Ranbaxy Laboratories LimitedArterolane maleate + Piperaquine phosphate

Shailesh Pednekar Global Therapy ManagementMumbai – 30th Sept 09

Ranbaxy Overview

Global Presence

•Top 10 Global Generic Company

Unique Strengths & Capabilities•Entrepreneurial & Empowering

Vertically Integrated

•Manufacturing – DF and APITop 10 Global Generic Company• Sales in Over 125 Countries• 2008 Revenue: $ 1.7 Billion• 80 % International; 20% India

•Ground Presence in 49 CountriesGl b l T i h Gl b l Mi d

• Entrepreneurial & Empowering Culture

• Strong Presence in Emerging Markets : 58% of DF Sales

• Foray into Biosimilars and S i lt I j t bl

Manufacturing  DF and API• 24 Plants in 11 Countries

• R&D• #1 Cumulative ANDA Filer from India• > 1400 R&D Personnel• World class Drug Discovery•Global Team with Global Mindset

• Over 12,000 Employees; Over 50 Nationalities

Specialty Injectables•Global Regulatory Prowess

• World‐class Drug Discovery Infrastructure

• NCE collaborations: GSK, Merck• Demonstrated NDDS capabilities

Largest pharmaceutical company out of Indiawith global reach and competencies across the value chain

Perhaps the largest front‐end in the generic industry

Other Emerging Markets

BRICS

• No. 1 in India • 43/54 countries in Africa• Large, reputed player in

CIS; growing rapidly• No. 6 in Brazil

No 5 in S Africa

43/54 countries in Africa• Latam & Asia Pacific:

long standing presence; good understanding; rrobust businesses

North America & Europe

• No. 5 in S. Africa rrobust businesses

North America & Japan

Europe

• Pioneer entrant from India

• Well established• 23/25 EU markets

• Strong local presence • Canada: New market,

growing rapidly

• No. 1 Generic player in Romania

Ground presence in 49 countries; products sold in 125

Background – RBx11160

Malaria is one of the most persistent killer diseases claiming more than 1 Million Lives every year. Majority being children and 40 % of world population at risk in more than 107 countries.  

Anti‐malarial research has been one of the neglected researchAnti malarial research has been one of the neglected research areas  in the world.  

D i t il bilit d ti l bilit dDrug resistance , availability , production , scalability and affordability still remain concern areas. 

MMV and Ranbaxy partnered for the drug development in year 2003 as a part of collaborative research program. 

Cont…

Originally RBx11160 was being jointly  developed by MMV and Ranbaxy as first line oral therapy for uncomplicated p.falciparumM l i l i f tiMalarial infection.  

RBx 11160 Maleate ( Arterolane Maleate ) is a synthetic Trioxolaneand would provide an alternate to plant  derivative compounds. 

Subsequently the development of the drug was doneSubsequently , the development of the drug was done independently by Ranbaxy with a goal to develop a once daily FDC that will retain all attributes of ACT’s. 

Partner Drugs was identified as Piperaquine phosphate.

The product is targeted to have a affordable cost of therapy and convenient dosing .

Targeted product profile 

Parameter TargetCombination 2 highly active drugs

(1 short half life and 1 long half life)(1 short half-life and 1 long half-life)Efficacy ACPR day 7 = 100% & day 28 PCR-corrected ≥

95%ACPR=Adequate Clinical & Parasitological Response

Gametocytocidal at least one drug in combination

Resistance no resistance at presentSafety comparable to present drugs or better

Dosing once daily for ≤ 3 daysCo-formulated must be a fixed dose combination

Shelf life ≥ 2 yearsCost of Treatment ≤ $1.00 dollar for an adult

Status of development 

Pre-clinical Phase I Phase II

Arterolane

Ph II Ph III

Pre-clinical Phase I

Filing PM CT

ComboArterolane + PQP Arterolane + PQP

Ph II Ph III Filing PM CT

Combo

Pre-clinical Phase I Phase II*

Piperaquine (PQP)

CT

CompletedOngoingOngoingTo be done

Clinical Trials with ArterolanePhase of

TrialStudy Population

(N)Country Doses in mg Findings

Young males (72) UK 25-600 mg Well tolerated

Phase I

(Safety

g ( )

(18 -45 Years)

g

(Rising single)

25-200 mg

(Rising multiple)

In healthy Vol) Elderly males & females (24)

(65 and above)

UK 100 mg (single) Well tolerated

Y l & Th il d 100 W ll t l t d PKYoung males & females (16)Pk Study – Health V

Thailand 100 mg

(single cross-over)

Well tolerated. PK similar to Caucasians

Phase II Patients (72) Thailand 25-200 mg Improved parasite

Proof of Concept

( )

Single Dose ( POC )

g

(Single)

p pclearance at 200 mg

Patients (16)

Pk Study

Thailand 100 mg

OD x7

7-day ACPR – 100%

Dose Range finding study

Patients (230)(Dose Range Finding )

Thailand India

Tanzania

50-200 mg

OD x7

Median PCT ~32 hours at 200 mg

Clinical Trials with PQP

Phase of Study Country Doses in mg FindingsTrial Population

(N)

Phase I Young Switzerland 500-1500 mg Well tolerated.

Safety In healthy Volunteers

gmales (72)

g

500-1500 OD x3

Mild AE’s

(nausea, vomiting & abdominal OD x3pain)

Published Data

Patients Vietnam

Cambodia

640 BD x2 or 640 OD

ACPR > 95%

(as non-GMP Artekin)

Cambodia

Thailand x3

Arterolane maleate + PQP ‐ Clinical DataPhase of

TrialStudy

Population (N)

Country Doses mg Findings

Phase I

( Safety )

Young males (70)

(Rising Single Dose)

Switzerland 100mg + 500mg upto 200mg + 1000mg (single)

Well tolerated.

Dose)

Young males (24 – 8 vol/cohort)

India (In-house -CPU,

Co-administration of 100mg + 500mg to 200 mg + 1000

• Well tolerated. • There seems to be a

positive interaction

(Rising Multiple Dose)

Noida) mg of RBx 11160 maleate + PQP

Multiple dose

between RBx 11160 & PQP .

• 750 mg PQP dose looks to be, just the right dose for a 3-Day regimen

Phase II

(Safety and Efficacy)

13-65 years (240) India, Thailand

Co-administration of 150mg + 750mg X 3 days

• Study completed• Well tolerated; efficacy

comparable to CoartemEfficacy) X 3 days compa able to Coa tem

Clinical Trial Sites

India

Thailand

Bangladesh

Africa ? 

Status of development – Trial Timelines

S No. Trial Title Expected C l iCompletion dates

1 Phase III Trial of FDC of arterolane End 20101 Phase III Trial of FDC of arterolanemaleate and PQP vs Coartem in India and SE Asia (P.fal)

End 2010

2 Phase II Paediatric trial in India (P.fal)

End 2010(P.fal)

3 Phase II trial in patients with Vivaxmalaria in India in Adult patients

End 2010

Future Collaborative Clinical Trials

1. Second Phase III (Pf) Trial

– Africa and India

2. Arterolane efficacy trial in artemisinin resistant patients

– Western Cambodia

3. Phase II, dose ranging trial (Pf) Trial

– African children

4. Phase III, P. vivax trial 

– India, SE Asia and Latin America

Queries? 

For any specific commercial queries : Mr. Shailesh Pednekar ‐ Business Lead E‐mail : Shailesh.Pednekar@ranbaxy.com

For any specific technical queries :     Dr. Nilanjan Saha ‐ Technical Lead E‐mail : Nilanjan.Saha@ranbaxy.comE mail : Nilanjan.Saha@ranbaxy.com

Thank You

Back Up SlidesBack Up Slides

Arterolane maleate + PQP ‐ Clinical Data

Phase of Trial

Study Population (N)

Country Doses mg Findings

Bio Avb Study with Adult formulation

Young Male volunteers

India(In-house, CPU, Noida)

150mg + 750mg (Single Dose FDC )

Comparative bioavailability

)

Bio Avb Study with Paediatricformulation

Young Male volunteers

India(In-house, CPU Noida)

37.5 mg + 187.5 mg(Single Dose FDC )

Failed formulation (Formulation issue )

CPU, Noida)

Repeat Bio Avb Young Male India 37.5 mg + 187.5 mg Showed Comparative Study with Paediatricformulation

volunteers (In-house, CPU, Noida)

(Single Dose FDC ) bioavailability