Candel Therapeutics to Present Preclinical Data at SITC Annual Meeting Showing Promise for CAN-3110 in Melanoma, Signaling Potential Indication Expansion Beyond Recurrent High-Grade Glioma
Candel Therapeutics announced preclinical results for CAN-3110 in melanoma models, showing potential expansion beyond high-grade glioma treatment. CAN-3110, a first-in-class HSV-1 oncolytic viral immunotherapy, demonstrated potent antitumor activity in both in vitro human cell lines and in vivo murine melanoma models. The therapy's effectiveness is linked to Nestin expression in cancer cells and specific genetic alterations. The data showed tumor-specific cytotoxicity with dose-dependent inhibition of tumor growth and regression in some cases. The treatment was well-tolerated and associated with systemic immune activation, similar to effects observed in high-grade glioma patients.
Candel Therapeutics ha annunciato i risultati preclinici per CAN-3110 in modelli di melanoma, mostrando un potenziale di espansione oltre il trattamento del glioma ad alto grado. CAN-3110, una immunoterapia virale oncolitica di prima classe basata su HSV-1, ha dimostrato una potente attività antitumorale sia in linee cellulari umane in vitro che in modelli di melanoma murino in vivo. L'efficacia della terapia è collegata all'espressione di Nestin nelle cellule tumorali e a specifiche alterazioni genetiche. I dati hanno mostrato citotossicità specifica per il tumore con un'inibizione della crescita tumorale dipendente dalla dose e regressione in alcuni casi. Il trattamento è stato ben tollerato e associato a un'attivazione immunitaria sistemica, simile agli effetti osservati nei pazienti con glioma ad alto grado.
Candel Therapeutics anunció resultados preclínicos para CAN-3110 en modelos de melanoma, mostrando un potencial de expansión más allá del tratamiento del glioma de alto grado. CAN-3110, una inmunoterapia viral oncolítica de primera clase basada en HSV-1, demostró una potente actividad antitumoral tanto en líneas celulares humanas in vitro como en modelos de melanoma murino in vivo. La efectividad de la terapia está relacionada con la expresión de Nestin en las células cancerosas y alteraciones genéticas específicas. Los datos mostraron citotoxicidad específica del tumor con una inhibición dependiente de la dosis del crecimiento tumoral y regresión en algunos casos. El tratamiento fue bien tolerado y se asoció con activación inmune sistémica, similar a los efectos observados en pacientes con glioma de alto grado.
Candel Therapeutics는 멜라노마 모델에서 CAN-3110에 대한 전임상 결과를 발표하며, 고등급 신경교종 치료를 넘어 확장의 잠재력을 보여주었습니다. CAN-3110은 1세대 HSV-1 온콜리틱 바이러스 면역요법으로, vitro 인간 세포주와 vivo 마우스 멜라노마 모델 모두에서 강력한 항종양 활성을 입증했습니다. 이 치료법의 효능은 암세포에서의 Nestin 발현 및 특정 유전적 변이에 관련이 있습니다. 데이터는 종양 특이적인 세포독성과 종양 성장의 용량 의존적 억제 및 일부 경우에서의 퇴행을 보여주었습니다. 이 치료법은 잘 견딜 수 있었고, 고등급 신경교종 환자에서 관찰된 것과 유사한 전신 면역 활성화와 관련이 있었습니다.
Candel Therapeutics a annoncé des résultats précliniques pour CAN-3110 dans des modèles de mélanome, montrant un potentiel d'expansion au-delà du traitement du gliome de haut grade. CAN-3110, une immunothérapie virale oncolytique de première classe basée sur le HSV-1, a démontré une puissante activité antitumorale tant dans des lignées cellulaires humaines in vitro que dans des modèles murins de mélanome in vivo. L'efficacité de la thérapie est liée à l'expression de Nestin dans les cellules cancéreuses et à des altérations génétiques spécifiques. Les données ont montré une cytotoxicité spécifique au tumeur avec une inhibition de la croissance tumorale dépendante de la dose et une régression dans certains cas. Le traitement a été bien toléré et associé à une activation immunitaire systémique, similaire aux effets observés chez les patients atteints de gliome de haut grade.
Candel Therapeutics gab präklinische Ergebnisse für CAN-3110 in Melanom-Modellen bekannt und zeigte ein potenzielles Wachstum über die Behandlung von hochgradigem Gliom hinaus. CAN-3110, eine erstklassige HSV-1-onkolytische Virusimmuntherapie, zeigte sowohl in vitro an menschlichen Zelllinien als auch in vivo an murinen Melanom-Modellen eine starke antitumorale Aktivität. Die Wirksamkeit der Therapie hängt mit der Nestin-Expression in Krebszellen und spezifischen genetischen Veränderungen zusammen. Die Daten zeigten tumorspezifische Zytotoxizität mit dosisabhängiger Hemmung des Tumorwachstums und teilweise Rückbildung. Die Behandlung wurde gut vertragen und war mit einer systemischen immunologischen Aktivierung verbunden, ähnlich wie die Effekte, die bei Patienten mit hochgradigem Gliom beobachtet wurden.
- Demonstrated potent antitumor activity in melanoma preclinical models
- Showed dose-dependent tumor growth inhibition and regression in some cases
- Well-tolerated in preclinical studies
- Potential expansion into new indication (melanoma) beyond high-grade glioma
- Results to preclinical stage, requiring further clinical validation
- Efficacy dependent on specific genetic markers (Nestin expression, CDKN2A loss)
Insights
The preclinical data for CAN-3110 in melanoma represents a significant potential expansion opportunity. The therapy shows dual mechanism benefits through both direct tumor cell killing (oncolysis) and immune system activation, specifically in tumors expressing Nestin protein and CDKN2A mutations.
The results demonstrate compelling efficacy markers: dose-dependent tumor growth inhibition, instances of tumor regression and increased T-cell proliferation - mirroring previous successful results in high-grade glioma patients. The genetic similarities between melanoma and glioma, particularly Nestin expression and Ras-Raf pathway alterations, provide a strong scientific rationale for this indication expansion.
However, investors should note these are early preclinical results. While promising, significant clinical development work lies ahead to validate these findings in human trials. The potential market opportunity in melanoma could substantially expand CAN-3110's commercial prospects, but timeline and development risks remain.
- Abstract selected as poster presentation during the Society for Immunotherapy of Cancer (SITC) Annual Meeting shows potent antitumor activity of CAN-3110 in preclinical models of melanoma
- CAN-3110's activity is designed to be conditional to the expression of Nestin in cancer cells and is associated with dual activity for oncolysis and immune activation
- Findings support potential indication expansion for CAN-3110 beyond high-grade glioma into melanoma, another Nestin-expressing solid tumor
NEEDHAM, Mass., Nov. 05, 2024 (GLOBE NEWSWIRE) -- Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical-stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, today announced preclinical results and therapeutic potential of CAN-3110 in the Ras-Raf pathway altered melanoma model. The data will be presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, taking place November 6-10, in Houston, Texas by Anne R. Diers, PhD, Senior Director of Research at Candel Therapeutics.
CAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation. CAN-3110 activity is conditional to the expression of Nestin in cancer cells and specific genetic alterations such as loss of the tumor suppressor gene CDKN2A.
The poster, titled “Therapeutic potential of CAN-3110 in Ras-Raf pathway altered melanoma,” will focus on new data demonstrating the mechanism of action and antitumor activity of CAN-3110 in preclinical models of melanoma, a tumor characterized by high Nestin expression, frequent loss-of-function in CDKN2A, and additional alterations in the Ras-Raf signaling pathway.
“Melanoma exhibits numerous genetic alterations in common with high-grade glioma, a tumor type for which CAN-3110 treatment has consistently shown promising biological and clinical activity,” said Francesca Barone, MD, PhD, Chief Scientific Officer at Candel. “The presence of this genetic profile, and in particular the high expression of Nestin, positions CAN-3110 as a potential first-in-class viral immunotherapy in this new indication. This hypothesis is supported by data showing marked anti-tumor activity in models of melanoma.”
Data presented at SITC showed potent monotherapy, anti-tumor activity of CAN-3110 in both in vitro human cell lines and in vivo murine models of melanoma. In vivo, CAN-3110 exhibited tumor-specific cytotoxicity with dose-dependent inhibition of tumor growth and tumor regression observed in a subset of tumors treated with a high dose of CAN-3110. Cytotoxic activity in melanoma-bearing mice was associated with systemic immune activation and increased proliferation of circulating T cells, mirroring the effect observed in patients with high-grade glioma treated with CAN-3110, as reported last year in Nature. CAN-3110 was well-tolerated in mice based on body weight and histopathological analysis following intratumoral administration.
“These encouraging preclinical results validate the broader potential of CAN-3110 in treating a variety of Nestin-positive solid tumors” said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. “The data supports the ability of CAN-3110 to selectively target and kill Nestin-positive tumor cells while eliciting profound immune activation. We are excited by the possibility to develop a new pipeline in a product centered around this first-in-class experimental medicine”.
For more information about the presented data, please visit the Candel website at: https://www.candeltx.com/media/
About CAN-3110
CAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation in a single therapeutic. CAN-3110 is being evaluated in a phase 1b clinical trial in patients with recurrent high-grade glioma (rHGG). In October 2023, the Company announced that Nature published results from this ongoing clinical trial. CAN-3110 was well tolerated with no dose-limiting toxicity reported. In the clinical trial, the investigators observed improved median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant condition.1 The Company and academic collaborators are currently evaluating the effects of multiple CAN-3110 injections in rHGG, supported by the Break Through Cancer foundation. CAN-3110 has previously received U.S Food and Drug Administration (FDA) Fast Track Designation and Orphan Drug Designation for the treatment of rHGG.
About Candel Therapeutics
Candel is a clinical stage biopharmaceutical company focused on developing off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. Candel has established two clinical stage multimodal biological immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus (HSV) gene constructs, respectively. CAN-2409 is the lead product candidate from the adenovirus platform and is currently in ongoing clinical trials in non-small cell lung cancer (phase 2), borderline resectable pancreatic ductal adenocarcinoma (phase 2), and localized, non-metastatic prostate cancer (phase 2b and phase 3). CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing investigator-sponsored phase 1b clinical trial in rHGG. Finally, Candel’s enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors.
For more information about Candel, visit: www.candeltx.com
Forward-Looking Statements
This press release includes certain disclosures that contain “forward-looking statements,” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the timing and advancement of current and future development programs, including key data readout milestones and presentations; expectations regarding early biological readouts as predictor of clinical response; expectations regarding the therapeutic benefit of the Company’s programs, including the ability of CAN-3110 to treat high-grade glioma, melanoma or other Nestin-expressing solid tumors; and expectations regarding the potential benefits conferred by orphan drug designation and fast track designation. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, those risks and uncertainties related to the timing and advancement of development programs; the Company’s ability to continue as a going concern; expectations regarding the therapeutic benefit of the Company’s programs; that final data from the Company’s pre-clinical studies and completed clinical trials may differ materially from reported interim data from ongoing studies and trials; the Company’s ability to efficiently discover and develop product candidates; the Company’s ability to obtain and maintain regulatory approval of product candidates; the Company’s ability to maintain its intellectual property; the implementation of the Company’s business model, including strategic plans for the Company’s business and product candidates; and other risks identified in the Company’s filings with the U.S. Securities and Exchange Commission (SEC) including the Company’s most recent Quarterly Report on Form 10-Q filed with the SEC and subsequent filings with the SEC. The Company cautions you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions, or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent the Company’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date.
Investor Contact:
Theodore Jenkins
VP, Investor Relations and Business Development
Candel Therapeutics, Inc.
tjenkins@candeltx.com
Media Contact:
Ben Shannon
Vice President
ICR Westwicke
CandelPR@icrhealthcare.com
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1 Ling AL, et al. Nature. 2023;623(7985):157-166.
FAQ
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