Investor Presentation Transforming Medicine Senescent cell clearance as a novel therapeutic treatment for aging associated and degenerative diseases SIWA THERAPEUTICS INC 222 Merchandise Mart Suite 1230 Chicago IL 60654 312 961 5109
Investor Presentation Transforming Medicine  Senescent cell clearance as a novel therapeutic treatment for aging-associate...
SIWA THERAPEUTICS AND SLOWING OF AGING We began SIWA to develop therapies for slowing or reversing the aging process by promoting tissue and organ regeneration through the removal of senescent cells Senescent cells are causally implicated in age related dysfunction and thus their removal obtains recognized benefits in health and well being SIWA 318 is designed to positively impact healthspan as well as lifespan However because the FDA currently does not recognize aging as a disease we have focused instead on specific aging associated and degenerative disease targets Consistently with our focus in 2010 we received an NIH grant for an animal study relating to treating adverse complications of Type 2 diabetes e g atherosclerosis by eliminating targeted senescent RBCs Building on this first successful demonstration of senescent cell removal we intend to continue focusing on aging associated and degenerative diseases 2
SIWA THERAPEUTICS AND SLOWING OF AGING We began SIWA to develop therapies for slowing or reversing the aging process by pr...
SIWA Therapeutics is A Pre Clinical Stage Company With A first in class humanized monoclonal antibody SIWA 318 that targets and destroys senescent cells SIWA 318 mouse version has demonstrated activity in mouse disease models A significant patent portfolio A focus initially on pancreatic cancer metastasis a disease that should receive fast tracking through the FDA Our goal is to file an IND in the next 12 15 months 3
SIWA Therapeutics is  A Pre-Clinical Stage Company With     A first-in-class humanized monoclonal antibody, SIWA 318, that...
Advancing Anti Senescent Antibody Toward Clinic HIGHLIGHT Lead antibody SIWA 318 4 DETAILS Targets SIWA identified cell surface marker Demonstrated in vivo preclinical safety and efficacy Senescence Is An Emerging Field Causally implicated in many diseases Clearance reduction cutting edge therapeutic approach Focus Fast Track Rare Diseases Cancer metastasis and muscle wasting e g Muscular Dystrophies Multiple Partner Opportunities Multiple licensing opportunities for generating a revenue stream for development Global Patent Estate Earliest priority for clearing senescent cells 1st filings on therapy for clearing senescent cells
Advancing Anti-Senescent Antibody Toward Clinic HIGHLIGHT Lead antibody  SIWA 318   4  DETAILS Targets SIWA-identified cel...
Senescence Causally Implicated In Multiple Diseases Causally implicated in or contributory Exacerbates and or causally to many common diseases implicated in several rare diseases Arthritis Osteo and Rheumatoid Alzheimer s disease Atherosclerosis Amyotrophic Lateral Sclerosis Cancer Cancer Metastasis Chronic obstructive pulmonary disease Cancer therapy related disability Huntington s Chorea Erectile dysfunction Cystic fibrosis Hypertension Juvenile Rheumatoid Arthritis Ocular diseases such as Glaucoma and Macular Degeneration Muscular Dystrophy Osteoporosis Sarcopenia Cachexia Transplantation rejection Type 2 diabetes 5 Rare Cancers such as Retinoblastoma Parkinson s disease Progeria
Senescence Causally Implicated In Multiple Diseases Causally implicated in or contributory Exacerbates and or causally to ...
Senescent Cells Promote Diseases Based On Tissue In Which They Occur Senescent Cells Lose function and ability to divide Secrete damaging inflammatory factors Stress induced e g cell division genetic dysfunction and chemotherapy Cell division inhibited by a protein produced by p16INK4a gene a characteristic marker Brain glial cells Alzheimer s Parkinson s Damage Physical Injury chemicals genetic disorders mutations Infection growth overstimulation Cellular Senescence Muscle stem cells Duchenne ALS Cardiovasc Foam cells Atherosclerosis Joints chondrocytes T cells Synoviocytes Osteoarthritis Rheumatoid arthritis JRA 6
Senescent Cells Promote Diseases Based On Tissue In Which They Occur Senescent Cells                   Lose function and a...
Images Of Senescent Cells And Non Senescent Cells blue shows SAB galactosidase staining As cells become senescent they grow larger flatten shape and express senescence associated galactosidase 7
Images Of Senescent Cells And Non-Senescent Cells  blue shows SAB galactosidase staining   As cells become senescent, they...
SIWA 318 Overview A Therapeutic Approach R D Progress to Date Preclinical in vivo studies have shown using a murine form of SIWA 318 over a short period of time achieved a statistically significant Reduction of senescent cells as measured by p16INK4a Increase in muscle mass in a naturally aged mouse model Inhibition of metastatic lung foci in a 4T1 triple negative breast cancer model Across these studies no adverse effects from SIWA 318 were found Optimization of SIWA 318 underway in preparation for toxicology and efficacy work preliminary to clinical studies 8
SIWA 318 Overview  A Therapeutic Approach R D Progress to Date  Preclinical in vivo studies have shown using a murine form...
SIWA 318 Reverses Muscle Wasting In Naturally Aged Mice Statistically Significant Increase in Muscle Mass Statistically significant increase of gastrocnemius muscle weight vs age matched controls Antibodydependent cytotoxicity instigated at 5 g gram in naturally aged mice 91 weeks No adverse effects or regression in post treatment 9 week treatment free period Young mice controls Old mice controls Old mice at 2 5 g per gram Old mice at 5 g per gram 9
SIWA 318  Reverses Muscle Wasting In Naturally Aged Mice Statistically Significant Increase in Muscle Mass  Statistically ...
SIWA 318 Reduces Senescent Cells In Naturally Aged Mice Statistically significant reduction in standard senescent cell biomarker p16Ink4a mRNA expression levels 2 55x in untreated aged mice 91 weeks vs untreated young mice at study initiation Remained 3 03x higher in the untreated vs treated aged mice Reduced statistically significantly in aged mice following injection of murine SIWA 318 Young mice controls Old mice controls Old mice at 2 5 g per gram Old mice at 5 g per gram 10
SIWA 318  Reduces Senescent Cells In Naturally Aged Mice Statistically significant reduction in standard senescent cell bi...
SIWA 318 Senescent Cell Clearing Inhibits Tumor Metastasis Statistically significant inhibition of lung foci Key Findings Statistically significant 30 inhibition of metastatic lung foci in a mouse 4T1 triple negative metastatic breast cancer model using 10 g gram 2x daily for 3 weeks No increase in tumor growth in treated animals over controls Body weights showed a trend toward increase in treated animals Metastatic Foci on Day 23 Enumerated Foci p 0 001 Saline 11 5 g gram 10 g gram 2x daily administration for 3 weeks
SIWA 318  Senescent Cell Clearing Inhibits Tumor Metastasis Statistically significant inhibition of lung foci Key Findings...
SIWA Pipeline Research Cancer Muscular dystrophy Arthritis Diabetes Alzheimer s See next slide for additional information 12 Preclinical Phase I
SIWA Pipeline Research Cancer Muscular dystrophy  Arthritis Diabetes  Alzheimer   s See next slide for additional informat...
Research Funding Opportunities Being Pursued Cancer Department of Defense grant submitted Pancreatic Cancer grant submitted Osteoarthritis SBIR grant submitted Type 2 Diabetes SBIR grant proposal being prepared Alzheimer s Disease collaborative research study at Arizona State University 13
Research Funding Opportunities Being Pursued Cancer     Department of Defense grant submitted Pancreatic Cancer     grant ...
Growing Global IP Position Earliest priority on patent filings worldwide for clearing senescent cells First patent filings to show a therapy for clearing senescent cells Issued granted patents in North America Australia Africa Europe Asia and the Middle East Extensive patent pipeline with pending applications in additional countries e g Japan and for specific disease indications Filings cover all ways of clearing senescent cells and a wide range of disease targets e g cancer Alzheimer s arthritis atherosclerosis sarcopenia cachexia 14
Growing Global IP Position     Earliest priority on patent filings worldwide for clearing senescent cells     First patent...
Other Products For Generating A Revenue Stream To Help Support Drug Development Work Toxin conjugated single domain molecules A toxin conjugated fragment of SIWA 318 may be particularly useful for treating privileged sites with barriers to large molecules such as the brain and joints Vaccines Using our SIWA Marker the cell surface antigen which binds to SIWA 318 we have constructed a preliminary immunogen vaccine for use in immunizing against senescent cells A vaccine may be particularly useful in products for veterinary applications e g in beef and dairy cattle service animals pets and horses Diagnostic Testing We are exploring a diagnostic test to detect metastatic senescent cells in the blood based on binding to a labeled version of our monoclonal antibody This could alert patients of the need for SIWA 318 treatment to attack the detected cells Separatory Equipment SIWA 318 or a binding fragment thereof may be attached to a support e g beads in a column to remove senescent cells from banked blood or to remove senescent cells from any type of cells being implanted into a patient e g chondrocytes in joints to treat joint damage 15
Other Products For Generating A Revenue Stream To Help Support Drug Development Work Toxin conjugated single domain molecu...
Key Personnel Lewis Gruber Founder Director Chief Executive Officer and Chief Scientific Officer Co Founder of Arryx Inc Co Founder and CEO Hyseq Inc Misty Gruber Founder Director Chief Financial Officer and Scientific Affairs Officer Co Chair of the Biotechnology Group at Dykema Gossett PLLC Co Founder of Arryx Co Founder and initial Director of Hyseq Inc Alex Kormushoff Director President of Strategic Healthcare Programs Executive Director of Accenture Analytics John O Peters III Director Founder Board Member and initial CFO of Triple Canopy Inc one of the largest private security firms providing services to the United States Government and commercial companies operating in high risk environments Triple Canopy now Constelis was sold to a private equity firm John Ford Ph D Senior Scientific Consultant Dr Ford is an intra entrepreneur with significant drug discovery development lifecycle management and business development experience from roles at both start up and global biopharmaceutical companies 16
Key Personnel Lewis Gruber Founder, Director, Chief Executive Officer and Chief Scientific Officer Co-Founder of Arryx, In...
Anticipated Business Developments Secure Funding Complete optimization of SIWA 318 Initiate IND enabling studies Continued execution and expansion of IP Pursue Development Licensing Partnerships Drive and maintain focus on metastasis and muscle wasting Expand and accelerate pipeline via collaborations Expand Operational Team Recruit key hires i e Clinical yet maintain virtual structure 17
Anticipated Business Developments Secure Funding     Complete optimization of SIWA 318     Initiate IND enabling studies  ...
Time Line For IND Filing 18
Time Line For IND Filing  18
Budget to IND 12 mos and to Phase 1 36 mos 12mos 1 000 000 00 Cash Studies Cancer IND Phase1 Employees 10 000 000 00 135 000 00 485 000 00 5 000 000 00 190 000 00 2 500 000 00 mAb Work mAb Optimization production 100 000 00 1 300 000 00 Legal Patents 224 000 00 700 000 00 General 15 000 00 50 000 00 Rent utilities 6 000 00 36 000 00 Acct Audit starting in 2017 15 000 00 80 000 00 PR 15 000 00 54 000 00 Travel Conf 15 000 00 80 000 00 Miscellaneous 70 000 00 200 000 00 Total 19 36mos 1 135 000 00 10 000 000 00
Budget to IND  12 mos.  and to Phase 1  36 mos.  12mos   1,000,000.00 Cash Studies  Cancer  IND Phase1   Employees    10,0...
Recent Liquidity Events Cancer and Rare Disease Issuer Symbol IPO Date IPO Price Raise Current Price Market Cap Stage Audentes Therapeutics BOLD 7 20 16 15X5 75MM 16 07 351MM PreRevenue Pre Clinical Audentes Therapeutics Inc is a biotechnology company which engages on development and commercialization of gene therapy products for patients with serious and rare diseases caused by single gene defects Fate Therapeutics FATE 10 1 13 6 x 6 67 40MM 2 76 117 95MM Revenue Clinical Clinical stage bio pharma company engaged in the discovery and development of pharmacologic modulators of adult stem cells to treat orphan diseases including certain hematologic malignancies lysosomal storage disorders and muscular dystrophies Juno Therapeutics JUNO 12 19 14 24 x 11 0229 264MM 21 21 2 25B PreRevenue Clinical Juno Therapeutics is a clinical stage company developing novel cellular immunotherapies based on two distinct and complementary platforms Chimeric Antigen Receptors CARs and T Cell Receptors TCRs technologies Our goal is to revolutionize medicine by re engaging the body s immune system to treat cancer Kite Pharma KITE 6 20 14 17 x 7 5 127 MM 52 98 2 64B PreRevenue Clinical Clinical stage biopharmaceutical company focused on the development and commercialization of novel cancer immunotherapy products designed to harness the power of a patient s own immune system to eradicate cancer cells 5 26 16 11 x 5 5 60 5MM 23 58 210 15MM Revenue Clinical Reata s mission is to develop novel therapeutics for patients with serious or life threatening diseases by targeting molecular pathways involved in regulating cellular metabolism and inflammation As of 2 06 2017 At IPO Date REATA Pharma RETA 20 Description
Recent Liquidity Events Cancer and Rare Disease Issuer  Symbol   IPO Date  IPO Price Raise  Current Price   Market Cap   S...
Competitors None Developing A Pan Anti Senescent Cell Antibody 1 Mount Tam Biotechnologies 2 Unity Biotechnology 3 everonbio com Pre clinical stage developing small molecule and immunotherapies to clear senescent cells Oisin Biotechnologies 21 unitybiotechnology com Pre clinical stage developing oral drugs to eliminate senescent cells Inflammatory Joint Diseases and Ophthalmology focus Raised 116M Series B Everon Bioscience 4 www mounttambiotech com Pre clinical stage developing mTORC1 inhibitors Systemic Lupus Erythematosis and Multiple Sclerosis focus Reverse IPO MNTM www oisinbio com Pre clinical stage developing genetic targeted approaches to clear senescent cells
Competitors   None Developing A Pan Anti-Senescent Cell Antibody 1.  Mount Tam Biotechnologies              2.  Unity Biot...
EXIT STRATEGY The most probable near term liquidity events include Licensing of vaccine related applications This could include either human or non human i e veterinary applications Licensing of SIWA 318 for one or more disease applications that we don t have capacity to develop ourselves This could include either human or non human i e veterinary applications Separatory applications such as removing senescent blood cells from banked blood or senescent stem cells for bone marrow transplants to improve the cells going into patient Our exit strategy is contingent on moving SIWA 318 into a clinical trial for one or a limited number of related senescent cell implicated diseases that have a limited or no viable treatments or b existing treatments with limited efficacy that we believe we can improve either separately or as an adjunct therapy given with existing therapies We believe that our highest exit value would be obtained through acquisition by a pharmaceutical company with disease areas that overlap our senescent cell areas Acquisition of one or more areas could also be by a licensee We believe that given our business strategy the foregoing exit strategies offer a better potential than an initial public offering Notwithstanding if conditions were appropriate we would consider an initial public offering as well 22
EXIT STRATEGY  The most probable near term liquidity events include                Licensing of vaccine related applicatio...