OTC: LBIO June 2014
Manish Singh, PhD ChairmanOO and CEO [email protected] 310-940-0998 (M) 818-992-3127 (O) http://www.lionbio.com http://www.lbio.com 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 Company Snapshot
• Genesis Biopharma (OTCBB: GNBP) and Lion Biotechnologies merger in July 2013 • Began trading on OTC Markets in October 2013 under “LBIO” • Focused on developing and commercializing adoptive cell therapy (ACT) using autologous tumor infiltrating lymphocytes (TILs) • Lead product with strong phase II data for stage IV metastatic melanoma • Potential applications in NSCLC, Cervical, TNBC and Head and Neck
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 New Breakthrough Solutions
. Personalized patient specific T-cells with greater potency and persistence . Control tumor microenvironment
Immunotherapy as the final frontier
5 Clinical Regressions in Late Stage Disease
Clinical Cancer Research December 15, 2010 16: 6122
6 Paradigm Shift in Immunotherapy: Delay in Disease Progression to Cure
Cancer Vaccines Adoptive T-cell Therapy Mixed successes in early stage Effective in early stage as well as disease or minimal disease (MRD) advanced disease Curative potential of T-cell therapies • Prior attempts to manage • CAR-T cells targeting CD-19 bulky disease or fast against advanced leukemia growing tumors have failed (UPenn/Novartis)
• NCI/Rosenberg using TILs to treat metastatic melanoma
GALE, IMUC, DNDN, NWBO, BLUE, CELG, NVS, Juno, Kite ADXS, NLNK
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 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 TIL Therapy Protocol 2 weeks
3 weeks
Primary expansion Select TIL (tumor reactivity) Secondary Expansion (REP)
TIL cytoxan fludarabine infusion
Day High-dose -7 -5 -1 IL-2
Lymphodepletion 0 1 5 21 22 26
10 Impressive Survival Benefit Even in Second and Third Line Setting
TIL therapy is clearly one of the best treatments for metastatic melanoma (Median Follow-up 62 months) - 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 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 % Patients Experiencing an Complete Response Overall Response Total Patients Treated (Partial + Complete Response)
Autologous TILs (ACT) NCI 12% 49% 43 Patients MD Anderson 7% 47% 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, 2011. Dacarbazine: Robert C., Thomas L., Bondarenko I., et. al., N. Engl. J. Med. 364:2517-2526 (2011). IL-2: Sparano, J., Fisher, R., Sunderland, M., et. al., J. Clin. Oncol. 11(10):1969-1977 (1993). Zelboraf®: Updated FDA approved prescribing information package insert. Yervoy®: FDA approved prescribing information package insert.
12 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 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 Reduction in Tumors in Majority of Patients (MD Anderson TILs trial summary, n= 31)
Radvanyi L G et al. Clin Cancer Res 2012;18:6758-6770
15 Tumor responses to TIL ACT
Change in tumor burden over time after TIL infusion
100 2379 2350 2267 2261 2215 2357 2180 2173 50 2150 2131 2124 2256 2340 2262 2258 0 2373 3 4 5 6 7 8 9 2338 1.5 10 11 12 13 14 15 16 17 18 19 20 21 22 2299 2281 2284 2144 2247 -50 2245 2175 Percent of initial tumorPercent initial burdenof 2136 2132 2125 2114 2104 -100 2044 2146 Time after TIL infusion (months)
Radvanyi et al., Clin. Cancer Res., 2012
16 Update on TILs trial at MD Anderson (PI Sponsored Trial)
Overall survival 73% of CR/PR patients alive for >4.5 yrs N=73
CR/PR Overall Survival Overall
PD/SD
Median OS > 24 months Overall Survival Overall
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 TILs Clinical Trials Status
Sponsor Indication Phase I Phase 2 Phase III
nd NCI/Lion 2 line metastatic melanoma Second phase II ongoing
1st line metastatic melanoma NCI/Lion in combination with Zelboraf
nd MD Anderson 2 line metastatic melanoma
2nd line metastatic melanoma NCI/Lion (second generation TILs CD137 sorted) 1st line metastatic melanoma Pilot Trials sponsored by Moffit Cancer in combination with Yervoy (BMS) Moffit in collaboration Center 1st line metastatic melanoma with BMS in combination with anti-PD1 Ab (BMS)
18 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 Effect of Prior Treatments on Response to TILs ______Evaluable Objective Response (number of patients %)
Any VEM 7 3 (43%)
Any IL-2 32 20 (63%)
Any ipi 37 20 (54%)
Any PD1 10 5 (50%)
None 39 21 (54%)
54% ORR in all patients
20 Combination with anti-PD1 has synergistic effect PD-1 mAb enhances TIL proliferation & tumor rejection
Source: Peng, et al. Cancer Res 2012.
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 tumor- bearing mice receiving anti-PD-1 Ab with or without adoptive T cell transfer (N=5 per group).
21 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 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 2011
23 TIL Manufacturing
GMP MANUFACTURING FACILITY ≥2 cm diameter
+IL-2 T T
T Excise Overnight T Tumor 1-3 mm3 fragments Bulk TILs (>75M)
Initial TIL Culture (Pre-REP) 3 weeks Rapid Expansion Protocol (REP) 2 weeks +IL-2 +OKT3 +feeder cells
T T IV infusion + IL-2 T T T
Overnight T T T Infusion bags Final TILs (>50B)
24 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
25 Intellectual Property
Non-exclusive license for melanoma, colon, breast and ovarian cancers
Number Title Issue Date
8,034,334 Immunotherapy with in vitro-selected antigen-specific lymphocytes 10/11/11 after nonmyeloablative lymphodepleting chemotherapy
7,998,736 Adoptive immunotherapy with enhanced T lymphocyte survival 8/16/11 (engineered with IL-15)
8,383,099 Adoptive cell therapy with young T cells 2/26/13
13/424,646 Methods of growing TILs in gas-permeable containers N/A
61/771,247* Methods of Producing Enriched Populations of Tumor-Reactive T Cells N/A from Tumor
* Under CRADA Option Agreement (exclusive)
26 Updated Phase 1 results for TILs with Upcoming Milestones Zelboraf (NCI) Initiate Phase I Anti-PD1 Phase I data on IPI TIL Combination Trials combination trial combination trial (Moffitt) (Moffitt)
Next Generation TILs IND next-Gen T cells Complete license for next-Gen T cells
st Update Phase II IST MD Anderson Company IND TILs (1 Generation) (AACR) (ASCO) for Phase II
Q1’14 Q2’14 Q3’14 Q4’14 Q1’15 Cumulative Burn Nasdaq Listing
Clinical Trials $2 M Exclusive IP 1st Gen Manufacturing $3 M New R&D Facility Development R&D $3.5 M
G&A $1.5 M
$2 M $4 M $7 M $10 M
27 Management Team
• Ex-CEO of ImmunoCellular Therapeutics (IMUC) Manish Singh, PhD, MBA Chairman and CEO • California Technology Ventures, Cell Genesys, Viagene (acquired by Chiron), Genetic Therapy Inc. (acquired by Novartis)
• Over 30 years of experience Elma Hawkins, PhD, MBA Head of Clinical Development • ImmunoCellular Therapeutics, Antigenics, ADVR, Genzyme, Warner-Lambert/Parke-Davis, Center for the Study of Drug Development • Over 20 years experience Michael Handelman, CPA • Oxis International, Technoconcepts, CFO Interglobal Waste Management, Janex International and the Los Angeles Kings
James Bender, PhD, MPA • Over 30 years of experience VP, Product Dev and Manufacturing • ImmunoCellular Therapeutics, IDM Pharma, Nexell Therapeutics, Baxter Healthcare
Peter Ho, PhD, MBA • Over 10 years of experience at ImmunoCellular Therapeutics, Allergan, DE Shaw and Prudential Director, Business Development Securities
28 Board of Directors
Manish Singh, PhD, MBA Chairman and CEO
• Chairman of Galena Biopharma (GALE), founder of Medco Research (acquired by King Sandy Hillsberg, JD Pharmaceuticals), founder of ImmunoCellular Therapeutics (IMUC) Director • Senior Partner at TroyGould PC
Jay Venkatesan, MD • Owner of Ayer Capital, Director Brookside Capital (Bain Capital), Analyst at Apax Partners and Director McKinsey & Co.
• 4 star general (ret.), former chief of staff, USAF, member of the Joint Chiefs of Staff • Chairman, Coast Plating, Inc. (privately-held). Director, GenCorp, Miller Energy, DGT Holdings. Merrill McPeak Former Chairman, Ethicspoint (now Navex Global, privately-held). Former director, Tektronix, Director TWA, ECC, Intl. (Chairman), Sensis Corp.
29 Scientific & Medical Advisory Board
Mario Sznol
Dr. James Mulé
Dr. Jeffrey Weber
TIL therapy "is clearly one of the best treatments for metastatic melanoma," said Dr. Hwu. Dr. Patrick Hwu
Dr. Laszlo Radvanyi
Dr. Cassian Yee
Dr. David DiGiusto
Dr. Daniel Powell
30 Financials Summary
List of Investors Total Common Shares 21.0 million Ayer Capital Actin Outstanding Broadfin Bristol Preferred Shares 7.7 million Perceptive Quogue Warrants/Options 12.7 million Three Arch venBio Cash $19.7 million Debt 0 75% institutional ownership on Projected Burn Rate $10 million in 2014 a fully diluted basis
Data current as of January 7, 2014
Well financed with strong institutional support
31 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
32