Cel-sci Corporation · AMEX:CVM
Cel-sci — Technical Presentation (September 2019)
40 slides from Cel-sci's technical presentation, September 2019
Slide 1: Multikine (Leukocyte Interleukin, Inj.) Cancer Immunotherapy
Multikine (Leukocyte Interleukin, Inj.) Cancer Immunotherapy A Multi-Targeted Approach to Cancer Treatment CEL-SCI Corporation Eyal Talor, PhD 8229 Boone Boulevard, Suite 802 NYSE American: CVM Chief Scientific Officer Vienna, VA 22182, USA - Phone: (703) 506-9460
Slide 2: Forward Looking Statements
Forward Looking Statements This presentations contains “forward-looking safety profile and related adverse events of our and uncertainties, the forward-looking events statements” within the meaning of the Private product candidates; our ability to manufacture and circumstances described in this pres
Slide 3: FDA Disclaimer Statement
FDA Disclaimer Statement Multikine is the trademark that CEL-SCI has Potential conclusions could only be drawn registered for this investigational therapy, if the initial observations in the early-phase and this proprietary name is subject to FDA studies relating to the potential adverse events revi
Slide 4: Product Candidates: Indications and current stage of development
Product Candidates Indications and current stage of development Candidate Preclinical Phase 1 Phase 2 Phase 3 Marketing approval MULTIKINE Head and neck cancer Neoadjuvant therapy in patients with squamous cell carcinoma of the head and neck (administered right after diagnosis, before the first stan
Slide 5: Working to Create the First Cancer Drug to Be Administered Before Surgery
Working to Create the First Cancer Drug to Be Administered Before Surgery Multikine is administered to previously untreated, newly diagnosed head and neck cancer patients right after diagnosis for three weeks before the current standard of care treatments (surgery followed by radiation or combined r
Slide 6: Why Head and Neck Cancer as a First Target?
Why Head and Neck Cancer as a First Target? Advanced primary (not yet treated) head and neck cancer was selected as the first indication because: ● Represents a large, unmet medical need ○ Last FDA approval of a therapy for advanced primary head and neck cancer was many decades ago (unmet medical ne
Slide 7: Head and Neck Cancer Market
Head and Neck Cancer Market ● World-wide about 650,000 new head and neck cancer patients diagnosed per year U.S. Europe About 60,000 new patients p.a. About 105,000 new patients p.a. ● About 90% of head and neck cancers are squamous cell carcinomas ● Following approval, Multikine would be used in ne
Slide 8: We Believe That Manufacturing is a Strategic Asset
We Believe That Manufacturing is a Strategic Asset ● Multikine is a complex biologic requiring special manufacturing ● We spent over 10 years and ~$80 million developing and validating the manufacturing process ● We explored the option of hiring an outside company to manufacture Multikine for Phase
Slide 9: State-of-the-Art Facility & Proprietary Manufacturing Process
State-of-the-Art Facility & Proprietary Manufacturing Process: Potential Barriers to Competition ● cGMP and BSL-1 facility ○ Built specifically for Multikine – but could easily be Multi-use ○ State-of-the art facility ○ Over 73,000 ft2 of Manufacturing and R&D space available ○ About 35,000 ft2 full
Slide 10: Multikine Supplies The Cytokines Needed for Tumor Rejection
Multikine Supplies The Cytokines Needed for Tumor Rejection Major Cytokine(s) and other Cellular Products in Multikine ● The cytokines listed to the right are those known to be present in Multikine IL-1 α IL-6 ● Research at the US National Institutes of Health (NIH) has shown that the cytokines (sho
Slide 11: 11 Clinical Studies Have Been Completed Across Indications
11 Clinical Studies Have Been Completed Across Indications Phase Indication No. of subjects Countries Published paper Phase 1/2 Head & Neck Cancer Recurrent 16 U.S. & Canada N/A Pilot Study Head & Neck Cancer Recurrent 4 U.S. Arch Otolaryngol Head and Neck Surgery Phase 1/2 Head & Neck Cancer Pre-su
Slide 12: Multikine Exhibits a Consistent Safety Profile Across Phase 1 and 2 Studies
Multikine Exhibits a Consistent Safety Profile Across Phase 1 and 2 Studies ● Multikine is administered in supra-physiological doses locally (near or close) to the tumor and the adjacent lymph nodes. The known cytokines contained in Multikine are present in amounts well below any published levels th
Slide 13: NCCN Guidelines – Standard of Care
NCCN Guidelines – Standard of Care 13
Slide 14: The Timing of Multikine Treatment Regimen
The Timing of Multikine Treatment Regimen Phase 3 Advanced Primary Head and Neck Cancer Current 1st Line SOC* 4 weeks Radiotherapy Surgery or Chemo / Radiotherapy Diagnosis Multikine Treatment (3 weeks) Pathology Pathology Proposed New 1st Line SOC* (upon Phase 3 success) * Standard of Care 14
Slide 15: Mechanism of Action Stimulates an Immune Response at the Injection Site
Mechanism of Action Stimulates an Immune Response at the Injection Site Multikine (perilymphatic) Tumoricidal / Tumoristatic Local / Regional Necrotic (e.g., TNFα) Antigen Presenting Cells (Dendritic Cells, Macrophages) Micro Metastases Neutrophils Tumor CD4 + T Cells Lymph Nodes Multikine (peritumo
Slide 16: Dendritic cells (CD1a) Infiltrate Redistribution – Phase 2
Observed Effects Following Multikine Treatment Regimen – Phase 2 Dendritic cells (CD1a) Infiltrate Redistribution* [Locally Advanced Primary H&N Cancer] 10.0 Control (n=20) MK (n=17) cells/HPF (mean + SEM) 7.5 [+2CR] density of CD1a+ 5.0 2.5 0.0 R1 R2 R3 R1 = Tumor Surface R2 = Tumor Center R3 = Tum
Slide 17: Observed Effects Following Multikine Treatment Regimen – Phase 2
Observed Effects Following Multikine Treatment Regimen – Phase 2 An Apparent Shift in Tumor Microenvironment MK Treated (n=17) CD4 MK Treated CD4 / CD8 > 2.5 CD8 P<0.05 [+2 CR] P<0.05 CD4 Control (n=20) Control CD8 CD4 / CD8 < 0.5 0 50 100 150 Density of cells/HPF (Mean ± SEM) Multikine Treatment Ef
Slide 18: Increased Neutrophil (MPX) Infiltrate
Observed Effects Following Multikine Treatment Regimen – Phase 2 Increased Neutrophil (MPX) Infiltrate* [Locally Advanced Primary H&N Cancer] P<0.05 20 Control (n=20) P<0.05 MK (n=17) 15 [+2CR] density of PMN/HPF (mean + SEM) 10 5 0 R1 R2 R3 R1 = Tumor Surface R2 = Tumor Center R3 = Tumor Stroma Int
Slide 19: Non-Multikine Treated vs. Multikine Regimen Treated – Phase 2 Results
Non-Multikine Treated vs. Multikine Regimen Treated – Phase 2 Results 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 regimen treated Lack of necrosis in the e
Slide 20: Conventional Treatment (SOC)
Conventional Treatment (SOC) 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 Lack of necrosis in the epithelial nests of OSCC * Adapted from Timar et al: Journal of Clin
Slide 21: Multikine – How it Helps the Immune System Kill Cancer Cells
Multikine – How it Helps the Immune System Kill Cancer Cells How Multikine is Designed to Circumvent the Tumor Defense Mechanisms In patients not treated with Multikine, CD8+ T-cells and NK cells are “blocked” by the tumor. Therefore they are unable to trigger a potential anti-tumor immune response.
Slide 22: Multikine Treatment Regimen
Multikine Treatment Regimen Oral Squamous Cell Carcinoma (Locally Advanced Primary H&N Cancer) Histological appearance of necrosis in Oral Squamous Cell Carcinoma (OSCC) [HE staining]: Multikine regimen treated Entire cancer nest is necrotic and filled with debris and leukocytes * Adapted from Timar
Slide 23: Multikine – How it Helps the Immune System Kill Cancer Cells
Multikine – How it Helps the Immune System Kill Cancer Cells How Multikine is Designed to Circumvent the Tumor Defense Mechanisms T cells Following Multikine administration, tumor-specific activated DC CD4+ (helper T) cells “rescue” and activate tumor-residing Lymph NK cells, which then trigger a po
Slide 24: Multikine Pathology and other Results - Final Phase 2 Study
Multikine Pathology and other Results - Final Phase 2 Study The Final “Proof of Concept” Phase 2 study (21 treated patients and 20 controls), following multiple Phase 2 studies that tested different treatment regimens, selected the best treatment for patients. The Multikine treatment regimen in this
Slide 25: Multikine Increased Overall Survival (OS) by 33%
Multikine Increased Overall Survival (OS) by 33% Approximately three years after the same “Proof of Concept” Phase 2 study we obtained the patients’ and their families’ consents for a survival follow-up Survival results in this Final “Proof of Concept” Phase 2 study were compared to results from 55
Slide 26: How Does the Multikine Patient Population Differ from the Checkpoint Inhibitor Population?
How Does the Multikine Treatment Patient Population Differ from the Checkpoint Inhibitor Patient Population? The checkpoint inhibitor Keytruda® by Merck was approved for head and neck cancer in June 2019, but it was approved for a very different patient population than that which CEL-SCI is pursuing
Slide 27: IT-MATTERS Global Phase 3 Head & Neck Cancer Study
IT-MATTERS Global Phase 3 Head & Neck Cancer Study CEL-SCI Corporation Eyal Talor, PhD 8229 Boone Boulevard, Suite 802 NYSE American: CVM Chief Scientific Officer Vienna, VA 22182, USA - Phone: (703) 506-9460
Slide 28: Developing a Novel Immunotherapy as First-Line Treatment for Advanced Primary Head and Neck Cancer
Phase 3 Study of Multikine® (Leukocyte Interleukin, Injection)* NCT# 01265849 Developing a Novel Immunotherapy as First-Line Treatment for Advanced Primary Head and Neck Cancer 8229 Boone Blvd., Ste 802 Vienna, VA22182 * Multikine is the trademark that CEL-SCI has registered for this investigational
Slide 29: Multikine H&N Cancer Phase 3 Study Summary
Multikine H&N Cancer Phase 3 Study Summary ● Open-label Phase 3 Study ● Started enrolling early 2011, fully enrolled by September 2016 ● 928 patients enrolled in the study ● The study is event driven. We are waiting for 298 events to occur among the two main groups (combined number of patients about
Slide 30: Multikine Phase 3 Trial Design
Multikine Phase 3 Trial Design Study Conducted in 24 Countries on 3 Continents Location Countries North America USA and Canada Europe UK, Austria, France, Spain, Italy, Hungary, Poland, Russia, Ukraine, Belarus, Serbia, Croatia, Bosnia, Turkey, Romania Asia / Far-East Israel, Taiwan, Malaysia, Phili
Slide 31: Multikine Phase 3 Trial Design: Randomization and Treatment
Multikine Phase 3 Trial Design Schematic: Randomization and Treatment of Enrolled Patients Current 1st Line SOC Group 1 Multikine 5X/week for 3 weeks (+ CIZ*) RTx 3 Radiotherapy (60 - 70 Gy, 30 - 35 fractions over 6 - 7 Weeks) RANDOMIZE SURGERY** ENROLL -OR- 1 Group 2 Multikine 5X/week for 3 weeks (
Slide 32: Head and Neck Tumors of Interest for this Phase 3 Study
Head and Neck Tumors of Interest for this Phase 3 Study ● Oral Cavity ○ Tongue (oral portion only) ○ Floor of mouth ○ Cheek ● Soft Palate 32
Slide 33: Standard of Care for Advanced Primary SCCHN
Standard of Care for Advanced Primary SCCHN ● Definitive Surgery – with curative intent ● Postoperative Radiation Therapy ● Radiotherapy + concurrent Chemotherapy for High-Risk Patients Source: NCCN Guidelines * SCCHN – Squamous Cell Carcinoma of the Head and Neck 33
Slide 34: Disease Stages Eligible for Multikine Trial
Disease Stages Eligible for Multikine Trial ● T1 N1-2 M0 ● T2 N1-2 M0 Disease Stage III and IVa ● T3 N0-2 M0 (Advanced Primary Disease) ● T4* N0-2 M0 * T4 is allowed if invasion of the mandible is minimal (defined as <0.5cm as confirmed by CT, and or MRI with CT imaging mandatory) and can be salvage
Slide 35: TNM Classification and Corresponding Tumor Stage
TNM Classification and Corresponding Tumor Stage Primary Tumor Nodal Involvement T1 T2 T3 T4 N0 NE NE Stage III Stage IVa N1 Stage III Stage III Stage III Stage IVa N2 Stage IVa Stage IVa Stage IVa Stage IVa Notes: 1. Stage IVb (T4b primary and all N3 disease) are not eligible. 2. All disease must b
Slide 36: Multikine Study Endpoints
Multikine Study Endpoints ● Primary Endpoint: ○ Overall Survival (10% improvement over SOC alone) ● Secondary Endpoint: ○ Progression Free Survival ○ Local/Regional Control ○ Safety ○ Histopathology of Tumor infiltrate ○ Quality of Life ● Tertiary Endpoint: ○ Tumor Response 36
Slide 37: When Will the Phase 3 Study End?
When Will the Phase 3 Study End? ● Patients are currently being followed for overall survival and other protocol specified endpoints. Two hundred ninety eight (298) events (deaths) must occur among the 2 main comparator groups (almost 800 patients out of the 928 patients enrolled) to be able to asse
Slide 38: Estimated Overall Survival Using the SOC for the Study Population
Estimated Overall Survival (OS) using the SOC for the Study Population Enrolled in CEL-SCI’s Phase 3 Clinical Trial - Using SEER Database Year OS Estimate 95% Confidence Bound 1 71.42% (69.84%, 72.92%) ● Three (3) Year OS – Approximately 47% 2 53.86% (52.09%, 55.59%) ● Five (5) Year OS – Approximate
Slide 39: Phase 3 Study Design - Timing of Multikine Treatment Regimen
Phase 3 Study Design -Timing of Multikine Treatment Regimen Advanced Primary Head and Neck Cancer Current 1st Line SOC* 4 weeks Radiotherapy Usual Drug Development Path Focuses Surgery or Chemo / Radiotherapy on Recurrent Cancer Diagnosis Multikine Treatment Keytruda (3 weeks) Proposed New 1st Line
Slide 40: CEL-SCI Corporation Eyal Talor, PhD Chief Scientific Officer
CEL-SCI Corporation Eyal Talor, PhD 8229 Boone Boulevard, Suite 802 NYSE American: CVM Chief Scientific Officer Vienna, VA 22182, USA - Phone: (703) 506-9460