KIF18A

Enables ATX-559 Phase 1 study in solid tumor patients with a focus on BRCA1/2-deficient breast cancer and solid tumors with microsatellite instability (MSI-H) and/or deficient mismatch repair (dMMR); first patient dosed anticipated in Q4 2024 Second program targeting KIF18A on track to enter clinical trials in early 2025, underscoring rapid advancement of novel therapies Clinical Advisory Board (CAB) of global oncology drug development experts formed to support the advancement of Accent's clinical pipeline LEXINGTON, Mass., Oct. 24, 2024 /PRNewswire/ -- Accent Therapeutics, a biopharmaceutical company pioneering novel small molecule targeted cancer therapeutics, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ATX-559, a first-in-class DHX9 inhibitor. In addition, Accent has established a Clinical Advisory Board (CAB) to help guide the Company's progress in the clinic. The ATX-559 Phase 1/2 trial (NCT06625515) is expected to begin dosing patients with a focus on BRCA1- or BRCA2-deficient breast cancer and patients with MSI-H and/or dMMR solid tumors (including certain patients with colorectal, endometrial, gastric, and other cancers) in the fourth quarter of 2024. The clinical study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of ATX-559. For more information on the trial, visit the study page on ClinicalTrials.gov. "The FDA's IND clearance is a pivotal moment for Accent Therapeutics, propelling our lead program into the clinical arena. This milestone not only validates our scientifically rigorous approach to identifying innovative targets, but also brings us one step closer to helping cancer patients with significant unmet need," said Jason Sager, M.D., Chief Medical Officer of Accent Therapeutics. "ATX-559 has shown remarkable promise in preclinical studies, and we're excited to now evaluate its potential to meaningfully improve outcomes for patients facing these challenging malignancies." As Accent prepares to initiate its first clinical trial, the company has also established a Clinical Advisory Board to guide the advancement of its clinical pipeline. The Clinical Advisory Board consists of renowned clinician-scientists and leaders whose strategic insights and clinical expertise will support the Company's efforts to advance its mission of creating life-changing therapeutics for patients living with cancer. The newly formed Clinical Advisory Board includes: Lillian L. Siu, M.D., FRCPC, medical oncologist, Director of the Phase I Program at Princess Margaret Cancer Centre, Professor of Medicine at the University of Toronto, and President-Elect of the American Association for Cancer Research (AACR) Josep Tabernero, M.D., Ph.D., Professor of Medicine, Head of the Medical Oncology Department at the Vall d'Hebron Barcelona Hospital Campus, and Director of the Vall d'Hebron Institute of Oncology (VHIO) Sam Blackman, M.D., Ph.D., co-founder and Head of Research and Development of Day One Biopharmaceuticals "We are honored to have such distinguished experts join our Clinical Advisory Board as we advance our programs into the clinic," said Shakti Narayan, Ph.D., J.D., Chief Executive Officer of Accent Therapeutics. "Their experience will be invaluable as we work to bring transformative therapies to patients." Accent is also on track to advance its second program, targeting KIF18A in chromosomally instable tumors, into the clinic with a Phase 1 trial anticipated to begin in early 2025. This marks an exciting phase of growth for the company as it continues to build on its foundational platform technology to develop innovative cancer therapies. About ATX-559 ATX-559 is a first-in-class DHX9 inhibitor with the potential to address high unmet need indications not adequately served by existing therapies, such as BRCA-deficient tumors (including breast, ovarian, and others), MSI-H and/or dMMR cancers (including colorectal, endometrial, gastric, and others) and additional undisclosed cancer types representing large patient populations. DHX9 is a DNA/RNA helicase that has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability. Inhibition of DHX9 exploits key tumor vulnerabilities, resulting in cancer-specific cell death, and thus this enzyme represents a compelling novel oncology target. Accent retains full worldwide rights to ATX-559 and the DHX9 program. About KIF18A Accent's second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability. A subset of tumor cells with an abnormal number of chromosomes (aneuploid) are reliant on KIF18A and show rapid cell killing in vitro and in vivo upon KIF18A inhibitor treatment, while cells with normal numbers of chromosomes (euploid) are unaffected. About Accent Therapeutics Accent Therapeutics is pioneering a new class of small molecule precision cancer therapies targeting critical intracellular dependencies that span multiple types of cancer. Building upon industry-leading expertise in RNA-modifying proteins (RMPs) and the systematic mapping of both the RMP space and adjacent high-value areas for drug discovery, the company is building a flexible model that allows for a diversity of approaches to developing potentially transformative biomarker-driven cancer medicines. Accent's therapies are designed for both novel and known, but suboptimally addressed, high-impact oncology targets with the potential to benefit large patient populations with significant unmet need. For more information on Accent's mission to translate extraordinary science into life-changing therapeutics for patients living with cancer, visit or follow us on LinkedIn. SOURCE Accent Therapeutics, Inc. 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SAN DIEGO--( BUSINESS WIRE )--Iambic Therapeutics, a clinical-stage biotechnology company developing novel therapeutics using its unique AI-driven discovery platform, today announced its inclusion in the 2024 Endpoints News list of “Biotech’s Most Promising Startups.” The annual Endpoints 11 award recognizes emerging life science companies pushing the frontiers of innovation to create breakthrough therapies for patients. “ Integrating AI and machine learning with automated experimentation has helped Iambic redefine the pace and precision of drug discovery. Our platform has enabled us to advance our lead program from discovery to the clinic in under 24 months – a transformative shift in traditional timelines,” said Tom Miller, PhD, Iambic’s CEO and co-founder. “ This acknowledgment by Endpoints underscores our team’s relentless dedication to advancing novel, potential best-in-class and first-in-class treatments that address critical unmet needs in oncology and beyond.” Iambic is developing an internal pipeline of candidates, discovered using its platform that integrates AI models for protein structure prediction and wholistic drug design with high-throughput chemistry and biology experimentation. Iambic’s pipeline currently includes IAM1363, a highly selective, brain penetrant small molecule inhibitor of both wild-type and oncogenic HER2 mutants currently in a Phase 1/1b study, as well as a potential first-in-class selective dual CDK2/4 inhibitor for multiple cancer indications, an allosteric inhibitor for KIF18A, and additional new programs. In a strategic research partnership announced this week with Lundbeck , Iambic will use its drug discovery platform to accelerate research into neurological disease – further expanding its potential impact in additional therapeutic areas. About the Iambic Therapeutics Physics-Informed AI-Driven Discovery Platform The Iambic Therapeutics AI-driven platform was created to address the most challenging design problems in drug discovery, leveraging technology innovations such as Iambic NeuralPLexer, which provides state-of-the-art structural predictions of protein-ligand complexes. The integration of physics principles into the platform’s AI architectures improves data efficiency and allows molecular models to venture widely across the space of possible chemical structures. The platform’s algorithms enable identification of new chemical mechanisms for engaging difficult-to-address biological targets, discovery of product profiles that optimize therapeutic window, and exploration of the chemical space to discover candidates for development with highly differentiated properties. Through close integration of AI-generated molecular designs with automated experimental execution, Iambic completes design-make-test cycles on a weekly cadence. About Iambic Therapeutics Founded in 2019 and headquartered in San Diego, California, Iambic Therapeutics is disrupting the therapeutics landscape with its unique AI-driven drug-discovery platform. Iambic has assembled a world-class team that unites pioneering AI experts and experienced drug hunters with strong track records of success in delivering clinically validated therapeutics. The Iambic platform has been demonstrated to deliver high-quality, differentiated therapeutics to clinical stage with unprecedented speed and across multiple target classes and mechanisms of action. The Iambic team is advancing an internal pipeline of clinical assets to address urgent unmet patient needs. Learn more about the Iambic team, platform, and pipeline at iambic.ai .

As two biotech rookies leaving long academic careers to co-found Iambic in 2019, CEO Tom Miller and CTO Fred Manby were “incredibly self-aware” of the science and business experience they lacked, Manby said. So they sought out advisors who could help fill in the gaps. Longtime chemist (and blogger) Derek Lowe joined their scientific advisory board, playing the role of “the reality check guy.” More recently, San Diego biotech executive Bill Rastetter became a director. In 2021, the biotech shifted focus from developing AI software for everyone from drug companies to industrial giants like Toyota and Dow, to building its own pipeline. It’s moved fast since, with its first drug already in the clinic and two more close behind, making Iambic one of AI bio’s most heads-down efforts to help produce better drugs. Its AI models, some made with the chipmaking giant Nvidia as a research partner, simulate protein-molecule interactions, generate molecules and predict properties like stability or toxicity. The goal is to make drugs, and move fast. It’s connected its AI models to an internal software system that researchers use to design experiments that are then run in the laboratory next door. “It’s not enough to just be excited about the current architecture,” Miller said, referencing the newest AI model designs. “People are in a show-me mode of, can these things lead to medicines that we can agree are better — on the basis of what that model provided.” Iambic is starting to see results from that platform, all before turning five years old. Its lead program, a HER2-targeting molecule called IAM1363, entered the clinic this spring. Miller said he expects a readout, including preliminary efficacy, for that Phase 1b study in mid-2025. HER2 is as well-validated as any target in cancer, dating back to the 1998 approval of Roche/Genentech’s Herceptin. But Iambic believes its molecule can stand apart by penetrating the brain and achieving 1,000-fold selectivity in hitting HER2 over a similar protein called EGFR. The theory is other drugs left efficacy on the table because they lack that selectivity, Miller said. Still, the only way to know if that idea translates to helping patients is the clinic. For all the help that Iambic’s AI technology plays in making the molecule, it isn’t providing insights into what targets or properties are worth focusing on. Iambic’s next programs take on more biological risk and design challenges. A CDK2/4 drug is “rapidly advancing” to the clinic, Miller said, targeting an IND filing in 2025. While therapies like Pfizer’s Ibrance and Eli Lilly’s Verzenio target CDK4 and CDK6, Iambic is betting on selectivity again. Avoiding CDK6 and other similar enzymes could translate to less toxicity and greater clinical benefit, the company says. A KIF18a inhibitor also could be IND-ready in 2025, Miller added. Both could be first-in-class drugs, with Iambic’s AI technology helping achieve drug characteristics that haven’t yet been possible, he said. “It’s not like 10% better or from 1 to 1.2,” Miller said. “It’s going from zero to one.” Miller, an ex-Caltech professor, has embraced the CEO role, raising $220 million from a syndicate including biotech insiders like OrbiMed and Abingworth, and tech investors like Sequoia and Coatue. The biotech also has inked its first pharma deal, working with Lundbeck to discover small molecules for migraine. With cash runway into at least 2026 and clinical data on the horizon, Iambic is poised to show if AI’s moment in biotech has finally arrived. “The proof of the pudding is in the eating,” Miller said of his vision for the AI bio field over the next five to 10 years. “Showing in our hand, and for the field at large, that AI is leading to medicines in a statistically meaningful way that lead to more successful approvals, faster approvals, better drugs. This is the measure we will begin to gather more meaningful data on in that timescale.” Key backers: OrbiMed, Sequoia, Coatue, Catalio, NVentures, Illumina Ventures, Abingworth, Exor, Mubadala, Qatar Investment Authority, Ascenta Find the full list of 2024 Endpoints 11 winners here .