Cel-sci Corporation · AMEX:CVM
Cel-sci — Technical Presentation (June 2024)
22 slides from Cel-sci's technical presentation, Jun 18, 2024
Slide 1: Neoadjuvant Immunotherapy for Head and Neck Cancer: Low Tumor PD-L1 Expression - IT-MATTERS – RCT
Leukocyte Interleukin, Injection (LI) Immunotherapy Neoadjuvant Immunotherapy for Head and Neck Cancer: Low Tumor PD-L1 Expression - IT-MATTERS – RCT By: Eyal Talor*, Philip Lavin, Jozsef Timar, Dusan Markovic, John Cipriano
Slide 2: Conflict of Interest Statement
Conflict of Interest Statement *Dr. Talor (PhD) • CSO, CEL-SCI Corporation, inventor and developer of Leukocyte Interleukin, injection (Immunotherapy) Dr. Lavin (PhD) • Independent Biostatistician consultant to CEL-SCI – Principal/Founder Lavin Consulting LLC Prof. Dr. Timar (MD, PhD, DSc) • Academi
Slide 3: LI-Multikine Immunotherapy: What, When, How, Who, & Why
LI-Multikine Immunotherapy: What, When, How, Who, & Why LI-Multikine is a mixture of cytokines and other small molecules with immune-cells Natural boosting capacity, that naturally occur in our bodies First-line LI-Multikine is given right after diagnosis, before surgery, when the immune system is (
Slide 4: What is LI-Multikine?
What is LI-Multikine? • LI-Multikine is a cGPM Manufactured investigational immunotherapy - a mixture of pro- inflammatory (and other) cytokines. • A combination of proteins derived from the stimulation of allogeneic normal blood- donor PBMCs, in short-term culture. • LI-Multikine is available off-t
Slide 5: 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 6: Mechanistic Support For The LI-Multikine Mechanism of Action Definition
Mechanistic Support For The LI-Multikine of Action Definition Target Population Mechanism • LI-Multikine activated immune cells potentially may: N0 means intact local immune architecture can • Recognize and present to immune cells or bind mount a more effective to multiple (different) antigens (or r
Slide 7: RCT LI-Multikine Phase 3 Trial Design
RCT LI-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 8: RCT - Phase 3 Locally Advanced OSCC and Soft Palate: LI-Multikine Treatment Timing and Regimen
RCT - Phase 3 Locally Advanced OSCC and Soft Palate (ITT=923): LI-Multikine Treatment Timing and Regimen LI-Multikine administered prior to the current Standard of Care, delivered locally via injections around the tumor and adjacent lymph nodes for three consecutive weeks, 5 days per week before sur
Slide 9: “First – Do No Harm” - LI-Multikine Demonstrated Excellent Safety Profile
“First – Do No Harm” - LI-Multikine Demonstrated Excellent Safety Profile • No LI-Multikine-related deaths. Percentage of subjects with AEs by study time period (N=879) 100% • Only two withdrawls due to LI- 90% LI-Multikine, 82.5% Control, 90.2% Multikine (pyrexia, oedema) both 80% 70% known and lis
Slide 10: Target Population for LI-Multikine: Clearly Defined And Well-Understood
Target Population for LI-Multikine: Clearly Defined And Well-Understood • Locally Advanced primary head and neck patients who present with: • No lymph node involvement (N0) (via PET-CT/MRI) • Low PD-L1 tumor expression (via biopsy) • Physicians routinely assess these features at baseline as part of
Slide 11: Pre-Surgical Responses In The Phase 3 Trial
Pre-Surgical Responses In The Phase 3 Trial • A pre-surgical response is a significant change in disease before surgery. • These emerged just a few weeks after treatment onset. • We saw two kinds of responses in the Phase 3 trial: • “Tumor reductions” - There were “reductions” in the size of the tum
Slide 12: Significant Increase In PSRs/PSDs Across The Phase 3 Study ITT Population (n=923)
Significant Increase In PSRs/PSDs Across The Phase 3 Study ITT Population (n=923) 12
Slide 13: PSRs/PSDs Resulted In Significantly Improved Survival Across The Phase 3 Study ITT Population
PSRs/PSDs Resulted In Significantly Improved Survival Across The Phase 3 Study ITT Population (n=923) 13
Slide 14: Higher PSR/PSD Rates In The Target Population (n=114)
Higher PSR/PSD Rates In The Target Population (N0 [no ECS], tPD-L1 TPS <10) (n=114) 14
Slide 15: Cellular Biomarkers and Ranges Pre-defined for Pathology Immunohistochemistry
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 14
Slide 16: Pathology IHC : Clearly Defined And Well-Understood
Pathology IHC : Clearly Defined And Well-Understood (Top row LI-Multikine treated; Bottom row Control) *3,3′-diaminobenzidine (DAB) 16
Slide 17: 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 18: Immunohistopathology Supports MoA of LI-Multikine
Immunohistopathology Supports MoA of LI-Multikine Significant Outcomes All Favoring LI (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 Grou
Slide 19: Overall Survival In The LI-Multikine Target Population
Overall Survival In The LI-Multikine Target Population (LA OC + Soft Plate SCC, N0 [no ECS], tPD-L1 TPS <10) 5-year survival 73% LI-Multikine vs 45% Log Rank p=0.0015 Control HR 0.35 (95% CI 018, 0.66; Wald p=0.0015) 19
Slide 20: LI-Multikine Treatment Cut The Risk Of Death At 5-years In Half In The Target Population
LI-Multikine Treatment Cut The Risk Of Death At 5-years In Half In The Target Population 60% Risk of death, 55% 5-year risk of death Reduction in death risk 50% 40% Control Risk of death, 30% 27% 20% Multikine 10% 0% 20
Slide 21: In Summary
In Summary Oral Cavity + Soft Palate (N0, tPD-L1 TPS <10) (n=114) ✓ 73% overall survival (OS) for LI-Multikine vs 45% in the control, at 5 years ✓ 28% increase in 5-year absolute overall survival (OS), Log Rank p = 0.0015 ✓ 5-year risk of death Reduced by ½ 55% (Control) to 27% (LI-Multikine) ✓ Haza
Slide 22: Thank You
Thank You The Study Sponsor and authors wish to thank: • The patient volunteers and their families • The dedicated Investigators and staff (in 23 countries on three continents) • The CROs who helped conduct and monitor the study • The international independent DSMB for safety oversight • The Central