Nurix Therapeutics Presents Preclinical Data from Two Autoimmune and Inflammatory Disease Programs, NX-5948 and GS-6791, at ACR Convergence 2024
Nurix Therapeutics (NRIX) presented preclinical data for two autoimmune and inflammatory disease programs at ACR Convergence 2024. The first program, NX-5948, is an oral BTK degrader showing potential superiority over kinase inhibitors in inflammatory diseases. The second program, GS-6791, developed with Gilead Sciences, is an IRAK4 degrader for rheumatoid arthritis treatment.
Both compounds demonstrated strong efficacy in preclinical models. NX-5948 showed superior results in arthritis models and other inflammatory conditions, while GS-6791 exhibited robust dose-dependent efficacy in arthritis models with better cytokine response reduction compared to IRAK4 kinase inhibitors.
Nurix Therapeutics (NRIX) ha presentato dati preclinici per due programmi riguardanti malattie autoimmuni e infiammatorie durante l'ACR Convergence 2024. Il primo programma, NX-5948, è un degrader BTK orale che mostra un potenziale di superiorità rispetto agli inibitori della chinasi nelle malattie infiammatorie. Il secondo programma, GS-6791, sviluppato con Gilead Sciences, è un degrader IRAK4 per il trattamento dell'artrite reumatoide.
Entrambi i composti hanno dimostrato una forte efficacia nei modelli preclinici. NX-5948 ha mostrato risultati superiori nei modelli di artrite e altre condizioni infiammatorie, mentre GS-6791 ha dimostrato un'elevata efficacia dose-dipendente nei modelli di artrite con una migliore riduzione della risposta delle citochine rispetto agli inibitori della chinasi IRAK4.
Nurix Therapeutics (NRIX) presentó datos preclínicos para dos programas de enfermedades autoinmunitarias e inflamatorias en la ACR Convergence 2024. El primer programa, NX-5948, es un degradador de BTK oral que muestra un potencial de superioridad sobre los inhibidores de quinasa en enfermedades inflamatorias. El segundo programa, GS-6791, desarrollado con Gilead Sciences, es un degradador de IRAK4 para el tratamiento de la artritis reumatoide.
Ambos compuestos demostraron una fuerte eficacia en los modelos preclínicos. NX-5948 mostró resultados superiores en modelos de artritis y otras condiciones inflamatorias, mientras que GS-6791 exhibió una robusta eficacia dependiente de la dosis en modelos de artritis, con una mejor reducción de la respuesta de citoquinas en comparación con los inhibidores de quinasa IRAK4.
Nurix Therapeutics (NRIX)는 ACR Convergence 2024에서 두 가지 자가면역 및 염증 질환 프로그램에 대한 전임상 데이터를 발표했습니다. 첫 번째 프로그램인 NX-5948은 염증 질환에서 키나제 억제제에 비해 잠재적인 우수성을 보이는 경구 BTK 분해제입니다. 두 번째 프로그램인 GS-6791은 Gilead Sciences와 개발한 것으로, 류마티스 관절염 치료를 위한 IRAK4 분해제입니다.
두 화합물 모두 전임상 모델에서 강한 효능을 나타냈습니다. NX-5948은 관절염 모델 및 다른 염증 조건에서 우수한 결과를 보였으며, GS-6791은 IRAK4 키나제 억제제와 비교하여 더 나은 사이토카인 반응 감소와 함께 관절염 모델에서 강력한 용량 의존적 효능을 보였습니다.
Nurix Therapeutics (NRIX) a présenté des données précliniques pour deux programmes de maladies auto-immunes et inflammatoires lors de l'ACR Convergence 2024. Le premier programme, NX-5948, est un dégradateur de BTK oral montrant un potentiel de supériorité par rapport aux inhibiteurs de kinases dans les maladies inflammatoires. Le deuxième programme, GS-6791, développé avec Gilead Sciences, est un dégradateur d'IRAK4 pour le traitement de la polyarthrite rhumatoïde.
Les deux composés ont démontré une forte efficacité dans des modèles précliniques. NX-5948 a montré des résultats supérieurs dans les modèles d'arthrite et d'autres conditions inflammatoires, tandis que GS-6791 a exhibé une efficacité robuste dépendante de la dose dans les modèles d'arthrite, avec une meilleure réduction de la réponse des cytokines par rapport aux inhibiteurs de kinases IRAK4.
Nurix Therapeutics (NRIX) präsentierte während der ACR Convergence 2024 präklinische Daten für zwei Programme zu Autoimmun- und entzündlichen Erkrankungen. Das erste Programm, NX-5948, ist ein oraler BTK-Degrader, der potenzielle Überlegenheit gegenüber Kinase-Inhibitoren in entzündlichen Erkrankungen zeigt. Das zweite Programm, GS-6791, wurde in Zusammenarbeit mit Gilead Sciences entwickelt und ist ein IRAK4-Degrader zur Behandlung von rheumatoider Arthritis.
Beide Verbindungen zeigten eine starke Wirksamkeit in präklinischen Modellen. NX-5948 zeigte überlegene Ergebnisse in Arthritis-Modellen und anderen entzündlichen Bedingungen, während GS-6791 eine robuste dosisabhängige Wirksamkeit in Arthritis-Modellen mit einer besseren Reduktion der Zytokinreaktion im Vergleich zu IRAK4-Kinase-Inhibitoren zeigte.
- NX-5948 demonstrated superior efficacy compared to BTK inhibitors in preclinical trials
- GS-6791 showed robust dose-dependent efficacy in arthritis models
- Partnership with Gilead Sciences for GS-6791 development
- Both programs still in early preclinical stages
- No clinical efficacy data available yet
Insights
The preclinical data for NX-5948 and GS-6791 demonstrates compelling potential in autoimmune and inflammatory diseases. Key findings show that NX-5948's BTK degradation approach achieves superior results compared to traditional BTK inhibitors across multiple disease models, including arthritis, lupus nephritis and multiple sclerosis. The drug's ability to penetrate the brain barrier and target both kinase and scaffold functions of BTK represents a significant advancement.
GS-6791's IRAK4 degradation mechanism shows enhanced efficacy over conventional kinase inhibitors in reducing inflammatory responses. The collaboration with Gilead Sciences adds substantial credibility and resources to its development pathway. Both candidates demonstrate strong potential to disrupt the
Data demonstrate potential superiority of a targeted protein degradation strategy compared to kinase inhibition for both BTK and IRAK4 targets in select inflammatory and autoimmune diseases
SAN FRANCISCO, Nov. 17, 2024 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today announced the presentation of preclinical data, including mechanism of action and relevant disease models, from two pipeline programs: NX-5948 and GS-6791. NX-5948 is Nurix’s proprietary, orally available, brain penetrant Bruton’s tyrosine kinase (BTK) degrader, which is being developed for the potential treatment of inflammation and autoimmune diseases in addition to its ongoing Phase 1b trial in patients with B-cell malignancies. GS-6791 is a selective, orally bioavailable degrader of interleukin-1 receptor-associated kinase 4 (IRAK4), which is being developed in collaboration with Gilead Sciences for the potential treatment of rheumatoid arthritis and other inflammatory diseases. These data were presented in two posters at ACR Convergence 2024, the annual meeting of the American College of Rheumatology (ACR), being held November 14–19, 2024, in Washington, D.C.
“The preclinical data presented at ACR Convergence underscore the exceptional potential of our targeted protein degradation strategy compared to kinase inhibition for both BTK and IRAK4, which are critical targets in inflammatory and autoimmune diseases, and support continued advancement of these drug candidates into clinical studies,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “These programs showcase the capability of Nurix’s DELigase platform to generate potent best-in-class degrader drug candidates with the potential to deliver superior efficacy in several inflammatory diseases.”
BTK mediates signaling downstream of the B cell receptor (BCR), toll-like receptors (TLRs), and Fc receptors (FcRs), making it an attractive therapeutic target in antibody-mediated autoimmune and inflammatory diseases. BTK has been shown to have both kinase and scaffold activities that are key to its function. Targeting BTK can reduce the production of new antibodies and mitigate the inflammation induced by existing antibodies, addressing key challenges in inflammatory and autoimmune diseases. In a poster titled: NX-5948, a Clinical-Stage BTK Degrader, Achieves Deep Suppression of BCR, TLR, and FcR Signaling in Immune Cells and Demonstrates Efficacy in Preclinical Models of Arthritis and Other Inflammatory Diseases, data illustrate the potential benefit of the BTK degrader NX-5948, which is equivalent or superior to inhibition of BTK across multiple mechanistic studies and models of inflammatory diseases. In primary B cells, NX-5948 promotes rapid degradation of BTK and more potently suppresses proximal BCR signaling and BCR- and TLR-mediated B cell activation than current BTK inhibitors under development. In a model of established collagen-induced arthritis, oral administration of NX-5948 achieves equal or superior improvement of clinical scores and deeper suppression of plasma cell numbers compared to BTK inhibitors. NX-5948 also demonstrates efficacy in several other models of inflammatory diseases including antibody-induced glomerulonephritis (a model of lupus nephritis), autoimmune lymphoproliferative syndrome (ALPS, a second model of lupus-like disease), passive cutaneous anaphylaxis (a model of allergic response including chronic spontaneous urticaria), and experimental autoimmune encephalitis (a model of multiple sclerosis).
IRAK4 plays a critical role in TLR- and interleukin-1 family receptor (IL-1R) signaling to induce inflammatory responses. Like BTK, IRAK4 has both kinase and scaffold functions, the latter of which have been shown to be particularly critical in IL-1 and TLR-mediated signaling across diverse cell types. GS-6791, a targeted protein degrader of IRAK4, provides a differentiated mode of action compared with inhibition of kinase activity.
In a poster titled: IRAK4 Degrader GS-6791 Inhibits TLR and IL-1R-Driven Inflammatory Signaling, and Ameliorates Disease in a Preclinical Arthritis Model, data demonstrate that GS-6791 is a potent degrader of IRAK4 in vitro and in vivo across a range of cell types. In PK/PD models GS-6791 inhibits IL-1- and TLR-induced cytokine release and results in deeper reduction of human B cell and synovial fibroblast cytokine responses compared to IRAK4 kinase inhibitors. In a preclinical model of arthritis, orally administered GS-6791 demonstrates robust, dose-dependent efficacy.
The poster presentations are available online in the Scientific Resources section of the Nurix Therapeutics website under Posters and Presentations.
About NX-5948: NX-5948 is an investigational, orally bioavailable degrader of BTK that is currently being evaluated in a Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies. Additional information on the Phase 1a/b clinical trial can be accessed at www.clinicaltrials.gov (NCT05131022).
About GS-6791 (previously NX-0479): GS-6791 is a potent, selective, oral IRAK4 degrader. Degradation of IRAK4 by GS-6791 has potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases. Nurix’s collaboration partner, Gilead Sciences, is responsible for conducting IND-enabling studies and advancing this program to clinical development.
About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cell and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and other federal securities laws. Any statements contained herein that do not describe historical facts, including, but not limited to, statements regarding the potential advantages and therapeutic benefits of NX-5948 and GS-6791 generally or as compared to inhibitors, the potential role of NX-5948 and GS-6791 in the treatment of inflammatory and autoimmune disease, the potential benefits and advantages of Nurix’s scientific approach and DELigase™ platform, and the extent to which mechanistic studies and preclinical model data predict human efficacy, are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those discussed in such forward-looking statements. Such risks and uncertainties include, but are not limited to, (i) the ability of each party to perform its obligations under the Nurix-Gilead collaboration; (ii) whether the parties will be able to successfully conduct and complete preclinical development, clinical development and commercialization of any drug candidates under the Nurix-Gilead collaboration; (iii) the risks inherent in the drug development process, including the unexpected emergence of adverse events or other undesirable side effects during clinical development; (iv) uncertainties related to the timing and results of preclinical studies and clinical trials; and (v) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the period ended August 31, 2024, and subsequent filings with the SEC. Any of these risks and uncertainties could materially and adversely affect Nurix’s business and results of operations, which could, in turn, have a significant and adverse impact on Nurix’s stock price. Nurix cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. Nurix undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date they were made or to reflect the occurrence of unanticipated events.
Contacts:
Investors
Jason Kantor, Ph.D.
Nurix Therapeutics, Inc.
ir@nurixtx.com
Elizabeth Wolffe, Ph.D.
Wheelhouse Life Science Advisors
lwolffe@wheelhouselsa.com
Media
Aljanae Reynolds
Wheelhouse Life Science Advisors
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