We Care for Proteins Stabilization and Protection of Biopharmaceuticals, Vaccines and Biologic-Device Combination Products

Transcription

1 We Care for Proteins Stabilization and Protection of Biopharmaceuticals, Vaccines and Biologic-Device Combination Products Munich, June 2013

2 LEUKOCARE AG Established 2003 Owner Management and Private Investors Location Martinsried / Munich, Germany QM-System according to EN ISO 9001 and EN ISO Business model Technology and service provider for stabilizing and protecting technologies for proteins and other biologics Current status 17 ongoing collaborations with partners in the fields of vaccines, therapeutic proteins and combination devices 1

3 Solution Provider for Stabilization of Biologics and Proteins LEUKOCARE provides proprietary formulation technologies and related development services for stabilization and protection of biologics The technology platform is based on compositions of various amino acids refined with saponins or oligopeptides. LEUKOCARE technologies are employed in collaborations with partners in the field of vaccines, therapeutic proteins, and biologic device combination products. LEUKOCARE provides development services based on fee for service during implementation of its technologies. LEUKOCARE s technologies provide manifold benefits: Improved shelf-life / stability / quality Terminal sterilization of biologics Significant production cost savings 2

4 Biotech versus Medtech In the past, these two markets have had separate requirements and regulations MEDTECH Engineers Material Scientists Terminal Sterilization BIOTECH Red Biotech (Life Sciences) Biologists, Pharmacists Aseptic Production 3

5 Combination Products Biotech meets Medtech Currently, the fields of Medtech and Biotech more and more overlap. This combination provides new market and business opportunities. 4

6 Stabilization Technologies für Biofunctional Molecules LEUKOCARE s stabilizing technologies increase the stress resistance of functional molecules and by this facilitate surface functionalization of medical devices and terminal sterilization of biologicals. Functional Molecules / Proteins / Antibodies Coupling Protecting Eluting LEUKOCARE s technology platform can stabilize biologicals applied in a broad range of medical applications 5

7 Principle of Stabilizing and Protecting Technologies I Stabilizing and Protecting Solutions (SPS) are specific compositions of 5-8 excipients. SPS are applied as aqueous solution. SPS Properties: Non-toxic and biocompatible (GRAS) Pharmaceutical grade Natural ingredients, not animal derived No pharmacological effect by its own Water soluble Easily adaptable to specific biomolecules and needs 6

8 Principle of Stabilizing and Protecting Technologies II SPS stabilize the three dimensional structure of proteins in de-hydrated conditions and thus increase their stress resistance. This results in extended shelf-life and protection against damage during sterilization. After drying the free stabilizing molecules form an amorphous layer Ingredients reversibly aggregate with proteins and thus protect the molecules against chemical or physical stress SPS layer is easily reversible by rinsing or dipping Successfully applied to proteins between 8 and 900 kda 7

9 Possible Applications LEUKOCARE s technology platform can be used for a wide range of possible applications. Field Biopharmaceuticals Medical devices In vitro and in vivo diagnostics or research products Applications Therapeutic antibodies Vaccines (human and veterinary) Other proteins (Enzymes etc.) Orthopedic implants Stents Wound dressings Catheters Extracorporeal blood treatment devices Cell culture products Protein arrays Microtiter plates Biofunctionalized micro- and nano-particles 8

10 SPS Stabilize Molecules from Viruses down to Peptides SPS are generally applicable across molecules of different size and function. All kinds of proteins and peptides have been successfully stabilized by SPS. Protection of various proteins by SPS using 25 kgy of irradiation 9

11 Stabilization of Herceptin (Commercial Formulation vs. SPS) SPS avoid aggregation of therapeutic antibodies even during irradiation UV Absorption Non-Irradiated SPS orig. Form. PBS UV Absorption Irradiated 25 kgy SPS orig. Form. PBS 0 0 Non-irradiated Control 25 kgy γ 40 kgy γ HMW [%] Main [%] LMW [%] HMW [%] Main [%] LMW [%] HMW [%] Main [%] LMW [%] SPS 0,3 99,7 0,0 1,1 98,7 0,2 1,6 98,2 0,2 orig. Roche- Formulation 0,7 99,3 0,0 8,8 90,8 0,4 11,6 87,8 0,6 PBS (Neg. Control) 2,2 97,8 0, ,5 1,5 26,6 72,0 1,4 Work has been performed in co-operation with Sterigenics 10

12 Stabilization of Freeze Dried Vaccines: H1N1 (Enveloped RNA Virus) SPS enable stabilization of inactivated viruses (here: Influenza A) after lyophilization and stressing by irradiation or accelerated aging. Activity as determined by Hemagglutination was improved dramatically. Hemagglutination Titer [log 2 scale] x 1 x 2 x 4 x 8 x 16 x 32 x 64 x

13 Stabilization of Air Dried Vaccines for Micro Needle Application SPS stabilize and protect inactivated viruses coupled and air dried on metallic surfaces (e.g. on micro needles). Hemagglutination Titer [log 2 scale] x 1 x 2 x 4 x 8 x 16 x 32 12

14 SPS also Improve Stability in Liquid Formulation SPS have been successfully employed in liquid formulations of vaccines based on inactivated viruses. 13

15 Broad Experience in Peripheral Processes and Methodologies LEUKOCARE supports its partners with related services and know how in order to implement the proprietary technologies in the partnered products. Development of customized lyophilization protocols Development of spray drying and spray-freeze drying processes Coupling of biological compounds to functionalize surfaces Establishment of biological read outs Due to the established quality management system according to EN ISO and EN ISO 9001 processes and methodologies developed by LEUKOCARE fulfill regulatory requirements. 14

16 Spray-Freeze Drying of Viral Vaccines SPS also have excellent excipient properties in the context of spray drying and spray-freeze drying. LEUKOCARE successfully developed a spray-freeze dried formulation and appropriate processes for anti-viral vaccines for an industrial partner. 15

17 LEUKOCARE s SPS Fulfill Regulatory Requirements The use of SPS as stabilizing excipient for the formulation of new and existing products is non-critical as all components are established and described in pharmacopoeia. Pharmacology: SPS ingredients don t exhibit a pharmacological effect themselves Amino acids are routinely applied in standard infusion solutions Components are available in GMP quality The SPS as semi-finished products are produced for LEUKOCARE by a certified CMO Toxicology: The ingredients are generally recognized as safe (GRAS) Toxicity tests at LEUKOCARE do not show a risk 16

18 Ongoing Activities in various Fields LEUKOCARE uses the versatility of the technologies by performing complementary projects, thus optimizing the risk-return-ratio. Thermal Stabilization of Vaccines and Proteins 1. Feasibility project with Sanofi Pasteur to increase stability of anti-viral vaccines (lyophilized) successfully completed 2. Feasibility project to stabilize liquid formulated animal vaccine ongoing 3. Feasibility project to stabilize immuno-therapeutic vaccine delivered by live viruses successfully completed 4. Feasibility project to stabilize genetically modified adeno viruses successfully completed Protection of Proteins against Sterilization 1. Feasibility project with a big 5 pharma company to protect an already marketed antibody against terminal sterilization in a new formulation 2. Collaborative project with another big 5 pharma company to show general feasibility of end sterilized biopharmaceuticals 3. Collaborative project to stabilize peptide-based antibiotic against ethylene oxide sterilization ongoing Surface Coating of Combination Devices 1. Feasibility project to stabilize antibody coated catheter during irradiation and storage successfully completed 2. Two ongoing projects for antibiotic coatings of orthopedic products 3. Development of an antiinflammatory device from idea to clinic successfully completed 4. Various projects in the field of functionalized wound dressing successfully completed and ongoing Other projects ongoing or upcoming Other projects ongoing or upcoming Other projects ongoing or upcoming 17

19 Production Costs of Proteins can be Reduced by > 50% A in B C & Isolator C & Termin. Sterilization Investment 1 65 M 57 M 49 M Operating Cost M 1.2 M 1.0 M Monitoring k 200 k 300 k Testing 1.5 M 1.5 M 1.5 M Clothes / Disinfection 204 k 84 k 108 k Loss of Batches 4 5 % 3 % 0 % Annual Costs EUR EUR EUR ) I.: higher duty air condition, air locks etc., II.: 2 Isolators account for 8 Mio difference 2) Difference between II & III: energy, maintenance, requalification costs for isolator 3) Monitoring is easiest in II, somewhat higher costs allocated to III to ensure low bio burden 4) Includes also batches where procedural errors or technical failures occurred which makes contamination likely but does not necessarily lead to detectable contamination based on batch inspection by samples. 18

20 Collaborative Model We start collaborations by proofing feasibility of SPS for specific applications in evaluation projects. After successful completion of feasibility project we grant license for proprietary technologies to our partners. Feasibility Term: 4-12 months Research License + Fees for Service Prod. Development Term: months Development License + Fees for Service Clinical Testing Term: 1-5 years Commercial License + Milestone payments + Fees for Service Marketing Commercialization of products employing LEUKOCARE s technology Running Royalties Co-Development Partnership based on Licenses 19

21 Thank You very much For further information please contact: Dr. Jens Altrichter Chief Operating Officer Fon: Fax: LEUKOCARE AG Am Klopferspitz Martinsried/Munich Germany 20