Oncternal Therapeutics Announces Termination of its Clinical Studies and Exploration of Strategic Alternatives
Oncternal Therapeutics (Nasdaq: ONCT) has announced the termination of its clinical studies and plans to explore strategic alternatives. The company is discontinuing trials for ONCT-534, a dual action androgen receptor inhibitor for metastatic castration resistant cancer, and ONCT-808, a ROR1-targeting autologous CAR T program for aggressive B-cell lymphoma. Interim Phase 1 results for ONCT-534 showed no clinically meaningful improvements in 20 patients across eight dosing cohorts. ONCT-808 demonstrated anti-tumor activity but faced safety concerns. The company will now focus on maximizing stockholder value through potential asset sales, licensing, or business combinations. Oncternal will discontinue all product development and reduce its workforce to preserve cash resources.
Oncternal Therapeutics (Nasdaq: ONCT) ha annunciato la cessazione dei suoi studi clinici e ha in programma di esplorare alternative strategiche. L'azienda sta interrompendo i trial per ONCT-534, un inibitore del recettore androgeno a doppia azione per il cancro metastatico resistente alla castrazione, e ONCT-808, un programma CAR T autologo mirato a ROR1 per il linfoma aggressivo a cellule B. I risultati intermedi della Fase 1 per ONCT-534 non hanno mostrato miglioramenti clinicamente significativi in 20 pazienti distribuiti in otto coorti di dosaggio. ONCT-808 ha dimostrato attività anti-tumorale ma ha affrontato preoccupazioni in termini di sicurezza. L'azienda si concentrerà ora su massimizzare il valore per gli azionisti attraverso potenziali vendite di asset, licenze o combinazioni aziendali. Oncternal interromperà tutte le attivita di sviluppo prodotto e ridurrà la propria forza lavoro per preservare le risorse di cassa.
Oncternal Therapeutics (Nasdaq: ONCT) ha anunciado la finalización de sus estudios clínicos y planes para explorar alternativas estratégicas. La empresa está descontinuando los ensayos para ONCT-534, un inhibidor de receptor de andrógenos de acción dual para el cáncer metastásico resistente a la castración, y ONCT-808, un programa CAR T autólogo dirigido a ROR1 para el linfoma agresivo de células B. Los resultados interinos de la Fase 1 de ONCT-534 no mostraron mejoras clínicamente significativas en 20 pacientes en ocho cohortes de dosificación. ONCT-808 demostró actividad antitumoral pero enfrentó preocupaciones de seguridad. La empresa se centrará ahora en maximizar el valor para los accionistas a través de posibles ventas de activos, licencias o combinaciones empresariales. Oncternal descontinuará el desarrollo de productos y reducirá su fuerza laboral para preservar los recursos en efectivo.
Oncternal Therapeutics (Nasdaq: ONCT)는 임상 연구 종료를 발표하고 전략적 대안 탐색 계획을 세웠습니다. 이 회사는 ONCT-534의 시험을 중단하고 있습니다. 이는 전이된 거세 저항성 암을 위한 이중 작용 안드로겐 수용체 억제제이며, ONCT-808는 공격적인 B 세포 림프종을 위한 ROR1 타겟 자가 CAR T 프로그램입니다. ONCT-534의 1상 임시 결과는 20명의 환자와 8개의 용량 집단에서 임상적으로 의미 있는 개선을 보여주지 못했습니다. ONCT-808은 항종양 활성을 나타냈지만 안전성 문제에 직면했습니다. 이제 회사는 잠재적 자산 판매, 라이센스 또는 사업 결합을 통해 주주 가치를 극대화하는 데 집중할 것입니다. Oncternal은 모든 제품 개발을 중단하고 현금 자원을 보존하기 위해 인력을 줄일 것입니다.
Oncternal Therapeutics (Nasdaq: ONCT) a annoncé la cessation de ses études cliniques et prévoit d'explorer des alternatives stratégiques. L'entreprise interrompt les essais pour ONCT-534, un inhibiteur des récepteurs androgènes à double action pour le cancer métastatique résistant à la castration, et ONCT-808, un programme CAR T autologue ciblant le ROR1 pour le lymphome agressif des cellules B. Les résultats intermédiaires de la phase 1 pour ONCT-534 n'ont montré aucune amélioration cliniquement significative chez 20 patients dans huit cohortes de dosage. ONCT-808 a montré une activité anticancéreuse mais a rencontré des préoccupations en matière de sécurité. L'entreprise se concentrera désormais sur l'optimisation de la valeur pour les actionnaires par le biais de ventes d'actifs potentiels, de licences ou de combinaisons commerciales. Oncternal cessera le développement de tous les produits et réduira sa main-d'œuvre pour préserver ses ressources financières.
Oncternal Therapeutics (Nasdaq: ONCT) hat die Beendigung seiner klinischen Studien bekannt gegeben und plant, strategische Alternativen zu prüfen. Das Unternehmen stellt die Studien für ONCT-534, einen Dual-Action-Androgenrezeptorhemmer für metastasierendes, kastrationsresistentes Krebs, und ONCT-808, ein ROR1-zielgerichtetes autologes CAR-T-Programm für aggressives B-Zell-Lymphom, ein. Die vorläufigen Ergebnisse der Phase 1 für ONCT-534 zeigten keine klinisch signifikanten Verbesserungen bei 20 Patienten in acht Dosierungsgruppen. ONCT-808 zeigte eine tumorhemmende Aktivität, hatte jedoch Sicherheitsbedenken. Das Unternehmen wird sich nun darauf konzentrieren, den Wert für die Aktionäre zu maximieren durch mögliche Vermögensverkäufe, Lizenzen oder Unternehmenszusammenschlüsse. Oncternal wird die gesamte Produktentwicklung einstellen und die Belegschaft reduzieren, um die Bargeldreserven zu sichern.
- ONCT-808 showed anti-tumor activity at every dose tested, including a complete metabolic response lasting eight months
- Long-term persistence of CAR-T cells observed in ONCT-808 trial
- Termination of clinical studies for ONCT-534 and ONCT-808
- ONCT-534 Phase 1 results showed no clinically meaningful improvements in disease
- One death due to complications of shock at the highest dose tested in ONCT-808 trial
- Discontinuation of all product development activities
- Workforce reduction to preserve cash resources
- Challenging financing environment noted by the company
Insights
This announcement is a significant setback for Oncternal Therapeutics. The termination of clinical trials for both ONCT-534 and ONCT-808 represents a major blow to the company's pipeline. The decision to explore strategic alternatives, including potential asset sales or mergers, signals a dire financial situation.
Investors should be aware of the following key points:
- The company is discontinuing all product development activities
- A workforce reduction is planned to preserve cash
- The current biotech financing environment is described as "challenging"
These factors combined suggest a high risk of bankruptcy or a potential fire sale of assets at discounted valuations. The stock price is likely to experience significant volatility and potential downward pressure in the near term.
The clinical trial results for ONCT-534 and ONCT-808 present a mixed picture. For ONCT-534, the lack of clinically meaningful improvements in PSA levels across eight dosing cohorts is concerning. This suggests efficacy in treating metastatic castration-resistant prostate cancer, a challenging indication with high unmet need.
On the other hand, ONCT-808 showed some promise with anti-tumor activity at all doses tested, including a complete metabolic response lasting eight months. However, the death due to complications of shock at the highest dose is a significant safety concern that could limit its potential even if development were to continue.
The termination of these trials is a setback for patients with advanced prostate cancer and aggressive B-cell lymphoma who are in need of new treatment options.
Oncternal's decision to terminate its clinical studies and explore strategic alternatives highlights the brutal reality of biotech drug development. Despite promising preclinical data, ONCT-534's failure to show clinically meaningful improvements in Phase 1 underscores the high attrition rate in oncology drug development.
The company's pivot to exploring strategic options, including potential asset sales or mergers, is a common endgame for small biotechs facing clinical setbacks. However, the value of Oncternal's assets may be given the disappointing clinical data.
This situation serves as a cautionary tale for investors in early-stage biotech companies, emphasizing the importance of diversified pipelines and strong cash positions to weather clinical setbacks. The broader implications for the sector include potential investor wariness towards similar early-stage oncology companies, potentially impacting fundraising efforts across the industry.
SAN DIEGO, Sept. 12, 2024 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT) (the “Company”) today announced its decision to discontinue its clinical trials evaluating ONCT-534, its dual action androgen receptor inhibitor for the treatment of patients with metastatic castration resistant cancer, and ONCT-808, its ROR1-targeting autologous CAR T program for the treatment of patients with aggressive B-cell lymphoma, and to explore strategic alternatives.
In the current study, interim Phase 1 results of ONCT-534 did not show clinically meaningful improvements of disease, including prostate-specific antigen (PSA) levels, in the 20 patients treated in eight dosing cohorts with various doses and schedules of administration of ONCT-534. ONCT-534 was generally well tolerated, with dose limiting toxicity observed in 2 of 3 patients at the highest dose tested, 1200 mg given orally once per day.
The results with ONCT-808 at an interim Phase 1 analysis showed anti-tumor activity at every dose tested, including a complete metabolic response lasting eight months and long-term persistence of the CAR-T cells, with expected treatment emergent adverse events for a CAR-T therapy, and one death due to complications of shock at the highest dose tested.
Based on the available clinical data and capital requirements for continued development, the Company has decided to terminate these studies. The Company will focus on exploring strategic alternatives with the goal of maximizing value for its stockholders, which may include asset sales, licensing or other strategic transactions relating to the Company’s development programs or a merger, reverse merger, acquisition, or other business combination involving the Company. While this strategic exploration is ongoing, the Company will discontinue all product development activities and will take other steps to reduce costs, including a reduction in its workforce to preserve cash resources.
“The early results during dose escalation in the Phase 1/2 studies of ONCT-534 in heavily pretreated patients are disappointing, as the study was supported by extensive preclinical data and was designed to address important unmet medical needs for patients with advanced prostate cancer,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab and ONCT-216.”
About Oncternal Therapeutics
Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. More information on our company and programs is available at https://oncternal.com/.
About ONCT-534
ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR mutation and aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. It is being investigated in Study ONCT-534-101 (NCT05917470) for the treatment of patients with mCRPC who are resistant to current AR pathway inhibitors.
About ONCT-808
ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced compared with currently approved CAR T products. Oncternal has dosed patients under Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment.
About zilovertamab
Zilovertamab (previously called cirmtuzumab and UC-961) is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in
About ONCT-216
ONCT-216 (previously called TK216) is an investigational targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as acute myeloid leukemia (AML), diffuse large B cell lymphoma (DLBCL), and prostate cancer. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. The results of a Phase 1/ 2 clinical trial of ONCT-216 in patients with Ewing sarcoma (NCT02657005) were recently published (Myers 2024).
Forward-Looking Information
Oncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negatives of these terms or other similar expressions. These statements are based on Oncternal’s current beliefs and expectations. Forward-looking statements include statements regarding: Oncternal’s ability to complete a strategic transaction or continue as a going concern even if a strategic transaction is completed; anticipated benefits of strategic transactions; and Oncternal’s ability to preserve cash during the strategic alternatives process. Forward-looking statements are subject to risks and uncertainties inherent in Oncternal’s business, including: Oncternal may not realize the benefits expected from the workforce reduction and discontinuation of product development activities, including its ability to conserve cash; Oncternal’s ability to retain remaining key personnel; whether Oncternal will be able to secure and complete or achieve the anticipated benefits from any potential strategic transactions on acceptable terms or at all; Oncternal may use its capital resources sooner than it anticipates, resulting in a liquidation and dissolution of the Company; Oncternal’s common stock may be delisted from Nasdaq; and other risks described in Oncternal’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Contact Information:
Investors
Richard Vincent
858-434-1113
rvincent@oncternal.com
Business Development
Pablo Urbaneja
415-316-8276
purbaneja@oncternal.com
FAQ
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