Multikine (leukocyte interleukin injection) / CEL-SCI, Teva, Orient Europharma - LARVOL DELTA

Neoadjuvant leukocyte interleukin injection immunotherapy improves overall survival in low-risk locally advanced head and neck squamous cell carcinoma -the IT-MATTERS study. (PubMed, Pathol Oncol Res) - P3 | "Randomization 3:1:3 to LI+/-CIZ (cyclophosphamide, indomethacin, and zinc)+SOC, or SOC (standard of care) alone. No excess safety issues were reported for LI over SOC alone post-surgery. NCT01265849, EUDRA:2010-019952-35."

Clinical • Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL2

CEL-SCI Reports New Data: Treatment with Multikine Resulted in up to 95% Improvement in Quality of Life for Head and Neck Cancer Patients (Businesswire) - P3 | N=928 | IT-MATTERS (NCT01265849) | Sponsor: CEL-SCI Corporation | "Data published in peer-reviewed scientific journal Pathology and Oncology Research; Quality of life improvements included reduction in or cessation of pain in the head and neck area, improvement or complete restoration in ability to eat, drink, and swallow, ability for selfcare including walking and using the toilet, and improved emotional wellbeing; Complete responders to Multikine treatment reported a 100% (wherein all respondents scored the highest possible improvement from baseline) on 60% (39/65) quality of life measures; 89.4% of partial responders to Multikine reported improved quality of life measures; Multikine is headed into a final confirmatory Registration Study in head and neck cancer."

New trial • P3 data • Squamous Cell Carcinoma of Head and Neck

Journal of the American Medical Association (JAMA) Study Provides Further Evidence that CEL-SCI’s Multikine Can Treat Unmet Need in ~70% of Head and Neck Patients Based on PD-L1 Expression (Businesswire) - P2 | N=36 | DEPEND (NCT03944915) | "CEL-SCI Corporation...announced that a third-party study published on March 6, 2025 in JAMA Oncology...provided data that support Multikine’s use as a neoadjuvant treatment in patients with tumors having low PD-L1 expression in its upcoming confirmatory head and neck cancer Registration Trial....The DEPEND study demonstrates that checkpoint inhibitor nivolumab (Opdivo) works best with high levels of PD-L1 biomarker, but does not work well with low levels of PD-L1."

P2 data • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Announces Closing of $2.5 Million Offering (Businesswire) - "The Company intends to use the net proceeds from the offering to fund the continued development of Multikine, general corporate purposes, and working capital."

Commercial • Squamous Cell Carcinoma of Head and Neck

CEL-SCI’s Head and Neck Cancer Registration Study Protocol Clears FDA Review—in Talks with Potential Partners Interested in Commercialization of Multikine (Businesswire) - "CEL-SCI Corporation...announced it received comments from the U.S. Food and Drug Administration (FDA) on the confirmatory Registration Study’s Statistical Analysis Plan (SAP) submitted in December of 2024 for the study of Multikine (Leukocyte Interleukin, Injection) as a neoadjuvant in the treatment of newly diagnosed previously untreated locally advanced head and neck cancer. The FDA stated no response to their comments were required from CEL-SCI and that the agency presently has no comments on the confirmatory study protocol, which was submitted for FDA review contemporaneously with the SAP in December 2024....'These discussions may lead to potential partnerships involving non-dilutive funding for the 212-patient confirmatory Registration Study designed to bring Multikine to market'."

Clinical protocol • Squamous Cell Carcinoma of Head and Neck

CEL-SCI to Initiate Multikine Confirmatory Phase 3 Cancer Trial (Businesswire) - "CEL-SCI Corporation...announced it is in the final stages for the launch of its 212-patient Confirmatory Registration Study for Multikine (Leukocyte Interleukin, Injection) in newly diagnosed locally advanced head and neck cancer patients. This final Registration Study is specifically designed to confirm the statistically significant efficacy and safety results from CEL-SCI’s previously completed randomized controlled Phase 3 trial....Key aspects of the new Confirmatory Registration Study are as follows: Enlisting clinical sites and investigators in numerous countries across 3 continents; Full enrollment expected by Q2 2026 with plans to seek early approval at that time based on early tumor responses—Potential to set a new standard of care; FDA concurred with the overall design of the Registration Study in meetings last year Final clinical protocol submitted to FDA in December 2024; Multikine extended median overall survival by nearly 4 years in prior Phase 3 study."

New P3 trial • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Reports Fiscal Q1 2025 Financial Results: Multikine Shows Pre-Surgical Tumor Elimination and Regression in Just 3 Weeks (Businesswire) - "'The statistical analysis shows that our very soon to be initiated small confirmatory Registration Study has a very high chance of success and we will have indications of efficacy as early as 2026. Should the pre-surgical tumor responses mirror what we saw in the Phase 3 data, we believe we will be on the path for accelerated and/or conditional approval for Multikine next year.'...The strong data from our completed Phase 3 study and the biological rationale for the use of Multikine in the treatment of head and neck cancer suggest a high likelihood of success for the confirmatory Registration Study. These data and rationale include: Multikine shows pre-surgical tumor regression in head and neck cancer in just 3 weeks - confirmed by pathology at surgery: Multikine led to significant rates of tumor regression prior to surgery....Pre-surgical tumor regressions confirmed at surgery forecast survival benefit."

FDA approval • New trial • Trial status • Head and Neck Cancer

CEL-SCI Reports Fiscal 2024 Results: Set to Commence Confirmatory Study That Could Bring New Standard of Care to Head & Neck Cancer (Businesswire) - "A 212-patient Confirmatory Registration Study for Multikine in PD-L1 low newly diagnosed head and neck cancer patients is currently in final stage of start-up preparations - full enrollment expected by Q2 2026....CEL-SCI’s cGMP state-of-the-art dedicated manufacturing facility commissioning was completed, a significant milestone toward regulatory approval of Multikine."

Commercial • New trial • Head and Neck Cancer

CEL-SCI Announces Closing of $5 Million Offering (Businesswire) - "CEL-SCI Corporation...announced the closing of its previously announced best-efforts offering of 16,130,000 shares of its common stock (or pre-funded warrants ('Pre-Funded Warrants') in lieu thereof). Each share of common stock (or Pre-Funded Warrant) was sold at an offering price of $0.31 per share (inclusive of the Pre-Funded Warrant exercise price), for gross proceeds of approximately $5,000,000, before deducting placement agent fees and other offering expenses. All the shares and Pre-Funded Warrants in the offering were offered by the Company. The Company intends to use the net proceeds from the offering to fund the continued development of Multikine, general corporate purposes, and working capital."

Commercial • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Announces Pricing of $5 Million Public Offering (Businesswire) - "CEL-SCI Corporation...announced the pricing of a best-efforts public offering of 16,130,000 shares of its common stock (or pre-funded warrants ('Pre-Funded Warrants') in lieu thereof). Each share of common stock (or Pre-Funded Warrant) is being sold at a public offering price of $0.31 per share (inclusive of the Pre-Funded Warrant exercise price). Total gross proceeds from the offering, before deducting the placement agent’s fees and other offering expenses, are expected to be approximately $5,000,000. The offering is expected to close on December 31, 2024, subject to satisfaction of customary closing conditions. The Company intends to use the net proceeds from the offering to fund the continued development of Multikine, general corporate purposes, and working capital."

Commercial • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Highlights Biological Rationale for the Use of Multikine in the Confirmatory Registration Head and Neck Cancer Study (Businesswire) - P3 | N=928 | IT-MATTERS (NCT01265849) | Sponsor: CEL-SCI Corporation | "CEL-SCI...today highlights strong biological rationale for the use of Multikine in the confirmatory registration head and neck cancer study...This study of 212 newly diagnosed locally advanced, resectable head and neck cancer patients was given the go-ahead as a confirmatory registration study by FDA and will focus on those patients who showed a 73% survival with Multikine vs. a 45% for the control patients not treated with Multikine in the prior Phase 3 study...The Phase 3 study missed the primary endpoint of 10% improvement in overall survival (OS) in the ITT population (all patients in the study) but showed a 46.5-month (almost 4 years) OS benefit vs control (101.7 months vs. 55.2 months) in the patients who received Multikine followed by surgery and radiotherapy....After this analysis was done and the evidence collected, CEL-SCI presented these selection criteria to FDA."

New trial • P3 data • Head and Neck Cancer

U.S. FDA and CEL-SCI Agree on Use of PD-L1 Biomarker to Select Head and Neck Cancer Patients for Marketing Registration Study to Commence Q1 2025 (Businesswire) - "CEL-SC...announced that in a recent meeting the U.S. Food and Drug Administration (FDA) concurred with the Company’s approach to patient selection using low PD-L1 tumor expression in its confirmatory Registration Study for Multikine (Leukocyte Interleukin, Injection). This study will focus on the treatment of newly diagnosed locally advanced primary head and neck cancer patients with no lymph node involvement and low (TPS <10) PD-L1 tumor expression. This Registration Study, slated to commence in the first quarter of 2025, will enroll approximately 212 patients....'We appreciate the ongoing dialog, exchange of ideas and information with the FDA in support of CEL-SCI’s groundbreaking work as we aim to treat an unmet need in cancer patients with low PD-L1 expression.'"

FDA event • New trial • Head and Neck Cancer • Oncology • Solid Tumor

FDA’s Oncologic Drugs Advisory Committee Decision on Checkpoint Inhibitors Substantiates Potential of CEL-SCI’s Multikine to Address Major Treatment Gap for PD-L1 Negative Cancer Patients (Businesswire) - "CEL-SCI...announced the potential positive impact on the clinical development of its immunotherapy Multikine...resulting from a recent U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) meeting...The September 27, 2024 ODAC meeting evaluated the use of checkpoint inhibitors on patients with various cancers...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....'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..."

ODAC • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Selects Ergomed as CRO as it Gears Up for Confirmatory FDA Registration Study of Multikine in Head and Neck Cancer (Businesswire) - "CEL-SCI Corporation...announced its renewed collaboration with Ergomed Clinical Research for its upcoming U.S. Food and Drug Administration (FDA) confirmatory Registration Study of Multikine (Leukocyte Interleukin, Injection) in head and neck cancer....Ergomed will provide global comprehensive clinical operations support to ensure the timely and efficient execution of the trial, supporting CEL-SCI in bringing a new treatment option for patients with locally advanced primary head and neck cancer to the market...In addition to the positive outcome from its recent meeting with the FDA regarding the path to approval for its first-line investigational cancer immunotherapy, CEL-SCI achieved other major milestones including receiving pediatric waivers from the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency...The study, set to enrol 212 newly diagnosed patients with locally advanced primary head and neck cancer..."

New trial • Squamous Cell Carcinoma of Head and Neck

CEL-SCI’s Multikine Increased 5-Year Survival Rate to 82.6% in Locally Advanced Resectable Head & Neck Cancer Patients Who Were Deemed to be in the Treatment Group for Surgery and Radiation (Businesswire) - P3 | N=928 | IT-MATTERS (NCT01265849) | Sponsor: CEL-SCI Corporation | "5-year survival rate of 82.6% and 73% reduction in overall risk of death (hazard ratio of 0.27) are the strongest Multikine efficacy results reported to date, reflecting results in patients who met the CEL-SCI confirmatory Registration Study target population criteria and were deemed at low risk for recurrence, therefore not recommended per NCCN guidelines to receive chemotherapy post-surgery; Data provide further evidence that the selection criteria for CEL-SCI’s upcoming confirmatory Registration Study may yield improved clinical outcomes; Clear unmet need: the 5-year survival rate remains below 50% in locally advanced resectable head and neck cancer patients who receive standard of care only."

P3 data • Squamous Cell Carcinoma of Head and Neck

Prognostic significance of diagnostic staging in treatment naïve, resectable locally advanced primary oral cavity squamous cell carcinoma for neoadjuvant leukocyte interleukin injection immunotherapy (ESMO 2024) - P3 | "Background: In a randomized controlled pivotal Phase III study neoadjuvant investigational proinflammatory biologic Leukocyte Interleukin Injection (LI) administered pre-surgery with CIZ (single low dose cyclophosphamide IV, indomethacin (po tid) and Zinc (po, daily) multivitamins + Standard of Care (SOC) to locally advanced treatment naïve oral and soft-palate SCCHN subjects, resulted in significantly prolonged overall survival (OS) in the locally advanced, node negative (N0) population with tumor cell PDL-1 proportional score (TPS) categorized as ≤10, in intent to treat (ITT) population vs SOC alone. Consenting subjects with available samples (n=114 ITT, 99 oral only) meeting entry criteria (AJCC Stage III/IVa OSCC, soft palate, treatment (Tx) naïve) randomized 3:1:3 to Tx arms LI (+/- CIZ) + SOC or SOC alone (control). Advantages for OS (HR 0.35 Oral + Soft Palate, and HR 0.36 Oral cavity) over control support LI's effect on efficacy in the..."

Clinical • Metastases • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IL2

CEL-SCI to Present New Data for Multikine Head & Neck Cancer Immunotherapy at the European Society for Medical Oncology 2024 Congress (Businesswire) - "CEL-SCI Corporation...reported it will report new data from its Phase 3 study of Multikine...at the European Society for Medical Oncology (ESMO) 2024 Congress which takes place from September 13 – 17, 2024 in Barcelona, Spain. A poster....will be presented by the study’s co-author József Tímár MD, PhD, DSc, a prominent and highly respected pathologist."

P3 data • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

The UK’s Medicines & Healthcare Products Regulatory Agency Grants CEL-SCI a Pediatric Waiver, Bringing Multikine One Step Closer to Future Marketing Clearance (Businesswire) - "CEL-SCI Corporation...reported it has received a decision letter from the United Kingdom’s Healthcare Products Regulatory Agency (MHRA) granting Multikine (Leukocyte Interleukin, Injection) a product specific waiver for the treatment of head and neck cancer in a pediatric population of people up to 18 years of age. As a result, CEL-SCI will not be required to evaluate Multikine in a pediatric population as part of license and marketing clearance review in the UK....'This pediatric waiver accelerates our path to marketing approval in the UK'."

European regulatory • Squamous Cell Carcinoma of Head and Neck

CEL-SCI’s Phase 3 Population Analysis for Upcoming Confirmatory Registration Study in Head & Neck Cancer Demonstrates Well Balanced Patient Population, Confidence in Clinical Results (Businesswire) - P3 | N=928 | IT-MATTERS (NCT01265849) | Sponsor: CEL-SCI Corporation | "CEL-SCI Corporation...reported positive results from a bias analysis conducted for its concluded Phase 3 study of Multikine (Leukocyte Interleukin, Injection) in the treatment of head and neck cancer....No bias was present in the study and none was detected in favor of the investigational product, Multikine. As such, the study data are reliably interpretable, statistically significant and have been shown to support the clinical effect of neoadjuvant (pre-surgery) Multikine immunotherapy in extending the life of these patients in the Phase 3 study. This is critically important information because CEL-SCI, with the FDA’s agreement, will be conducting a 212-patient confirmatory registration study for Multikine."

P3 data • Head and Neck Cancer • Oncology • Solid Tumor

CEL-SCI Presents Head & Neck Cancer Data at Iddst Annual Congress in Budapest: Risk of Death Cut in Half for Patients Treated With Multikine in the Target Population (Businesswire) - P3 | N=928 | IT-MATTERS (NCT01265849) | Sponsor: CEL-SCI Corporation | "Multikine significantly increases overall survival in patients with low levels of tumor cell PD-L1 expression in contrast to approved checkpoint inhibitors; 73% survival for Multikine vs 45% in the control arm at 5 years; Statistically significant log rank p = 0.0015; 5-year risk of death cut in half from 55% to 27%; Hazard ratio = 0.35 (95% CIs [0.19, 0.66]); Working to commence FDA confirmatory Registration Study for Multikine."

P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Receives FDA Go-Ahead for Its Confirmatory Study of Multikine in the Treatment of Head & Neck Cancer (Businesswire) - "CEL-SCI Corporation...announced a significantly positive outcome from its recent meeting with the U.S. Food and Drug Administration (FDA) regarding the path to approval for its first-line investigational cancer immunotherapy Multikine (Leukocyte Interleukin, Injection). Based on strong safety and efficacy data from CEL-SCI’s completed Phase 3 head and neck cancer study, the FDA indicated CEL-SCI may move forward with a confirmatory Registration Study of Multikine in newly diagnosed 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)....The FDA accepted the selection criteria and the proposed study design, which now permits CEL-SCI to enroll patients in the confirmatory study."

New P3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Corporation Reports First Quarter Fiscal 2024 Financial Results (Businesswire) - "CEL-SCI Corporation...today reported financial results for the quarter ended December 31, 2023, as well as key recent clinical and corporate developments...CEL-SCI plans to submit the target population data to the U.S. Food and Drug Administration (FDA) this quarter. Health Canada advised CEL-SCI to request advance consideration for approval under a Notice of Compliance with Conditions (NOCC) policy. Meetings with the UK regulators and the EMA are expected H1 2024."

Canadian regulatory • European regulatory • FDA event • Head and Neck Cancer • Oncology • Solid Tumor

CEL-SCI Announces Pricing of $7.75 Million Public Offering of Common Stock (Businesswire) - "CEL-SCI Corporation...today announced the pricing of an offering of 3,875,000 shares of its common stock at an offering price of $2.00 per share, for gross proceeds of $7.75 million, before deducting underwriting discounts and offering expenses. All of the shares of common stock are being offered by the Company. The offering is expected to close on February 13, 2024, subject to satisfaction of customary closing conditions....The Company intends to use the net proceeds from this offering to fund the continued development of Multikine, for general corporate purposes, and working capital."

Financing • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

CEL-SCI Completes Commissioning of Its Multikine Manufacturing Facility for Commercial Scale Production of Head & Neck Cancer Drug (Businesswire) - "CEL-SCI Corporation...reported that its Multikine (Leukocyte Interleukin, Injection) cGMP state-of-the-art dedicated manufacturing facility commissioning has been completed....Originally constructed to supply Multikine for the world’s largest global pivotal Phase 3 trial in locally advanced squamous cell carcinoma of the head and neck, CEL-SCI’s facility has been expanded and upgraded in preparation for the Company’s submission of Multikine for regulatory approval and commercial scale manufacturing."

Commercial • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

European Medicines Agency Grants CEL-SCI a Waiver of Strict Pediatric Requirements, Clearing the Path Towards Marketing Authorization for Multikine (Businesswire) - "CEL-SCI Corporation...today announced that the European Medicines Agency (EMA) Paediatric Committee granted CEL-SCI a product-specific waiver of strict requirements for commercialization of cancer drugs in the European Union (EU)....CEL-SCI’s investigational cancer immunotherapy Multikine (Leukocyte Interleukin, Injection)* is intended for newly diagnosed adult (>18 years old) patients with locally advanced resectable primary squamous cell carcinoma of the head and neck (SCCHN)."

European regulatory • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck