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Cel-Sci Investors Presentation Cel-Sci Investors Presentation Presentation Transcript

  • CEL-SCI Corporation NYSE AMEX: CVM Geert Kersten Chief Executive Officer 8229 Boone Boulevard, Suite 802 Vienna, VA 22182, USA Phone: (703) 506-9460
  • Forward-Looking StatementsStatements made during the course of this presentation that state the Company’sor management’s intentions, hopes, beliefs, expectations or predictions of thefuture are forward-looking statements. It is important to note that the Company’sactual results could differ materially from those projected in such forward-lookingstatements. This presentation only highlights some of the progress CEL-SCI hasmade to date. It is not meant to be a complete document as it forms only thevisual basis of the company’s presentation.Additional information in general and concerning factors that could cause actualresults to differ materially from those in the forward-looking statements iscontained from time to time in the Company’s SEC filings, including but notlimited to the Company’s report on Form 10-K for the year ended September 30,2011. Copies of this presentation may be obtained by contacting the Company. 2
  • Explanatory StatementMultikine is the trademark that CEL-SCI has registered for this investigationaltherapy, and this proprietary name is subject to FDA review in connection withour future anticipated regulatory submission for approval. Multikine has not beenlicensed or approved for sale, barter or exchange by the FDA or any otherregulatory agency. Similarly, its safety or efficacy has not been established forany use. Moreover, no definitive conclusions can be drawn from the early-phase,clinical-trials data summarized in this presentation involving the investigationaltherapy Multikine (Leukocyte Interleukin, Injection). Further research is required,and early-phase clinical trial results must be confirmed in the well-controlledPhase III clinical trial of this investigational therapy that is currently in progress.Each page of this presentation must be looked at in the context of the wholepresentation, not by itself, and is merely meant to be a summary of the full anddetailed information on the Company in its public filings and its website.Potential conclusions could only be drawn if the initial observations in the early-phase studies relating to the potential adverse events associated with Multikineadministration in treating head and neck cancer are confirmed in the wellcontrolled Multikine Phase III clinical study, CEL-SCIs Phase III study iscompleted successfully, and the FDA licenses the product following their review ofall of the data related to Multikine submitted in CEL-SCIs license application. 3
  • CEL-SCI Stock Summary• Name of Company: CEL-SCI Corporation• Location: Washington, D.C. (USA) metro area• Stock symbol: NYSE AMEX: CVM• Shares outstanding: 230 million• Current valuation: About $70 million• Average daily trading volume, last 30 days: About 500,000• 52 week range: $0.27 - $1.05 4
  • Product PipelineCANDIDATE PRECLINICAL PHASE I PHASE II PHASE III SALESMULTIKINEHead and Neck Cancer (first-line)Cervical CancerEnhancement ofradiation/chemotherapyL.E.A.P.S. TechnologyPandemic Flu treatmentRheumatoid Arthritis CEL-2000MalariaViral EncephelitiesHerpes 5
  • Multikine Cancer Immunotherapy Summary of ”What is Multikine”What is Multikine?• Is an investigational immunotherapy drug consisting of 14 cytokines.• Is being tested in a global Phase III clinical trial to determine its effectiveness against advanced primary head and neck cancer (US orphan drug status).• Has a unique mechanism of action.• Is given for 3 weeks BEFORE any other cancer therapies (surgery, radiation and/or chemotherapy) because that would appear to be the best time to produce an effective immune response.• Teva Pharmaceuticals (Israel) and Orient Europharma (Taiwan) are partners and participate in the Phase III trial.• Multikine, once approved for sale, would be mass produced in the Company’s existing manufacturing plant.• Multikine uses the patient’s own tumor antigens to provide specificity for the anti- tumor immune response.• The primary focus of Multikine is to eliminate the micro-metastases, believed to be the cause of cancer recurrence. 6
  • Multikine Cancer Immunotherapy Next Class of Immunotherapy DrugsMultikine represents the next class of generation immunotherapy drugs because:1) Multikine is given before any other cancer therapy – optimal time, biggestmarket.2) Multikine contains both active and passive immunity and therefore does notrequire an outside antigen.3) Multikine is mass produced at the Company’s manufacturing facility. It is NOTmade from the patient’s own blood and/or tumor – reasonable price with excellentprofit margin. 7
  • Clinical Development of MultikineMultikine – Lead Indication is First-Line H&N Cancer• Locally advanced primary head & neck cancer patients• Current standard of care as defined by the NCCN Clinical Practice Guidelines in Oncology, Head and Neck Cancer, is:  Surgery followed by Radiation Therapy (+/- Chemo)• Upon the success of the Multikine Phase III study and approval by the FDA and other regulatory agencies, one would expect that doctors will elect to give Multikine to head and neck cancer patients ahead of surgery.Multikine Treatment Surgery Radiation Therapy (+/- Chemo) 8
  • Initial target marketHead and neck cancer:6% of all cancers, or about 650,000 new cases annually worldwide, 150,000 ofthose are in the US and EU. About 2/3 of these head and neck cancer patients haveadvanced primary disease. • Unmet medical need. • Uniform standard of care world-wide for advanced primary head and neck cancer. • Approval could potentially lead to Multikine becoming part of the standard of care treatment along with the first treatment of surgery, radiation and chemo (first line standard of care). • Multi-billion $ market opportunity. • Likelihood of world-wide approval on successful single Phase III study. 9
  • Multikine “Proof of Concept” Phase II Results• Summary of “Proof of Concept” Phase II results using the same treatment schedule as is being used in Phase III study Multiple studies were conducted to select the final treatment regimen  Improvement in overall survival at 3.5 years (J. Oral Oncology; n=19)  Long term survival in Multikine treated group (n=19) was 63.2%  Long term survival of all patients in literature (n=7,294) was 47.5%  No Severe Adverse Events related to Multikine (All Phase I/II Studies to date: n=220)  No deaths related to Multikine (All Phase I/II Studies to date: n=220)  Phase I/II studies conducted in US, Canada, Europe and Israel Impact of Multikine (after 3 week treatment, PRIOR to surgery)  12% of the patients had no tumor after only Multikine treatment (by pathology) (ASCO and Journal of Clinical Oncology; MK Treated n=19: 17 SCC; CR 2, PR 4 by RECIST)  50% reduction in the number of tumor cells after only Multikine treatment (by pathology) (Journal of Clinical Oncology; n=19) Additional and confirmatory survival, pathology and tumor response data published in: – Archives of Otolaryngology August 2003 (Feinmesser et al) (n=12) – The Laryngoscope Dec. 2003 (Timar et al) (n=54) 10
  • Multikine Clinical Development Phase I-II Safety Profile• In safety and dose finding studies:During the early investigational phase, in Phase I and Phase II clinical trials ina total of over 220 subjects who received the investigational therapy Multikinein daily doses of 200 to 3200 IU as IL-2 (over 2-3 weeks in Phase II and up toa few months in early-Phase I), no serious adverse events were reported bythe clinical investigators as being expressly due to administration of thisinvestigational therapy Multikine. Adverse events which were reportedincluded pain at the injection site, local minor bleeding and edema at theinjection site, diarrhea, headache, nausea, and constipation. No "abnormal"laboratory results were reported following Multikine treatment - other thanthose commonly seen by treating physicians in this patient population -regardless of Multikine administration. Similarly, in these early-phase clinicalstudies in patients, there was no reported increased toxicity of follow-ontreatments as a result of Multikine administration. No complications followingsurgery (such as increased time for wound healing) were reported. 11
  • MultikineMultikine Potential Treatment Effect – Changes in Tumor Microenvironment 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 Non-Multikine treated: Lack of necrosis in the epithelial nests of OSCC Multikine treated: Entire cancer nest is necrotic and filled with debris and leukocytes This complete destruction of the tumor was seen in only 12% of the patients * Modified from Timar et al., Journal of Clinical Oncology 23(15) May 20, 2005 12
  • Multikine Mechanism of action Tumoricidal / Tumoristatic Multikine (perilymphatic) Necrosis Local / Regional (e.g., TNF) Antigen Presenting Cells (Dendritic Cells, Macrophages) Micro Metastases Lymph Neutrophils Nodes Multikine Tumor (peritumoral) CD4 + T Cells CD8 + T Cell Micro Chemotactic Metastases (e.g., IL-6, IL-8) Lymphoproliferative (e.g., IL-2)Source: Timar et al., Journal of Clinical Oncology 23(15) May 20, 2005 13
  • Multikine Treatment Effect A Paradigm Shift in Tumor Microenvironment CD4 MK Treated (n=17)MK Treated CD4/CD8 > 2.5 CD8 P<0.05 [+2 CR] P<0.05 CD4 Control (n=20) Control CD4/CD8 < 0.5 CD8 0 50 100 150 Density of cells/HPF (Mean ± SEM) Multikine Treatment Effect on Host CD4 and CD8 Tumor Infiltrating Cell Density in OSCC (Locally Advanced Primary H&N Cancer) * Talor et al., ASCO Annual Meeting Proceedings 22(14S): 189S, 2004 Timar et al., Journal of Clinical Oncology 23(15) May 20, 2005 14
  • Multikine T cellsHow Multikine circumvents the tumor defense mechanisms! LYMPHCD8+ T-cells and NK cells not treated with Multikineare “blocked” by the tumor. Therefore they are unable NODEto trigger a potential anti-tumor immune response. No potential anti- No potential anti- T tumor response DC cells tumor response DC Class I Class I NK Tumor CD8 Cells CTL Inhibition No Activation NKR Class II ? 15
  • Multikine T cellsHow Multikine circumvents the tumor defense mechanisms! LYMPHFollowing Multikine administration tumor-specificactivated CD4+ helper T cells “rescue” and activate NODEtumor residing NK cells, which then trigger a potentialanti-tumor response. T DC cells No potential anti- DC tumor response Class I Class I NK Tumor CD8 Cells CTL (Activated) No Activation NKR Class II ? IL-2, IFN-γ TCR CD4 (Activated) Help (Including MIP-1α) IL-2, 16 IFN-γ
  • Multikine: Phase III trial One pivotal Phase III trial• Advanced primary (not yet treated) head & neck cancer represents an unmet medical need (about 50% of the patients die within 3 years following treatment) with minimal progress over the last 50 years.• FDA, Canadian and seven other regulators on three continents gave go-ahead to Multikine Phase III study.• Effort was led by CEL-SCI’s Senior VP of Regulatory Affairs, John Cipriano, MS, RPh, who was the prior Deputy Director, Division of Biologics Investigational New Drugs, Office of Biologics Research and Review at the FDA.• Orphan drug designation in the US codifies that only one trial should be needed. 17
  • Multikine Phase III trial Phase III Trial• USA, Canada, Hungary, Poland, Russia, Israel, India and Taiwan. Started the study in all 8 countries to date.• Planned enrollment: 880 patients.• To date, 36 centers have passed SIV and are screening/accruing patients; goal is to reach about 50 centers in total.• Partners in Phase III study: Israel - Teva Pharmaceuticals. Taiwan- Orient Europharma of Taiwan.• Primary endpoint = 10% improvement in overall survival.• Event-driven study.• NIH participation for measurement of genetic and molecular markers of patients. 18
  • Multikine: Phase III trial Study Design and Statistical ParametersMethodology:• Phase III open-label, randomized, controlled, multi-center study.  Enroll about 880 patients to have about 780 evaluable patients.  Reference Therapy: Standard of Care = Surgery + Radiation +/- Chemotherapy.  Three (3) week administration of Multikine + standard of care and median three year follow-up (event–driven).  Primary end point: Overall Survival.Statistics:• 80% Power; 95% confidence - to show a 10% Overall Survival advantage. 19
  • Multikine Phase III Schematic Randomization and Treatment of Enrolled Patients R Group 1 (approx. 377 pat.) RTx Standard of Care S** E A U Radiotherapy (60 - 70 Gy, N N 3 30 - 35 fractions over 6 - 7 Weeks) D Group 2 (approx. 377 pat.) R R Multikine 5X/week for 3 weeks -OR- O 3 (+ CIZ*) G O L M E CRTx I R L Z Group 3 (approx. 125 pat.) *** High Risk: Concurrent Multikine 5X/week for 3 weeks radiochemotherapy (60 – 70) Gy, 30 - 35 1 Y fractions, over 6-7 weeks + IV cisplatin E (No CIZ) (Dose 100 mg/m2) 1X per week on first day of weeks 1, 4, 7 of RTx The overall survival comparison will be made between groups 1 and 2. The primary purpose of the smaller Group 3 is to gain more information on the mechanism of action of Multikine. CIZ is added to decrease tumor suppressor mechanisms and thereby increase Multikine effectiveness.* CIZ: Cyclophosphamide 300 mg/m2 (x1,IV, day -3); Indomethacin 25mg tid, po (day 1 to 24 hrs prior to surgery) + 15-45mg Zinc (as Multivitamin) i.d., p.o.** Surgery: complete surgical resection of primary tumor and any positive lymph nodes.*** High risk patients are defined as those with: positive surgical margins, 2 or more clinically positive nodes, or extra capsular nodal spread (any or all of the above).
  • Multikine Phase III trialPurpose of Multikine + CIZ and Multikine without CIZ study arms CIZ Arm - CIZ included to enhance Multikine activity • Cyclophosphamide - low (non-chemotherapeutic) dose decreases tumor suppressor cells (Berd Cancer Res. 1984, 1986; North J. Exp. Med 1982; Kameda Int. J. Immunother. 1992; Timar JCO 2005) • Indomethacin - Low dose indomethacin retards the secretion of prostaglandin E-2 (PGE-2) by tumor residing monocytes/macrophages a potent inhibitor of lymphocyte proliferation (Feinmesser Arch Otolaryngol H&N Surg 2003). • Zinc - known to increase activation of thymus factors associated with increased T cell activity. Non-CIZ Arm – Included to attempt to determine the extent of the contribution of CIZ to Multikine effects. 21
  • Multikine Phase III trialLarge Phase III Study Designed To Position Multikine As Part of the Standard of Care • World-wide: Eight countries on three continents: North America, Europe, Asia. • Largest pathology study ever done in head and neck cancer. • Partners enrolling in the study: Israel - Teva Pharmaceuticals. Taiwan- Orient Europharma of Taiwan. • Subjects enrolled in approximate proportion to world distribution of the disease. • Expect rapid enrollment and relatively fast results. • NIH participation for measurement of genetic and molecular markers of patients (personalized medicine). 22
  • Multikine Phase III trialPreparation and Management of Large Global Phase III Trial Attention to detail is key: • Radiation qualifications conducted by RPC (MD Anderson Cancer Center, The University of Texas). • Central Imaging qualifications conducted by a leading US company specializing in Clinical Trial Imaging. • Central Pathology Laboratory. • All study drugs (e.g. chemotherapy) are sourced from same place only. • Cold shipping around the world provided by leading US company with fully validated containers. 23
  • Multikine IP Intellectual property protectionPatents and other protection for Multikine: • Composition of matter patent protection until 2024. • US Patent # 6,896,879 and European Patent # 1,773,395. • Additional pending patent applications world-wide. • Orphan drug designation in US gives 7 year market exclusivity. • Proprietary manufacturing and quality control know-how (most important since Multikine is a complex biologic and practically impossible to copy). 24
  • Multikine Manufacture Steps to improve risk/reward• Commercial sized $25 million manufacturing facility outside Baltimore, Maryland, USA.• Facility includes True Cold Fill (+4°C) capability to avoid loss of biological activity during fill.• Successful EU Audit in Fall 2010: CEL-SCI Corporations Manufacturing and Laboratory Operations Deemed Compliant with GMP Requirements Following Audit by European Union Qualified Person.• Facility will supply Phase III study and subsequent commercial sale.  Current capacity about 20,000 treatments annually.  Fully built out capacity about 60,000 treatments annually. 25
  • Multikine Phase III partners Steps to improve shareholder reward/risk prospectsRetain head and neck cancer indication rights for the US and Europe, offeringshareholders the full upside potential.Additional partnerships are anticipated outside of US/EU and for other tumorindications.CEL-SCI’s current partners funding and participating in Phase III trial: • Teva Pharmaceuticals of Israel (Territories: Israel and Turkey, added Serbia and Croatia in summer of 2011).  Teva will run and pay for part of the Phase III trial in Israel.  Revenue share upon sale. • Orient EuroPharma (OEP) of Taiwan (Territories: parts of the Far East, not Japan or China).  OEP will run and pay for part of the Phase III trial in Taiwan.  Revenue share upon sale. 26
  • Key Management Team BusinessMaximilian de Clara • Founder, President and Chairman of the Board, CEL-SCI Corporation, 1983 - Present • Personally funded research in the fields of biotechnology and biomedicine • Awarded the "Pour le Merit" honorary medal of the Austrian Military Order "Merito Navale" • Awarded the Honor Cross of the Austrian Albert Schweitzer SocietyGeert Kersten, MBA, JD • Chief Executive Officer, CEL-SCI Corporation, 1987 – PresentPatricia B. Prichep • Senior Vice President of Operations, CEL-SCI Corporation, 1992 – Present • Manager, Quality and Productivity, National Association of Securities Dealers (NASD), Rockville, MD, 1989 - 1992 27
  • Key Management Team ScienceEyal Talor, PhD • Chief Scientific Officer 2010 – Present • Senior Vice President of Research and Manufacturing, CEL-SCI Corporation, 1994 – Present • Director of R&D and Clinical Development, CBL, Inc., Baltimore, MD • Principal Scientist - Project Director, Clinical Laboratory Director, SRA Technologies, Inc. • Adjunct Professor at Johns Hopkins University Medical InstitutionsJohn Cipriano, MS, RPh • Senior Vice President of Regulatory Affairs, CEL-SCI Corporation • Deputy Director, Division of Biologics Investigational New Drugs, Office of Biologics Research and Review, Food and Drug Administration (FDA) • Deputy Director, IND Branch, Division of Biologics Evaluation, Office of Biologics, Food and Drug Administration (FDA)Daniel Zimmerman, PhD • Senior Vice President of Research, Cellular Immunology, CEL-SCI Corporation • L.E.A.P.S. Technology Inventor • Founder and President, CELL-MED, Inc., 1987 – 1995 • Scientist, Sr. Scientist, Technical Director and Program Manager, Electronucleonics, Inc., 1973 – 1987 28
  • Key Management Team ScienceWilliam “Brooke” Jones • Vice President of Quality Assurance, CEL-SCI Corporation, 1999 – Present • Director of Quality Control and Quality Assurance at the Systemix Facility in Lyon, France, 1994 - 1997 • Management positions at Biogen, 1983 - 1991 • Head of GMP Compliance at Fort Detrick, NCI- Frederick Cancer Research Center, 1979 - 1983Todd Burkhart • Vice President of Manufacturing/Facilities & Commercial Operations, CEL-SCI Corporation, 2010 – Present • 30 years of experience in the manufacture and process development of biologics, medical devices and other Active Pharmaceutical Ingredients (APIs) • Previously ran a number of major pharmaceutical facilities at companies such as Cephalon, Human Genome Sciences and Univax Biologics 29
  • Thank You