Moji Christianah Adeyeye, PhD President and Chief Scienti8ic Of8icer - - PowerPoint PPT Presentation

Moji ¡Christianah ¡Adeyeye, ¡PhD President ¡and ¡Chief ¡Scienti8ic ¡Of8icer Professor ¡of ¡Pharmaceutics ¡and ¡Drug ¡Product ¡Evaluation Chair, ¡Biopharmaceutical ¡Sciences, ¡College ¡of ¡Pharmacy Roosevelt ¡University, ¡Schaumburg, ¡IL, ¡USA

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University-Based Development: Cheaper Means to Treat Children Living with HIV/AIDS

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Inte tellectu tual Pate tent t and Licensing

} Patents: Antiretroviral Drug Formulations for

Treatment of Children Exposed to HIV/AIDS PCT/US2009/031285

• UK Patent Application – GB 10118925
• US Patent Application – 12/863,111
• South Africa Patent Application – 2010/05070

} License obtained in 2009 from Duquesne

University with royalty agreement

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} 2009/2010

IND Filed

} January/May 2010

FDA Approval of IND

} September 2010

Clinical Batch Manufactured

by Emerson Resources Inc.

} October 2010-April 2012

Clinical Trial

} May/June 2012

Pre-NDA Discussion Clinical Trial Data

Submission

} September 2012

FDA Advise to submit two New Drug Applications (NDA) 505(b)2, one for each product

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Manufactured for Elim Pediatric Pharmaceuticals Inc. September 2010 by Emerson Resources, USA

GMP* Taste-masked FDC Granules (Reconstitutable Suspension

* Good Manufacturing Practice (in FDA-certified facility)

GMP* Batch (Taste- masked FDC Tablets for Suspension)

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Dissolution Profile of Zidovudine, Lamivudine and Nevirapine in 3 in 1 tablet

10 20 30 40 50 60 70 80 90 100 5 10 15 20 25 30 35 40 45 50 55 60 65 Time(min) % Drug Release Nevirapine Zidovudine Lamivudine

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Release of drugs met FDA’s requirements

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Nevirapine Lamivudine Zidovudine

Versus Versus El Elim Products ts

Comparison of amount t of commercially available individual drugs admixed For a ch For a child’s u ild’s use: Nev se: Nevirapin irapine plu e plus lam s lamiv ivudin dine plu e plus s Zidov Zidovudin dine (15 m (15 ml~ 1/1/2 l~ 1/1/2 ta tablespoons ) - Bitte tter ta taste te TES EST – – 1 ta tablet t (te teste ted pleasant t ta taste te) TES EST – – 5ml (I te teaspoon) (te teste ted pleasant t ta taste te)

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} Comparison of amount

t of commercially available in indiv dividu idual dru al drugs adm s admixed for a ch ixed for a child’s u ild’s use: se:

• Ref

Referen erence: Liqu ce: Liquid id ne nevi virapine ne plu plus lam lamiv ivudin dine plu e plus zidov zidovudin dine

• 15 ml~ 1/1/2 ta

tablespoons with th bitte tter ta taste te

} El

ElimPP Inc. th three drugs-in-one ta tablet t or liquid dose

• Granules for reconsti

titu tuti tion (liquid)

– 5 ml or 1 te teaspoon (te teste ted pleasant t ta taste te)

• Fast

t dissolving ta tablet t for suspension

– 1 ta tablet t (te teste ted pleasant t ta taste te)

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Bioequ Bioequiv ivalen alence: ce: El ElimPP Inc. Products ts distr tribute te similarly in th the body (bioequivalent) t) – – Met t FDA DA’s requirement t

100 200 300 400 500 600 700 0 ¡ 2 ¡ 4 ¡ 6 ¡ 8 ¡ 10 ¡ 12 ¡ 14 ¡ Conc ¡(ng/mL) ¡ Time ¡(h) ¡ Plasma concetration profile for Zidovudine Ref Susp Tab 100 200 300 400 500 600 700 800 900 0 ¡ 2 ¡ 4 ¡ 6 ¡ 8 ¡ 10 ¡ 12 ¡ 14 ¡ Conc ¡(ng/mL) ¡ Time ¡(h) ¡ Plasma concentration profile for Lamivudine Ref Susp Tab 50 100 150 200 250 300 350 400 20 40 60 80 100 Conc ¡(ng/mL) ¡ Time ¡(h) ¡ Plasma concetration profile for Nevirapine Ref Test Sus

Tmax Cmax Tm Tmax ax – time to reach maximum concentration (Cmax Cmax) )

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§ Patients will tend to continue drug use due

to less number of pills to use

§ Less death among HIV infected children § Improved quality of life § Better formulation choice esp. in areas

where there is a lack of drinkable water ( developing countries)- for the fast dissolving tablet

§ Granules (powder) for reconstitution can

be dispensed for one month use

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Mis Missin ing P Puzzle zzle

} Funding of Registr

trati tion Batc tches:

• Clinical batch manufacturing by contract research
• rganization – pharmaceutical company
• Stability testing (up to six months)
• Testing for drug release (dissolution)

– [Items 2 and 3 can be done in house (within the university )] – a cost-saving approach

• Labeling and Packaging
• Filing of application

} Marketing (PEPFAR, WHO, Clinton Foundation,

etc.)

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Proposed Transaction Details

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} Elim Pediatric Pharmaceuticals Inc. signs contract

manufacturing agreement with a company for the clinical batch, submission of NDA and registration

} Elim Pediatric Pharmaceuticals Inc. performs

analytical assay development, testing and stability studies at Roosevelt University under good laboratory practice and signed cooperative research agreement with the university

} All data are complied by EPP Inc. } A consultant (form Investor) aids ElimPP Inc. in

submission

} Marketing outlets facilitated by a consultant and

aided by investor

} Distribution – consultant/investor aided

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} 1 in 4 children currently receive

treatment

} Promising market potential in Africa

• 75% of HIV infections are in sub-Saharan Africa

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Weste tern & Centr tral Eu Europe

1400 1400

[<1000 – 1800] Middle Ea East t & North th Africa

21 000 21 000

[13 000 – 28 000] Sub Sub-Sa

• Saha

haran n Afr Africa

2.3 m 2.3 million illion

[1.4 million – 3.1 million] Ea Easte tern Eu Europe 
 & Centr tral Asia

18 000 18 000

[8600 – 29 000] South th & South th-Ea East t Asia

150 000 150 000

[97 000 – 200 000] Oceania Oceania

3100 3100

[1500 – 4800] North th America

4500 4500

[4000 – 5800] Centr tral & South th America

36 000 36 000

[25 000 – 50 000] Ea East t Asia

8000 8000

[3600 – 13 000] Carib Caribbean ean

17 000 17 000

[8500 – 26 000]

Children (<15 years) estimated to be living with HIV | 2009

Tota tal: 2.5 million [1.6 million – 3.4 million]

Weste tern & Centr tral Eu Europe

<100 <100

[<200] Middle Ea East t & North th Africa

6400 6400

[4000 – 8900] Sub Sub-Sa

• Saha

haran n Afr Africa

330 000 330 000

[190 000 – 460 000] Ea Easte tern Eu Europe 
 & Centr tral Asia

3400 3400

[1500 – 6000] South th & South th-Ea East t Asia

20 000 20 000

[12 000 – 29 000] Oceania Oceania

<1000 <1000

[<500 – 1200] North th America

<100 100

[<200] Centr tral & South th America

4300 4300

[2600 – 6500] Ea East t Asia

1900 1900

[<1000 – 3600] Carib Caribbean ean

1900 1900

[<1000 – 3100]

Estimated number of children (<15 years) newly infected with HIV | 2009

Tota tal: 370 000 [230 000 – 510 000]

Weste tern & Centr tral Eu Europe

<100 <100

[<200] Middle Ea East t & North th Africa

3300 3300

[2100 – 4500] Sub Sub-Sa

• Saha

haran n Afr Africa

230 000 230 000

[130 000 – 330 000] Ea Easte tern Eu Europe 
 & Centr tral Asia

1800 1800

[<1000 – 3300] South th & South th-Ea East t Asia

14 000

[8300 – 20 000] Oceania Oceania

<500 <500

[<200 – <1000] North th America

<100 <100

[<200] Centr tral & South th America

2700 2700

[1400 – 4200] Ea East t Asia

1000 1000

[<500 – 1900] Carib Caribbean ean

1600 1600

[<1000 – 2600]

Estimated deaths in children (<15 years) from AIDS | 2009

Tota tal: 260 000 [150 000 – 360 000]

} Nearly 700,000 children need

treatment

} Estimated cost for a year treatment/

child

• $192-352

} 20% of market = 140,000 children

• Es

Esti timate ted $272 x 140,000

• $38,080,000

$38,080,000

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} Faster (tentative) approval by FDA for HIV/AIDS

drugs

} Excerpts (from personal FDA’s e-mail subscription) } Examples:

– The Food and Drug Administration, on March 18, 2009, granted tentative approval for stavudine and lamivudine fixed dose combination tablets, 30mg/150mg & 40mg/ 150mg, indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection as a component

• f combination therapy. Fixed dose combination products

such as this can ease pill burden and simplify dosing, and can help increase drug adherence.

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} Excerpts

– On On March March 30, 30, 2009, 2009, FDA granted tentative approval for abacavir sulfate and lamivudine tablets, 600 mg / 300 mg, manufactured by Matrix Laboratories Limited of Hyberdad, India, for use in combination with other antiretrovirals in the treatment of HIV infection. The application was reviewed under expedited review provisions for the President’s Emergency Plan for AIDS Relief (<http:// www.pepfar.gov/>PEPFAR).

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– On On March March 31, 31, 2009, 2009, the Food and Drug Administration granted tentative approval for a generic formulation of nevirapine tablets, USP, 200 mg indicated for combination antiretroviral treatment of HIV-1

• infection. Manufactured by MacLeods Pharmaceuticals

Limited of Daman, India, this tentatively approved formulation is a generic version of the Nonnucleoside Reverse Transcriptase Inhibitor, (NNRTI), Viramune tablets, USP, 200 mg, manufactured by Boehringer Ingelheim.

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• "Tentative approval" means that FDA has concluded

that a drug product meets all required quality, safety and efficacy standards, but is not presently eligible for final approval or marketing in the U.S. because of existing patents and/or exclusivity

• rights. However, tentative approval does make the

product eligible for purchase outside the United States under the President’s Emergency Plan for AIDS Relief (<http://www.pepfar.gov/>PEPFAR).

• The application was reviewed under expedited

review provisions for PEPFAR.

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} Preferred Manufacturing (PM) of ARVs

(through smaller companies or CROs)

• Could cut cost by 60-80%

– Lower overhead

– Virtual co.

– Facilities – Salaries

• Development and feasibility

– University Partnership – ElimPP Inc VP’s development and manufacturing expertise

• PM makes drugs affordable to children

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