Nurix Announces U.S. FDA Orphan Drug Designation Granted to Bexobrutideg (NX-5948) for the Treatment of Waldenström Macroglobulinemia
Nurix Therapeutics (NRIX) announced that its drug bexobrutideg (NX-5948) has received Orphan Drug Designation (ODD) from the FDA for treating Waldenström macroglobulinemia (WM). Bexobrutideg is an oral, brain-penetrant BTK degrader currently in Phase 1a/b clinical trials for relapsed/refractory B-cell malignancies.
The ODD grants several benefits including tax credits for clinical testing, FDA fee waivers, and seven years of market exclusivity upon approval. The drug represents a new class of targeted protein degraders, marked by the novel 'deg' suffix, distinguishing it from traditional inhibitors that use the 'ib' suffix.
The designation follows positive Phase 1 data presented at the 12th International Workshop on Waldenström Macroglobulinemia. The drug's mechanism involves catalytic degradation of target proteins through the proteasome, potentially eliminating mutant oncoproteins resistant to inhibitor therapy.
Nurix Therapeutics (NRIX) ha annunciato che il suo farmaco bexobrutideg (NX-5948) ha ricevuto la Designazione di Farmaco Orfano (ODD) dalla FDA per il trattamento della macroglobulinemia di Waldenström (WM). Bexobrutideg è un degrader BTK orale, in grado di penetrare nel cervello, attualmente in fase di sperimentazione clinica di Fase 1a/b per le neoplasie B-cellulari recidivanti/rifrangenti.
L'ODD offre diversi vantaggi, tra cui crediti d'imposta per i test clinici, esenzioni dalle tasse FDA e sette anni di esclusività di mercato dopo l'approvazione. Il farmaco rappresenta una nuova classe di degrader proteici mirati, contraddistinta dal nuovo suffisso 'deg', che lo distingue dagli inibitori tradizionali che utilizzano il suffisso 'ib'.
La designazione segue dati positivi della Fase 1 presentati al 12° Workshop Internazionale sulla Macroglobulinemia di Waldenström. Il meccanismo del farmaco prevede la degradazione catalitica delle proteine target attraverso il proteasoma, eliminando potenzialmente le oncoproteine mutanti resistenti alla terapia con inibitori.
Nurix Therapeutics (NRIX) anunció que su medicamento bexobrutideg (NX-5948) ha recibido la Designación de Medicamento Huérfano (ODD) de la FDA para el tratamiento de la macroglobulinemia de Waldenström (WM). Bexobrutideg es un degradador de BTK oral, que penetra en el cerebro, actualmente en ensayos clínicos de Fase 1a/b para malignidades B-celulares en recaída/refractarias.
La ODD otorga varios beneficios, incluidos créditos fiscales para pruebas clínicas, exenciones de tarifas de la FDA y siete años de exclusividad en el mercado tras la aprobación. El medicamento representa una nueva clase de degradadores de proteínas dirigidos, marcado por el nuevo sufijo 'deg', que lo distingue de los inhibidores tradicionales que utilizan el sufijo 'ib'.
La designación sigue a datos positivos de la Fase 1 presentados en el 12º Taller Internacional sobre Macroglobulinemia de Waldenström. El mecanismo del medicamento implica la degradación catalítica de proteínas objetivo a través del proteasoma, eliminando potencialmente oncoproteínas mutantes resistentes a la terapia con inhibidores.
Nurix Therapeutics (NRIX)는 그 약물 bexobrutideg (NX-5948)가 FDA로부터 월든스트롬 다중단백혈증 (WM) 치료를 위한 고아약 지정 (ODD)을 받았다고 발표했습니다. Bexobrutideg는 경구용 BTK 분해제로, 현재 재발/내성 B세포 악성종양에 대한 1a/b 임상시험 단계에 있습니다.
ODD는 임상 시험에 대한 세금 공제, FDA 수수료 면제 및 승인 후 7년간의 시장 독점권을 포함한 여러 가지 혜택을 제공합니다. 이 약물은 'ib' 접미사를 사용하는 전통적인 억제제와 구별되는 새로운 'deg' 접미사가 있는 표적 단백질 분해제의 새로운 클래스를 나타냅니다.
이 지정은 제12회 월든스트롬 다중단백혈증 국제 워크숍에서 발표된 긍정적인 1단계 데이터에 따른 것입니다. 이 약물의 메커니즘은 프로테아좀을 통해 표적 단백질의 촉매 분해를 포함하며, 억제제 치료에 저항하는 돌연변이 온코단백질을 제거할 수 있습니다.
Nurix Therapeutics (NRIX) a annoncé que son médicament bexobrutideg (NX-5948) a reçu la désignation de médicament orphelin (ODD) de la FDA pour le traitement de la macroglobulinémie de Waldenström (WM). Bexobrutideg est un dégradateur de BTK oral, capable de pénétrer dans le cerveau, actuellement en essais cliniques de phase 1a/b pour des malignités B-cellulaires en rechute/réfractaires.
L'ODD accorde plusieurs avantages, y compris des crédits d'impôt pour les essais cliniques, des exonérations de frais FDA et sept ans d'exclusivité sur le marché après approbation. Le médicament représente une nouvelle classe de dégradateurs de protéines ciblés, marqué par le nouveau suffixe 'deg', le distinguant des inhibiteurs traditionnels qui utilisent le suffixe 'ib'.
La désignation fait suite à des données positives de la phase 1 présentées lors du 12e atelier international sur la macroglobulinémie de Waldenström. Le mécanisme du médicament implique la dégradation catalytique des protéines cibles par le protéasome, éliminant potentiellement les oncoprotéines mutantes résistantes à la thérapie par inhibiteurs.
Nurix Therapeutics (NRIX) gab bekannt, dass sein Medikament bexobrutideg (NX-5948) von der FDA die Orphan Drug Designation (ODD) zur Behandlung der Waldenström-Makroglobulinämie (WM) erhalten hat. Bexobrutideg ist ein oraler, das Gehirn durchdringender BTK-Degrader, der sich derzeit in klinischen Phase 1a/b Studien für rezidivierende/refraktäre B-Zell-Malignome befindet.
Die ODD gewährt mehrere Vorteile, darunter Steuervergünstigungen für klinische Tests, Gebührenbefreiungen von der FDA und sieben Jahre Marktexklusivität nach der Genehmigung. Das Medikament stellt eine neue Klasse von zielgerichteten Protein-Degradern dar, die durch das neuartige Suffix 'deg' gekennzeichnet ist, was es von traditionellen Inhibitoren mit dem Suffix 'ib' unterscheidet.
Die Designation folgt positiven Phase 1-Daten, die auf dem 12. Internationalen Workshop zur Waldenström-Makroglobulinämie präsentiert wurden. Der Wirkmechanismus des Medikaments umfasst die katalytische Degradation von Zielproteinen durch das Proteasom, was potenziell mutierte Onkoproteine, die gegen die Inhibitortherapie resistent sind, eliminieren kann.
- Received FDA Orphan Drug Designation, providing potential market exclusivity and financial benefits
- Positive Phase 1 clinical trial data reported
- Novel drug mechanism potentially effective against resistant forms of cancer
- First-in-class BTK degrader with brain penetration capability
- Early-stage clinical development (Phase 1) indicates long path to potential commercialization
- Targets rare disease with market size (fewer than 200,000 patients in US)
Insights
Nurix's Orphan Drug Designation (ODD) for bexobrutideg represents a significant regulatory achievement with multiple strategic advantages. This designation provides substantial financial benefits including tax credits for clinical trials, waived FDA application fees, and seven years of market exclusivity upon approval - creating a protected commercial runway for this novel BTK degrader.
The ODD validates bexobrutideg as addressing a critical unmet need in Waldenström macroglobulinemia, a rare cancer affecting fewer than 200,000 Americans. Beyond the regulatory advantages, the USAN Council's creation of the new "deg" suffix establishes Nurix as pioneering a distinct therapeutic class, differentiating their molecular approach from BTK inhibitors like ibrutinib.
This classification separation is pharmacologically significant - while inhibitors temporarily block protein function, degraders like bexobrutideg catalytically eliminate the entire protein, potentially overcoming resistance mechanisms to existing inhibitors. The compound's brain penetrance also suggests potential applications beyond WM in neurological conditions.
The designation builds momentum following positive Phase 1 data presented at a major scientific workshop, suggesting clinical validation of their approach. For a company with
The FDA granting Orphan Drug Designation for bexobrutideg addresses a important gap in Waldenström macroglobulinemia treatment landscape. WM patients typically develop resistance to BTK inhibitors through mutations that prevent drug binding, creating a significant clinical challenge.
Bexobrutideg's mechanism represents a fundamental therapeutic advantage - rather than simply inhibiting BTK activity, it triggers the cell's own protein disposal machinery to eliminate BTK entirely. This approach can potentially overcome the C481S and other mutations that render ibrutinib and second-generation inhibitors ineffective.
The designation follows positive Phase 1 data, suggesting early clinical validation. The drug's brain penetrance is particularly noteworthy as approximately 5-15% of WM patients develop neurological manifestations (Bing-Neel syndrome) that respond poorly to standard treatments due to blood-brain barrier limitations.
The new "deg" suffix recognition is scientifically significant, acknowledging that degraders operate through fundamentally different pharmacological principles - rather than occupancy-driven inhibition, they function through catalytic, event-driven mechanisms requiring only transient target engagement. This distinction enables degraders to achieve more complete target suppression at potentially lower drug exposures, possibly improving therapeutic index.
For WM patients with options after BTK inhibitor failure, this development represents genuine hope for a mechanistically distinct approach to overcome treatment resistance.
Orphan Drug Designation follows positive Phase 1 data presented at the 12th International Workshop on Waldenström Macroglobulinemia
First-in-class Bruton’s tyrosine kinase (BTK) degrader NX-5948 assigned nonproprietary name “bexobrutideg” in newly named degrader class of drugs
SAN FRANCISCO, March 17, 2025 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to bexobrutideg (NX-5948) for the treatment of Waldenström macroglobulinemia (WM). Bexobrutideg is an orally bioavailable, brain penetrant degrader of BTK which is being evaluated in an ongoing Phase 1a/b clinical trial in adults with relapsed or refractory B-cell malignancies.
The FDA's Orphan Drug Designation program provides orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the United States. This designation provides certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved.
“The FDA’s Orphan Drug Designation for bexobrutideg, also known as NX-5948, represents an important milestone in our regulatory strategy and underscores the significant unmet medical need for improved treatments for Waldenström macroglobulinemia,” said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. “Granting of the designation highlights bexobrutideg’s potential to provide patients with WM a promising new therapeutic option. We are also pleased to announce that our investigational therapy bexobrutideg has been assigned a nonproprietary name reflecting its novel mechanism of action, designated with the unique suffix “deg” for degrader.”
In collaboration with the national naming authority, United States Adopted Name (USAN) Council, Nurix’s lead BTK degrader, NX-5948, was assigned the nonproprietary name “bexobrutideg.” The U.S. and international drug naming convention is designed to select a single name of worldwide acceptability for each active substance that is intended to be marketed as a pharmaceutical. Most notable with bexobrutideg is the designation of a new suffix, “deg,” which references bexobrutideg’s novel degradation mode of action. Targeted protein degraders are characterized by their bifunctional nature, binding to both a target protein and a ligase to drive ubiquitination and catalytic degradation of the target through the proteasome. The new deg suffix is an important recognition that the mechanism of action, pharmacokinetics and pharmacodynamics of targeted protein degraders are fundamentally different than inhibitors, which all use the “ib” suffix. The central stem of the name, “bruti,” references the target, Bruton’s tyrosine kinase (as used in ibrutinib, zanubrutinib and acalabrutinib). The prefix “bexo” is the unique identifier of a specific agent in the class and is often used for ease of reference to the agent.
“We are excited that bexobrutideg has been recognized by the USAN Council as a unique entity and member of a new class of small molecule drugs, targeted protein degraders,” said Gwenn Hansen, Ph.D., chief scientific officer of Nurix. “The catalytic mechanism of action and event driven pharmacology triggering ubiquitination and proteasomal degradation of a target protein is highly differentiated from inhibitors and allows degraders to eliminate the totality of a protein’s function. In our BTK degrader clinical program, we have also established that degraders can eliminate mutant oncoproteins that have proven to be resistant to inhibitor therapy.”
About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK that is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported encouraging safety and efficacy data in patients with WM treated in the ongoing Phase 1a/b clinical trial of bexobrutideg demonstrating early promise of clinical benefit with potential for durable outcomes. Nurix continues to enroll patients with WM in an ongoing Phase 1b expansion cohort and anticipates sharing additional clinical data in 2025. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022). Nurix is also developing bexobrutideg for the potential treatment of inflammatory diseases.
About Waldenström Macroglobulinemia (WM)
WM is a rare, slow growing type of non-Hodgkin’s lymphoma that is characterized by the replacement of normal bone marrow cells by malignant lymphocytic cells that produce monoclonal IgM. This replacement leads to anemia, bleeding, and impaired immune function, while the elevated IgM levels may cause neurologic symptoms. The incidence of Waldenström macroglobulinemia ranges from 0.361,2 to 0.573 per 100,000 people in the United States or approximately 1,200 to 1,900 annually. With a median disease duration approaching 10 years, 4 approximately 12,000 to 19,000 patients are living with Waldenstrom’s macroglobulinemia in the United States. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor (BTKi) therapy. There are no therapies approved to treat WM patients after a BTKi.
About Nurix Therapeutics, Inc.
Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and inflammatory diseases. Nurix’s wholly owned, clinical stage pipeline includes degraders of Bruton’s tyrosine kinase (BTK), a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Nurix also is advancing multiple potentially first-in-class or best-in-class degraders and degrader antibody conjugates (DACs) in its preclinical pipeline. Nurix’s partnered drug discovery pipeline consists of preclinical stage degraders of IRAK4 and STAT6, as well as multiple additional programs under collaboration agreements with Gilead Sciences, Inc., Sanofi S.A. and Pfizer Inc., within which Nurix retains certain options for co-development, co-commercialization and profit sharing in the United States for multiple drug candidates. Powered by a fully AI-integrated discovery engine capable of tackling any protein class, and coupled with unparalleled ligase expertise, Nurix’s dedicated team has built a formidable advantage in translating the science of targeted protein degradation into clinical advancements. Nurix aims to establish degrader-based treatments at the forefront of patient care, writing medicine’s next chapter with a new script to outmatch disease. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com.
Forward-Looking Statements
This press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding: Nurix’s future plans, prospects and strategies, including with respect to bexobrutideg; the potential benefits of Orphan Drug Designation; the tolerability, safety profile, therapeutic potential and other advantages of bexobrutideg; and the planned timing for the provision of updates and findings from Nurix’s clinical trials. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) whether Nurix will be able to advance, obtain regulatory approval of and ultimately commercialize bexobrutideg; (ii) whether Nurix will be able to fund development activities and achieve development goals; (iii) the impact of global business, political and macroeconomic conditions, cybersecurity events, instability in the banking system, and global events, including regional conflicts around the world, on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (iv) whether Nurix will be able to protect intellectual property and (v) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Annual Report on Form 10-K for the year ended November 30, 2024, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law.
Contacts:
Investors
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Nurix Therapeutics, Inc.
ir@nurixtx.com
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FAQ
What benefits does the FDA Orphan Drug Designation provide for Nurix's bexobrutideg (NRIX)?
How does bexobrutideg's mechanism of action differ from traditional BTK inhibitors?
What stage of clinical development is bexobrutideg (NRIX) currently in?
Why was bexobrutideg given the 'deg' suffix instead of 'ib' in its naming convention?
