Siva Therapeutics Inc Precision Tumor Targeting Len Pagliaro, PhD, - PowerPoint PPT Presentation

Siva Therapeutics Inc ‘Precision Tumor Targeting’ Len Pagliaro, PhD, CEO Angel Capital Summit Presentation March 22, 2012

Why Siva?  There are many limitations of current cancer therapies. Cancer patients face therapies that are:  Invasive,  Risky,  Disfiguring,  Moderately effective at best, and  Extremely costly.  Siva’s approach addresses all of these issues. 2 Siva Therapeutics Inc

Business Opportunity  Siva is developing a cancer treatment that will be:  Safer and less invasive than current therapies;  Effective and competitively priced ;  Not dreaded by patients;  And will be a compelling option for reimbursement. 3 Siva Therapeutics Inc

Market Need and Business Model  Skin cancer will be our entry market.  We will sell a non- surgical skin cancer therapy, through channel partners to oncology clinics, that uses SivaRods™ to target and heat tumors. NCI 4 Siva Therapeutics Inc

Initial Target Market: Skin Cancer  Goal: To capture 50% of Stage II and beyond melanoma, and 10% of Stage II and beyond non- melanoma patients 2 years after launch of the FDA-approved product. (does not include RoW) Melanoma Non-Melanoma Total 70,000 3,500,000 3,570,000 New Cases 8,400 70,000 78,400 Stage II + 11,200 4,200 7,000 Siva Target 5 Siva Therapeutics Inc

Initial (Skin Cancer) Market Projection  Projected market 2 years post launch: $340M . Number of Patient Treatments per Year Price Per Treatment 8,000 10,000 12,000 14,000 $20,000 $160M $200M $240M $280M $25,000 $200M $250M $300M $350M $300M $360M $30,000 $240M $420M $35,000 $280M $350M $420M $490M $40,000 $320M $400M $480M $560M 6 Siva Therapeutics Inc

Financial Projections Stage 2B and beyond melanomas (50%) and carcinomas (10%) (dollars in thousands) $80,000 $70,000 Siva Revenue $60,000 COGS $50,000 EBITDA $40,000 $30,000 $20,000 $10,000 $0 2012 2013 2014 2015 2016 2017 2018 2019 2020 -$10,000 7 Siva Therapeutics Inc

The Product: SivaRods ™  A suspension of precision gold nanorods in sterile saline for injection.  Very safe – excreted in urine.  SivaRods ™ concentrate in solid tumors following injection.  After injection, SivaRods ™ are heated with infrared light to destroy the tumor tissue. 8 Siva Therapeutics Inc

In Vivo Photothermal Tumor Therapy 1 of 2 InfraRed (IR) irradiation 72 hrs following injection of: Nanorods Saline Siva Therapeutics Inc 9

In Vivo Photothermal Tumor Therapy 2 of 2 Siva Therapeutics Inc 10

Milestones for Development Feb-2012 Jul-2013 Nov-2014 Mar-2016 Aug-2017 First Funding Round Preclinical Studies First FDA pre-IDE Meeting Draft Clinical Study Plan EXIT IDE Second FDA pre-IDE Meeting Pilot Clinical Study Pivotal Clinical Study PMA Submission and Approval Product Launch Launch of FDA Approved Product $2.2M ANGEL FINANCING Full pre-clinical package and entry to clinic Acquisition / Strategic $5.5M TOTAL to EXIT Partnership $23.8M (72% R&D) TOTAL to MARKET Costs in MUSD 11 Siva Therapeutics Inc

Competition and Risks LOW Cost / Invasiveness SivaRod ™ Colloidal Gold Therapy Nanoshells / Nanospheres Directed Energy Radiation Surgery HIGH Chemotherapy LOW HIGH Efficacy / Safety 12 Siva Therapeutics Inc

Competitive Advantages  Safe, Effective, and Minimally Invasive  Simple – Device , not Drug  Strong collaboration with Anschutz Medical Center  Strong and growing IP portfolio for:  Scale-up of manufacture of gold nanorods (exclusive),  Large-scale purification of gold nanorods (exclusive),  Surface modifications of gold nanorods (exclusive), &  Use of nanorods for human cancer therapy. 13 Siva Therapeutics Inc

Funding Sought and Exit Strategy  $2.2 million will enable us to:  Complete full pre-clinical data set.  File and obtain Investigative Device Exemption (IDE), and  Develop protocols for first clinical studies.  Total to Exit: ~$5.5 million.  Exit via acquisition or strategic partnership during Phase 1 clinical trials.  Pharmaceutical, device, or healthcare company.  Partnership, milestone, and royalty payments 14 Siva Therapeutics Inc

Management and Advisory Team  Len Pagliaro, PhD – CEO  Colin Shepherd, PhD, MBA - CFO  Bill Young – VP Business Development  Steve Kregstein, JD – Chief Legal Officer  Candidate Identified, PhD – VP of R&D Advisors  Jack Wheeler, MicroPhage (FDA clearance Q4 2011)  Sangeeta Bhatia, MD, PhD, MIT  Antonio Jimeno, MD, PhD, Anschutz Medical Center  Arlen Meyers, MD, MBA, Anschutz Medical Center 15 Siva Therapeutics Inc

Thank You ACS and RVC Members ‘Precision Tumor Targeting’ Len Pagliaro, PhD, CEO len.pagliaro@sivatherapeutics.com www.sivatherapeutics.com +1 425 443 4344 16 Siva Therapeutics Inc

SIVA – The Name SIVA (also Siva Nataraja or Shiva) is the Hindu deity representing destruction and recreation – the natural process enabled by SivaRods ™. Backup Slide 17 Siva Therapeutics Inc

The Technology  Hyperthermic treatment of - gold cancer – known for many - 12 x 50 nm years, difficult to target - absorb at 810 nm tumors.  Enhanced permeability and retention (EPR) – ‘leakiness’ of tumor vasculature.  SivaRods ™ localize to tumors and are heated with infrared light. 18 Siva Therapeutics Inc

Milestones for Development Feb-2012 Jul-2013 Nov-2014 Mar-2016 Aug-2017 First Funding Round Preclinical Studies First FDA pre-IDE Meeting Draft Clinical Study Plan EXIT IDE Second FDA pre-IDE Meeting Pilot Clinical Study Pivotal Clinical Study PMA Submission and Approval Product Launch Launch of FDA Approved Product R&D Costs $1.6 $2.5 $9.5 $3.5 G & A Costs $0.6 $0.8 $2.6 $2.7 Subtotals $2.2 $3.3 $12.1 $6.2 Acquisition or Strategic Partnership TOTAL to EXIT $5.5M TOTAL to MARKET $23.8M (72% R&D) Costs in MUSD 19 Siva Therapeutics Inc

Competition and Risks  Chemotherapy, radiation, surgery.  Yervoy (ipilimumab), BMS, approved March 2011, metastatic melanoma. Treatment costs $120,000; median survival increased from 6.4 months to 10 months.  Zelboraf (PLX4032), Roche-Genentech, approved August 2011. Treatment costs $56,000 and targets ~45% of patient population (BRAF V600E positive).  Colloidal gold – No known risks; doesn’t heat adequately.  Directed energy - Radio frequency, ultrasound, and microwave lack selectivity.  Nanoshells, nanospheres - Large (140 nm) particles, clearance issues in clinical trials. 20 Siva Therapeutics Inc

Does it Work?  Experimentally induced tumors in mice.  Mice injected with gold nanorods and control animals (saline-injected).  Areas exposed to infra-red laser irradiation, and control areas (non- irradiated).  Work published in: von Maltzahn et al. (2009) Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas. Cancer Research , 69:3892-3900. (Laboratory of Sangeeta Bhatia, MD, PhD) 21 Siva Therapeutics Inc

Melanoma Staging NCI NCI website Backup Slide 22 Siva Therapeutics Inc