1. IPHAR DRUG DEVELOPMENT FOR FOREIGN AND DOMESTIC MARKETS Tomsk 2014 2014 Copyright © IPHAR

2. IPHAR IS A GROUP OF COMPANIES Main activities: Development of Innovative Drugs for Russian and Global market Development of Generic Drugs and Food Supplements Pilot Manufacturing (Drugs and Food Supplements) Contract Services for Preclinical and Clinical studies (more than 60 studies for Russian and foreign customers in the past 5 years) 2014 Copyright © IPHAR

3. IPHAR - DRUG DEVELOPMENT CENTRE (accredited by Skolkovo) API screening Project “packaging” Attraction of investments IP protection Drug formulation Technology scaling Preclinical research Clinical trials Registration Pilot manufacturing Commercialization Manufacturing and Sales Customers Development and Commercialization 2014 Copyright © IPHAR

4. Commercialization department (preparing projects, attraction of investments, IP protection) Management (planning, management and control of all activities – from idea to implementation) Clinical department (clinical trials of new drugs in Russian clinical centers) Technological department (development and scaling drug synthesis technology) R&D center specializing in preclinical trials of drug safety and efficacy Team (over 100 employees, 6 D.Sc., 12 PhD) STRUCTURE OF IPHAR 2014 Copyright © IPHAR

5. PRECLINICAL TRIALS OF EFFICACY, SAFETY AND PHARMACOKINETICS  In vitro screening of pharmacological activity  Detailed studies of mechanism of action and specific activity in experimental pathology models in vivo and in vitro  Safety studies (acute and chronic toxicity, specific toxicity)  Studies of active compound metabolites, identification of main metabolites;  Studies of absorption, distribution and excretion of active compound and its metabolites;  Analysis of pharmacokinetic interaction with other drugs. 2014 Copyright © IPHAR

6. CLINICAL TRIALS. DRUG REGISTRATION  Development of registration dossier for substances and drugs;  Drafting documents for obtaining permission for clinical trials of drugs (clinical trial protocol, Investigator’s Brochure, instructions for use);  Organization and conduct of clinical trials of all phases: Bioequivalence and therapeutic equivalence of generic drugs Phase I, II, III trials of clinical efficacy and safety of novel drugs; post-registration clinical trials 2014 Copyright © IPHAR

7. 2013 2014 2015 2016 1. Antiulcer drug – peptic ulcer and GERD 2. Anti-inflammatory drug - rheumatism, arthritis 3. Anti-Parkinson drug - Parkinson's disease 4. Antiplatelet drug - cardiovascular disease 5. Antiviral drug – flu 6. Non-narcotic analgesic 7. Antidepressant DEVELOPMENT OF INNOVATIVE DRUGS FOR GLOBAL MARKETS In 2014 - 2016 IPHAR plans to complete preclinical studies and start clinical trials of 7 novel drugs, including: 2014 Copyright © IPHAR

8. Product – new molecule based on pyridopyrazindione with a new mechanism of action on the H + /K + ATPase: a reversible potassium- independent proton pump inhibitor. IP: Patent RU 2465274, priority date 05.03.2010; PCT/RU2011/000103; US patent # 8440670 dated 14.05.2013; EPO application 11750980.2 dated 04.10.2012; Ukraine and EAPO applications. Competitive advantages compared to the best drugs on the market (proton pump inhibitors ): reversibly inhibits gastric mucosa enzyme (proton pump); does not suppress normal gastric acid secretion level; does not inhibit gastrointestinal peristalsis; reduces the risk of night-time acid “breakthrough” and “rebound” – sudden increase in acidity after cancelling the drug. Consumer benefits – sustained normal digestion level in long-term treatment, reduction in adverse effects incidence and disease recurrence. ANTIULCER DRUG 2014 Copyright © IPHAR

9. The drug is based on a new small molecule (a terpenoid derivative), different in its properties from the known antiparkinson compounds. IP: patent RU 2418577, priority date 24.12. 2009; PCT/RU2010/000778; US patent #8809391 dated 19.08.2014; EPO application 10844832.5 dated 20.07.2012; EAPO patent No 019658 dated 30.05.2014. Competitive advantages : does not cause dyskynesia and other motor and non-motor adverse effects, present in levodopa; effectiveness – as good as levodopa, unlike most competitors (dopamine agonists or MAO and COMT inhibitors); can potentially have neuroprotective action and eliminate some non- motor disorders of Parkinson disease; can be used to treat drug-induced parkinsonism. Consumer benefits : 1) Makes safe and long-term PD monotherapy possible; 2) Slows down the disease progression; 3) Eliminates non-motor disorders. ANTI-PARKINSON DRUG 2014 Copyright © IPHAR

10. Product - the new patented compound - N-[3-(4-nitrophenylamino)-indole- 2-ilmethylene]aminoguanidine hydrochloride with a new mechanism of action - selective inhibition of inducible NO-synthase. IP: Patent RU 2478618, priority date 15.03.2010; PCT/RU 2011/000142; US patent #8642784 dated 04.02.2014; European patent No2548866 dated 09.07.2014; Ukraine and EAPO applications. The main advantage of the drug over the worldwide used analogs (NSAIDs) is the absence of dangerous ulcerogenic effects, because its pharmacological target is NO-synthase and not cyclooxygenase. Efficiency - the new compound exerts anti-inflammatory action as potent as voltaren and indomethacin in peritonitis and arthritis models (ED 50 – 50 mg/kg, mice, rats) Safety - the compound has low toxicity (LD 50 >5000 mg/kg, mice). Market. There are no direct market analogs of the new drug. World market of NSAIDs amounts to $10 billion. ANTI-INFLAMMATORY DRUG 2014 Copyright © IPHAR

11. Product – a new molecule - indolinone-3 derivative with a new mechanism of action - a nitric oxide donor and a stimulator of soluble guanylate cyclase and cGMP synthesis. IP: Patent RU No 2483066, priority 08.11.2011; PCT/RU2012/000884; US and EPO applications. Competitive advantages: Unlike aspirin, the new molecule does not have ulcerogenic side effect. Unlike the known antiplatelet drugs, it has anti- hypertensive and cardioprotective properties, reducing xenobiotic load, the incidence of adverse effects and costs of cardiovascular disease treatment. Efficacy is proven in in vitro (GC activity) and in vivo models (platelet aggregation, parenchymal hemorrhage, hypertension). Effective doses: 10 -7 mol in vitro, 4-12 mg/kg (per os), 0,01-1,0 mg/kg (intravenously). Low toxicity - LD 50 = 8900 mg/kg in oral administration in mice. Market. The world antiplatelet drug market amounts to $15 billion. The novel drug aims to be a possible alternative to clopidogrel and new antiplatelet drugs (prasugrel, ticagrelor) used in CVD therapy. ANTIPLATELET DRUG 2014 Copyright © IPHAR

12. OOO IPHAR President: Veniamin Khazanov, Professor, MD, Ph.D., D.Sc. Address: Elizarovykh str. 79/4, Tomsk, Russia Tel./fax: +7(3822)248721 Mob.: +79138295599 e-mail: mail@iphar.ru www.iphar.ru 2014 Copyright © IPHAR