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

988*-****-****

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 3

Synthesized 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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