Slide 1: Multikine First In Class Immunotherapy Cancer Therapy
Multikine “First In Class Immunotherapy” Cancer Therapy First Indication: Head & Neck Cancer Neoadjuvant Immunotherapy November 2024 NYSE American: CVM 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” standards; our expectations regarding federal, state by applicable laws and regulations, we undertake no within the meaning of the Private Securities Litigation and foreign regulatory requirements; the therapeutic obl
Slide 3: The CEL-SCI Team
The CEL-SCI Team Geert Kersten, Esq. Eyal Talor, PhD Giovanni Selvaggi, MD Chief Executive Officer & Director Chief Scientific Officer since 2009 CEL-SCI Acting Chief since 1995 Inventor / developer of Multikine® Medical Officer since Experience in finance and law 2024 30 years at CEL-SCI in R&D, Ac
Slide 4: Top-Tier Physician Consultants
Top-Tier Physician Consultants Barbara Burtness, MD Marshall Posner, MD Anthony N. Brady Professor of Medicine (Medical Consultant for CEL-SCI since 2005 Oncology) at Yale School of Medicine Principal Investigator and Chair of the IDMC in CEL-SCI’s Phase 3 Chief Translational Research Officer, Yale
Slide 5: Key Facts About CEL-SCI Corporation
Key Facts About CEL-SCI Corporation → NYSE American, stock symbol CVM. → We believe cancer immunotherapy should be administered before surgery, radio and chemotherapy have destroyed the immune system. The goal is to make the first cancer treatment more successful so that the tumor does not kill the
Slide 6: Key Facts About CEL-SCI Corporation
Key Facts About CEL-SCI Corporation → Expects to initiate the confirmatory registration study in Q1 2025. → By Q2 2026, we expect full enrollment, data on pre-surgical response rates (indicative of overall survival results), and we plan to seek early approval in the U.S. and other countries based on
Slide 7: What is Multikine?
What is Multikine? • Multikine is a consistent mixture of cytokines. Research at the US National Institutes of Health (NIH) has shown that the cytokines (shown in yellow) are the ones that are required to reject a tumor. • Multikine is a non-toxic mass-produced immunotherapy that becomes specific to
Slide 8: Multikine Mechanism of Action
Multikine Mechanism of Action 8
Slide 9: Tumor Cell Death Without And With Multikine
Tumor Cell Death Without And With Multikine Without Multikine With Multikine How the Tumor Defense Mechanisms Can How Multikine May Circumvent T cells T cells Circumvent An Anti-tumor Immune Response The Tumor Defense Mechanisms! LYMPH LYMPH NODE NODE T DC cells T Kill Tumor DC DC cells (GzmB, PFN;
Slide 10: Dedicated State-of-the-Art Manufacturing Facility
Dedicated State-of-the-Art Manufacturing Facility c GMP and BSL-1 facility near Washington, DC, USA → Built specifically for Multikine → State-of-the art facility → Over 73,000 ft 2 of Manufacturing and R&D space available → About 45,000 ft 2 fully developed → Proprietary automated cold fill to ensu
Slide 11: The Multikine Treatment Regimen
The Multikine Treatment Regimen Multikine would be added to the current standard of care, delivered locally via injections around the tumor and adjacent to the draining lymphatic chain area before surgery: Current Standard Of Care Locally advanced primary head and neck cancer Radiotherapy Diagnosis
Slide 12: What is the Target Population?
What is the Target Population? The 212 patient confirmatory study will focus on these Kaplan-Meier Overall Survival for Multikine target population (n=114) in the Phase 3 study patients: → Newly diagnosed locally advanced primary (stage 3 and 4) head and 5-year survival 73% neck cancer patients with
Slide 13: What are the Characteristics of the Selected Population?
What are the Characteristics of the Selected Population? Why N0? • Healthier immune system can mount better anti-tumor immune response. • Less likely to have chemotherapy added following surgery. • Therefore, the target population for the confirmatory study is mostly composed of patients who receive
Slide 14: Are Multikine and Checkpoint Inhibitors in Competition? NO!
Are Multikine and Checkpoint Inhibitors in Competition? NO! • Checkpoint Inhibitors (CI) (e.g., Keytruda, Opdivo) are currently approved in head and neck cancer for use after the first treatments have failed. We are pursuing the treatment of newly diagnosed patients. Why do we use PD-L1 level to sel
Slide 15: Is this PD-L1 Distinction Relevant for the FDA?
Is this PD-L1 Distinction Relevant for the FDA? Yes, very relevant: • September 27, 2024: FDA Oncologic Drugs Advisory Committee (ODAC) discussed this very issue. • The title was: “Risks Outweigh Benefits for Checkpoint Inhibitors in Some Cancers”. • A U.S. FDA advisory committee determined that the
Slide 16: Target Population: Improved Survival In the Completed Phase 3 Study
Target Population (N0 & PD-L1 low) for Confirmatory Study: Improved Survival In the Completed Phase 3 Study Kaplan-Meier Overall Survival for Multikine target population (n=114) Data Presented at ESMO 2023 Multikine • No safety signals or toxicities vs standard of care • Statistically significant (l
Slide 17: Target Population for Confirmatory Study - Chances of Success
Target Population (N0 & PD-L1 low) for Confirmatory Study - Chances of Success - • Subgroup analysis is of a large size of over 100 patients • Baseline and demographics of the two groups are well balanced • Analysis was pre-specified in the protocol of the previous Phase 3 study and SAP • HR CI uppe
Slide 18: Leading KOL will lead Confirmatory Registration Study
Leading KOL will lead Confirmatory Registration Study • Dr. Nabil F. Saba, MD, FACP will serve as the confirmatory global Phase III clinical trial Lead, as a member of the Study Steering Committee, for CEL-SCI’s upcoming confirmatory registration study • Nationally and internationally recognized exp
Slide 19: Our Registration Study Design
Our Registration Study Design Stage 1: Treatment Period Stage 2: Follow-up period Treatment Arm Multikine treatment first then standard of care n=106 Assess overall survival as the primary Randomized 1:1 between the efficacy endpoint, and then treatment arm and the control arm histopathology biomark
Slide 20: Increased Pre-Surgical Tumor Responses Predict for Survival Across All Patients
Increased Pre-Surgical Tumor Responses Predict for Survival Across All Patients (n=928) in the Phase 3 Trial 20
Slide 21: Higher PSR/PSD Rates in the Target Population (n=114)
Higher PSR/PSD Rates in the Target Population (n=114) 21
Slide 22: Summary: Highlights and Milestones
Summary: Highlights and Milestones Planning to Why we Strong Request believe in a survival data FDA approval Enrollment Accelerated/ positive for unmet pathway commences outcome of the medical need Conditional Approval confirmatory trial The goal of the confirmatory Confirmatory study of Enrollment
Slide 23: Thank you!
Thank you! NYSE American: CVM
Slide 24: Appendix
Appendix CEL’ Sc NYSE American: CVM
Slide 25: Cartoon Adapted from: NCCN Guidelines – Standard of Care
Cartoon Adapted from: NCCN Guidelines – Standard of Care NOTE: Head and neck cancer world’s 6th most prevalent cancer, with an estimated 850,000 annual cases globally; about 90% are SCCHN and approximately 66% present at diagnosis with Advanced Disease. Of all H&N cancer approx. 46% are Oral Cavity.
Slide 26: Phase 1 / 2 Trial
Phase 1 / 2 Trial Confidential & Proprietary 26 Screening/Baseline Post- MK treatment Regimen • Pre-surgical tumor response and histopathological evidence of MK’s mechanism of action • pCR (Determined at surgery: Necrosis) 26
Slide 27: Non-Multikine Treated vs. Multikine Treated
Non-Multikine Treated vs. Multikine Treated Oral Squamous Cell Carcinoma (Locally Advanced Primary H&N Cancer) Histological appearance of necrosis in Oral Squamous Cell Carcinoma (OSCC) [HE staining]: Non-Multikine treated Multikine treated Lack of necrosis in the epithelial nests of OSCC Entire can
Slide 28: RCT Multikine Phase 3 Trial Design
RCT Multikine Phase 3 Trial Design Schematic: Randomization and Treatment of Enrolled Current 1st Line SOC (NCCN Guidelines) Patients with Disease Stage III and IVa Group 1 Multikine 5X/week for 3 weeks (+ CIZ*) RTx 3 Radiotherapy (60 - 70 Gy, 30 - 35 fractions over 6 - 7 Weeks) RANDOMIZE SURGERY**
Slide 29: Overall Survival: ITT (p=0.4051)
Overall Survival: ITT (p=0.4051) (n=923, 462 deaths) 29
Slide 30: OS ITT Low Risk: LI(MK)+CIZ+SOC Advantage
OS ITT Low Risk: LI(MK)+CIZ+SOC Advantage (p=0.0478) (n=380, 166 Deaths) Median OS (months) Group 1 = LI(MK)+CIZ+SOC 101.7 Group 2 = LI(MK)+SOC 68.5 Group 3 = SOC alone (Control) 55.2 A 46.5 Median OS advantage HR=0.68 95% CI (0.48, 0.95); Wald p=0.0236 30 Talor E., et al, ASCO ‘22 Abstract/ Poster
Slide 31: Tumor Response Rate pre-surgery: Phase 3 (Study CS001P3)
Tumor Response Rate pre-surgery: Phase 3 (Study CS001P3) ITT Pre-surgical responders ITT Group 1 ITT Group 2 ITT Groups 1+2 ITT Group 3 (N=395) (N=134) (N=529) (N=394) Risk group N % N % N % N % Pre-surgical response rate 32 8.1 13 9.7 45 8.5 0 0 [95%CI (%)] [5.6, 11.2] [5.3, 16.0] [6.4, 11.2] [0, 0
Slide 32: Clinical: Phase 3 (Study CS001P3)
Clinical: Phase 3 (Study CS001P3) Lavin P., et al, ESMO ’22 Abstract/Poster 690P Post-LI(MK) pre-Surgery (within 3 weeks) pCR (CR confirmed by Pathology at surgery) Screening/Baseline Screening/Baseline 32
Slide 33: Clinical (OS): Phase 3 (Study CS001P3) ITT LR
Clinical (OS): Phase 3 (Study CS001P3) ITT LR K-M of LR Group 1 PSRs, LR Group 1 non-PSRs, and LR Group 3 (N=326) Censored Group1-Responders Group 1 = 100 Group1-NonResponders MK+CIZ+SOC SOC Alone Group 3 = SOC 90 alone (Control) 80 Survival Probability 70 60 50 40 30 20 Log Rank P-value 10 Group 1-
Slide 34: AJCC Stage Migration Pre-surgery Impact on OS
AJCC Stage Migration Pre-surgery Impact on OS Overall (ITT) Group 1 (TN) improvement, no change (relative to entry) resulted in OS benefit Censored Improved 100 No Change/Same Worsening 90 Overall Survival Probability (%) 80 70 60 50 40 30 20 Log Rank P-value 10 Im proved vs Wors ening: <.0001 No Ch
Slide 35: Data From the Bias Analysis
Data From the Bias Analysis Phase 3 Study Selected Target Population N0, TPD-L1 <10 (n=114, baseline characteristics, demographics) Baseline Covariate Covariate Level MK+CIZ+SOC (n=60) SOC Only (n=54) Percents Percents Age Mean 56.9 58.0 (Range) (33-76) (35-80) Sex % Male 76.7 88.9 Race % Asian 0.0
Slide 36: What If We Could Avoid/Reduce Chemotherapy Through a Better Selection Process
What If We Could Avoid/Reduce Chemotherapy Through a Better Selection Process → The selection process included 35 patients out of 114 who received chemoradiotherapy (79 received only Radiotherapy after surgery) → Chemotherapy is expected to negatively affect immune response → The data shows that wit
Slide 37: Cellular Biomarkers and Ranges Pre-defined for Pathology
Cellular Biomarkers and Ranges Pre-defined for Pathology Immunohistochemistry Prospectively Defined Biomarkers (2 [L/H] or 3 levels [L/M*/H]) 1. p16: 10% positivity threshold 11. CD68: L<50, H>100 2. HLA: L<45, H>90 12. CD163: L<60, H>120 3. B2M: L<40, H>80 13. CD1a: L<15, H>30 4. MR1: L<50, H>100 1
Slide 38: Pathology IHC: Clearly Defined And Well-Understood
Pathology IHC : Clearly Defined And Well-Understood (Top row = Multikine treated; Bottom row = Control) *3,3′-diaminobenzidine (DAB) 38
Slide 39: Prospectively Defined Ratios and Combinations of Cellular Biomarkers
Prospectively Defined Ratios and Combinations of Cellular Biomarkers Two ratios were constructed with L, M, and H thresholds (based on above definitions of H & L, M was neither H nor L) as follows: 1. CD8/FOXP3 ratio: 1 and 2 2. CD4/CD8 ratio: 1 and 2 Fourteen combinations were constructed as follow
Slide 40: Immunohistopathology Supports MoA of Multikine
Immunohistopathology Supports MoA of Multikine Significant Outcomes All Favoring MK + CIZ + SOC vs SOC Histopathology Results: Proportion Statistically Significant, 1-sided p<0.025 Overall Group Lower-risk Group Overall Group Endpoint (n=453) (n=210)* (n=453) Favoring Group 1** Favoring Group 1 Favo
Slide 41: Clear Pathway to Market for Major Unmet Need
Clear Pathway to Market for Major Unmet Need • In the target population from the Phase 3 trial, Multikine showed a significant survival benefit of 73% vs 45% in the control group at 5 years, with a statistically significant log rank p-value of 0.0015. That is a 28% absolute survival benefit. We only