in CPCs, but negative annexin V staining and lack of protection by caspase inhibitors indicated this was not the cell death pathway activated. Further investigation found sunitinib was concentrated in the lysosomes and autophagosomes within CPCs, but did not induce accumulation of acidic organelles. In conclusion, these data confirm that cell death is caused by sunitinib in CPCs at concentrations equivalent to clinical plasma levels, inducing cell death pathway signals that lead to non-apoptotic cell death.

01 Nov 2023·Future oncology (London, England)

Ripretinib Versus Sunitinib in Patients with Advanced Gastrointestinal Stromal Tumor after Treatment with Imatinib: A Plain Language Summary of the Phase 3 INTRIGUE Trial

Review

Author: Symcox, Marina ; Jones, Robin L

WHAT IS THIS SUMMARY ABOUT?:

This document presents a patient-friendly summary of the phase 3 INTRIGUE clinical trial results, which were published in the Journal of Clinical Oncology in August 2022. A phase 3 trial is a study that tests the safety of a proposed treatment and how well it works compared with a standard treatment or a treatment with no active ingredient (also called a placebo). The aim of the INTRIGUE trial was to understand whether treatment with a drug called ripretinib (brand nameQINLOCK^®) was superior to treatment with sunitinib (brand name SUTENT^®) in participants with advanced gastrointestinal stromal tumor (also known as GIST) who cannot tolerate or whose disease progressed beyond first-line treatment with imatinib (brand name GLEEVEC^®). The INTRIGUE trial included 453 participants with advanced GIST who had previously been treated with a tyrosine kinase inhibitor (also known as a TKI) medicine called imatinib. For patients with advanced GIST who cannot tolerate or whose disease progresses while taking imatinib, the recommended second-line TKI medicine is sunitinib. The recommended third-line TKI medicine is called regorafenib (brand name STIVARGA^®). Ripretinib is currently the only medication approved for adults with advanced GIST who have previously been treated with 3 or more TKIs (fourth-line).

WHAT WERE THE RESULTS?:

The trial showed that ripretinib did not significantly increase the time that participants survived without their cancer getting worse (progression-free survival or PFS) over sunitinib. However, participants treated with ripretinib had similar PFS to those treated with sunitinib. Importantly, treatment with ripretinib resulted in fewer severe adverse events, or side effects, compared with sunitinib, and participants reported better quality of life with ripretinib compared with sunitinib.

WHAT DO THE RESULTS MEAN?:

Treatment with ripretinib, after imatinib stops working or can no longer be tolerated, provided similar PFS for participants with advanced GIST and had fewer severe adverse events compared with sunitinib. Sunitinib is the only medication currently approved for use as a second-line treatment in patients with advanced GIST previously treated with imatinib. With more investigation, ripretinib could be a treatment option for these patients. Patients should always talk to their medical team before making any decisions about their treatment.

200

News (Medical) associated with Sunitinib Malate

14 Nov 2024

·www.businesswire.com

IDRx Announces Updated Phase 1 Data from Ongoing Phase 1/1b StrateGIST 1 Trial of IDRX-42 in Advanced Gastrointestinal Stromal Tumors (GIST) at CTOS 2024

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 .

Clinical ResultPhase 1Fast TrackPhase 3Orphan Drug

12 Nov 2024

·www.globenewswire.com

Cogent Biosciences Reports Recent Business Highlights and Third Quarter 2024 Financial Results

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

Phase 1Phase 2Clinical ResultFinancial StatementPhase 3

24 Oct 2024

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Kura Oncology Reports Preclinical Data Supporting Opportunity for Ziftomenib in Treatment of Gastrointestinal Stromal Tumors (GIST)

– Combination of ziftomenib and imatinib shows robust and durable antitumor activity in imatinib-sensitive (1L) and imatinib-resistant (2L/3L) GIST models – – Proof-of-concept study of ziftomenib plus imatinib in patients with advanced GIST after imatinib failure to begin in 1H 2025 – SAN DIEGO, Oct. 24, 2024 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today reported preclinical data supporting the development of the Company’s menin inhibitor, ziftomenib, for the treatment of advanced gastrointestinal stromal tumors (GIST). The new findings are being presented at the 36th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona. A copy of the poster, entitled “Menin Inhibitor Ziftomenib Synergizes with Imatinib in Tyrosine Kinase Inhibitor (TKI)-Resistant Gastrointestinal Stromal Tumor Models,” is available in the Posters and Presentations section on Kura’s website. “Kura has generated a substantial body of preclinical data that support potential for ziftomenib in combination with KIT inhibitors for the treatment of patients with advanced GIST,” said Francis Burrows, Ph.D., Senior Vice President, Translational Research. “Our results indicate that the combination of ziftomenib and imatinib acts via a synthetic lethal mechanism through which ziftomenib targets an epigenetic vulnerability of GIST tumors, creating potent synergy even with KIT inhibitors that are otherwise inactive as monotherapy. Indeed, the activity of ziftomenib appears to be agnostic to the mutational status of KIT in GIST, suggesting an opportunity to explore the combination for all patients, even in the frontline setting.” The combination of ziftomenib and imatinib unexpectedly showed robust and durable antitumor activity in both imatinib-sensitive and imatinib-resistant GIST patient-derived xenograft models, and in all cases was significantly superior to imatinib monotherapy. Mechanistically, the data reveal a KIT-dependent mechanism, with ziftomenib and imatinib combining to sharply reduce KIT expression and/or activity, effectively silencing both the ERK and AKT/mTOR signaling pathways and driving robust cell cycle arrest and apoptosis. Given that imatinib is well established as the frontline standard of care in patients with GIST, and that generic versions are available, imatinib represents a promising combination partner for ziftomenib. In August 2024, Kura announced clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for ziftomenib for the treatment of advanced GIST. The Company is now preparing to initiate a proof-of-concept study evaluating ziftomenib and imatinib in patients with advanced GIST after imatinib failure in the first half of 2025. For more information regarding the study, please visit www.clinicaltrials.gov (identifier: NCT06026410). About GIST Gastrointestinal stromal tumors (GIST) are the most common form of sarcoma, characterized as KIT-dependent solid tumors. Despite the successful disease control achieved with imatinib in advanced GIST patients, most patients eventually progress due to acquired secondary KIT mutations. TKIs such as sunitinib can target imatinib-resistant genotypes and are approved in later lines, but response rates and long-term outcomes are modest, so new therapeutic options are needed. Previously published data show that the menin-MLL complex regulates KIT expression in GIST cells, and menin inhibitors display additive therapeutic activity in combination with imatinib in imatinib-sensitive GIST models1. About Ziftomenib Ziftomenib is a potent, selective and oral menin inhibitor currently in development for the treatment of genetically defined AML patients with high unmet need. In April 2024, ziftomenib received Breakthrough Therapy Designation (BTD) by the FDA for the treatment of relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML) based on data from Kura’s ongoing KOMET-001 clinical trial. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib. About Kura Oncology Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The Company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways. Ziftomenib, a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction, has received BTD for the treatment of R/R NPM1-mutant AML. Kura has completed enrollment in a Phase 2 registration-directed trial of ziftomenib in R/R NPM1-mutant AML (KOMET-001). The Company is also conducting a series of clinical trials to evaluate ziftomenib in combination with current standards of care in newly diagnosed and R/R NPM1-mutant and KMT2A-rearranged AML. Kura is evaluating KO-2806, a next-generation farnesyl transferase inhibitor (FTI), in a Phase 1 dose-escalation trial as a monotherapy and in combination with targeted therapies (FIT-001). Tipifarnib, a potent and selective FTI, is currently in a Phase 1/2 trial in combination with alpelisib for patients with PIK3CA-dependent head and neck squamous cell carcinoma (KURRENT-HN). For additional information, please visit Kura’s website at www.kuraoncology.com and follow us on X and LinkedIn. Forward-Looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, and progress and expected timing of the ziftomenib program and clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company’s periodic and other filings with the Securities and Exchange Commission (SEC), including the Company’s Form 10-Q for the quarter ended June 30, 2024 filed with the SEC on August 8, 2024, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contacts Investors:Pete De SpainExecutive Vice President, Investor Relations &Corporate Communications(858) 500-8833pete@kuraoncology.com Media:Cassidy McClainVice PresidentInizio Evoke Comms(619) 849-6009cassidy.mcclain@inizioevoke.com 1 Hemming ML et al., Cancer Discov. 2022;12:1804-1823.

Phase 1Phase 2INDAACR

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KEGG	Wiki	ATC	Drug Bank
D06402	Sunitinib Malate	L01XE04	DB01268

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Malignant Gastric Gastrointestinal Stromal Tumor	EU	Accord Healthcare SLU	11 Feb 2021
Malignant Gastric Gastrointestinal Stromal Tumor	IS	Accord Healthcare SLU	11 Feb 2021
Malignant Gastric Gastrointestinal Stromal Tumor	LI	Accord Healthcare SLU	11 Feb 2021
Malignant Gastric Gastrointestinal Stromal Tumor	NO	Accord Healthcare SLU	11 Feb 2021
Islet Cell Carcinoma	US	C.P. Pharmaceuticals International CV	20 May 2011
Renal Cell Carcinoma	JP	Pfizer Japan, Inc.	16 Apr 2008
Islet Cell Adenoma	CN	Pfizer Inc.	30 Oct 2007
Metastatic Renal Cell Carcinoma	EU	Pfizer Ltd.	19 Jul 2006
Metastatic Renal Cell Carcinoma	IS	Pfizer Ltd.	19 Jul 2006
Metastatic Renal Cell Carcinoma	LI	Pfizer Ltd.	19 Jul 2006
Metastatic Renal Cell Carcinoma	NO	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	EU	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	IS	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	LI	Pfizer Ltd.	19 Jul 2006
Neuroendocrine tumor of pancreas	NO	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	EU	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	IS	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	LI	Pfizer Ltd.	19 Jul 2006
Pancreatic neuroendocrine tumour metastatic	NO	Pfizer Ltd.	19 Jul 2006
Well Differentiated Pancreatic Endocrine Tumor	EU	Pfizer Ltd.	19 Jul 2006

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Hepatocellular Carcinoma	Phase 3	US	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	CN	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	JP	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	AU	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	BE	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	CA	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	FR	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	DE	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	HK	Pfizer Inc.	01 Jul 2008
Advanced Hepatocellular Carcinoma	Phase 3	IT	Pfizer Inc.	01 Jul 2008

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02465060 (NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V, Pubmed \| JCO Precis Oncol)	Phase 2	Recurrent Multiple Myeloma \| Recurrent Cervical Cancer \| Recurrent Bladder Cancer ... c-KIT mutations View more	10	Sunitinib 50 mg	ecsfjdiyhf(cvlkrebuww) = srgnsvnmxr iypprpexdo (wzjpicwfvx, 4.1 - 55) View more	Negative	01 Dec 2024
NCT00843037 (SNIPP, CTgov)	Phase 2	Pheochromocytoma	25	Sunitinib	umdmwbnclc(etdvikessa) = eshsmrbdqb vmbbzupofs (corzcjyepg, jmifduxiyr - luhotqsdtl) View more	-	17 Oct 2024
NCT00931450 (SUT_EXE-08, Pubmed \| Sci Rep) Manual	Phase 1/2	Hormone receptor positive HER2 negative breast cancer Neoadjuvant Hormone Receptor Positive \| HER2 Negative	18	Sunitinib 25exemestane	xyobborlnv(vjwarhqnqz) = znanfvbuus kvwuzeauam (wgpsljanyk )	Positive	09 Oct 2024
NCT02761057 (S1500, Pubmed \| J Clin Oncol) Manual	Phase 2	Papillary Renal Cell Carcinoma Second line \| First line	147	Sunitinib	wkcwvmvzyb(tmqudwyrox) = uynnguxfcy svxpwqlbcj (veypvbjkve, 12.8 - 21.8) View more	Negative	10 Sep 2024
				Cabozantinib	wkcwvmvzyb(tmqudwyrox) = ntgkipynii svxpwqlbcj (veypvbjkve, 12.0 - 28.1) View more
ASCO2024 Manual	Not Applicable	Renal Cell Carcinoma First line	99	IO + targeted therapy doubletslenvatinibpembrolizumab	bgabrhgbmy(mkyvadkuej) = pmeubcgjil snwblvyucj (edugrqrwap, 17 - 56) View more	Positive	24 May 2024
				Pure IO monotherapy and doubletsipilimumabnivolumab	bgabrhgbmy(mkyvadkuej) = ywbondmnxj snwblvyucj (edugrqrwap ) View more
ASCO2024 Manual	Not Applicable	Metastatic Renal Cell Carcinoma First line	611	Ipilimumab + Nivolumab (IPI/NIVO) (Favorable Risk)	qjtvrdadlz(uxxxxsjubi) = demelpndpv lwkzioehdd (yrnwquaeif, 77.4 - 95.4) View more	-	24 May 2024
				IO-VEGF (Pembrolizumab and Axitinib or Lenvatinib, Avelumab and Axitinib, or Nivolumab and Cabozantinib) (Favorable Risk)	qjtvrdadlz(uxxxxsjubi) = ywvbmsparu lwkzioehdd (yrnwquaeif, 77.0 - 91.2) View more
NCT03141177 (CheckMate 9ER, Pubmed) Manual	Phase 3	Advanced Renal Cell Carcinoma First line	651	Nivolumab plcabozantinibnib	repnitypdi(jaeckemgyc) = ckwllnvvqw mwtevlaffd (rcgcfhynoo ) View more	Positive	01 May 2024
				Sunitinib	repnitypdi(jaeckemgyc) = hqdmycamul mwtevlaffd (rcgcfhynoo ) View more
NCT01371201 (FIRSTMAPPP, Pubmed) Manual	Phase 2	Paraganglioma \| Pheochromocytoma SDHB status (mutation present vs wild type) \| number of previous systemic therapies (0 vs ≥1)	78	Sunitinib	agyhmopdfl(kxgnrfeujg) = nknmtdnlzp uflvlzvcgi (jhdjmsvuca, 23 - 50) View more	Positive	22 Feb 2024
				Placebo	agyhmopdfl(kxgnrfeujg) = gzwsmruxyt uflvlzvcgi (jhdjmsvuca, 11 - 31) View more
NCT02693535 (Targeted Agent and Profiling Utilization Registry Study, Pubmed \| JCO Precis Oncol)	Phase 2	Advanced Malignant Solid Neoplasm \| Multiple Myeloma FGFR1 \| FGFR2	40	Sunitinib	ajzxntsyeb(ifiunaunrw) = ulvvcbujrn iosthmvtyf (hsclboxxzq, 13 - 100)	Negative	01 Feb 2024
NCT01517243 (CTgov)	Phase 2	Metastatic Renal Cell Carcinoma	37	Sunitinib+Temsirolimus	hpcblpkupu(dnjtqvhlvj) = jycarnoyux euosbhdikx (kohrndtdap, bikvqsskxw - xongyzaaxw) View more	-	21 Sep 2023

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