Targeted Chemotherapy Delivery Platform Igor Sherman, PhD President & CEO Richard Potts, Chairman 2014
Change in Age Adjusted US Death Rates by Cause Almost unchanged over 50 years Source: U.S. National Center for Health Statistics, National Vital Statistics Reports, Vol. 59, No. 4, March 16, 2011.
THE STORY Harnessing Nature AFP is a human protein produced by the embryo during fetal development and serves at least two critical functions: 1. Picks up nutrients from the mother and delivers them to the embryo; and 2. Is thought to normalizes the immune system responses so the mother s immune cells don t attack the embryo. AFP circulates in the maternal bloodstream and picks up free fatty acids, steroids, and other hydrophobic substances, needed by rapidly dividing cells. The loaded AFP continues to circulate until it finds receptors which are exclusively found on all embryonic cells. It then transports the nutrients into the cell and releases them once inside. When the embryo matures the production of AFP stops and the receptors disappear. Cancer cells in many ways can be viewed as reverting to an embryonic state and > 80% of solid and liquid tumors (leukemia, lymphoma) express AFP receptors on their surface while healthy cells do not. By attaching a chemotherapy payload to AFP we can selectively deliver toxins to cancer cells. This targeted delivery prevents chemotherapy from entering healthy cells resulting in increased efficacy and a significant reduction in toxicity. It is well known that symptoms of autoimmune diseases (Multiple Sclerosis, Myasthenia Gravis, Lupus, Arthritis etc.) go into remission during pregnancy and return soon after. This seems to correlates very well with the rise and fall of AFP. In various pre-clinical models of autoimmune diseases administration of AFP is a very effective therapy. ACT has exclusive worldwide rights to recombinant human alpha fetoprotein (rhuafp).
ACT IS A DRUG DELIVERY COMPANY WITH A TARGETED CHEMOTHERAPY DELIVERY PLATFORM Toronto-based company (MaRS Discovery District) Company Background Exclusive worldwide rights to targeted delivery platform Alpha Fetoprotein (AFP) AFP - shuttle protein that selectively targets cancer cells (most solid and liquid tumors) Paclitaxel - generic chemotherapy payload Lead Asset ACT-901 (AFP + Paclitaxel) In-licensed technology with over $100 million spent on development, demonstrated safety in over 400 patients, 20+ international patents, large Drug Master file already with FDA including manufacturing, toxicology, and human safety mitigated development path Leading world authority in oncology lends his support and agrees to be the principal investigator for clinical studies Financing To Date $3.05M equity previously completed 52.5 million Shares Outstanding $1.0M in Federal Government funding (FedDev, IRAP) SRED Leverage refundable tax credits 35% of expenditures
Management Team OUTSOURCED / RESOURCES MANAGEMENT Richard Potts Chairman Igor Sherman President & CEO Virtual company ensuring efficient cash utilization and a focus on asset development via external (i.e. outsourced) support
Management Richard Potts Chairman Demonstrated a rich blend of leadership roles with a track record of management, finance and marketing of growth companies across a diverse spectrum of industries, including biotechnology, medical and information technology. Mr. Potts has co-founded, established strategic plans, secured multi-million dollars in financing, public listings and facilitated partnerships as a founder, owner and executive in numerous companies in the knowledge-based industry. Dr. Igor Sherman, President & CEO Extensive experience and expertise in the pharmaceutical and biotechnology industries, particularly in oncology. Prior to ACT, Dr. Sherman was Director of Clinical Research and Director of Scientific Affairs for YM Biosciences Inc., where he was responsible for preclinical and clinical development, as well as registration strategies for all oncology and pain products in YM Biosciences portfolio. Dr. Sherman was also Scientific Director of Oncology for AstraZeneca Canada Inc.
Life Science Risk Mitigation Seeking Alpha TO SUCCEED IN LIFE SCIENCE MITIGATE RISK Scientific Risk combination of safe targeted delivery platform (AFP) and effective chemotherapy Manufacturing Risk AFP manufacturing is outsourced and was already cleared by the FDA Regulatory Risk large existing drug master file with the FDA Clinical Risk demonstrated safety in ~400 patients and carries an approved generic chemotherapy drug as its payload Intellectual Property Risk 20+ patents in place plus 12 years exclusivity Financing Risk Very low ~$25 million to complete Phase II and apply for accelerated approval as an orphan drug Execution Risk outsourced development pathway manufacturing, Clinical Research Organizations (CROs), teaching hospitals.
ACT-901 Animation www.alpha-cancer.com
Pipeline Overview Therapy Indication Partners Discovery Pre-clinical Phase I Phase II ACT-901 (AFP + Paclitaxel) Targeted Oncology Solid and liquid tumors Collaboration University Health Network ACT-902 (AFP+Thapsigargin) Targeted Oncology Solid and liquid tumors Collaboration University Health Network ACT-903 (AFP+Linker+Myatansinoid) Targeted Oncology Solid and liquid tumors Collaboration Polytherics U.K. AFP Autoimmune Rheumatoid Arthritis Looking to Partner out Myasthenia Gravis (muscle weakness) Multiple Sclerosis, Uveitis, other
Lead Asset ACT-901 Lead Asset - ACT-901 (AFP + Paclitaxel) AFP a shuttle protein that targets AFP receptors on cancer cells Majority of solid and liquid cancer cells (>80%) have AFP receptors AFP receptors are only present on cancer cells - healthy cells do not have AFP receptors Paclitaxel is a widely used generic chemotherapy ACT-901 combines its highly targeted transporter protein AFP with a paclitaxel payload This payload is delivered selectively to cancer cells Benefits of this Targeted Approach: Reformulation of two well-known compounds Fast Track Approval Currently in development for ovarian cancer Orphan Drug / Breakthrough Therapy Will expand to Non-Small Cell Lung Cancer, Prostate, Colon and other indications Overcomes chemotherapy drug resistance as delivery bypasses membrane pumps AFP is non-immunogenic in humans - demonstrated in over 400 patients (as safe as placebo) Frequency of treatment driven by efficacy, not toxicity avoidance Treatment expected to minimize pain, suffering and healthcare cost
ACT-901 is the 3 rd Generation Paclitaxel Therapy Generation Image Formulation Maximum Tolerated Dose Peak Sales 1 st Taxol Paclitaxel Cremophor EL excipient: Polyoxyethylated castor oil 175 mg/m2 ~ $1.6B (WW in 2000) 2 nd Abraxane (Albumin+paclitaxel) Biological polymer: Donor-derived human serum albumin (HSA) 260 mg/m2 Est. >$1.7B* (US) ($430M in 2012) Mean size 130nm 3 rd ACT-901 (AFP+paclitaxel) Biological Targeted carrier No MTD Targeted Therapy Conversion of Abraxane sales + new indications Mean size ~8 nm
Evidence of Safety of AFP (delivery platform) in Humans 300 Patient Clinical Study of Delivery Platform (AFP) A randomized, double-blind, placebo-controlled trial of a recombinant version of human alpha-fetoprotein in patients with active rheumatoid arthritis as conducted. Patients were injected with either MM-093 (AFP) or a placebo subcutaneously every weeks for 12 weeks. Results AFP was well tolerated The incidence of adverse events was similar in the AFP and placebo groups Most common adverse events were headaches, upper respiratory tract infections, musculoskeletal pain and injection site reactions L C Pollard, J Murray, M Moody, E J Stewart, E H S Choy Ann Rheum Dis 2007;66:687 689.
Evidence of Efficacy Free dox IC50=25.0 ug/ml AFP-dox IC50=2.7 ug/ml Overcoming multidrug resistance in human ovarian cell line Chemo-resistant ovarian carcinoma cell line SKVLB IC50 (dose that kills 50%): AFP-Dox = 2.7 ug/ml IC50 for Dox = 25.0 ug/ml (of Dox equivalent) Moskaleva et al. (1997), Cell Biol. Internat., 21, 793-799
UHN Princess Margaret Cancer Centre Evidence of Efficacy in vivo Tumor Volume Daily treatment - 2.6 mg/kg of Paclitaxel for 2 weeks from days 7 to 21 Treatment Period
% Survival Evidence of Efficacy in vivo Survival Results UHN Princess Margaret Cancer Centre 120 100 80 60 40 20 0 Saline Paclitaxel 180 mg/week Paclitaxel 300 mg/week ACT-901(AFP+Paclitaxel) 180 mg/week (of Paclitaxel) Treatment Period 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 Days
Why Invest in Alpha Cancer Technologies? 1 The Return TOP 8 CANCER DEALS (AT PRECLINICAL STAGE) IN LAST 4 YEARS - VALUATION RANGE ~$500M - $1.2B ABRAXANE (ALBUMIN + PACLITAXEL) VALUATION ~$6B VALUED ASSET FOR CELGENE 2 Time to Market ACCELERATED APPROVAL - ORPHAN DRUG FOR OVARIAN CANCER IN THE US AND EUROPE BY ~2018 MUCH SHORTER PATH WITH GREATER CERTAINTY DUE TO: DRUG DELIVERY TECHNOLOGY, FOCUS ON ORPHAN INDICATION, AND EXISTING DRUG MASTER FILES WITH FDA FOR AFP + PACLITAXEL 3 Cost VIRTUAL COMPANY MODEL WITH EFFICIENT CLEARLY DEFINED CLINICAL DEVELOPMENT PATHWAY 4 Risk SIGNIFICANTLY MITIGATED RISK IN EVERY AREA OF DEVELOPMENT ~ INCLUDING EXISTING 400 PATIENT SAFETY DATA DELIVERY TECHNOLOGY NOT NEW DRUG DEVELOPMENT
1 Top Down Valuation Companies Payout* Deal Terms $1B + royalties July 2011 - Worldwide rights to develop and commercialize Bi-specific T cell engager antibodies against 2 solid tumour targets. $964M + royalties Dec 2010 - Exclusive rights to develop and commercialize targeted covalent drugs for cancer treatment based on Avila s Avilomics Technology. $912M + royalties Aug 2010 -Worldwide rights to develop and commercialize cancer drug candidates using Seattle Genetics antibody-drug conjugate program. $815M + royalties Jan 2012 - Collaboration to discover and develop small molecule drugs against oncology-relevant protein-protein interactions. * Prospective deals include up-front, milestone and royalty payments (on net sales).
1 Top Down Valuation cont d Companies Payout* Deal Terms $700M + royalties Jan 2012 - Collaboration to discover and develop drugs that target tumor metabolism mechanisms. $540M + royalties June 2010 - Rights to discover, develop and commercialize novel anti-cancer stem cell therapeutics targeting the Wnt signaling pathway. $508M + royalties Aug 2010 - Exclusive worldwide rights to develop and commercialize drug candidates arising from its PD-1 program for treatment of cancer. $466M + royalties Oct 2010, Dec 2011 - Exclusive worldwide rights to discover, develop, manufacture and market TAP compounds for the treatment of cancer. * Prospective deals include up-front, milestone and royalty payments (on net sales).
1 Comparable - Abraxane ACT-901 Abraxane Valuation Delivery AFP + Paclitaxel Targeted to Receptor on cancer cells only Albumin + Paclitaxel $6 Billion In vivo Study Survival 125% * 84% ** Non-targeted penetrates healthy and cancer cells Delivery amount Low Dose Maximum Tolerated Dose Toxicity Little to none Maximum (Dose dependant) * Princess Margaret Cancer Centre 2012 median survival 45 days compared to 20 days for control at low dose * * AACR Hospital for Sick Children 2013 median survival 59 days compared to 32 days for control at high dose
2 Time to Market Preclinical Development Phase I Phase II Expedited Approval Phase III Post-Marketing $$ 2014 Q1 2015 Q2 2016 Q3 2018 Q4 2020 Prospective partnership(s) to initiate development in other indications or new product(s) Market launch in Canada and select Asia for ovarian cancer Market launch in the US and Europe for ovarian cancer (orphan drug approval) Market launch in US, Canada, Europe and select Asia for NSCLC/prostate/Colon etc. cancer Expedited commercial approval of ACT-901 in US and Europe by targeting orphan disease population Clear clinical development plan will bring ACT-901 to all target markets Co-development/co-marketing with biopharma will facilitate early or later expansion into additional indications
3 Cost Proceeds added to Working Capital used as follows: Start Preclinical File to IND $2.0mm ongoing Phase I Study (~14 months) (~35 patients treated to efficacy) $5mm ~Q2 2015 Phase II Study (Commercialization Ovarian cancer two arms ~220 patients) (~24 months) $18mm ~Q2 2016 Accelerated Approval ~Q3 2018 Virtual company ensuring efficient cash utilization and a focus on asset development via external (i.e. outsourced) support
4 Risk Mitigation DEVELOPMENTAL RISKS - MITIGATED Efficacy Efficacy of paclitaxel established, as is its widespread use in multiple forms of cancer Enhanced efficacy of ACT-901 vs. free paclitaxel in multiple tumor cell lines and mice with cancer already demonstrated Safety AFP shown to be safe in 400 humans in Phase I/II clinical testing Paclitaxel safety profile (an approved chemotherapy drug) well understood Development Path is Clear Validated targeted chemotherapy platform, delivering an approved chemotherapy drug to cancer cells
4 Risk Mitigation cont d MANUFACTURING RISKS - MITIGATED Production of ACT-901 FDA-approved processes for both AFP and paclitaxel Outsourced commercial manufacturing to combine AFP and paclitaxel COMMERCIAL RISKS - MITIGATED Competition ACT-901 will substitute for paclitaxel s established use delivering a targeted and less toxic therapy Pricing & Reimbursement Less expensive compared to other targeted therapy options High probability of reimbursement in target markets
News Collaboration for 2 nd Product PolyTherics and Alpha Cancer Technologies Collaborate to Produce Novel Drug Conjugates to Target Tumours ThioBridge linker to attach cytotoxic payloads to alpha fetoprotein London, UK and Toronto, Canada 28 May 2014 PolyTherics Limited ( PolyTherics ), an Abzena company that provides technologies and services to enable the development of better biopharmaceuticals, today announced a collaboration with Alpha Cancer Technologies Inc. ( ACT ), a Canadian company with a targeted drug delivery platform based on alpha fetoprotein ( AFP ). PolyTherics will produce a range of AFP drug conjugates for ACT to test using its proprietary ThioBridge technology.
Business Development Checklist Novel targeted chemotherapy delivery platform - AFP Delivery protein fully characterized Mechanism of action well understood Massive safety data in over 400 humans non-immunogenic 20+ international patents in place Receptors found on >80% of all cancers (solid and liquid) Confirmation of efficacy even in drug resistant tumors Demonstrated superior activity at low treatment dose Outsourced FDA approved manufacturing in place Outsourced development underway (reduced burn rate) Significant risk mitigation and short path to value Business Development Checklist Lead asset ACT-901 (AFP+ Paclitaxel) clear path to success ACT www.alpha-cancer.com
For further information, please contact: Richard Potts Chairman E-mail: rpotts@alpha-cancer.com Tel: 416.464.2768 Igor Sherman President and CEO E-mail: isherman@alpha-cancer.com Tel: 416.826.6626
Forward Looking Statements Caution Regarding Forward Looking Information: Certain statements contained in this material constitute forward looking information within the meaning of applicable Canadian provincial securities legislation (collectively, the "forward looking statements"). These forward looking statements relate to, among other things, ACT's objectives, goals, targets, strategies, intentions, plans, beliefs, estimates and outlook, and can, in some cases, be identified by the use of words such as "believe," "anticipate," "expect," "intend," "plan," "will," "may" and other similar expressions. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward looking statements. These statements reflect management's current beliefs and are based on information currently available to management. Certain material factors or assumptions are applied in making forward looking statements, and actual results may differ materially from those expressed or implied in such statements. Important factors that could cause actual results to differ materially from these expectations include, among other things: uncertainties and risks related to, the availability of capital, changes in capital markets, uncertainties related to clinical trials and product development, rapid technological change, uncertainties related to forecasts, competition, potential product liability, unproven markets for technologies in development, the cost and supply of raw materials, management of growth, effects of payers ' willingness to pay for products, risks related to regulatory matters and risks related to intellectual property matters. When relying on ACT's forward looking statements to make decisions with respect to ACT, investors and others should carefully consider the foregoing factors and other uncertainties and potential events. Such forward looking statements are based on a number of estimates and assumptions which may prove to be incorrect, including, but not limited to, assumptions regarding the availability of financing for research and development companies in addition to general business and economic conditions. These risks and uncertainties should be considered carefully and investors and others should not place undue reliance on the forward looking statements. Although the forward looking statements contained in this material are based upon what management believes to be reasonable assumptions, ACT cannot provide assurance that actual results will be consistent with these forward looking statements. ACT undertakes no obligation to update or revise any forward looking statement.