OTC: LBIO June Manish Singh, PhD (M) (O)

Transcription

1 OTC: LBIO June 2014 Manish Singh, PhD Chairman OO and CEO (M) (O)

2 Forward-looking Statements This presentation contains forward-looking statements that can be identified by such terminology such as expects, potential, suggests, may, or similar expressions. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. In particular, management s expectations regarding future results could be affected by, among other things, uncertainties relating to clinical trials and product development; unexpected regulatory delays or government regulation generally; the Company s ability to obtain or maintain patent and other proprietary intellectual property protection; and competition in general. Forward-looking statements speak only as to the date they are made. The Company does not undertake to update forward-looking statements to reflect circumstances or events that occur after the date the forward looking statements are made. 2

3 What Makes Solid Cancer Difficult to Treat? Cancer originates from dysfunction in the immune system Tumor heterogeneity Redundancy of pathways for tumor escape Immunosuppressive microenvironment Insufficient and weak immune response 4

4 New Breakthrough Solutions Personalized patient specific T-cells with greater potency and persistence Control tumor microenvironment Immunotherapy as the final frontier 5

5 Clinical Regressions in Late Stage Disease Clinical Cancer Research December 15, :

6 Paradigm Shift in Immunotherapy: Delay in Disease Progression to Cure Cancer Vaccines Mixed successes in early stage disease or minimal disease (MRD) Prior attempts to manage bulky disease or fast growing tumors have failed Adoptive T-cell Therapy Effective in early stage as well as advanced disease Curative potential of T-cell therapies CAR-T cells targeting CD-19 against advanced leukemia (UPenn/Novartis) NCI/Rosenberg using TILs to treat metastatic melanoma GALE, IMUC, DNDN, NWBO, ADXS, NLNK BLUE, CELG, NVS, Juno, Kite 7

7 Investment Highlights Leveraging 30 years of Dr. Steve Rosenberg s research and development at NCI to build a T-cell engineering company Lead product with strong phase II data for stage IV metastatic melanoma Addressing large unmet needs (metastatic melanoma and other late stage cancers) Significant value catalysts in near term Large IP portfolio and CRADA with NIH Strong management, board and SAB 8

8 Technology Portfolio TILs - Phase II clinical data in stage IV metastatic melanoma completed at NCI - Applicable to ovarian, cervical, breast, colorectal, lung, head and neck, bladder and other solid cancers Next Gen TILs - Cells enriched for higher potency Lower cost of goods, shorter manufacturing process Phase I clinical trial planned at NCI - Designer T-cells to incorporate cytokines to enhance activity and check-point inhibition to control tumor micro-environment Genetic Engineering of T-cells (Next Gen TILs) Universal approach to all solid tumors to create patient specific T-cells 9

9 Impressive Survival Benefit Even in Second and Third Line Setting (Median Follow-up 62 months) TIL therapy is clearly one of the best treatments for metastatic melanoma - Dr. Patrick Hwu Chairman of Melanoma and Sarcoma MD Anderson Cancer Center Source: Steven A. Rosenberg, James C. Yang, Richard M. Sherry, et al. Immunotherapy with Metastatic Melanoma Using T Cell Transfer Durable Complete Responses in Heavily Pretreated Patients. April 15, 2011 Durable Remission Rates Regardless of Use of Other Therapies 11

10 Summary of Phase I/II Clinical Data at 4 Sites Stage IV Metastatic Melanoma in Patients Refractory to Standard of Care (Second Line Treatment) % Patients Achieving Complete Response % Patients Experiencing an Overall Response Total Patients Treated (Partial + Complete Response) Autologous TILs (ACT) NCI MD Anderson 12% 7% 49% 47% 43 Patients 38 Patients H.L. Moffitt 13% 46% 13 Patients Sheba Hospital (Israel) 10% 48% 42 Patients 136 Patients Consistent and superior clinical experience References: Steven A. Rosenberg, et al. Immunotherapy with Metastatic Melanoma Using T-Cell Transfer Durable Complete Responses in Heavily Pretreated Patients, Clin. Chem. Res., April 15, Dacarbazine: Robert C., Thomas L., Bondarenko I., et. al., N. Engl. J. Med. 364: (2011). IL-2: Sparano, J., Fisher, R., Sunderland, M., et. al., J. Clin. Oncol. 11(10): (1993). Zelboraf : Updated FDA approved prescribing information package insert. Yervoy : FDA approved prescribing information package insert. 12

11 Competitive Landscape Metastatic melanoma (Stage IV) Objective Response Rate Complete Response Rate TILs 50% TILs 12% Anti-PD1 31% Anti-PD1 2% Yervoy 11% Yervoy 2% Zelboraf 48% Zelboraf 2% IL-2 15% IL-2 5% DTIC 15% DTIC 3% *Nivolumab (anti-pd1 mab) is currently in Phase 3 clinical trials. Zelboraf is only indicated for patients who have BRAF mutation. TILs have superior clinical response over other treatments 13

12 Clinical Regressions in Late Stage Disease Objective clinical regressions in patients with metastatic melanoma treated with cell transfer therapy (a) Regression of melanoma metastases in the heart (upper), adrenal (middle) and peritoneal cavity (lower) at 34 months (b) Regression of multiple liver metastases at 60 months (c) Rapid regression of multiple subcutaneous and nodal metastases at 35 months (d) Regression of a large fungating scalp mass at 34 months 14

13 Reduction in Tumors in Majority of Patients (MD Anderson TILs trial summary, n= 31) Radvanyi L G et al. Clin Cancer Res 2012;18:

14 Overall Survival Overall Survival Update on TILs trial at MD Anderson (PI Sponsored Trial) Overall survival N=73 73% of CR/PR patients alive for >4.5 yrs CR/PR Median OS > 24 months PD/SD N=73 Log Rank, P <0.001 Time (months from TIL infusion) Time (months from TIL infusion) Significantly longer OS than anti-pd-1 antibodies in clinic 17

15 TILs Clinical Trials Status Sponsor Indication Phase I Phase 2 Phase III NCI/Lion NCI/Lion MD Anderson NCI/Lion Moffit Cancer Center 2 nd line metastatic melanoma 1 st line metastatic melanoma in combination with Zelboraf 2 nd line metastatic melanoma 2 nd line metastatic melanoma (second generation TILs CD137 sorted) 1 st line metastatic melanoma in combination with Yervoy (BMS) 1 st line metastatic melanoma in combination with anti-pd1 Ab (BMS) Second phase II ongoing Pilot Trials sponsored by Moffit in collaboration with BMS 18

16 Second Phase II Clinical Trial at NCI Two Arm Randomized Trial to Determine Effect of Improved Lymphodepletion on the Clinical Outcomes - Chemoablation + TILs + high-il-2 - Chemoablation + TBI + TILs + high-il-2 Trial enrollment completed (101 patients) Data was presented at AACR in April (Steve Rosenberg) 19

17 Effect of Prior Treatments on Response to TILs Evaluable Objective Response (number of patients %) Any VEM 7 3 (43%) Any IL (63%) Any ipi (54%) Any PD (50%) None (54%) 54% ORR in all patients 20

18 Combination with anti-pd1 has synergistic effect PD-1 mab enhances TIL proliferation & tumor rejection Source: Peng, et al. Cancer Res Increased accumulation of pmel-1 T cells to tumor sites and enhanced anti-tumor immune response in mice receiving ACT combined with anti-pd-1 antibody treatment. Tumor growth curve of B16 tumorbearing mice receiving anti-pd-1 Ab with or without adoptive T cell transfer (N=5 per group). 21

19 Next Generation TILs Genetic engineering of TILs - Expression of certain cytokines to increase potency - Modulation of PD-1/CTLA-4 on cell surface - Persistence over longer time - Shorter manufacturing - Lower COGS - Stronger IP protection Pre-sorted TILs - Pick higher potency TILs - Need lower cell numbers - Shorter manufacturing - Lower COGS - Stronger IP protection Both strategies lead to cheaper and better product 22

20 Metastatic Melanoma: Large Unmet Need Blockbuster Market Opportunity Stage IV metastatic melanoma (MM) ~8,000-9,000 stage IV MM patients annually in US (1) ~10,000-12,000 stage IV MM patients annually outside of US ~20% die before treatment or are not candidates for ACT/TIL therapy Total Available MM Market on Annual Basis 6,400 7,200 in US 8,000 9,600 ex-us 50% market penetration Reimbursement of $200K $1 Billion Peak Sales Potential of TIL therapy* * Projected Melanoma Market over $4 Billion by 2018 (Appendix) (1) National Cancer Institute

21 TIL Manufacturing 2 cm diameter GMP MANUFACTURING FACILITY T +IL-2 T Excise Tumor Overnight 1-3 mm 3 fragments T Bulk TILs (>75M) T Initial TIL Culture (Pre-REP) 3 weeks Rapid Expansion Protocol (REP) 2 weeks +IL-2 +OKT3 +feeder cells IV infusion + IL-2 T T T T T Overnight T T T Infusion bags Final TILs (>50B) 24

22 Key Agreements Cooperative Research and Development Agreement with Dr. Steven Rosenberg, Chief, Surgery Branch, National Cancer Institute Exclusive rights to new adoptive cell therapy technologies for the treatment of metastatic melanoma Conduct clinical trials at the NCI Access to all clinical data, manufacturing data, and SOPs Background Intellectual Property License Worldwide non-exclusive license for adoptive cell therapy technologies from National Institutes of Health Process development and scale-up agreement 22

23 Upcoming Milestones TIL Combination Trials Updated Phase 1 results for TILs with Zelboraf (NCI) Initiate Phase I Anti-PD1 combination trial (Moffitt) Phase I data on IPI combination trial (Moffitt) Next Generation TILs IND next-gen T cells Complete license for next-gen T cells TILs (1 st Generation) Update Phase II (AACR) IST MD Anderson (ASCO) Company IND for Phase II Cumulative Burn Clinical Trials Manufacturing Development R&D Q1 14 Q2 14 Q3 14 Q4 14 Q1 15 $2 M $3 M $3.5 M Nasdaq Listing New R&D Labs Exclusive IP 1 st Gen G&A $1.5 M $2 M $4 M $7 M $10 M 27

24 Management Team Manish Singh, PhD, MBA Chairman and CEO Ex-CEO of ImmunoCellular Therapeutics (IMUC) California Technology Ventures, Cell Genesys, Viagene (acquired by Chiron), Genetic Therapy Inc. (acquired by Novartis) Elma Hawkins, PhD, MBA Head of Clinical Development Michael Handelman, CPA CFO James Bender, PhD, MPA VP, Product Dev and Manufacturing Over 30 years of experience ImmunoCellular Therapeutics, Antigenics, ADVR, Genzyme, Warner-Lambert/Parke-Davis, Center for the Study of Drug Development Over 20 years experience Oxis International, Technoconcepts, Interglobal Waste Management, Janex International and the Los Angeles Kings Over 30 years of experience ImmunoCellular Therapeutics, IDM Pharma, Nexell Therapeutics, Baxter Healthcare Peter Ho, PhD, MBA Director, Business Development Over 10 years of experience at ImmunoCellular Therapeutics, Allergan, DE Shaw and Prudential Securities 24

25 Scientific & Medical Advisory Board Mario Sznol Dr. James Mulé Dr. Jeffrey Weber Dr. Patrick Hwu TIL therapy "is clearly one of the best treatments for metastatic melanoma," said Dr. Hwu. Dr. Laszlo Radvanyi Dr. Cassian Yee Dr. David DiGiusto Dr. Daniel Powell 25

26 Financials Summary Total Common Shares Outstanding Preferred Shares Warrants/Options Cash Debt million 7.7 million 12.7 million $19.7 million Projected Burn Rate $10 million in 2014 List of Investors Ayer Capital Broadfin Perceptive Three Arch Actin Bristol Quogue venbio 75% institutional ownership on a fully diluted basis Data current as of January 7, 2014 Well financed with strong institutional support 31

27 Investment Highlights Leveraging 30 years of Dr. Steve Rosenberg s research and development at NCI to build a T-cell engineering company Technology platform with strong Phase II data for stage IV metastatic melanoma - Objective Response Rate of 49% - 30% patients with survival over 5 years - Autologous TIL therapy currently being used at NCI, Moffitt and MD Anderson Addressing large unmet needs (metastatic melanoma and other late stage cancers) Significant value catalysts in near term - Licensing of next generation TIL technology - Clinical data from combination trials Large IP portfolio and CRADA with NIH Strong management, board and SAB - Who s Who of melanoma and immunotherapy on SAB - Successful experience in immunotherapy development - Record of increasing shareholder value 27