Glenmark introduces Favipiravir (FabiFlu®) for the treatment of mild to moderate COVID-19 in India

UNLOCKING THE TREATMENT FOR MILD TO MODERATE COVID-19 IN INDIA Glenmark Pharmaceuticals Limited June 2020 Glenmark Press Brief Private & Confidential Glenmark Pharmaceuticals – An Overview Leading Integrated research-led global pharmaceutical company Consolidated revenue: INR 9,865 Crores1 Global Operations in more than 80 countries with over 14000 employees 1. FY 1819 Financial Figures 2. As per SCRIP 100 Rankings 2019 Among the Top 80 Pharma companies globally2 Integrated across the pharmaceutical value chain with strong presence in drug discovery, API and finished dose formulations Established research prowess in both novel small molecule and biologics research with molecules in different stages of development 15 facilities across formulations and API in 4 continents Glenmark Press Brief Private & Confidential Glenmark Pharmaceuticals – India Business Among the fastest growing companies for the last 5 years* ₹2,788 Cr Sales 14th Rank (Value-wise) Leadership positions in Dermatology, Respiratory & Anti-Hypertensive therapies Source: IQVIA SSA MAT Mar 2020 *In Top 20 companies in Indian Pharmaceutical Market Glenmark Press Brief Private & Confidential – For Internal Circulation Only COVID 19 – Situation Today Glenmark Press Brief Private & Confidential COVID19 – Global Situation 83,85,440 Confirmed Cases 4,50,686 Deaths 5.37% Fatality Rate 216 Affected Countries* Source: WHO (Accessed on 9AM, 20th June 2020) *Countries/Regions as recognized by WHO Glenmark Press Brief Private & Confidential COVID 19 – Current Situation in India 0 2000 4000 6000 8000 10000 12000 14000 16000 0 50000 100000 150000 200000 250000 300000 350000 400000 450000 1-Apr 6-Apr 11-Apr 16-Apr 21-Apr 26-Apr 1-May 6-May 11-May 16-May 21-May 26-May 31-May 5-Jun 10-Jun 15-Jun 20-Jun Total Cases New Cases 3,95,048 Confirmed Cases 1,68,269 Active Cases 12,948 Deaths 3.28% Fatality Rate 2,13,831 Recovered Source: MoHFW (Accessed on 9AM, 20th June 2020) Glenmark Press Brief Private & Confidential COVID 19 – Current Situation in India 3967 4987 4970 5609 6654 6977 6387 7466 8380 8171 9304 9887 9983 9985 10956 11929 10667 12881 14516 500 2500 4500 6500 8500 10500 12500 14500 16500 Daily Increase in cases Source: MoHFW (Accessed on 9AM, 20th June 2020) COVID-19 Need of the hour Glenmark Press Brief Private & Confidential Need of the hour… 1. Help the healthcare professionals to fight back 2. Help in faster recovery of patients & save lives Glenmark Press Brief Private & Confidential is at the forefront of Leading the fight against COVID19 Glenmark Press Brief Private & Confidential Initiated evaluation of treatment options for COVID-19 and identified Favipiravir as a potential candidate. Glenmark Press Brief Private & Confidential Why did we initiate work on Favipiravir? 1 2 It had shown promising results in a couple of studies in China3,4 3 4 It is an oral product & that is a big benefit especially when the hospital infrastructure is under strain It has a proven in-vitro activity against SARS CoV21 5 It already was approved for novel or re-emerging pandemic influenza virus infection in Japan5 It has a wide therapeutic safety margin for COVID-19 dose2 1,2. Cell Research (2020) 0:1–3; https://doi.org/10.1038/s41422-020-0282-0) 3. Cai Q et al. Engineering (Beijing). 2020;10.1016/j.eng.2020.03.007. 4. Chen C et al. MedRxiv. 2020 Jan 1. 5. Avigan® Tablet 200 mg- Deliberation Results by PMDA. (2014). Favipiravir: Report on the Deliberation Results; Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau; Ministry of Health, Labour and Welfare; March 4, 2014. Avigan® is registered brand name of the innovator. Glenmark Press Brief Private & Confidential Favipiravir – Global status update • COVID-19 therapeutic management guidelines include Favipiravir in Russia, Japan & Saudi Arabia • ~18 global CTs in 3000+ subjects in clinical trials globally including India, USA, Canada, Italy, China, France, UK and other countries • Compassionate Use in Japan: ~2050 patients already administered Favipiravir in Japan for clinical use – high recovery rates observed at both 7 and 14 days of therapy in both mild and moderate patients • Approved by Italy & China for experimental use/compassionate use in COVID-19 • 760 patient trial of Favipiravir initiated in Canada recently in long term care centres Glenmark Press Brief Private & Confidential Favipiravir – Global status update • Under regulatory licensing process in Turkey, expected to be made available to patients soon • Commercially launched by many companies in Bangladesh • Commercialization approval granted in UAE; protocol approved in Jordan • Under registration approval process by more than 15 companies for launch in Egypt. • Indonesia and Thailand approved clinical protocol; companies developing locally for launch • Adopted in the COVID-19 treatment protocol in multiple CIS countries such as Ukraine, Kazakhstan, Uzbekistan and Moldova • Evaluation ongoing in other middle eastern countries such as Iraq and Bahrain based on Saudi Arabia COVID-19 treatment guidelines Glenmark Press Brief Private & Confidential Glenmark demonstrated end-to-end development capabilities… 1 2 3Synthesized the Active Pharmaceutical Ingredient (API) Developed the Formulation Received approval to conduct Clinical Trials in India - Make In India - Glenmark Press Brief Private & Confidential The Approval Journey Glenmark Press Brief Private & Confidential Glenmark Favipiravir Clinical Trial – An Overview • Randomized, multi-centric study in Indian patients evaluating efficacy and safety of Favipiravir with standard of care vs. standard of care alone in mild to moderate COVID-19 • Sample size: 150 subjects (90 mild and 60 moderate patients) • Dosing regimen: Favipiravir tablets; 3,600 mg (1,800 mg BID) (Day 1) + 1,600 mg (800 mg BID) (Day 2 or later) for up to maximum of 14 days, along with supportive care. • Treatment duration: Maximum of 14 days • Patient population: Hospitalized subjects with confirmed RT-PCR positivity • Conducted in 11 sites across India. Glenmark Press Brief Private & Confidential Promising global evidence of safety & efficacy Russian Study basis which approved by Russian Ministry of Health • No. of patients: 390 (Part 1- 60 and Final part 360) • Median elimination time for the SARS CoV-2 was 4 days with Favipiravir compared to 9 days with standard therapy. • With Favipiravir, Day 4 of treatment 65% of patients turned RT-PCR negative for SARS CoV-2, Day 10 of treatment, 90% of patients turned RT-PCR negative for SARS CoV-2 • Favipiravir gr. 68% reached Fever resolution on day 3 vs Std. therapy on day 6 • Overall reported efficacy of favipiravir is >80% (Ref: https://rdif.ru/Eng_fullNews/5224/) Observational Study from Japan • No. of patients: 2141 In Mild to Moderate COVID-19 patients- • Clinical improvement with Favipiravir upto 74% by Day 7 of treatment • Clinical improvement with Favipiravir upto 88% by Day 14 of treatment (Ref: http://www.kansensho.or.jp/uploads/files/topics/ 2019ncov/covid19_casereport_en_200529.pdf) Glenmark Press Brief Private & Confidential Promising global evidence of safety & efficacy Chinese Study 1 (Cai et al.) • No. of patients: 80 • Significantly shorter viral clearance time with Favipiravir (4 days) compared to 11 days for LPV/RTV (Lopinavir/Ritonavir) • Significantly higher improvement in chest CT changes with Favipiravir (91.4%) compared to LPV/RTV(62.2 %) • Favipiravir has better Safety profile than LPV/RTV (Ref: Cai Q et al. Engineering (Beijing), 2020;10.1016/j.eng.2020.03.007.) Chinese Study 2 (Chen et al.) • No. of patients: 236 • Significantly superior clinical recovery rate (71.4%) at day 7 with favipiravir than that of umifenovir (55.8%) in moderate COVID-19 patients • Favipiravir had significantly shorter time to relief from fever and cough than umifenovir (Ref: Chen C et al. MedRxiv. 2020 Jan 1.) Glenmark Press Brief Private & Confidential All these studies point to the following… Rapid reduction in viral load1,2 Faster fever resolution1,3 Faster resolution of Chest CT changes4 Faster clinical recovery2,3 References: 1. https://rdif.ru/Eng_fullNews/5224/ 2. http://www.kansensho.or.jp/uploads/files/topics/ 2019ncov/covid19_casereport_en_200529.pdf 3. Chen C et al. MedRxiv. 2020 Jan 1 4. Cai Q et al. Engineering (Beijing), 2020;10.1016/j.eng.2020.03.007 Glenmark Press Brief Private & Confidential has received permission from the Indian drug regulator To Manufacture and Market Favipiravir in India for treatment of Mild to Moderate COVID-19* *Under the Accelerated Approval Process Glenmark Press Brief Private & Confidential Favipiravir – Accelerated Approval Process • Accelerated approval process takes into account the disease severity, rarity, and the availability or lack of alternative treatment. • Glenmark has received approval to manufacture and market Favipiravir in India for mild to moderate COVID-19 cases. • Emergency Use Authorization is a provision that allows countries to use drugs urgently needed in an emergency situation or healthcare crisis. (COVID-19 pandemic) • “Emergency” here does not refer to patients in an emergency status of the disease, but refers to the emergency pandemic situation prevalent in the country and the need for effective and timely treatment. • Restricted use entails “responsible medication” use where every patient must have signed informed consent before treatment initiation Glenmark Press Brief Private & Confidential *Under the Accelerated Approval Process Favipiravir An important step for Oral Treatment of Mild to Moderate COVID-19* Glenmark Press Brief Private & Confidential Favipiravir – Mechanism of Action • Favipiravir is incorporated into cells and converted to favipiravir ribofuranosyl-5′-triphosphate (favipiravir-RTP) by host cells. • Favipiravir-RTP , inhibits the activity of RNA dependent RNA polymerase (RdRp) of SARS CoV2. • The inhibition of RdRp leads to inhibition of the viral replication. Glenmark Press Brief Private & Confidential Starting early is the key… Glenmark Press Brief Private & Confidential Favipiravir – Starting early is a key in COV Early stages – Mild and Moderate Later stages- Severe and Critical • High rate of viral replication • Can be controlled with early use of Antiviral drugs • Limited immune response mediated damage - Immune response subsides quickly Viral replication Body’s immune response Body’s violent immune response Viral replication • Viral replication slows down • Body’s violent immune response drives disease leading to complications and organ failure • Diminishing effects of Antiviral drugs • Higher dependence on other drugs and ventilators for survival Glenmark Press Brief Private & Confidential Favipiravir – Contraindications & Cautions Contraindications: • The drug is contraindicated in patients with severe renal, hepatic impairment, pregnant & lactating women. • The drug is contraindicated in patients with history of hypersensitivity to Favipiravir. Cautions: • The drug should be used with caution in patient with history of abnormalities in metabolism of uric acid or having Gout. Glenmark Press Brief Private & Confidential Favipiravir and Umifenovir Combination – An update • COVID-19 patients show high viral load at time of symptom onset suggests treating with combination of antiviral drugs- highly effective and minimize the emergence of resistance. • In line with this strategy, Glenmark proposes to combine two anti-viral drugs Favipiravir (Approved drug for novel flu pandemics) with Umifenovir (Approved drug for Influenza) – safety well established. • Both drugs acting on different mechanisms the combined use of Favipiravir and Umifenovir offers a comprehensive antiviral cover on pre-entry and post-entry life-cycle of SARS-CoV-2 virus. • Umifenovir: Interaction with viral attachment, fusion with infected cell • Favipiravir: Prevention of viral replication by inhibition of RNA dependent RNA polymerase Glenmark Press Brief Private & Confidential The Next Step… Glenmark Press Brief Private & Confidential proudly introduces The First Oral Anti-viral Treatment Option for Mild to Moderate COVID-19 cases* *Under the Accelerated Approval Process Glenmark Press Brief Private & Confidential Available as a tablet of 200mg It will be available in a strip of 34 tabs Glenmark Press Brief Private & Confidential Dosage: Price: MRP ₹3500 for a pack of 34 tablets (Approx. ₹ 103 per tablet) Day 1 Day 2 to max 14 days Total Daily Dose 1800 mg BID 800 mg BID Morning 200 mg x 9 tabs 200 mg x 4 tabs each day Evening 200 mg x 9 tabs 200 mg x 4 tabs each day Glenmark Press Brief Private & Confidential A significant step in the fight against Mild to Moderate COVID-19 cases* *Under the Accelerated Approval Process Glenmark Press Brief Private & Confidential Thank you! www.glenmarkpharma.com

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