Transcript Dr. Swati Bal-Tembe - RIS
Incentives for Innovation Partnerships for Drug Development
Dr. Swati Bal-Tembe May 12, 2011 International Conference on Equity and Access to Medicine Role of Innovation and Institutions
Drug discovery and development
• New drug in the market > $1 billion • Patents to protect market exclusivity • Leverage for obtaining funds, technologies; or for licensing/cross-licensing • Attractive assets to potential investors, collaborators and acquiring companies • Strategy based on Company’s business model and business environment © 2011 Dr. Swati Bal-Tembe May 12, 2011
Drug Discovery and Development
• HTS / Virtual Screening • NP / Focused Library / Combichem/ Fast Follow-on • Rational Drug design
Target Identification & Validation Lead Development Preclinical Studies
IND
Clinical Trials
NDA
Market
• NCE • Me-Too • Lifecycle Extensions • NDDS © 2011 Dr. Swati Bal-Tembe May 12, 2011
“Me-Too Drugs”
N N O Rosiglitazone US 5,002,953 O S N H O N O Pioglitazone US 4,687,777 O S N H O O N S O N N H Omeprazole US 4,255,431 O F F F O N S O N N H Lansoprazole US 4,628,098 © 2011 Dr. Swati Bal-Tembe O O N S O N N H Pantoprazole US 4,758,579 O F F May 12, 2011
Markush Structure
We claim: A compound of Formula 1
R A L 1 (R X ) 0-4 X (R Y ) 0-4 Y L 2 L 3 R B Formula 1
Wherein rings X and Y independently represent 5 to 7 membered heterocycle, aryl or heteroaryl ring that may be substituted with 0-4 substituents described by R X and R Y respectively Wherein L 1 L 2 , L 3 R A , R B , R X , R Y is O, NH, CH 2 or a bond © 2011 Dr. Swati Bal-Tembe May 12, 2011
CHALLENGES
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Challenges
• Crisis in the Pharmaceutical industry • Patent cliff • Expiration of blockbuster patents • Fewer regulatory approvals of NMEs © 2011 Dr. Swati Bal-Tembe May 12, 2011
Measures
• Spending cuts, downsizing • Focus • Mergers, acquisitions - Merck acquired Schering Plough for $41 billion in 2009 - Pfizer acquired Wyeth for $68 billion in 2010 - Sanofi Aventis to acquire Genzyme for $20.1 billion • Line extensions, branded/authorized generics • Collaborations – outsourcing, contract research © 2011 Dr. Swati Bal-Tembe May 12, 2011
Blockbuster Line-Extensions To sustain revenue after Patent Expiry:
Crystalline forms (ranitidine), particle size (griseofulvin), specific enantiomer, new uses, combinations NDDS - novel formulations, extended release systems • Nexium ® (Esomeprazole) - single enantiomer • Allegra ® (Fexofenadine) - active metabolite (COOH) minus the side effects of Seldane ® (Terfenadine) • Fosamax ® and Prozac ® – daily therapy to weekly • Thalidomide ( Lenalidomide) – new use in multiple myeloma • © 2011 Dr. Swati Bal-Tembe May 12, 2011
INVENTION AND INNOVATION
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Invention and innovation
• Strategy will have to focus more on inventions that have a good chance of benefiting the patient • The test of an innovation lies not (only) in its novelty, its scientific content, or its cleverness but its success in the marketplace - Peter Drucker • 3M Dr Spencer Silver discovered the formula for an adhesive, but Art Fry, a product development researcher, came up with a marketable use for it in the form of Post-it ® notes © 2011 Dr. Swati Bal-Tembe May 12, 2011
OPPORTUNITIES
© 2011 Dr. Swati Bal-Tembe May 12, 2011
ABRAXANE
® © 2011 Dr. Swati Bal-Tembe May 12, 2011
To Market – Nanomedicines
• Paclitaxel, active ingredient in Taxol ® , is poorly soluble in biological fluids. • Solubilizing agents often produce dose-limiting side effects • Abraxis BioScience Inc. developed a nanoparticle formulation of the potent anticancer drug paclitaxel • Abraxane ® approved in 2005 • Revenue >$ 300 million in 2007, 2008 and 2009 • Loading paclitaxel into a nanoparticle made of the natural protein albumin eliminated the need for additional chemicals • Targeted therapy • Premedication with steroids or antihistamines that treat hypersensitivity reactions caused by solvents not required • Patients could be given higher doses of paclitaxel with fewer side effects © 2011 Dr. Swati Bal-Tembe May 12, 2011
Elan v. Abraxis
• Elan Pharmaceuticals sued Abraxis BioScience, Inc. for patent infringement • Delaware district court jury awarded Elan $55.2 million in damages for Abraxis's past infringement based upon a reasonable royalty rate of 6%. • Celgene acquired Abraxis for $2.9 billion in July 2010 • Elan has entered into a settlement and license agreement with Celgene resolving the patent infringement litigation involving ABRAXANE ® • Celgene will pay Elan a one-time fee of $78 million.
© 2011 Dr. Swati Bal-Tembe May 12, 2011
FIDAXOMICIN
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Fidaxomicin
Being developed by Optimer Pharmaceuticals, San Diego Phase III trial results (Feb 2011): Superior to Vancomycin in the treatment of Clostridum difficile infections. On April 7, 2011, FDA Panel unanimously recommended approval of Fidaxomicin for the treatment of CDAD. Patents issued for production method, polymorph, dosage forms, and method of treatment of gastrointestinal infection caused by Clostridum difficile using “R-Tiacumicin B” Licensing deal with Astellas Pharma Inc. API manufacture - Biocon © 2011 Dr. Swati Bal-Tembe May 12, 2011
Fidaxomicin
© 2011 Dr. Swati Bal-Tembe • Antibiotics Tiacumulin A-F isolated by fermentation of culture of microorganism belonging to the Actinoplanaceae family • Patent application assigned to Abbott Labs; filed in 1986, issued in 1990 • Activity against a number of Gram positive microorganisms; Clostridium not specifically disclosed • Except on sugars, stereochemistry not specifically indicated • “R-Tiacumicin B” is Optimer’s Fidaxomicin May 12, 2011
PLX4032
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Opportunities
• Difficult targets, new first-in-class drugs for unmet medical needs • FDA’s indicators of “innovativeness” – priority status - Novel mechanism of action - Novel structure • Personalized medicine © 2011 Dr. Swati Bal-Tembe May 12, 2011
PLX4032
• Presence of B-Raf gene mutation in over 50% of melanoma patients and 10% in other cancers discovered in 2002 by Prof Marais in the UK cancer research labs funded by the Wellcome Trust • Soon after discovery of the gene mutation, Plexxikon set up a screening method for the discovery of inhibitors of the B-Raf gene mutation using its scaffold-based drug discovery platform. • Resulted in the discovery of PLX4032.
• Developed in partnership with Roche • Companion diagnostic © 2011 Dr. Swati Bal-Tembe May 12, 2011
PLX4032
• In 2006, Roche agreed to pay $40 million cash and up to $700 million after reaching predefined milestones. • Phase III trial (March 2011) showed that PLX4032 met co primary endpoints of overall survival and progression-free survival in patients with previously untreated metastatic melanoma expressing the B-Raf mutation • Daiichi Sankyo to buy Plexxikon acquiring rights to PLX4032 - Upfront payment of $805 million - Near-term milestone payments of $130 million - Daiichi Sankyo to gain certain co-promotion rights in the USA for PLX4032, being jointly developed by Plexxikon and Roche © 2011 Dr. Swati Bal-Tembe May 12, 2011
Opportunities
• Natural products – Bioprospecting • Enabling technologies • Less explored biodiversity, extreme conditions - Convention on Biological Diversity (CBD) - Convention on International Trade in Endangered Species and Flora and Fauna (CITES) • Biological deposits • Patentability in different jurisdictions • Biological material obtained from India • Partnerships © 2011 Dr. Swati Bal-Tembe May 12, 2011
Microbial metabolites as pharmaceuticals
H O H N O N H 3 C O O H N O CH 2 N H CH 2 O NH 2 N O N O S N H N O S N S S S N N O N N N H CH 2 H N O O CH 3 NH 2 N H O PM181104 From marine microorganism Kocuria sp.
Partnership with NIO, Goa Effective against resistant bacteria MRSA, VRE PCT Publication: WO 2007/119201 (PLSL – CSIR) © 2011 Dr. Swati Bal-Tembe May 12, 2011
PUBLIC-PRIVATE PARTNERSHIPS
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Public Private Partnership Innovative partnership models
Antimalarial compound NITD609 developed through a Novartis led collaboration: Novartis Institute for Tropical diseases Singapore, Scripps Research Institute, Swiss Tropical Institute and the Public Health Institute Major support from the Wellcome Trust, MMV, A*STAR Singapore and the US Govt GlaxoSmithKline’s (GSK) drug discovery center for diseases of the developing world in Spain Employs more than 100 scientists Clinical development experts from UK & US.
The GSK facility works closely with the Medicines for Malaria Venture and the TB Alliance GSK is contributing a matching number of staff and all remaining overhead costs.
Around 1.5 million compounds have now been tested for anti-TB activity and four pre-clinical TB projects are underway.
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Public Private Partnership Innovative partnership models
Eli Lilly and Company launched the “Lilly Not-for-Profit Partnership for TB Early Phase Drug Discovery” research institute International alliance with several public and private organizations Partnership with groups such as Afya World Medicines Inc., the Infectious Disease Research Institute, Jubilant Biosys and Academia Sinica, Taiwan The company has opened its library of more than 500,000 Lilly medicinal compounds to researchers To conduct early-phase discovery research of new medicines to treat TB including emerging resistant strains.
The AstraZeneca Bangalore Research Institute in India Dedicated to finding a new therapy for TB that will act against drug-resistant disease and reduce the duration of treatment.
In addition to the initial investment in buildings and state-of-the-art equipment of US$20 million, AstraZeneca has committed a minimum of US$5 million a year to supporting the research program.
More than 80 scientists recruited from leading research institutions and universities now work at the facility © 2011 Dr. Swati Bal-Tembe May 12, 2011
The Indian scenario
• DBT Mission Programme on "Screening for Bio-molecules from microbial diversity collected from different ecological niches" • First project in the country with industry & academia collaboration to screen a large number of bacterial isolates isolated from diverse ecological niches against targets for Cancer, Diabetes, Inflammation and Infectious diseases • Indian government initiative OSDD Open Source Drug Discovery for compounds effective against latent and drug-resistant TB • Computation, Biology, Medicinal Chemistry, Preclinical, Clinical • 2008-2012-2018 • No IP constraint © 2011 Dr. Swati Bal-Tembe May 12, 2011
Indian pharma companies at the crossroads
• Generic drugs • Drug discovery research • Money spent without guaranteed returns • Different business models - Go it alone - Go it alone / licensing - Licensing from Academia - Research collaborations with universities/institutes - Research collaborations with big pharma - Contract research © 2011 Dr. Swati Bal-Tembe May 12, 2011
INDIAN PATENT SCENARIO
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Indian patent scenario
• Provisions of Section 3(d) – Higher standards for inventive step to discourage evergreening • Efficacy data?
• Interpretation of “derivatives” • New use exempted • Evolving case law • Strategy on opposing patents/patent applications © 2011 Dr. Swati Bal-Tembe May 12, 2011
DUE DILIGENCE
© 2011 Dr. Swati Bal-Tembe May 12, 2011
Due diligence University/Small company/Large company model
Developing Strategy and Implementation • Institutional IP Policy • Ownership, title, assignment/licensing agreements • Analysis of patents/patent applications/file histories • Freedom-to-operate assessment • Identify gaps in portfolio or potential blocking patents • Strength of patents/patent applications • Review and audit • Costs © 2011 Dr. Swati Bal-Tembe May 12, 2011
Indian pharma companies at the crossroads
• Lifestyle diseases – eye on the global market • Unmet medical need • Neglected/Infectious diseases – Market? Recovering costs?
– “Orphan drug” type status – priority review?
– Tax benefits (Clinical trials) – Validated herbal medicines • Hybrid model Public funding Health Impact fund Public-private partnerships Guaranteed purchase contracts Tax credits on sales © 2011 Dr. Swati Bal-Tembe Philanthropy Corporate social responsibility Drug donation Differential pricing May 12, 2011
Initiatives
Measures for reducing occurrence/recurrence of infectious/neglected diseases - Poverty alleviation - Health, sanitation, nutrition, maternal and child health - Safe water, minimize drug resistance Development of rapid POC detection tests Healthcare Management / Insurance © 2011 Dr. Swati Bal-Tembe May 12, 2011
© 2011 Dr. Swati Bal-Tembe
Thank you
May 12, 2011