From Development to Commercial Production: don t contemplate but anticipate

Transcription

1 From Development to Commercial Production: don t contemplate but anticipate Automation in the Pharmaceutical Industry Leiden July 8, 2011 Richard Holslag, VP Manufacturing

2 Our Mission To develop innovative, RNA-based therapeutics to fill unmet medical needs for patients with genetic diseases

3 Duchenne Muscular Dystrophy Rapid progression of muscle degeneration, due to the absence of dystrophin Affects 1 in 3,500 newborn males* Age Rare, severely debilitating progressive disease walking problems wheel chair - skeletal deformity very limited use of arms ventilation at night ventilation 24 death Clinical symptoms DMD * TREAT-NMD website

4 Duchenne Muscular Dystrophy Cause: no dystrophin protein in muscles Picture 1. Healthy control Picture 2. Duchenne patient

5 The Dystrophin Gene Exon skipping can restore the reading frame

6 Product Pipeline Indication Compound Discovery Pre-clinical Phase I/II Phase III Duchenne PRO051 GSK 968 PRO044 PRO045 PRO053 PRO052 PRO055 Myotonic Dystrophy Huntington s Disease PRO135 PRO289

7 First Human Study Four DMD patients Single intramuscular 0.8 mg dose Biopsy performed after 28 days Effective in specifically inducing exon 51 skipping and dystrophin restoration in the majority of muscle fibers in the treated area Safe and well-tolerated Key Publication: van Deutekom et al. (2007) Local Dystrophin Restoration with Antisense Oligonucleotide PRO051. The New England Journal of Medicine

8 First Human Study Immunohistochemical Analysis

9 Landmark Publication 1

10 Landmark Publication 2 N Engl J Med 2011; 364:

11 Strategic Partnership GSK

12 Strategic Partnership GSK

13 Bloomberg news Glaxo s $679 Million Accord Signals Foray Into Rare Diseases Share Print A A A By Trista Kelley Oct. 13 (Bloomberg) -- GlaxoSmithKline Plc agreed to pay as much as 460 million euros ($679 million) to develop drugs from closely held Dutch biotechnology company Prosensa aiming to treat a rare disease called Duchenne muscular dystrophy. The London-based company will get rights to develop and sell Prosensa s most advanced experimental treatment, called PRO051, and three others as part of the research collaboration the companies announced today in an ed statement. Glaxo joins Genzyme Corp. of the U.S. and Switzerland s Santhera Pharmaceuticals AG in developing therapies for Duchenne, a rare neuromuscular disease with no known cure that affects one in 3,500 newborn boys. PRO051, scheduled to enter the final stage of human tests next year, may get orphan-drug designation, a benefit extended to medicines that address rare diseases, spokeswoman Claire Brough said. The status would allow Glaxo to charge more and give the product a seven-year monopoly in the U.S. This is a move to have a much broader portfolio base, WestLB analyst Simon Mather said in an interview. Orphan drugs and specialty pharma is attractive because you can charge a higher price and you don t need to do much marketing. Chief Executive Officer Andrew Witty has struck about a dozen acquisitions or development partnerships since taking over in May 2008 in an effort to replace revenue that will be lost when generic treatments rival Glaxo s best-sellers. Most of Witty s deals so far have focused on expansion in emerging markets and consumer products. Defending Margins The problem with the strategy until now is that they ve been furthering the consumer and emerging-market credentials, which tend to be low-margin, Charles Stanley & Co. analyst Jeremy Batstone-Carr said in an interview. So perhaps with this deal, Glaxo is cognizant that it has to defend its margins. Under the terms of the agreement, Glaxo will pay Prosensa 16 million pounds ($25 million) upfront, as much as 412 million pounds for reaching development targets, and double-digit royalties on potential sales. Moncef Slaoui, Glaxo s head of research and development, last month told Bloomberg that the company was preparing a move into so-called orphan drugs. Brough declined to say whether the company would further expand into the area. Duchenne muscular dystrophy is characterized by progressive muscle weakening that eventually affects the heart and breathing, and survival is rare beyond age 30, according to the Muscular Dystrophy Association.

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15 Patients as Inspiration Just wanted to acknowledge your great success with GSK and thank you for working so hard to possibly save this generation of boys! To think that this could really become a reality and that I might not have to watch my only grandson die before me just sends chills up my spine!

16 Prosensa s Ambition To create value with Prosensa Development Discovery Commercialization Development Discovery Discovery To grow Prosensa into a specialty biopharma company focused on rare diseases 15

17 Corporate Overview Founded in 2002, The Netherlands Drug development addressing the unmet medical needs of neuromuscular diseases Lead compound in Duchenne Muscular Dystrophy in Phase III Orphan Status in EU and US Key collaboration with GSK signed in Oct 2009 Technology Platform: RNA modulation 8 compounds identified in 3 disease areas Strong partnerships with academia and patient organizations Currently 80 employees

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19 Corporate Highlights Focused on rare diseases, specifically addressing the unmet medical needs of neuromuscular diseases Lead compound in Duchenne Muscular Dystrophy in Phase III Encouraging efficacy data from long-term extension study Key collaboration with GSK Deal value EUR 460 million (USD 680 million) for selected part of DMD franchise Significant retained value through non-partnered assets in DMD RNA modulation platform, broadly applicable to rare and common diseases Experienced management team & strong investor basis

20 Prosensa s Partnerships

21 Support Mibiton invests in equipment and facilities for industry and research institutions within the life science sector. Through these investments mibiton stimulates public-private cooperation, entrepreneurship, and the growth of young life science companies and the (growth of the)life science sector in the Netherlands. Investments via a revolving fund

22 Don t contemplate but anticipate It is all a matter of timing: Contemplation at the beginning of a project Planning Contemplation during the height of activities of a project try to keep the Overview Contemplation at the end of the project doing the Review Do contemplate and anticipate

23 Prosensa anticipates investments with Partners & mibiton anticipation What to realize? Equipment Partner Multiple suppliers Standardization of analysis Investigate composition Scale up/down Smallest size manufacturing Innovative automation Innovative chemistry, Scale up/down Analysis accuracy, reproducibility and affordability Bench scale discovery, Smallest size LCMS/ MS Synthesizer Robot Complete chemical production line PROXY Laboratories PROXY Laboratories ISA Therapeutics ISA Therapeutics

24 Anticipation in the development of oligonucleotides Multiple suppliers for all important GMP steps Avoid being the first client Avoid unique know how Stimulate open source for analysis and be the best in the core-technology Determine commercial size and downscale to bench-scale for product development Use 10% of commercial scale for development/clinical batches Stimulate the use of disposables for formulation & sterile filling Re: Dali Look for new technologies in Discovery

25 Anticipation in the development of oligonucleotides Automation and software, conflicting priorities for Operations: Core technology is innovative and this might also apply to new equipment and new automation New developments often need systemintegration Timelines are important, prevent delays, use only proven technology In most cases the choice is for proven track record in order to minimize surprises of delay. New developments in a satellite development program and incorporation in mainstream after success

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