A Universal Manufacturing Platform For Vaccine Production

Transcription

1 A Universal Manufacturing Platform For Vaccine Production Manon M.J. Cox 18Mar2013

2 Topics The Company Baculovirus Technology Platform (BEVS) Flublok and Pandemic Influenza Other vaccines opportunities Conclusions 2

3 The Company: Protein Sciences 3

4 Overview FluBlok UMN/Astellas BARDA (PanBlok) Influenza, HIV, Diverse customer base Research Antigen Partners BEVS Technology Platform FluBlok Diamyd BioArctic NIAID (SARS) Others Protein Sciences Core Business Merck and B. Ingelheim cell line license

5 Product Realization 36 Our Team and the Road Ahead Production Operations 22 G&A 21 QA Med & RA Expanded the workforce to over 100 employees Strengthen leadership and external advisors Manufacturing, Finance, Development, Regulatory, QA and Legal Secured a facility for large scale manufacturing Initiated Manufacturing Team build-up Our Mission: To save lives and improve health by effectively responding to our changing world with innovative vaccines and biopharmaceuticals. 5

6 PCAST Report Issued following H1N1 pandemic Fault was not with the execution of the response, but in inherent shortcomings of current technologies for development & production of influenza vaccines All US influenza vaccines are currently produced in embryonated chicken eggs: Delayed response time Limited capacity Limited flexibility PCAST recommended short-term improvements in surveillance, strain development, testing & fill/finish. The greatest potential for substantially shortening the time and increasing the reliability of influenza vaccine production lies in the use of recombinant DNA technologies - PCAST 6

7 Demand for Healthcare Services Availability of Recombinant Pandemic Influenza Vaccines Recombinant pandemic influenza vaccines are projected to be available much sooner than those produced with egg-based technology. Projected Availability of Recombinant Vaccines weeks Adapted from R. Robinson s presentation to FDA s VRBPAC on February 29, 2012

8 Flublok BREAKING NEWS 16JAN2013 FDA approves Flublok for the prevention of influenza in adults years old The Evolution, and Revolution, of Flu Vaccines First recombinant influenza vaccine The pandemic solution Only pandemic vaccine that can be quickly manufactured and/or transferred to and manufactured in other countries 8

9 The Platform Technology BEVS 9

10 BEVS Technology Enabling products where speed, cost and safety matter Baculovirus Expression Vector System (BEVS) Engineer baculovirus with the gene of interest (e.g. Hemagglutinin) Baculoviruses highly specific to insect cells Powerful promoter generates high yield of protein of interest Culture expression of insect cells in a fermenter Infect cells with engineered virus Incubate infection for ~48-72 hours Flublok Approval Validation Protein forms rosettes Purify protein to > 90% into final product Formulate with PBS into vaccine 10

11 Universal Plug and Play Process From gene to production in 21days 11

12 Flublok and Pandemic Influenza 12

13 Influenza Vaccine: HA = Major Surface Protein HA (Hemagglutinin): Coat of the influenza virus Antibodies against HA protect against influenza Changes in HA require annual update of vaccine 13

14 Flublok Timeline BLA Submitted April Inspections CR Letters and Response CR Letter response Initiation of FluBlok Clinical Studies Clinical, Tox and CMC 9 studies performed in collaboration with NIAID CMC, RT Investigation Inspection FDA Approval 16 Jan 2013

15 Flublok Manufacturing Challenge The way to get there! Four (4) weeks to GMP production Universal Process Ready to optimize for strain changes Platform Technology Product Launch Anchor Point 500L Efficient scale-up but limited supply Proof of Concept Yield Increase 4X 2nd Generation Process Large Scale Manuf. Initial target, 5M Cadence 1.75 doses, batch/week CMO, partnership, Phased approach Green field or ADAPT! 15

16 From a Manufacturing Perspective Key Advantages Versatility Multiproduct facility design Maximize Capacity utilization Speed Serum-free cell line for all products Cloning in 4 weeks GMP Production Low cost High yields in a lowcost proprietary media High-density fermentation Concentrated DS Reliable scale-up Current scale 500L; others up to 5000L Process design space optimization for new antigens Safety BV highly specific to Insect cells No handling of dangerous virus 16

17 Summary Panblok development: Pandemic Flu Vaccine based on rha NIAID conducted two clinical studies with rha 2 x90 mcg rha induced reasonable immune response / /2013 Revaccination study Broad immunogenicity after a single dose in subjects who previously received rha Study PSC22: rha in combination with SE/GLA Significant dose sparing Study PSC25: rha in combination with SE only Significant dose sparing Note: UMN is also performing studies in Japan non-adjuvanted rha; Alum did not provide benefit 17

18 Other Vaccine Opportunities 18

19 Vaccines produced in insect cells (1) Approved Vaccines for Human or Veterinary Use Disease Brand name(s) Originator Protective Antigen VACCINES FOR HUMAN USE Cervical cancer CERVARIX GSK L1 protein Influenza FLUBLOK Protein Sciences HA Prostate cancer PROVENGE Dendreon PSA VACCINES FOR VETERINARY USE PCV2 Porcilis PCV Merck PCV2 ORF2 protein PCV2 CircoFLEX B. Ingelheim PCV2 ORF2 protein Classical swine fever Porcilis Pesti Merck E2 protein Adjusted from M.M.J. Cox/ Vaccine 30 (2012):

20 Vaccines produced in insect cells (2) Vaccines Candidates for Human Use in Clinical Development Disease Protective Antigen Originator Development Stage Diabetes GAD Diamyd Phase III Hepatitis E ORF 2 GSK Phase II Influenza NA Protein Sciences Phase II Influenza HA/NA/M1 Novavax Phase II ParvovirusB-19 Parvovirus VLP Meridian Life Sciences Phase II Influenza H5 HA Protein Sciences Phase I Norwalk Norwalk capsid VLP Ligocyte Phase I Adjusted from M.M.J. Cox/ Vaccine 30 (2012):

21 Vaccines produced in insect cells (3) Antigen targets for recommended viral vaccines VACCINE ETIOLOGICAL AGENT PROTECTIVE ANTIGEN Hepatitis B Hepatitis B Virus (HBV) HbSAg Polio Polio Virus serotypes (types 1, 2 or 3). VP1 and VP4 Rotavirus Rotavirus VP6, VP7 and major outer capsid protein Measles Measles virus (genus Morbillivirus, family Paramyxoviridae) H and F proteins H, F, and N viral proteins Rubella Rubella virus (= togavirus of the genus Rubivirus) E1 HPV Human papilloma virus (>100 subtypes) L1 structural protein Japanese JapaneseEncephalitis (JE) virus Glycoprotein E Encephalitis (Flaviviridae) Yellow Fever Yellow fever virus (Flaviviridae) E, and E/NS1 Tick-Borne Tick-borne encephalitis virus (Flaviviridae) E and C Encephalitis Hepatitis A Hepatitis A virus (HAV) Polyproteins Rabies Rabies virus (RABV) (Rhabdoviridae) Protein G Mumps Mumps virus (Paramyxoviridae) Protein H and N Influenza Influenza virus (Orthomyxoviridae) HA; NA; HA, NA, M1 VLP Adjusted from M.M.J. Cox/ Vaccine 30 (2012):

22 Conclusions 22

23 Universal production process Universal Process Working Virus Bank (WVB) Recombinant baculovirus Identify Protective Antigen Single Cell Line SF+ Plug & Play Insect Cell culture WVB is added Centrifugation Pellet is solubilized Depth filtration Capture (IEX) Purification (HIC) Membrane Filtration Ultrafiltration Sterile Filtration 23

24 Concluding Remarks Key advantage = universal plug and play process The BEVS technology is a versatile rapid production technology to tackle emerging diseases of viral or parasitic origin (SARS, H5, Ebola) Safe vaccines can be produced fast & for low cost. Production facility can be multi-use to manufacture a broad range of products (disposable technology offers flexibility) Establishment of large scale manufacturing is high priority! (disposable technology may speed up this process) No need to handle live dangerous viruses. 24

25 And finally. FDA approval of Flublok validates this technology! We are working on the scale-up of our robust manufacturing process to ensure availability of products in sufficient quantity! 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." 25