Prelude Therapeutics Presents Preliminary Results of Phase 1 Dose-escalation Study of PRT2527 as Monotherapy and in Combination with Zanubrutinib in Patients with Relapsed/Refractory Lymphoid Malignancies
Prelude Therapeutics (NASDAQ: PRLD) presented interim clinical data from its Phase 1 dose-escalation trial of PRT2527, a CDK9 inhibitor, both as monotherapy and combined with zanubrutinib in relapsed/refractory lymphoid malignancies. The study included 46 patients across multiple dosing cohorts.
Key findings showed an overall response rate of 17.4% (4 of 23 patients) for monotherapy and 38.5% (5 of 13 patients) for combination therapy. The drug demonstrated an acceptable safety profile, with neutropenia (48%) and nausea (33%) as the most common side effects. The company has selected the 18 mg/m2 dose level for confirmation and plans to seek a partner for future development while focusing resources on their SMARCA degrader programs.
Prelude Therapeutics (NASDAQ: PRLD) ha presentato dati clinici preliminari del suo studio di fase 1 per il trial di dose escalation di PRT2527, un inibitore di CDK9, sia come monoterapia che in combinazione con zanubrutinib nelle neoplasie linfomatose recidivanti/ripetitive. Lo studio includeva 46 pazienti in diversi gruppi di dosaggio.
I risultati chiave hanno mostrato un tasso di risposta globale del 17,4% (4 su 23 pazienti) per la monoterapia e un 38,5% (5 su 13 pazienti) per la terapia combinata. Il farmaco ha dimostrato un profilo di sicurezza accettabile, con neutropenia (48%) e nausea (33%) come gli effetti collaterali più comuni. L'azienda ha selezionato il livello di dosaggio di 18 mg/m2 per conferma e prevede di cercare un partner per lo sviluppo futuro, concentrando al contempo le risorse sui loro programmi di degradazione SMARCA.
Prelude Therapeutics (NASDAQ: PRLD) presentó datos clínicos interinos de su ensayo de fase 1 de escalado de dosis de PRT2527, un inhibidor de CDK9, tanto como monoterapia como combinado con zanubrutinib en neoplasias linfáticas refractarias/recaídas. El estudio incluyó a 46 pacientes en varios grupos de dosis.
Los hallazgos clave mostraron una tasa de respuesta general del 17.4% (4 de 23 pacientes) para la monoterapia y del 38.5% (5 de 13 pacientes) para la terapia combinada. El medicamento mostró un perfil de seguridad aceptable, con neutropenia (48%) y náuseas (33%) como los efectos secundarios más comunes. La compañía ha seleccionado el nivel de dosis de 18 mg/m2 para confirmación y planea buscar un socio para el desarrollo futuro mientras enfoca recursos en sus programas de degradadores SMARCA.
Prelude Therapeutics (NASDAQ: PRLD)는 PRT2527의 1상 용량 증량 시험의 중간 임상 데이터를 발표했습니다. 이는 CDK9 억제제로, 재발성/난치성 림프악성종양에서 단독 요법 및 자누브루티닙과 병용하여 사용되었습니다. 이 연구에는 여러 용량 코호트에서 46명의 환자가 포함되었습니다.
주요 결과는 단독 요법의 전체 응답률이 17.4% (23명 중 4명)이고 병용 요법의 경우 38.5% (13명 중 5명)으로 나타났습니다. 이 약물은 중립구 감소증 (48%) 및 메스꺼움 (33%)이 가장 흔한 부작용으로, 수용 가능한 안전성 프로파일을 보였습니다. 이 회사는 확인을 위해 18 mg/m2의 용량 수준을 선택하고 향후 개발을 위한 파트너를 찾을 계획이며, SMARCA 분해제 프로그램에 자원을 집중하고 있습니다.
Prelude Therapeutics (NASDAQ: PRLD) a présenté des données cliniques préliminaires de son essai de phase 1 d'escalade de dose de PRT2527, un inhibiteur de CDK9, tant en monothérapie qu'en combinaison avec le zanubrutinib dans les malignités lymphoïdes récurrentes/réfractaires. L'étude a inclus 46 patients répartis sur plusieurs cohortes de dosage.
Les résultats clés ont montré un taux de réponse global de 17,4% (4 sur 23 patients) pour la monothérapie et de 38,5% (5 sur 13 patients) pour la thérapie combinée. Le médicament a démontré un profil de sécurité acceptable, avec une neutropénie (48%) et des nausées (33%) comme les effets secondaires les plus courants. L'entreprise a sélectionné le niveau de dose de 18 mg/m2 pour confirmation et prévoit de chercher un partenaire pour le développement futur, tout en concentrant ses ressources sur ses programmes de dégradateurs SMARCA.
Prelude Therapeutics (NASDAQ: PRLD) hat vorläufige klinische Daten aus seiner Phase 1-Dosissteigerungsstudie von PRT2527, einem CDK9-Hemmer, sowohl als Monotherapie als auch in Kombination mit Zanubrutinib bei rezidivierenden/refraktären lymphatischen Erkrankungen vorgestellt. Die Studie umfasste 46 Patienten in mehreren Dosierungsgruppen.
Wesentliche Ergebnisse zeigten eine gesamtantwortquote von 17,4% (4 von 23 Patienten) für die Monotherapie und 38,5% (5 von 13 Patienten) für die Kombinationstherapie. Das Medikament zeigte ein akzeptables Sicherheitsprofil, wobei Neutropenie (48%) und Übelkeit (33%) die häufigsten Nebenwirkungen waren. Das Unternehmen hat die Dosisstufe von 18 mg/m2 zur Bestätigung ausgewählt und plant, einen Partner für die zukünftige Entwicklung zu suchen, während es die Ressourcen auf ihre SMARCA-Abbauprogramme konzentriert.
- Overall response rate of 38.5% in combination therapy cohort
- Acceptable safety profile demonstrated in both monotherapy and combination therapy
- Evidence of activity in patients who received prior CAR-T therapy
- Successful dose level identification (18 mg/m2) for future development
- Lower response rate (17.4%) in monotherapy cohort
- High rate of neutropenia (48%) as adverse event
- Company seeking external partner for further development instead of advancing independently
- Five patients discontinued treatment due to adverse events in monotherapy cohort
Insights
The preliminary Phase 1 results for PRT2527 show promising clinical activity and safety profile. The 38.5% overall response rate in combination with zanubrutinib, including responses in patients who previously failed CAR-T therapy, is particularly noteworthy in the relapsed/refractory setting. The selected dose of 18 mg/m2 demonstrates an acceptable balance of efficacy and manageable side effects, with neutropenia being the main toxicity that can be addressed with growth factor support.
However, Prelude's decision to seek a partner for future development signals resource constraints and strategic prioritization of their SMARCA degrader programs. This could potentially slow down PRT2527's development timeline unless a suitable partner is found quickly.
The market impact of this announcement is mixed. While the clinical data shows promise, Prelude's decision to seek a partnership for PRT2527 instead of advancing it independently suggests a strategic pivot that may concern investors. With a relatively small market cap of
The partnership strategy could provide future milestone payments and royalties while conserving cash, but it also indicates reduced internal commitment to what appears to be a viable drug candidate. Investors should watch closely for partnership announcements as these could significantly impact the stock's value.
• PRT2527 demonstrated activity across a range of relapsed/refractory lymphoid malignancies, including patients who received prior CAR-T therapy
• Prelude plans to seek a partner for future development of PRT2527 in hematologic malignancies
WILMINGTON, Del., Dec. 11, 2024 (GLOBE NEWSWIRE) -- Prelude Therapeutics Incorporated (Nasdaq: PRLD) (“Prelude” or the “Company”), a clinical-stage precision oncology company, today announced the presentation of the first interim clinical data from its ongoing open-label, dose-escalation trial of PRT2527, a potent and highly selective CDK9 inhibitor, as monotherapy and in combination with zanubrutinib in patients with relapsed/refractory lymphoid malignancies. The data were presented at a poster session of the 66th American Society of Hematology Annual Meeting in San Diego, California.
The study investigators reported on the 46 patients that were enrolled, treated, and safety evaluable as of September 17, 2024. PRT2527 was generally well-tolerated through 4 dosing cohorts as monotherapy and 3 dosing cohorts in combination with zanubrutinib. PRT2527 monotherapy and in combination with zanubrutinib demonstrated an acceptable safety profile with evidence of preliminary activity in patients with relapsed/refractory lymphoid malignancies, including patients who received prior CAR-T therapy.
“CDK9 has long been considered a potential therapeutic approach for treating hematologic malignancies and a highly selective CDK9 inhibitor was sought to minimize off target toxicity,” stated Jane Huang, M.D., President and Chief Medical Officer of Prelude. “We are encouraged by the results demonstrated to date by PRT2527 both as a monotherapy and particularly in combination with zanubrutinib resulting in an overall response rate of
PRT2527 Interim Phase 1 Results
PRT2527 is an investigational, potent and highly selective CDK9 inhibitor being evaluated in select relapsed/refractory (R/R) hematologic malignancies as monotherapy and in combination with zanubrutinib.
As of the cutoff date, 46 patients with relapsed/refractory lymphoid malignancies were treated with PRT2527. 29 patients were treated once weekly via intravenous infusion at four dose levels of PRT2527 monotherapy (9 mg/m2, 15 mg/m2, 18 mg/m2, 24 mg/m2) and 17 patients were treated once weekly at three dose levels of PRT2527 (9 mg/m2, 15 mg/m2, 18 mg/m2) in combination with zanubrutinib administered orally starting on C1D1 at 320 mg daily or 160 mg BID.
Initial Safety Data
The most frequent treatment emergent adverse events (TEAEs) observed in ≥
PRT2527 dose interruptions due to TEAEs occurred in 17 patients (11 monotherapy; 6 combination therapy). Most dose interruptions were due to neutropenia and were managed with growth factor support. One DLT of grade 3 tumor lysis syndrome (TLS) occurred in a patient with primary cutaneous peripheral T cell lymphoma who had extensive disease at the 24 mg/m2 monotherapy dose level and did not receive ramp-up dosing. TLS was managed with rasburicase and IV fluids and resolved. The patient was able to resume study treatment as planned. No DLTs were observed in the combination therapy cohort.
Dose level 3 (18 mg/m2) was selected for dose confirmation for monotherapy and in combination with zanubrutinib due to higher rates of grade 3/4 neutropenia and of dose interruptions and reductions in the 24 mg/m2 dose level.
Analysis of Initial Clinical Activity
Of the 23 efficacy evaluable patients in the monotherapy cohort, complete responses (CRs) were observed in 1 patient (DLBCL) and 3 partial responses observed (TCL), with an overall response rate (ORR) of
The above-noted presentation can be found at Publications - Prelude Therapeutics (preludetx.com).
“We believe the clinical data presented today with PRT2527 confirm our hypothesis that a highly selective and potent inhibitor of CDK9 has the potential to offer meaningful clinical activity for patients with hematologic malignancies, while avoiding the off-target toxicities observed with less selective agents,” stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. “However, given the significant progress and potential of our SMARCA degrader programs that are currently advancing in the clinic, along with our productive discovery organization, we plan to focus our resources towards the continued advancement of those programs. As a result, we will only advance the CDK9 program with a partner beyond completion of the current ongoing Phase 1 study.”
About Prelude Therapeutics
Prelude Therapeutics is a leading precision oncology company developing innovative medicines in areas of high unmet need for cancer patients. Our pipeline is comprised of several novel drug candidates including first-in-class, highly selective IV and oral SMARCA2 degraders, and a potentially best-in-class CDK9 inhibitor. We are also leveraging our expertise in targeted protein degradation to discover, develop and commercialize next generation degrader antibody conjugates (Precision ADCs) with partners. We are on a mission to extend the promise of precision medicine to every cancer patient in need. For more information, visit preludetx.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated discovery, preclinical and clinical development activities for Prelude’s product candidates, the potential safety, efficacy, benefits and addressable market for Prelude’s product candidates, and clinical trial results for Prelude’s product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The words “believes,” “anticipates,” “estimates,” “plans,” “expects,” “intends,” “may,” “could,” “should,” “potential,” “likely,” “projects,” “continue,” “will,” “schedule,” and “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on the Company’s current expectations and projections about future events and various assumptions. Although Prelude believes that the expectations reflected in such forward-looking statements are reasonable, Prelude cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause Prelude's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Prelude's ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, clinical trial sites and our ability to enroll eligible patients, supply chain and manufacturing facilities, Prelude’s ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, Prelude's ability to fund development activities and achieve development goals, Prelude's ability to protect intellectual property, and other risks and uncertainties described under the heading "Risk Factors" in Prelude’s Annual Report on Form 10-K for the year ended December 31, 2023, its Quarterly Reports on Form 10-Q and other documents that Prelude files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Prelude undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof, except as may be required by law.
Investor Contact:
Robert A. Doody Jr.
Senior Vice President, Investor Relations
484.639.7235
rdoody@preludetx.com
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