• Oncologic Drugs Advisory Committee (ODAC) determines risks outweigh benefits in some cancers for frontline immune checkpoint inhibitors, including blockbuster drugs such as Keytruda and Opdivo, in patients with low PD-L1 expression
• Multikine has shown survival benefit and favorable safety profile in a randomized controlled Phase 3 study of treatment naïve resectable locally advanced head and neck cancer patients with low PD-L1 expression
• Multikine has potential as a combination drug with current checkpoint inhibitors such as Keytruda which is projected to be the top selling drug in the world with $27 billion in 2024 sales
• To the Company’s knowledge, Multikine is the only neoadjuvant immunotherapy that has shown overall survival benefit in the low and negative PD-L1 head and neck cancer population

VIENNA, Va. / Oct 22, 2024 / Business Wire / CEL-SCI Corporation (NYSE American: CVM) today announced the potential positive impact on the clinical development of its immunotherapy Multikine® (Leukocyte Interleukin, Injection)* resulting from a recent U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) meeting, a public forum.

FDA advisory committees provide independent expert advice to the FDA on the safety and effectiveness of new and marketed drugs and help the agency make sound and informed decisions. Advisory committees make non-binding recommendations to the FDA, which generally follows the recommendations but is not legally bound to do so.

The September 27, 2024 ODAC meeting evaluated the use of checkpoint inhibitors on patients with various cancers. PD-L1 is the biomarker most often used for patient selection for checkpoint inhibitors, the most successful class of cancer drugs including Keytruda and Opdivo. The FDA sought the ODAC’s opinion on the following:

• adequacy of PD-L1 expression as a predictive biomarker for patient selection in this patient population
• differing risk-benefit assessments in different subpopulations defined by PD-L1 expression
• adequacy of the cumulative data to restrict the approvals of immune checkpoint inhibitors based on PD-L1 expression

Following a thorough analysis of peer-reviewed published data, the panel of experts on the ODAC voted 10-2 and 11–1 against the risk-benefit profile for PD-L1 inhibitors in various cancers in two separate votes. Most ODAC members expressed concerns about the lack of benefit demonstrated for patients with low PD-L1 expression, while some members pointed to evidence that the use of the immune checkpoint inhibitors may add unnecessary toxicities for patients while also increasing financial burdens on patients.

Checkpoint inhibitors were an estimated $48 billion global market in 2023, with PD-L1 inhibitors representing 73% of the market. Current labeling for approved checkpoint inhibitors in the indications evaluated by the FDA’s ODAC include broad approvals for all patients, regardless of PD-L1 expression.

“The FDA advisory committee’s findings and public statement on the risk-benefit of checkpoint inhibitors based on PD-L1 expression is potentially a turning point in cancer treatment, pointing to a major treatment gap in low and negative PD-L1 patients. While the approved blockbuster checkpoint inhibitors, including Keytruda which is expected to be the biggest selling drug in 2024, work well in high PD-L1 expressing patients, to our knowledge, Multikine is the only immunotherapy that is targeted to and has shown survival benefit in the low and negative PD-L1 population. CEL-SCI has already identified in our prior study low PD-L1 expression as a predictive biomarker, representing about 70% of head and neck cancer patients, which will be used as a selection criterion for our upcoming FDA confirmatory Registration Study of Multikine in the treatment of treatment-naïve resectable locally advanced head and neck cancer,” stated CEL-SCI CEO Geert Kersten.

“The FDA’s ODAC decision further supports our belief that Multikine holds strong potential in treating patients across a wider range of solid tumor cancer indications alone and in combination regimens,” Kersten concluded.

About CEL-SCI Corporation

CEL-SCI believes that boosting a patient’s immune system while it is still intact should provide the greatest possible impact on survival. Multikine is designed to help the immune system "target" the tumor at a time when the immune system is still relatively intact and thereby thought to be better able to mount an attack on the tumor.

Multikine (Leukocyte Interleukin, Injection), a true first-line cancer therapy, has been dosed in over 740 patients and received Orphan Drug designation from the FDA for neoadjuvant therapy in patients with squamous cell carcinoma (cancer) of the head and neck. Based on the very strong data from the completed randomized controlled Phase 3 study, the FDA agreed to CEL-SCI’s target patient selection criteria and gave the go-ahead to conduct a small, focused, confirmatory Registration Study which will enroll 212 patients. CEL-SCI will enroll newly diagnosed locally advanced primary head and neck cancer patients with no lymph node involvement (determined via PET scan) and with low PD-L1 tumor expression (determined via biopsy), representing over 100,000 patients annually.

The Company has operations in Vienna, Virginia, and near/in Baltimore, Maryland.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. When used in this press release, the words "intends," "believes," "anticipated," "plans" and "expects," and similar expressions, are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include an inability to duplicate the clinical results demonstrated in clinical studies, timely development of any potential products that can be shown to be safe and effective, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital and the risk factors set forth from time to time in CEL-SCI's filings with the Securities and Exchange Commission, including but not limited to its report on Form 10-K for the year ended September 30, 2023. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.

* Multikine (Leukocyte Interleukin, Injection) is the trademark that CEL-SCI has registered for this investigational therapy. This proprietary name is subject to FDA review in connection with the Company's future anticipated regulatory submission for approval. Multikine has not been licensed or approved for sale, barter or exchange by the FDA or any other regulatory agency. Similarly, its safety or efficacy has not been established for any use.