Candel Therapeutics(CADL) - 2024 Q4 - Annual Report

Clinical Trial Results - CAN-2409 demonstrated a statistically significant improvement in disease-free survival (DFS) by 30% compared to the control arm, with a median DFS not reached for the treatment arm versus 86.1 months for the placebo arm (p=0.0155) [21]. - In a phase 3 clinical trial, CAN-2409 achieved a 38% decreased risk of prostate cancer recurrence or death compared to placebo (p=0.0046) [22]. - The phase 3 trial enrolled 745 patients, with 496 receiving CAN-2409 plus prodrug and 249 receiving placebo plus prodrug [21]. - CAN-2409 induced 80.4% pathological complete responses in post-treatment biopsies compared to 63.6% in the control arm (p=0.0015) [22]. - The median follow-up time for the recruited population in the phase 3 trial was 50.3 months [22]. - The addition of CAN-2409 to SoC was well tolerated, with no dose-limiting toxicities reported [28]. - In a phase 2 clinical trial for NSCLC, CAN-2409 plus valacyclovir showed a median overall survival (mOS) of 20.6 months, compared to 11.6 months with standard chemotherapy [22]. - Estimated median overall survival (mOS) was 31.4 months in the CAN-2409 group versus 12.5 months in the control group for borderline resectable pancreatic ductal adenocarcinoma (PDAC) [28]. - 71.4% survival rate at 24 months for patients receiving CAN-2409 during standard of care (SoC) chemoradiation and surgery, compared to 16.7% in the control group [6]. - CAN-3110 achieved a median overall survival (mOS) of 14.2 months in 66% of patients with anti-HSV1 antibodies [27]. - Initial data from the ongoing clinical trial of CAN-3110 showed mOS of 11.8 months in arm A and 12.0 months in arm B [26]. - In a phase 2 clinical trial for NSCLC, a disease control rate of 77% was observed in patients with disease progression [98]. - The median overall survival (mOS) for NSCLC patients receiving CAN-2409 was reported at 20.6 months, compared to 11.6 months for standard docetaxel-based chemotherapy [98]. - In the pancreatic cancer trial, estimated survival was 71.4% for patients receiving 2-3 courses of CAN-2409 compared to 16.7% for the control group at 24 and 36 months [101]. - CAN-2409 treatment resulted in a 4-fold increase in CD8+ T cells and a 3-fold increase in CD68+ macrophages in treated prostate cancer patients, indicating an immune response [85]. - CAN-2409 demonstrated a median overall survival of 31.4 months compared to 12.5 months in the control group for patients with borderline resectable PDAC [103]. - In the CAN-3110 phase 1b trial, the median overall survival (mOS) was reported as 11.8 months for the first 41 patients, with an independent cohort showing mOS of 12.0 months [107]. - 3 out of 6 patients treated with multiple injections of CAN-3110 for recurrent high-grade glioma were still alive after more than one year, with survival times of 12.2, 13.0, and 18.7 months [108]. Regulatory Designations - The FDA granted fast track designation for CAN-2409 in combination with radiation therapy for localized prostate cancer [21]. - The FDA granted fast track designation for CAN-3110 for recurrent high-grade glioma (HGG) to improve overall survival [25]. - CAN-2409 has received Fast Track Designation from the FDA for multiple indications, including pancreatic adenocarcinoma and localized intermediate/high-risk prostate cancer [51]. - The FDA granted orphan drug designation for CAN-2409 for pancreatic cancer treatment, with a reported mOS of 28.8 months in the treatment group versus 12.5 months in the control group [57]. - The FDA granted orphan drug designation for CAN-3110 for the treatment of recurrent high-grade glioma in May 2024 [107]. - The FDA's fast track designation allows for rolling review of marketing applications, expediting the process for drugs addressing serious conditions [167]. - Breakthrough therapy designation offers substantial improvement over existing therapies and includes benefits of fast track designation [168]. - Orphan product designation provides financial incentives, including grant funding opportunities and tax advantages, and grants seven years of exclusivity upon FDA approval for the same indication [166]. Company Strategy and Development - The company plans to submit a biologics license application for CAN-2409 in the fourth quarter of 2026 [22]. - The company plans to prepare for a larger, late-stage, randomized controlled clinical trial of CAN-2409 in PDAC based on promising findings [28]. - The company is advancing the development of CAN-2409 in stage III/IV NSCLC patients, aiming to improve median overall survival (mOS) compared to standard of care (SoC) immune checkpoint inhibitors [40]. - A phase 2 clinical trial for CAN-2409 in pancreatic cancer is ongoing, targeting improved mOS compared to SoC [40]. - The company is conducting a phase 1b clinical trial for CAN-3110 in recurrent high-grade glioma (HGG), focusing on therapy-resistant disease to enhance mOS compared to optimal SoC [40]. - The company has established two clinical off-the-shelf viral immunotherapy platforms based on genetically modified adenovirus and herpes simplex virus constructs [20]. - The enLIGHTEN™ Discovery Platform is being utilized to develop new viral immunotherapy candidates for solid tumors [31]. - The enLIGHTEN™ Discovery Platform enables rapid vector engineering for new HSV-based product candidates, utilizing computational biology and artificial intelligence [40]. - The company plans to establish strategic partnerships to enhance the value of current and future product candidates, potentially pairing them with novel agents from partners [40]. - The manufacturing process for CAN-2409 and CAN-3110 is designed to be cost-efficient, with expectations of significantly lower cost-of-goods compared to cell- and antibody-based therapies [40]. - The company has an advanced pipeline with late-stage and early-stage assets, including CAN-2409 and CAN-3110, as well as a preclinical pipeline [50]. - The company has entered into various license agreements, including a significant agreement with Periphagen, involving a $1,000,000 loan assumption and$ 811,000 upfront payment [110][111]. - Under the MGB License Agreement, the company is required to pay cumulative milestone payments up to $39,000,000 based on clinical and commercial achievements [121]. - The company intends to retain significant development and commercial rights to its product candidates and plans to commercialize them independently or with partners [137]. Market Opportunity - The prostate cancer therapy market is projected to exceed$ 16.1 billion by 2026, highlighting the significant commercial opportunity for CAN-2409 in preventing disease recurrence [63]. - Global sales for immune checkpoint inhibitors (ICIs) in 2019 were approximately $23 billion, with non-small cell lung cancer (NSCLC) accounting for 50% to 55% of overall sales [66]. - CAN-2409 is expected to provide a significant commercial opportunity for NSCLC patients with inadequate response to ICIs, aiming for overall survival improvement of more than 12 months [67]. - In 2023, an estimated 64,050 people were diagnosed with pancreatic cancer in the US, with about 50,550 expected to die from the disease [68]. - There are approximately 12,340 patients with borderline resectable pancreatic cancer in the US/EU5, indicating a significant unmet need for effective treatment options [68]. - CAN-3110 has shown nearly double the expected median overall survival after a single injection, presenting a significant opportunity for recurrent high-grade glioma treatment [73]. - CAN-2409 has been administered to over 700 patients with localized prostate cancer, demonstrating favorable tolerability and safety data [83]. - In a phase 2b trial, 190 patients were randomized, with 127 receiving CAN-2409, showing numerical improvement in time to radical treatment, although not statistically significant [87]. Regulatory Process and Challenges - Regulatory approvals for biological products require substantial time and financial resources, and the company may not be able to obtain necessary approvals [143]. - The FDA's process for licensing biological products involves multiple stages, including preclinical studies and submission of a Biologics License Application (BLA) [145]. - The FDA requires an IND submission before commencing initial clinical trials in humans, which becomes effective 30 days after submission unless placed on hold [147]. - Clinical trials are conducted in three phases: Phase 1 focuses on safety in healthy subjects, Phase 2 evaluates efficacy in a limited patient population, and Phase 3 assesses safety and efficacy in a larger group [156]. - The BLA review process typically takes twelve months, with the FDA targeting ten months for standard applications and six months for priority reviews [158]. - The FDA may require post-approval phase 4 clinical trials to gather additional information about a product after it has been approved [151]. - The FDA conducts inspections of manufacturing facilities and clinical sites to ensure compliance with cGMP and GCP requirements before approving a BLA [160]. - A Complete Response letter from the FDA outlines deficiencies in a BLA and may recommend actions for approval [162]. - The FDA may require Risk Evaluation and Mitigation Strategies (REMS) to ensure the safe use of a biological product before granting approval [159]. - The Hatch-Waxman Amendments allow for patent term restoration of up to five years, but cannot extend beyond 14 years from product approval [176]. - Pediatric market exclusivity can add six months to existing exclusivity periods if a pediatric study is completed [177]. - The Biologics Price Competition and Innovation Act (BPCIA) allows for abbreviated approval pathways for biosimilar products, with a 12-year exclusivity period for reference products [178][179]. - Companion diagnostics, essential for identifying patient populations, require FDA approval and must be developed alongside therapeutic products [181][182]. - The FDA requires PMA approval for companion diagnostics to be obtained concurrently with therapeutic approval, which can take several years [183]. - If the FDA's evaluation is favorable, a PMA approval letter is issued, which may include post-approval conditions to ensure device safety and effectiveness [185]. - The FDA may issue a not approvable letter outlining deficiencies in the PMA application, potentially delaying approval for several months or years [186]. International Regulations - In the EU, innovative medicinal products receive eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization [198]. - Products with orphan designation in the EU can receive ten years of market exclusivity, with potential extensions for pediatric studies [199]. - The maximum timeframe for EMA evaluation of a marketing authorization application is 210 days, with accelerated assessment possible in exceptional cases [196]. - The application process for clinical trials in the EU requires submission to national competent authorities and ethics committees, with a single application now possible for multiple countries [194]. - Post-approval, the marketing authorization holder must comply with various manufacturing, marketing, and promotion requirements [203]. - The European Commission introduced legislative proposals in April 2023 to replace the current regulatory framework for all medicines in the EU, with amendments proposed by the European Parliament in April 2024 [206]. - The UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with the "Windsor Framework," effective January 1, 2025, which changes the regulation of medicinal products in the UK [207]. - The MHRA is now responsible for approving all medicinal products for the UK market, allowing a single UK-wide marketing authorization for novel medicinal products [207]. Economic and Legislative Impact - The Affordable Care Act (ACA) significantly impacts the U.S. pharmaceutical industry by increasing Medicaid rebates and creating a new Medicare Part D coverage gap discount program [208]. - The Budget Control Act of 2011 includes a 2% reduction in Medicare payments to providers, which remains in effect through 2031 [209]. - The Inflation Reduction Act of 2022 introduces provisions that may impact the business, including a$ 2,000 out-of-pocket cap for Medicare Part D beneficiaries starting in 2025 [210]. - The IRA allows the U.S. government to negotiate price caps for certain high-cost drugs and biologics, which may affect pricing strategies [210]. - Recent U.S. legislative initiatives aim to bring transparency to drug pricing and reduce prescription drug costs under Medicare [211].