Nurix Therapeutics Presents Positive Results from the Ongoing Clinical Trial of Its BTK Degrader NX-5948 in Patients with Relapsed/Refractory Waldenstrom’s Macroglobulinemia
Nurix Therapeutics presented positive results from its ongoing Phase 1a/1b clinical trial of NX-5948, an oral BTK degrader, in patients with relapsed/refractory Waldenstrom's macroglobulinemia (WM) at the 12th International Workshop on Waldenstrom's Macroglobulinemia. Key findings include:
- 77.8% objective response rate (7 of 9 evaluable patients)
- Durable responses deepening over time
- Two patients on treatment for over a year
- Tolerable safety profile consistent with overall population
- Responses observed regardless of MYD88 and CXCR4 mutation status
The trial included heavily pretreated patients with a median of 3 prior lines of therapy. These results support the advancement of NX-5948 into the ongoing Phase 1b expansion cohort, including patients previously treated with BTK inhibitors and those with Bing-Neel syndrome.
Nurix Therapeutics ha presentato risultati positivi dal suo studio clinico in corso di fase 1a/1b riguardante NX-5948, un degradatore orale di BTK, nei pazienti con macroglobulinemia di Waldenström (WM) recidivante/refrattaria durante il 12° Workshop Internazionale sulla Macroglobulinemia di Waldenström. I risultati chiave includono:
- 77,8% tasso di risposta obiettiva (7 su 9 pazienti valutabili)
- Risposte durature che si approfondiscono nel tempo
- Due pazienti in trattamento da oltre un anno
- Profilo di sicurezza tollerabile in linea con la popolazione generale
- Risposte osservate indipendentemente dallo stato di mutazione di MYD88 e CXCR4
Lo studio ha incluso pazienti con un elevato numero di trattamenti pregressi, con una mediana di 3 precedenti linee di terapia. Questi risultati supportano l'avanzamento di NX-5948 nel corrente coorte di espansione di fase 1b, compresi pazienti già trattati con inibitori di BTK e quelli con sindrome di Bing-Neel.
Nurix Therapeutics presentó resultados positivos de su ensayo clínico en fase 1a/1b de NX-5948, un degradador oral de BTK, en pacientes con macroglobulinemia de Waldenström (WM) en recaída/refractaria durante el 12º Taller Internacional sobre Macroglobulinemia de Waldenström. Las principales conclusiones incluyen:
- Tasa de respuesta objetiva del 77.8% (7 de 9 pacientes evaluables)
- Respuestas duraderas que se profundizan con el tiempo
- Dos pacientes en tratamiento por más de un año
- Perfil de seguridad tolerable consistente con la población general
- Respuestas observadas sin importar el estado de mutación de MYD88 y CXCR4
El ensayo incluyó pacientes con múltiples tratamientos previos, con una mediana de 3 líneas de tratamiento anteriores. Estos resultados respaldan el avance de NX-5948 hacia la actual cohorte de expansión de fase 1b, incluidos pacientes tratados previamente con inhibidores de BTK y aquellos con síndrome de Bing-Neel.
Nurix Therapeutics는 Waldenstrom's macroglobulinemia (WM) 재발/불응 환자를 대상으로 하는 NX-5948의 진행 중인 1a/1b 임상 시험에서 긍정적인 결과를 발표했습니다. 이는 제12회 국제 월든스트롬 매크로글로불리네미아 워크숍에서 발표되었습니다. 주요 발견 사항은 다음과 같습니다:
- 객관적 반응률 77.8% (평가 가능한 환자 9명 중 7명)
- 시간이 지남에 따라 심화되는 지속적인 반응
- 1년 이상 치료받은 환자 2명
- 전체 모집단과 일치하는 수용 가능한 안전성 프로필
- MYD88 및 CXCR4 변이 상태와 관계없이 관찰된 반응
이 시험에는 중증의 사전 치료 환자가 포함되었으며, 평균 3회의 이전 치료 라인을 가진 환자들이었습니다. 이러한 결과는 BTK 억제제로 치료받은 환자와 Bing-Neel 증후군 환자를 포함하는 현재의 1b 확장 코호트로 NX-5948의 발전을 지지합니다.
Nurix Therapeutics a présenté des résultats positifs de son essai clinique en cours de phase 1a/1b avec NX-5948, un dégrader oral de BTK, chez des patients atteints de macroglobulinémie de Waldenström (WM) en rechute/résistante lors du 12e Atelier International sur la Macroglobulinémie de Waldenström. Les résultats clés comprennent :
- Taux de réponse objective de 77,8% (7 sur 9 patients évaluables)
- Réponses durables qui s'approfondissent au fil du temps
- Deux patients en traitement depuis plus d'un an
- Profil de sécurité tolérable cohérent avec l'ensemble de la population
- Réponses observées indépendamment du statut de mutation de MYD88 et CXCR4
L'essai a inclus des patients ayant été fortement prétraités, avec une médiane de 3 lignes de thérapie précédentes. Ces résultats soutiennent l'avancement de NX-5948 dans la cohorte d'expansion en cours de phase 1b, incluant des patients précédemment traités avec des inhibiteurs de BTK et ceux ayant le syndrome de Bing-Neel.
Nurix Therapeutics hat positive Ergebnisse aus seiner laufenden Phase 1a/1b klinischen Studie mit NX-5948, einem oralen BTK-Degrader, bei Patienten mit rezidivierter/refraktärer Waldenström-Makroglobulinämie (WM) auf dem 12. Internationalen Workshop zur Waldenström-Makroglobulinämie vorgestellt. Wichtige Ergebnisse umfassen:
- 77,8% objektive Ansprechrate (7 von 9 evaluierten Patienten)
- Dauerhafte Reaktionen, die sich im Laufe der Zeit vertiefen
- Zwei Patienten waren über ein Jahr in Behandlung
- Verträgliches Sicherheitsprofil, das mit der Gesamtbevölkerung übereinstimmt
- Reaktionen wurden unabhängig vom Mutationsstatus von MYD88 und CXCR4 beobachtet
Die Studie umfasste stark vorbehandelte Patienten mit einer Mediananzahl von 3 vorherigen Therapie-Linien. Diese Ergebnisse unterstützen den Fortschritt von NX-5948 in die laufende Phase 1b-Erweiterungsgruppe, einschließlich Patienten, die zuvor mit BTK-Inhibitoren behandelt wurden, sowie Patienten mit dem Bing-Neel-Syndrom.
- High objective response rate of 77.8% in evaluable Waldenstrom's macroglobulinemia patients
- Durable responses with two patients on treatment for over a year
- Responses observed regardless of MYD88 and CXCR4 mutation status
- Tolerable safety profile in line with overall study population
- Advancement to Phase 1b expansion cohort based on positive results
- None.
Insights
The clinical trial results for NX-5948 in Waldenstrom's macroglobulinemia (WM) patients are highly encouraging. The 77.8% objective response rate in evaluable patients is impressive, especially considering the heavily pretreated population with a median of 3 prior lines of therapy. All patients had previously received BTK inhibitors and chemotherapy, indicating NX-5948's potential in overcoming resistance to existing treatments.
The durability of responses is particularly noteworthy, with 5 out of 7 responders still on treatment, including two patients for over a year. This suggests NX-5948 may offer long-term disease control. The rapid onset of response, observed at the first 8-week assessment in all responders, is also clinically significant.
The drug's efficacy across different mutation profiles (MYD88 and CXCR4) is promising, as these mutations can impact treatment outcomes. The brain-penetrant property of NX-5948 could be a game-changer for patients with Bing-Neel syndrome, addressing an unmet medical need in WM with CNS involvement.
While the sample size is small, these results warrant further investigation and support the ongoing Phase 1b expansion. The tolerable safety profile adds to the drug's potential as a new treatment option for relapsed/refractory WM patients.
The positive clinical data for NX-5948 in Waldenstrom's macroglobulinemia (WM) patients is a significant development for Nurix Therapeutics. This news could potentially impact the company's market valuation and future revenue prospects.
Key financial implications include:
- Expanded market opportunity: Success in WM, in addition to previously reported activity in chronic lymphocytic leukemia, broadens the potential patient population for NX-5948.
- Competitive advantage: The brain-penetrant property of NX-5948 could differentiate it from other BTK inhibitors, potentially capturing market share in the lucrative hematological malignancies space.
- Accelerated development timeline: Strong early-phase results may expedite the path to later-stage trials and potential regulatory submissions, potentially bringing forward future revenue streams.
- Increased partnering/licensing potential: Positive data could attract interest from larger pharmaceutical companies, potentially leading to lucrative deals or collaborations.
Investors should monitor for updates on the ongoing Phase 1b expansion and any announcements regarding future pivotal trials. While promising, it's important to note that further studies with larger patient populations will be needed to confirm these early results and support potential regulatory approvals.
NX-5948 demonstrated robust clinical activity with objective responses observed in 7 of 9 (
Responses are durable and deepen over time with two patients on treatment for greater than one year
Data were presented at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12)
SAN FRANCISCO, Oct. 19, 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 clinical data from its ongoing Phase 1a/1b clinical trial of NX-5948, an orally bioavailable, brain penetrant degrader of Burton’s tyrosine kinase (BTK), in patients with relapsed/refractory Waldenstrom’s macroglobulinemia (WM) at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM-12) which is being held in Prague, Czech Republic October 17–19, 2024.
“We are encouraged by the emerging positive data from NX-5948 in patients with Waldenstrom’s macroglobulinemia, which add to the previously disclosed robust clinical activity observed in patients with chronic lymphocytic leukemia,” said Paula G. O’Connor, M.D., chief medical officer of Nurix. “These data support our decision to advance NX-5948 into the ongoing Phase 1b expansion cohort in patients who have previously received at least one prior line of therapy including a BTK inhibitor and patients presenting with Bing-Neel syndrome, a rare form of WM with central nervous system involvement where NX-5948’s ability to penetrate the brain may offer a distinct advantage.”
The data presented at IWWM-12 included previously reported safety findings for all patients in the Phase 1a dose escalation study treated with NX-5948 at doses ranging from 50 mg to 600 mg once daily by oral administration regardless of diagnosis (n=79) based on an April 17, 2024 data cut. NX-5948 demonstrated a tolerable safety profile, and the safety profile for patients with WM was consistent with the safety profile for the overall population (WM patient safety data not shown separately).
New data from an October 10, 2024 data cut include the baseline characteristics of the first 13 patients with WM enrolled across both the Phase 1a and Phase 1b portions of the trial, clinical response assessments in 9 response-evaluable patients, and duration on study for all 13 patients. Among the 13 WM patients, the median age was 74 years and the median number of prior lines of therapy was 3. All 13 patients previously had been treated with both BTK inhibitors (BTKi) and chemotherapy/chemo-immunotherapy. Three patients (
Two illustrative cases studies of patients treated with NX-5948 were presented. The first case study is a patient with baseline MYD88 and CXCR4 mutations and four prior lines of therapy, including autologous bone marrow transplantation and ibrutinib, who demonstrated a rapid response observed at the first assessment and remained on study at the time of the October 10, 2024 data cut with greater than one year of treatment (currently in cycle 16; 28 days per cycle). NX-5948 treatment resulted in deepening of response over time as measured by reduction in serum IgM levels, a key biomarker of clinical response in WM patients. The second case study is a patient with baseline MYD88 mutation and three prior lines of treatment, having most recently progressed while on zanubrutinib. This patient also experienced a rapid response at the first assessment with decreasing IgM through treatment which was ongoing in cycle 15 at the time of the October 10, 2024 data cut.
The IWWM-1 presentation is available in the Scientific Resources section of Nurix website in the Posters and Presentations section.
About NX-5948
NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported that NX-5948 is highly potent against a range of tumor cell lines that are resistant to current BTK inhibitor therapies, an important consideration in heavily pretreated CLL/SLL patient populations. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022).
About Waldenstrom’s Macroglobulinemia
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. In the United States the annual incidence rate is approximately 3 per million or between 1,000 to 1,500 newly diagnosed patients per year. Recommended first-line treatments including chemoimmunotherapy and BTK inhibitor therapy. There are no therapies approved to treat patients after BTKi. Additional therapeutic options are needed.
About Nurix
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 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 plans and strategies with respect to NX-5948 and the potential advantages and therapeutic benefits of NX-5948, including its potential role in the treatment of B-cell malignancies, including Waldenstrom’s macroglobulinemia. 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) the risks inherent in the drug development process, including the unexpected emergence of adverse events or other undesirable side effects during clinical development; (ii) uncertainties related to the timing and results of clinical trials; (iii) whether Nurix will be able to fund its research and development activities and achieve its research and development goals; (iv) the impact of economic and market conditions and global and regional events on Nurix’s business, clinical trials, financial condition, liquidity and results of operations; (v) whether Nurix will be able to protect intellectual property and (vi) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal period ended August 31, 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
ir@nurixtx.com
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Wheelhouse Life Science Advisors
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Media
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Wheelhouse Life Science Advisors
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