Recursion announces first patient dosed in Phase 1/2 clinical study of REC-1245, a potential first-in-class, RBM39 degrader for Biomarker-Enriched Solid Tumors and Lymphoma
Recursion (NASDAQ: RXRX) has initiated dosing in its Phase 1/2 DAHLIA clinical trial of REC-1245, a novel RBM39 degrader targeting biomarker-enriched solid tumors and lymphoma. The drug, developed using AI-powered biology mapping, moved from target identification to IND studies in under 18 months. REC-1245 works by inducing splicing defects that downregulate DNA Damage Response networks and cell cycle checkpoints, potentially addressing over 100,000 patients in the US and EU5. The DAHLIA trial aims to evaluate safety, tolerability, and preliminary activity, while determining maximum tolerated dose for both single-agent use and combinations with other treatments.
Recursion (NASDAQ: RXRX) ha avviato la somministrazione del farmaco nella sua sperimentazione clinica di Fase 1/2 chiamata DAHLIA per REC-1245, un nuovo degradatore di RBM39 che mira a tumori solidi arricchiti da biomarcatori e linfomi. Il farmaco, sviluppato utilizzando mappature biologiche potenziate dall'IA, è passato dall'identificazione del bersaglio agli studi IND in meno di 18 mesi. REC-1245 agisce inducendo difetti di splicing che downregolano le reti di risposta al danno del DNA e i punti di controllo del ciclo cellulare, potenzialmente beneficiando oltre 100.000 pazienti negli Stati Uniti e nei cinque paesi dell'UE. La sperimentazione DAHLIA mira a valutare la sicurezza, la tollerabilità e l'attività preliminare, determinando la dose massima tollerata sia per l'uso singolo che in combinazione con altri trattamenti.
Recursion (NASDAQ: RXRX) ha comenzado la dosificación en su ensayo clínico de Fase 1/2 DAHLIA de REC-1245, un nuevo degradador de RBM39 que se dirige a tumores sólidos enriquecidos con biomarcadores y linfomas. El fármaco, desarrollado utilizando mapeo biológico impulsado por IA, pasó de la identificación de objetivos a estudios IND en menos de 18 meses. REC-1245 actúa induciendo defectos de empalme que downregulan las redes de respuesta al daño del ADN y los puntos de control del ciclo celular, abordando potencialmente a más de 100,000 pacientes en EE. UU. y EU5. El ensayo DAHLIA tiene como objetivo evaluar la seguridad, tolerabilidad y actividad preliminar, mientras determina la dosis máxima tolerada tanto para uso como agente único como en combinaciones con otros tratamientos.
Recursion (NASDAQ: RXRX)는 REC-1245의 1/2상 DAHLIA 임상 시험에서 투여를 시작했습니다. 이 새로운 RBM39 분해제는 바이오마커가 풍부한 고형 종양과 림프종을 표적으로 합니다. AI 기반 생물학 매핑을 사용하여 개발된 이 약물은 타겟 식별에서 IND 연구로 18개월도 채 되지 않아 진행되었습니다. REC-1245는 스플라이싱 결함을 유도하여 DNA 손상 반응 네트워크와 세포 주기 체크포인트를 다운레귤레이트하는 방식으로 작용하여 미국과 EU5에서 100,000명 이상의 환자를 대상으로 할 수 있습니다. DAHLIA 시험의 목적은 안전성, 내약성 및 초기 활동을 평가하고 단일 제제 및 다른 치료와의 병용을 위한 최대 내약 용량을 결정하는 것입니다.
Recursion (NASDAQ: RXRX) a lancé la dose dans son essai clinique de Phase 1/2 DAHLIA pour REC-1245, un nouvel degradateur de RBM39 ciblant les tumeurs solides enrichies en biomarqueurs et les lymphomes. Le médicament, développé grâce à la cartographie biologique alimentée par IA, est passé de l'identification des cibles aux études IND en moins de 18 mois. REC-1245 agit en induisant des défauts d'épissage qui régulent à la baisse les réseaux de réponse aux dommages de l'ADN et les points de contrôle du cycle cellulaire, potentiellement en aide à plus de 100 000 patients aux États-Unis et dans les cinq pays de l'UE. L'essai DAHLIA vise à évaluer la sécurité, la tolérabilité et l'activité préliminaire, tout en déterminant la dose maximale tolérée tant pour l'utilisation en monothérapie que pour les combinaisons avec d'autres traitements.
Recursion (NASDAQ: RXRX) hat mit der Dosierung in seiner Phase 1/2 DAHLIA-Studie von REC-1245, einem neuartigen RBM39-Degrader, begonnen, der auf biomarker-reiche solide Tumoren und Lymphome abzielt. Das Medikament, das mit KI-gesteuerter biologischer Kartierung entwickelt wurde, durchlief in weniger als 18 Monaten den Prozess von der Zielidentifizierung zu IND-Studien. REC-1245 funktioniert, indem es Splicing-Defekte induziert, die die DNA-Schadenantwortnetzwerke und Zellzykluskontrollen herunterregulieren und potenziell über 100.000 Patienten in den USA und EU5 ansprechen können. Die DAHLIA-Studie hat zum Ziel, Sicherheit, Verträglichkeit und vorläufige Aktivität zu bewerten sowie die maximale verträgliche Dosis sowohl für die Einzelanwendung als auch in Kombination mit anderen Behandlungen zu bestimmen.
- Rapid development from target ID to IND studies in under 18 months
- Large addressable market of >100,000 patients in US and EU5
- First-in-class potential for RBM39 degrader in oncology
- Versatile treatment potential as both single agent and combination therapy
- Early-stage Phase 1/2 trial with uncertain outcomes
- Safety and efficacy yet to be established
Insights
This clinical trial initiation represents a significant milestone in targeted cancer therapy development. REC-1245's mechanism as an RBM39 degrader is particularly noteworthy for its potential in treating biomarker-enriched cancers. The rapid development timeline - from target identification to IND studies in under 18 months - demonstrates remarkable efficiency in drug development.
Key technical achievements include:
- Novel target identification of RBM39's regulatory role on CDK12 function
- Preclinical evidence showing DDR network downregulation
- Potential applications both as monotherapy and in combination treatments
The addressable market of >100,000 patients in US and EU5 indicates substantial commercial potential. The open-label Phase 1/2 trial design will accelerate preliminary efficacy data collection through ORR measurements while establishing safety parameters.
The successful application of AI-powered biological mapping to identify novel drug targets marks a significant advancement in TechBio drug discovery. The platform's ability to facilitate rapid development with only ~200 compounds synthesized demonstrates remarkable efficiency compared to traditional drug discovery methods that often require thousands of compounds.
This represents a validation of Recursion's AI-enabled platform approach, potentially establishing a new paradigm for accelerated drug development. The integration of AI with biological insights could significantly reduce both time and resources required for future drug development programs, potentially transforming the economics of pharmaceutical R&D.
- First program to result from end-to-end use of OS to identify a novel target and new chemical matter, which moved from target ID to IND enabling studies in under 18 months with ~200 compounds synthesized
- REC-1245 is a potent and selective RBM39 degrader with a potential first-in-class profile in Solid tumors and Lymphoma
- >100,000 patients in the US and EU5 initially addressable
SALT LAKE CITY, Dec. 03, 2024 (GLOBE NEWSWIRE) -- 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.
Media Contact
Media@Recursion.com
Investor Contact
Investor@Recursion.com
Forward-Looking Statements
This document contains information that includes or is based upon “forward-looking statements” within the meaning of the Securities Litigation Reform Act of 1995, including, without limitation, those regarding the potential efficacy of REC-1245; timing of the Phase 1/2 clinical trial of REC-1245; early and late stage discovery, preclinical, and clinical programs; prospective products and their potential future indications and market opportunities; Recursion OS and the ability achieve results of REC-1245 on other targets and/or compounds, and other technologies; business and financial plans and performance; and all other statements that are not historical facts. Forward-looking statements may or may not include identifying words such as “plan,” “will,” “expect,” “anticipate,” “intend,” “believe,” “potential,” “continue,” and similar terms. These statements are subject to known or unknown risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements, including but not limited to: challenges inherent in pharmaceutical research and development, including the timing and results of preclinical and clinical programs, where the risk of failure is high and failure can occur at any stage prior to or after regulatory approval due to lack of sufficient efficacy, safety considerations, or other factors; our ability to leverage and enhance our drug discovery platform; our ability to obtain financing for development activities and other corporate purposes; the success of our collaboration activities; our ability to obtain regulatory approval of, and ultimately commercialize, drug candidates; our ability to obtain, maintain, and enforce intellectual property protections; cyberattacks or other disruptions to our technology systems; our ability to attract, motivate, and retain key employees and manage our growth; inflation and other macroeconomic issues; and other risks and uncertainties such as those described under the heading “Risk Factors” in our filings with the U.S. Securities and Exchange Commission, including our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and other filings. All forward-looking statements are based on management’s current estimates, projections, and assumptions, and Recursion undertakes no obligation to correct or update any such statements, whether as a result of new information, future developments, or otherwise, except to the extent required by applicable law.
FAQ
What is the purpose of Recursion's DAHLIA trial for REC-1245?
How many patients could potentially benefit from REC-1245 (RXRX)?
How long did it take Recursion to develop REC-1245 from target identification to IND studies?
What is the mechanism of action for REC-1245?
