Candel Therapeutics Gains EMA Orphan Designation for CAN-2409, Advancing Pancreatic Cancer Treatment

Pancreatic cancer, one of the deadliest cancer types, has long lacked effective therapeutic options, leaving many patients with modest hope for extended survival. However, a promising breakthrough in treatment emerged as Candel Therapeutics (NASDAQ: CADL) secured the European Medicines Agency (EMA) Orphan Designation for CAN-2409 for the treatment of pancreatic cancer. This milestone not only underscores the innovative potential of CAN-2409 but also opens doors to critical benefits that can support its clinical development and availability in Europe.

Significance of EMA Orphan Designation

EMA Orphan Designation is a critical regulatory acknowledgment given to therapies aimed at rare, life-threatening, or chronically debilitating diseases that affect fewer than five in 10,000 people across the European Union. This designation brings multiple advantages, including reduced regulatory fees, protocol assistance, research grants, and exclusive market protection for up to 10 years following approval within the EU.

For Candel Therapeutics, this recognition of CAN-2409 represents a major regulatory milestone. It aligns with prior achievements such as the U.S. Food and Drug Administration (FDA) Orphan Drug Designation and FDA Fast Track Designation for the same therapy in pancreatic ductal adenocarcinoma (PDAC). Together, these global regulatory designations validate the compelling need for therapies that address pancreatic cancer’s complex and aggressive progression.

“Our goal has always been to create innovative, multimodal therapies to tackle the most challenging forms of cancer,” said Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel Therapeutics. “The EMA Orphan Designation for CAN-2409 affirms the therapy’s potential to transform pancreatic cancer treatment worldwide.”

Unveiling the Innovative Mechanism Behind CAN-2409

CAN-2409 (aglatimagene besadenovec) offers a novel approach to cancer treatment as an off-the-shelf therapy. It leverages a replication-defective adenovirus engineered to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene directly to the tumor site. Upon intratumoral administration and subsequent prodrug activation (using valacyclovir or acyclovir), the HSV-tk enzyme converts the prodrug into compounds that disrupt the tumor’s DNA synthesis processes. This triggers immunogenic cell death, effectively releasing various tumor neoantigens into the tumor microenvironment (TME).

One of the striking capabilities of CAN-2409 is its ability to remodel the TME. Pancreatic tumors are notoriously “cold,” meaning they are immunosuppressive and resistant to immune system attacks. CAN-2409 transforms these “cold” tumors into “hot” ones—characterized by active, inflammation-driven immune infiltration. This transformation often leads to systemic immune responses against multiple tumors, potentially including those resistant to current therapies.

Beyond Pancreatic Cancer

CAN-2409 is not limited to addressing PDAC. Candel’s extensive research hints at the therapy’s broader implications across multiple solid tumors, such as non-small cell lung cancer (NSCLC) and prostate cancer. The same mechanism that drives antitumor immunity in pancreatic tissue holds promise across these other forms of cancer, showcasing its versatility and systemic effectiveness when paired with standard care treatments like chemotherapy, radiotherapy, and checkpoint inhibitors.

Promising Clinical Trial Results

Clinical evidence substantiates the groundbreaking potential of CAN-2409. During a randomized, controlled phase 2a trial, Candel observed remarkable outcomes in borderline resectable PDAC patients. Key findings include:

• Improved Survival Rates: The trial group receiving CAN-2409 and standard of care demonstrated a median survival of 31.4 months compared to just 12.5 months in the standard of care control arm.
• Potential for Long-Term Survival: At the trial’s data cut-off, three out of seven patients treated with CAN-2409 survived more than three years post-enrollment, reaching 66.0, 63.6, and 35.8 months.

This “long tail” of survival signals hope for extended patient outcomes and suggests that CAN-2409 can do more than merely prolong life—it can alter the disease trajectory.

Implications for Pancreatic Cancer Treatment

Pancreatic cancer remains, to this day, one of the most difficult malignancies to treat, primarily due to late diagnosis and its aggressive nature. For decades, standard treatments like chemotherapy have offered only incremental improvements in survival. CAN-2409, however, introduces a new dynamic into this treatment ecosystem, carrying the promise to:

Enhance Current Treatment Paradigms: CAN-2409 has shown effectiveness in combination with other therapies, enhancing systemic immune responses.

Increase Accessibility: With its off-the-shelf availability, CAN-2409 could become a viable option for more patients, particularly those with limited access to rare immunotherapies.

Redefine Survival Metrics: By significantly extending median survival and showcasing potential for long tail outcomes, CAN-2409 could redefine what is considered achievable for patients with advanced pancreatic cancer.

Broader Impacts for Candel Therapeutics

While the EMA Orphan Designation represents a critical step forward for CAN-2409, it also highlights the strength of Candel Therapeutics’ pipeline and regulatory strategy. The therapy has garnered a constellation of designations, including FDA Fast Track and Regenerative Medicine Advanced Therapy (RMAT) statuses for other solid tumor indications like localized prostate cancer.

Candel’s approach to gene-based immunotherapies uniquely positions it to address cancer using individualized systemic immune responses. Additionally, its ongoing clinical trials underline a commitment to tackling unmet medical needs across a variety of tumor profiles.

By pursuing international regulatory opportunities such as those granted by the EMA, Candel is poised to bring its therapies to patients worldwide. This global perspective, coupled with robust clinical backing and innovative therapeutic solutions, cements its reputation as a frontrunner in cancer immunotherapy.

The Road Ahead

Candel Therapeutics’ receipt of EMA Orphan Designation for CAN-2409 is more than a regulatory milestone—it is a signal of hope for patients battling pancreatic cancer and other challenging malignancies. With the ability to reshape the TME, enhance systemic immune responses, and deliver long-lasting survival benefits, CAN-2409 represents a novel frontier in cancer treatment.

Moving forward, all eyes are on Candel as they continue their pivotal trials, scale their regulatory efforts across global markets, and refine immunotherapies that could ultimately change the landscape of cancer care. These advancements underscore Candel’s mission to provide innovative solutions for patients who face limited treatment options, aiming for a future where survival is not merely extended but redefined.

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.

For more information about Candel Therapeutics please visit https://candeltx.com