Trends and Challenges in Technical and Manufacturing Collaboration. Alex Neverov Vaccine World MENA & CIS NOV 2014

Transcription

1 Trends and Challenges in Technical and Manufacturing Collaboration Alex Neverov Vaccine World MENA & CIS NOV 2014

2 Topics to Cover Identifying Partners Who we are What do our partners share Exploring BEVS Platform Technology Therapeutic focus Flublok, Panblok, Ebola, Rabies Geographic focus Host country Japan case study Exploring manufacturing partnerships Co-development Licensing Pitfalls to avoid and summary 2

3 Who we Are? The Company: Protein Sciences Manufacturing Vaccines for 30 Years Meriden, CT Pearl River, NY 3

4 Company Business Overview Proprietary Vaccines Panblok and FluNhance TM SARS/MERS Rabies Ebola Partners UMN/Astellas Laboratorios Liomont $147 million BARDA contract funds work on Flublok and Panblok GeneXpress and Technology Licenses Boehringer Ingelheim Vetmedica - CircoFLEX uniqure - Glybera Merck Japan Tobacco Pfizer Wako (Takeda) Diamyd BioArctic BEVS Technology Platform Research Antigens Ebola Influenza HIV Diverse customer base Focus on quality Profitable, cash flow positive business. Rapid growth: 40 to >130 in 2 years Privately held, common stock only no debt 4

5 A New Approach to Vaccine Manufacture Traditional Grow pathogen (in eggs) Inactivate pathogen Purify antigen (i.e., the active ingredient) Formulate vaccine Modern: BEVS Produce antigen (in cell culture) Use genetic code no live pathogen Purify antigen Formulate vaccine Fast Pure Pathogen- & Egg-free TRADITIONAL METHOD MODERN VACCINE 5

6 What Do Our Partners Share? Right connections is a key Know how to deal with government Regulatory Pricing and reimbursement for public market Local market specifics Strictly follow highest international standards Ethical Technical Financial Have manufacturing capacity in host country Ability to produce pandemic vaccine when needed BEVS advantage low cost and ability to switch to other vaccine if needed Willing to invest Meticulous in their execution In the game for a long term to reap full benefits of the platform 6

7 Technology Platform Baculovirus Expression Vector System (BEVS) Only need genetic code Patented expressf+ cells Pure protein Engineer baculovirus with gene Powerful promoter generates high yield Proprietary baculovirus stable during scale-up Seed insect cells in a bioreactor Infect cells with baculovirus Harvest cells Purify protein Formulate with PBS into vaccine 7

8 Cell Line Qualification Summary Extensive Cell Line Characterization Traditional methods (FDA Guidance) Specific tests for adventitious agents of concern (retroviruses) Molecular methods (inch. degenerate primer PCR) Biochemical methods Cell culture based infectivity methods Process yields good retroviral clearance up to 16 log 10 total clearance Conclusion: Data indicates no evidence of adventitious agents in the expressf+ cell line. New cell lines will have to resolve new questions such as Rhabdoviruses high barriers to entry for competitors! 8

9 Manufacturing Advantages of BEVS Safe eukaryotic expression system no need to handle pathogens Speed change virus vector insert, not cell line Single qualified cell line for ALL products Single qualified master virus bank for ALL products Multiple genes may be co-expressed From gene to production in 21 days Universal Plug & Play process Expression High level protein expression Ability to express large proteins Biologically active Processing Cleavage of signal peptides Post-translational processing (i.e., glycosylation) Correct folding Scale-up up to 21,000L with instant success Regulatory approval US - PSC, Flublok Japan UMN/Astellas, Flublok submitted, expected 2015 Worldvide Boehriger Ingelheim, PCV2 EU uniqure, Glybera Mexico Laboratorios Liomont expected

10 Favorable Economics of Production Easy access to production capacity Cheap to built or lease Possible to repurpose existing Pearl River converted in 60 days, 1% of full value/year Low operating cost Simple media, standard US and DS processing Flexible one facility several products Ideal for pandemic response if located in a host country Available when needed the most Fast changeover for new threats response 10

11 Therapeutic focus: Flublok Influenza Vaccine BREAKING NEWS 16 JAN 2013 FDA approves Flublok for the prevention of influenza in adults years old Extended to 18 and above on 30 OCT 2014 The Evolution, and Revolution, of Flu Vaccines World s first recombinant influenza vaccine The pandemic solution Only realistic pandemic vaccine Rapid development and manufacture Transfer manufacturing to other countries THE GAME CHANGER benefit or curse? New benefit: Jobs Act -7 years exclusivity 11

12 Flublok: Product Attributes Purified protein vaccine 3X the active ingredient vs. conventional Strong immunogenicity in older adults Exact match, conventional adapted H3 -> egg adapted not protective No egg protein No influenza virus No thimerosal No antibiotics No latex No gelatin Partnered in Japan and Mexico 12

13 Flublok: Product Attributes CDC Advisory Committee on Immunization Practices Only Flublok preferential to be given to egg allergic people, regardless of severity New Developments Quadrivalent formulation - in trials (9K outcome vs. competitor) Prefilled syringes Successful scale up to 21K Liters in Japan New baculoviruses Four-fold yield increase FDA approved and implemented Ten-fold yield increase applied for FDA approval Room temperature stable Flublok and Panblok Applied for FDA approval, likely need small US clinical trial Clinical trials in Japan completed successfully 13

14 Ebola Response PSC resumed development of Ebola in 2014 Request by USG: BARDA and NIH Surface protein (GP) protective PSC will provide protein for animal studies, results - Feb2015 Mice Guinea pigs Non-human primates (immunogenicity and challenge) Production based on approved Flublok process Pure protein likely will gain EUA status Clinical studies before completion of animal Produced at 40L scale, developed purification scheme Ongoing efforts to produce at 600L scale in GMP run 14

15 Demand for Healthcare Services 2009 H1N1 Pandemic Influenza Vaccine Supply-Demand Gap Recombinant pandemic influenza vaccines are projected to be available much sooner than those produced with egg-based technology. Projected Availability of Recombinant Vaccines Availability of Egg- Based Vaccines weeks weeks Adapted from R. Robinson s presentation to FDA s VRBPAC on February 29,

16 Panblok Monovalent recombinant vaccine for pandemic influenza First recombinant pandemic influenza vaccine The pandemic solution Only pandemic vaccine that can be quickly manufactured and/or transferred to and manufactured economically in other countries We made the first pandemic vaccine in 1998 Contract issued by NIAID for vaccine against the Hong Kong Bird Flu Delivered over 1,700 doses of vaccine to NIH in only eight weeks NIH and first responders vaccinated We were the first to have an H1N1 vaccine available in 2009 Tested in Australia because of lack of USG support Results as good as any other vaccine no side effects 16

17 Other Projects in Development Alternative Influenza vaccine (NA) SARS/MERS SARS ready for clinical trial if needed MERS Focus on veterinary VLP vaccines (2 projects) >99% AND >95% purity, correct size and shape Rabies Cheaper, cleaner Mice protective Additional studies - early

18 Collaboration in Japan UMN/Astellas Large Companies Initial technology transfer 3x600L Build 2 x 21,000L capacity, could add more First run contamination, all subsequent success Trained people in US Sent our tech transfer team to Japan Assisted in troubleshooting, QC testing 18

19 Pitfalls to avoid and conclusions Planning and evaluation are the keys Understanding cost components Risk/reward Tech transfer is not easy. Be ready to help! No manufacturing capacity in the country No vaccine when critically needed Safe technology, no actual pathogen needed Only genetic information Fast Technology. No need to wait for reassortant Flexible. One facility many products 19

20 Closing remarks Thank You! Questions? This recombinant influenza vaccine became a reality thanks to support of contract HHSO C and perseverance of the Protein Sciences team!. and as Benjamin Franklin Stated: "Energy and persistence conquer all things." 20

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