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Tsrl modified dosage forms august_non-confidential


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Description of our unique formulation technology for modified release

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Tsrl modified dosage forms august_non-confidential

  1. 1. Driving Value from Lead to Clinic 1NON-CONFIDENTIAL Elke Lipka, PhD, MBA President Drew Hertig, MBA Business Development Modified Dosage Forms for Water-Insoluble Drugs A Patented Approach for Extended or Delayed Release Delivery
  2. 2. Contents • Team • Strategy • Intellectual Property • Proof-of concept • PK/PD Rationale • Commercial Rationale • TSRL Proposal 2NON-CONFIDENTIAL
  3. 3. TSRL Management Team Gordon Amidon, PhD, Chairman and CSO Professor of Pharmacy, University of Michigan, Internationally recognized expert in the field of solubility, transport phenomena, prodrugs, and drug absorption with more than 40 year of research experience Elke Lipka, PhD, MBA, President Director Strategic Operations & Assoc. Research Fellow (Parke-Davis, Pfizer, Esperion); 20 years of drug development experience and management of business operations and strategic partnerships Dawn Reyna, Senior Director Laboratory Services 17 years experience in quality assurance, toxicology study conduct, and pharmaceutical research management (MPI Research, Pfizer) 3NON-CONFIDENTIAL
  4. 4. TSRL Formulation Strategy • Unique Formulation for Modified Release •  Solubility;  Bioavailability • Match Region of Interest & Release Rate • Allow for Reduced Dose(s) • Minimize Toxicity • Improve Compliance • Patented Formulation • 505(b)(2)Submission • Reduced Cost • Reduced Time NON-CONFIDENTIAL 4
  5. 5. Technology Highlights • Pharmaceutical Composition • Hydrophilic Solubility Technology • Aqueous-based coating system • Controlled release excipient • Delayed release coating • Method of Making such Composition • Flexible formulation platform for designing optimized drug product release rates 5NON-CONFIDENTIAL
  6. 6. Extended Delivery Addressing Common Disease States:  Cholesterol Synthesis  Cardiovascular Disease  Asthma Bronchial  Peptic Ulcer Disease  Gastric Secretion  Metabolic syndrome, and consequently obesity, Type 2 diabetes and dyslipidemia NON-CONFIDENTIAL 6  Pain  Renal  Antiparasitics  Antibacterials  Antifungals  Immunosuppressants  Inflammation
  7. 7. IP: US 8,535,716 • Broad coverage: Any API and combinations of active ingredients (platform patent) • There are nine layers of claims on how it is formulated (heightens barrier to entry) • Patent valid through Sept 2033 • Initial FTO: no issues found regarding similar valid patents 7NON-CONFIDENTIAL Methods and Composition of Delayed and Extended Delivery of Water Insoluble Drugs
  8. 8. • Initial freedom to operate opinion– no issues found regarding similar issued or valid patents NON-CONFIDENTIAL 8 Supported IP Cont’d Our family of drug delivery IP: Supported IP for this proposal
  9. 9. Clinical Proof-of-concept Goal – To demonstrate scale up of HST formulations and proof-of- concept for example drug in normal healthy volunteers • BA/BE study conducted at the University of Mainz, Germany • Simvastatin was chosen as the example drug/API • Dosage forms prepared – HST-immediate release, HST-delayed release • 7 normal healthy volunteers (6 male, 1 female) • Study design – randomized, open, three phase, single dose study • Reference agent - Zocor® • Bioanalysis – Validated LC/MS/MS method • PK analysis - WinNonlin NON-CONFIDENTIAL 9
  10. 10. Results – Simvastatin and acid metabolite NON-CONFIDENTIAL 10 Tubic-Grozdanis et al., Pharm. Res., 25(7), 2007, page 1591-1600
  11. 11. Results – Summary • Simvastatin is a substrate for CYP3A in the intestine and liver; a major reason for low oral bioavailability • HST-delayed release increases exposure of Simvastatin by ~3-fold compared to Zocor® or HST-immediate release • HST-delayed release increases half-life of Simvastatin compared to Zocor® • Exposure of metabolite (acid) was similar although half-life was longer in HST-delayed release compared to Zocor® or HST-immediate release NON-CONFIDENTIAL 11 Tubic-Grozdanis et al., Pharm. Res., 25(7), 2007, page 1591-1600
  12. 12. • Drugs and disease state mechanisms that follow circadian pattern and underserved by marketed immediate release formulations can be more effectively delivered using HST-delayed or extended release • HST technology can provide for extended or delayed release formulations to achieve better therapeutic efficacy at lower doses by modulating plasma or target organ delivery of drug or metabolite(s) • For approved drugs that result in poor compliance due to high peak concentration or exposure, HST formulations can modulate PK profile to retain efficacy and concomitantly reduce systemic toxicity. NON-CONFIDENTIAL 12 PK/PD Rationale for choice of APIs
  13. 13. Examples of possible APIs Market Size >5 billion: Cyclosporin, griseofulvin, digoxin, nifedipine, itraconazole, carbamazepine, piroxicam, fluconazole, finasteride, diflunisal, lovastatin, simvastatin and glipizide NON-CONFIDENTIAL 13 0 200 400 600 800 1000 1200 1400 1600 1800 MILLIONS USD 2013 WW Sales of Select Generics Simvastatin Nifedipine Cyclosporin
  14. 14. Commercial Feasibility & Testing • Process inexpensive to test and scale up • No harmful solvents used • Modified pharmaceutical ingredients can be manufactured with standard mixing/coating/freeze drying equipment • Preparation of 5-8 batches of API/polymer systems and assessment of their dissolution characteristics per USP dissolution under $10k • Cost does not include API & excipients TSRL will provide: • Relevant data regarding technology • Suggestions for excipients covered under IP NON-CONFIDENTIAL 14
  15. 15. Expectations • Low-cost option to test technology • Upfront payment upon transfer • Development & commercial milestones • Royalties on net revenues • Flexibility on licensing terms (field of use, scope) NON-CONFIDENTIAL 15
  16. 16. Summary  Match Region of Interest & Release Rate  Allow for Reduced Dose & Minimize Toxicity  Simple Manufacturing Steps, Non-Toxic Solvents  Opportunity for Data Exclusivity & Unique Label Claims  Potential for 505(b)(2) Submission  Issued Patent Protection Until 2033  Flexible Terms  Covers Formulations with Significant Market Potential NON-CONFIDENTIAL 16