CEL-SCI Corporation (NYSE American: CVM) is a clinical-stage biotechnology company dedicated to developing innovative immunotherapies for the treatment of cancer and other diseases. The company's lead investigational therapy, Multikine (Leukocyte Interleukin, Injection), has demonstrated promising results in a Phase 3 clinical trial for the treatment of advanced primary head and neck cancer.

Business Overview

CEL-SCI's primary focus is the development of Multikine, a biological medicinal immunotherapy comprised of a mixture of natural cytokines and small biological molecules. Multikine is administered by local injection around the tumor and adjacent lymph nodes as a first-line treatment before the standard of care, which is surgery followed by either radiotherapy or chemoradiotherapy. The rationale behind Multikine's use is to incite a locoregional immune response against the tumor before the local immune system has been compromised by the standard of care and/or disease progression.

The target population for Multikine is treatment-naïve adult patients with resectable locally advanced primary squamous cell carcinoma of the head and neck (SCCHN) in the oral cavity who have no lymph node involvement (via PET scan) and low PD-L1 tumor expression (TPS<10, via biopsy). CEL-SCI estimates that patients with tumors having low PD-L1 represent about 70% of locally advanced primary SCCHN patients.

Phase 3 Clinical Trial Results

CEL-SCI's Phase 3 clinical trial for Multikine involved 928 patients and demonstrated that Multikine was able to significantly improve overall survival in the target population. Specifically, Multikine-treated patients in the target population had a 73% 5-year survival rate compared to a 45% 5-year survival rate in the control group, representing a 28.6% absolute 5-year overall survival benefit (p=0.0015). Additionally, Multikine reduced the risk of death by 65% compared to the control group, with a hazard ratio of 0.35 (95% CIs [0.18, 0.66], Wald p=0.0012).

The Phase 3 trial also showed that Multikine was able to induce significant pre-surgical responses, with over 35% of Multikine-treated patients experiencing either a 30% or greater reduction in tumor size (pre-surgical reduction or PSR) or a downstaging of their disease (pre-surgical downstaging or PSD) prior to surgery, compared to only 13% in the control group. Importantly, these pre-surgical responses were strongly correlated with improved overall survival, further supporting Multikine's mechanism of action.

Multikine's Safety Profile

Multikine has been tested in 928 patients in the Phase 3 clinical trial. No demonstrable safety signals or toxicities have been observed. Adverse event (AE) and serious adverse event (SAE) incidences were not significantly different among treatment and control groups, and there were no Multikine-related deaths and only two discontinuations. Multikine-related AEs before surgery were local and resolved after surgery.

Regulatory Strategy and Unmet Need

Based on the strong safety and efficacy data from the completed Phase 3 study, CEL-SCI has reached an agreement with the FDA to conduct a 212-patient confirmatory Registration Study of Multikine in the target population of newly diagnosed advanced primary head and neck cancer patients with no lymph node involvement and low PD-L1 tumor expression. This smaller confirmatory study is designed to confirm the positive results seen in the prior Phase 3 trial.

The target population for Multikine represents a significant unmet medical need, as current standard of care provides only about a 50/50 chance of surviving five years. Multikine's ability to cut the risk of death in half in this population, along with its favorable safety profile, positions it as a potentially transformative therapy for these patients.

Liquidity

As of March 31, 2024, CEL-SCI had cash and cash equivalents of $5.3 million. During the six months ended March 31, 2024, the company's cash increased by $1.2 million, primarily due to net proceeds of $11.5 million from two public offerings, offset by $9.4 million in cash used to fund operations.

For the six months ended March 31, 2024, CEL-SCI reported a net operating loss of $13.6 million, which included significant non-cash expenses such as $3.2 million in share-based compensation and $2.0 million in depreciation and amortization. Research and development expenses decreased by 22% compared to the prior-year period, primarily due to lower costs related to the Phase 3 study.

Due to recurring losses from operations and future liquidity needs, there is substantial doubt about CEL-SCI's ability to continue as a going concern. The company will need to raise additional capital or find additional long-term financing to continue its operations and complete the development of Multikine.

Risks and Challenges

CEL-SCI faces several risks and uncertainties, including the ability to obtain regulatory approval for Multikine, the successful completion of the confirmatory Registration Study, the ability to raise sufficient capital to fund its operations, and the potential for competition from other immunotherapies or standard of care treatments. Additionally, the company's reliance on third-party manufacturers and clinical research organizations introduces operational and execution risks.

Outlook

CEL-SCI's Multikine has demonstrated impressive survival benefits in the target population of newly diagnosed advanced primary head and neck cancer patients with no lymph node involvement and low PD-L1 tumor expression. The company's agreement with the FDA to conduct a smaller 212-patient confirmatory study, based on the strong data from the prior Phase 3 trial, represents a significant milestone and de-risks the path to potential approval.

Conclusion

If approved, Multikine could provide a much-needed treatment option for a patient population that is currently underserved by existing therapies. The company's focus on this unmet medical need, combined with Multikine's favorable safety profile and compelling efficacy data, make CEL-SCI a compelling investment opportunity for those interested in the rapidly growing immunotherapy market.