CDK12

SALT LAKE CITY, UT, USA I December 03, 2024 I Recursion (NASDAQ: RXRX), a leading clinical stage TechBio company decoding biology to radically improve lives, today announced that the first patient has been dosed in its Phase 1/2 clinical trial of REC-1245, a new chemical entity for the treatment of biomarker-enriched solid tumors and lymphoma. Recursion identified the novel regulatory role of RBM39 on CDK12 function using its AI-powered maps of biology. Recursion believes the modulation of RBM39 may be associated with a therapeutic effect in certain biomarker-enriched solid tumors and lymphoma. Preclinical data support that RBM39 degradation induces splicing defects which downregulate DNA Damage Response (DDR) networks and cell cycle checkpoints. Dr. McKean, a Clinical Investigator at START Mountain Region in Salt Lake City, Utah shared “The evolution of precision and personalized treatment options for oncology patients provides promising alternatives. We are so pleased to be working with Recursion as a participating site in the DAHLIA trial, and look forward to advancing the science of cancer treatment.” “Dosing the first patient in the DAHLIA trial marks a pivotal moment for Recursion as we combine the power of our AI-enabled platform with cutting-edge science to pioneer a new class of targeted therapies,” added Najat Khan, PhD, Chief R&D Officer and Chief Commercial Officer of Recursion “REC-1245 represents not only a potential breakthrough for patients with biomarker-enriched cancers but also a testament to our ability to rapidly translate novel insights into clinical programs. This milestone exemplifies our commitment to transforming the future of oncology with precision and speed.” The DAHLIA clinical trial is an open-label Ph1/2 study to characterize the safety, tolerability, PK, PD, and preliminary activity (ORR) of REC-1245 and to identify the maximum tolerated dose (MTD) and / or recommended phase 2 dose (RP2D). REC-1245 is a potential single agent or for use in combination with other agents (DDR inhibitors, checkpoint inhibitors, chemotherapy). About the potential patient population Based on an as of yet undisclosed specific set of biomarkers, Recursion estimates that the initially addressable population for this potential therapeutic to be >100,000 patients in the US and EU5. About REC-1245 REC-1245 is a novel molecular glue that leads to the degradation of RBM39 via E3 ligase adaptor DCAF15, which disrupts RNA splicing to downregulate cell cycle checkpoints and DDR networks, including CDK12. REC-1245 was characterized to selectively mimic the phenotype associated with CDK12 loss of function, and is an alternative target for modulating DNA damage response (DDR) pathways. It was developed with Recursion’s AI-enabled drug discovery platform. About the Trial The DAHLIA trial is a multi-center, open-label Ph1/2 study to characterize the safety, tolerability, PK, PD, and preliminary activity (ORR) of REC-1245 and to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). In the DAHLIA trial REC-1245 will be administered orally on a once daily (QD) schedule in participants with unresectable, locally advanced, or metastatic cancer and refractory to, had a relapse, or were intolerant of established standard of care treatments. Following the completion of Part 1A (monotherapy dose-finding), up to two previously examined dose levels will be randomized 1:1 in the monotherapy dose confirmation (Part 1B) portion of the study to determine the RP2D. The Phase 2 portion of this study will independently enroll one or more cohorts in parallel at the chosen RP2D dose. About Recursion Recursion (NASDAQ: RXRX) is a leading, clinical-stage TechBio company decoding biology to industrialize drug discovery. Central to its mission is the Recursion Operating System (OS), a platform built across diverse technologies that continuously expands one of the world’s largest proprietary biological, chemical and patient-centric datasets. Recursion leverages sophisticated machine-learning algorithms to distill from its dataset a collection of trillions of searchable relationships across biology and chemistry unconstrained by human bias. By commanding massive experimental scale—up to millions of wet lab experiments weekly—and massive computational scale—owning and operating one of the most powerful supercomputers in the world—Recursion is uniting technology, biology, chemistry and patient-centric data to advance the future of medicine. Recursion is headquartered in Salt Lake City, where it is a founding member of BioHive, the Utah life sciences industry collective. Recursion also has other primary offices in Toronto, Montreal, the San Francisco Bay Area, New York, the Oxford area, and London. SOURCE: Recursion

SALT LAKE CITY, UT, USA I October 02, 2024 I Recursion (NASDAQ: RXRX), a leading clinical stage TechBio company decoding biology to industrialize drug discovery, today announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for a Phase 1/2 clinical trial of REC-1245, a new chemical entity for the treatment of biomarker-enriched solid tumors and lymphoma. Chris Gibson, Ph.D., Co-founder and CEO of Recursion said, “REC-1245 is a prime example of using an expansive AI-enabled platform for drug discovery. After exploring many predicted biological and chemical relationships across our maps of biology, we identified RMB39 as a novel target that looks functionally similar to the well-known but hard to drug target CDK12. We also identified and optimized small molecules that target RBM39 without directly impacting CDK12 or CDK13 using these same AI-enabled maps. In under 18 months , leveraging some of our newer chemistry tools, Recursion rapidly progressed REC-1245 from novel target biology to preclinical drug candidate, more than twice the speed of industry average.” Recursion identified the novel regulatory role of RBM39 associated with CDK12 using its maps of biology and first reported this relationship in early 2023 at Download Day, Recursion’s R&D and investor event. Recursion believes the modulation of RBM39 may be associated with a therapeutic effect in certain biomarker-enriched solid tumors and lymphoma. Additionally, Recursion estimates that the initially addressable population for this potential therapeutic to be >100,000 patients in the US and EU5. REC-1245 is a potent and selective RBM39 degrader with a potential first-in-class profile. Preclinical data support that RBM39 degradation induces splicing defects which downregulate DNA Damage Response (DDR) networks and cell cycle checkpoints. “RBM39 degraders may offer a promising therapeutic approach for patients with solid tumors, particularly those with limited treatment options,” said Najat Khan, Ph.D., Chief R&D Officer and Chief Commercial Officer at Recursion. “Recursion’s platform was among the first to rapidly uncover the therapeutic potential of RBM39 degradation, a finding now validated by independent research. This mechanism provides new opportunities for targeting tumors, which are often resistant to conventional treatments. By advancing this research, we aim to deliver a critical option for patients facing significant unmet needs, ultimately improving their prognosis and quality of life.” The Phase 1/2 clinical trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and potential monotherapy efficacy of REC-1245, and is expected to initiate in Q4 2024. About Recursion Recursion (NASDAQ: RXRX) is a clinical stage TechBio company decoding biology to industrialize drug discovery. Enabling its mission is the Recursion OS, a platform built across diverse technologies that continuously expands one of the world’s largest proprietary biological and chemical datasets. Recursion leverages sophisticated machine-learning algorithms to distill from its dataset a collection of trillions of searchable relationships across biology and chemistry unconstrained by human bias. By commanding massive experimental scale — up to millions of wet lab experiments weekly — and massive computational scale — owning and operating one of the most powerful supercomputers in the world, Recursion is uniting technology, biology and chemistry to advance the future of medicine. Recursion is headquartered in Salt Lake City, where it is a founding member of BioHive, the Utah life sciences industry collective. Recursion also has offices in Toronto, Montréal, London, and the San Francisco Bay Area. Learn more at www.Recursion.com , or connect on X (formerly Twitter) and LinkedIn . SOURCE: Recursion Therapeutics

On June 20, 2023, the Food and Drug Administration approved talazoparib (Talzenna, Pfizer, Inc.) with enzalutamide for homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC). View full prescribing information for Talzenna Efficacy was evaluated in TALAPRO-2 (NCT03395197), a randomized, double-blind, placebo-controlled, multi-cohort trial enrolling 399 patients with HRR gene-mutated mCRPC. Patients were randomized (1:1) to receive enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Patients were required to have a prior orchiectomy and, if not performed, received gonadotropin-releasing hormone (GnRH) analogs. Patients with prior systemic therapy for mCRPC were excluded; however, prior CYP17 inhibitors or docetaxel for metastatic castration-sensitive prostate cancer (mCSPC) was permitted. Randomization was stratified by previous treatment with a CYP17 inhibitor or docetaxel. HRR genes (ATM, ATR, BRCA1, BRCA2, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) were assessed prospectively using tumor tissue and/or circulating tumor DNA (ctDNA)-based next generation sequencing assays. The major efficacy outcome measure was radiographic progression-free survival (rPFS) per RECIST version 1.1 for soft tissue and Prostate Cancer Working Group 3 criteria for bone, assessed by blinded independent central review. A statistically significant improvement in rPFS for talazoparib with enzalutamide compared to placebo with enzalutamide was observed in the HRR gene-mutated population with a median that was not reached vs 13.8 months (HR 0.45; 95% CI: 0.33, 0.61; p<0.0001). In an exploratory analysis by BRCA mutation status, the hazard ratio for rPFS in patients with BRCA-mutated mCRPC (n=155) was 0.20 (95% CI: 0.11, 0.36) and, in patients with non-BRCAm HRR gene-mutated mCRPC, was 0.72 (0.49, 1.07). The most common adverse reactions (≥10%), including laboratory abnormalities, were decreased hemoglobin, decreased neutrophils, decreased lymphocytes, fatigue, decreased platelets, decreased calcium, nausea, decreased appetite, decreased sodium, decreased phosphate, fractures, decreased magnesium, dizziness, increased bilirubin, decreased potassium, and dysgeusia. Among all patients with mCRPC treated with talazoparib with enzalutamide on TALAPRO-2 (n=511), 39% required a blood transfusion, including 22% who required multiple transfusions, and 2 patients were diagnosed with myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). The recommended talazoparib dose is 0.5 mg taken orally once daily in combination with enzalutamide until disease progression or unacceptable toxicity. The recommended enzalutamide dose is 160 mg taken orally once daily. Patients receiving talazoparib and enzalutamide should also receive a GnRH analog concurrently or should have had bilateral orchiectomy. This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted priority review. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088. For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov. For information on the COVID-19 pandemic, see the following resources: FDA: Coronavirus Disease 2019 (COVID-19) NCI: Coronavirus: What People With Cancer Should Know CDC: Coronavirus (COVID-19) Follow the Oncology Center of Excellence on Twitter @FDAOncologyExternal Link Disclaimer. Content current as of: 06/20/2023 Regulated Product(s) Drugs 06/20/2023 Drugs Drug Approvals and Databases Resources for Information | Approved Drugs Resources for Information | Approved Drugs