Business Overview and History
Candel Therapeutics, Inc. (NASDAQ:CADL), a clinical-stage biopharmaceutical company leading the charge in multimodal biological immunotherapies, has emerged from a challenging period with a remarkable triumph. The company's flagship product candidate, CAN-2409, has delivered impressive results in a pivotal phase 3 trial for the treatment of intermediate-to-high-risk, localized prostate cancer, showcasing the resilience and transformative potential of Candel's innovative approach.
Candel Therapeutics was incorporated in Delaware in June 2003, initially operating under the name Advantagene, Inc. The company's core focus has been the development of off-the-shelf viral immunotherapies that harness the power of the immune system to combat cancer. In December 2019, Advantagene acquired the assets of Periphagen, a company specializing in engineering herpes simplex virus (HSV) as a gene therapy vector. This strategic move expanded Candel's technological capabilities, leading to the creation of its proprietary enLIGHTEN Discovery Platform, a systematic, iterative HSV-based platform that leverages human biology and advanced analytics to develop novel viral immunotherapy candidates.
In September 2020, the company in-licensed the rights to CAN-3110, an engineered oncolytic HSV product candidate, from Mass General Brigham. This addition to Candel's pipeline complemented the adenovirus-based CAN-2409, the company's most advanced product candidate. Candel formally changed its name to Candel Therapeutics, Inc. in December 2020, reflecting the evolution of its strategic focus and pipeline.
Financials and Liquidity
Candel's financial position has been shaped by its reliance on equity and debt financing to fuel its research and development efforts. As of December 31, 2024, the company had cash and cash equivalents of $102.7 million, which it believes will be sufficient to fund its current operating plan into the first quarter of 2027. The company has raised approximately $270.9 million in gross proceeds since its inception through the sale of convertible notes, common stock, and convertible preferred stock, as well as government grants.
For the year ended December 31, 2024, Candel reported a net loss of $55.2 million, primarily driven by $19.3 million in research and development expenses and $14.1 million in general and administrative expenses. The company's research and development costs have focused on advancing its CAN-2409 and CAN-3110 product candidates through clinical trials across various solid tumor indications.
In the most recent quarter (Q3 2024), Candel reported no revenue and a net loss of $10.65 million. The decrease in net income compared to the previous year was primarily due to increased research and development expenses as the company continued to advance its clinical trials.
Regarding liquidity, Candel's debt-to-equity ratio is not available, but the company has a current ratio and quick ratio of 1.18. The company has a $25 million term loan facility with Silicon Valley Bank, of which $12.5 million was outstanding as of December 31, 2024. In December 2024, Candel completed a public offering, raising approximately $85.9 million in net proceeds, which the company intends to use to further advance the development of its product candidates.
The company's pipeline is anchored by its two lead product candidates, CAN-2409 and CAN-3110, both of which are in clinical development for various solid tumor indications. CAN-2409, an adenovirus-based product candidate, is being evaluated in a pivotal phase 3 trial for the treatment of intermediate-to-high-risk, localized prostate cancer, as well as in phase 2 trials for non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC). CAN-3110, an engineered oncolytic HSV product candidate, is currently in an ongoing phase 1b trial for the treatment of recurrent high-grade glioma (rHGG).
In its early years, Candel focused on research and preclinical development of its technology platform. The company completed its initial public offering in July 2021, raising $71.3 million to support the advancement of its pipeline. Despite facing challenges common to many early-stage biotechs, including the need to continue raising capital to fund its clinical development activities, Candel has persevered and achieved important clinical milestones.
Prostate Cancer Trial Success: A Turning Point
Candel's recent success with its phase 3 trial of CAN-2409 in localized prostate cancer is a testament to the company's resilience and the promise of its viral immunotherapy approach. The randomized, double-blind, placebo-controlled trial enrolled 745 patients with intermediate-to-high-risk, localized prostate cancer, who were randomized to receive either CAN-2409 plus the prodrug valacyclovir in combination with standard-of-care (SOC) radiation therapy, or SOC radiation therapy alone.
In December 2024, Candel announced positive topline data from this pivotal study, reporting that the trial met its primary endpoint. Patients treated with the CAN-2409 combination therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) compared to the control arm. Specifically, treatment with CAN-2409 reduced the risk of prostate cancer recurrence or death by 30% (p=0.0155, HR=0.70, 95% CI: 0.52-0.94). Median DFS was not reached in the CAN-2409 arm, compared to 86.1 months in the placebo arm.
Furthermore, the CAN-2409 combination therapy resulted in a 38% decreased risk of prostate cancer-specific events (p=0.0046, HR=0.62, 95% CI: 0.44-0.87), and a significant increase in the proportion of patients achieving a prostate-specific antigen (PSA) nadir of ≤0.2 ng/mL (67.1% vs. 58.6%, p=0.0164). Notably, the DFS improvement was observed in both patients receiving short-term androgen deprivation therapy (ADT) and those not receiving ADT.
The safety profile of CAN-2409 in this trial was generally consistent with previous studies, with no new safety signals identified. The most common CAN-2409-related adverse events were flu-like symptoms, fever, and chills, which were mostly mild to moderate in severity and self-limiting.
These positive results from the phase 3 trial position CAN-2409 as a potential first-in-class therapy for localized prostate cancer, a disease area that has seen limited new treatment options in over 20 years. Candel is now preparing to initiate discussions with the FDA regarding the regulatory pathway for CAN-2409 in this indication, with the goal of submitting a Biologics License Application (BLA) in the fourth quarter of 2026.
Expanding the Pipeline and Navigating Challenges
Alongside the success in prostate cancer, Candel has continued to advance its broader pipeline of viral immunotherapy candidates. The company's phase 2 trial of CAN-2409 in NSCLC patients with inadequate response to immune checkpoint inhibitors (ICIs) has shown promising results, with prolonged overall survival observed in patients treated with the CAN-2409 combination therapy compared to historical controls. In May 2024, Candel announced topline data showing a median overall survival of 20.6 months following two administrations of CAN-2409 plus valacyclovir, compared to historical results of 11.6 months with standard-of-care chemotherapy. Candel expects to present updated overall survival data from this trial in the first quarter of 2025.
In PDAC, Candel's randomized phase 2 trial of CAN-2409 in borderline resectable and locally advanced disease has also yielded positive interim data. In February 2025, the company announced the final analysis of this trial, reporting a median overall survival of 31.4 months in the CAN-2409 group compared to 12.5 months in the control group. Importantly, three out of the seven patients treated with CAN-2409 were still alive at the time of data cut-off, with survival of 66.0, 63.6, and 35.8 months after enrollment.
The company's lead HSV-based product candidate, CAN-3110, has also demonstrated encouraging results in the ongoing phase 1b trial for recurrent HGG. In October 2023, Candel published clinical data in Nature demonstrating extended survival associated with immune activation in patients with recurrent HGG treated with CAN-3110. In October 2024, Candel presented clinical activity and biomarker data from the repeat dosing cohort, reporting improved survival compared to historical controls in patients treated with multiple injections of CAN-3110. The company expects to present initial median overall survival data from this cohort in the fourth quarter of 2025.
Despite the positive momentum, Candel has not been immune to the challenges faced by the biotechnology industry in recent years. In November 2023, the company undertook a restructuring plan that resulted in a 45% reduction in its workforce, as it prioritized the clinical development of CAN-2409 and CAN-3110, as well as the advancement of its enLIGHTEN Discovery Platform. This difficult decision allowed Candel to focus its resources on its key value drivers while navigating the turbulent market conditions.
On March 15, 2024, the company faced a significant challenge when it notified Dr. Aguilar-Cordova, the former CEO and CSO, that allegations had been uncovered suggesting he had instructed personnel to falsify sterility testing results submitted to the FDA for CAN-2409 and failed to implement a compliant stability testing program. Dr. Aguilar-Cordova denied these allegations. His term as a director expired at the 2024 annual meeting, marking a significant change in the company's leadership.
Looking Ahead
Candel Therapeutics' unwavering commitment to its viral immunotherapy approach has paid off, as evidenced by the landmark success of its CAN-2409 phase 3 trial in prostate cancer. This achievement underscores the company's resilience and the potential of its multimodal biological immunotherapies to transform the treatment landscape for cancer patients.
As Candel prepares to engage with the FDA and initiate the BLA submission process for CAN-2409 in prostate cancer, the company remains focused on advancing its broader pipeline. The upcoming data readouts for CAN-2409 in NSCLC and CAN-3110 in rHGG, as well as the continued development of its enLIGHTEN Discovery Platform, represent significant value drivers that could propel Candel to new heights.
The viral immunotherapy market is expected to grow significantly over the next five years, driven by increased adoption of these therapies for cancer treatment. This trend bodes well for Candel's innovative approach and product pipeline.
Despite the challenges faced, including the recent leadership change and allegations related to regulatory compliance, Candel has demonstrated the ability to adapt and prioritize its resources to maximize the potential of its innovative therapies. With a strengthened financial position and a pipeline brimming with promise, Candel Therapeutics is well-positioned to continue its mission of developing transformative immunotherapies that empower the immune system to fight cancer.
As a small-cap company currently focused on the U.S. market, Candel has the potential for significant growth as it advances its product candidates through clinical trials and potentially towards commercialization. The company's success in prostate cancer and promising results in other indications highlight the versatility and potential of its viral immunotherapy platform, setting the stage for potential expansion into additional markets and indications in the future.