Introduction to Enteris BioPharma

Transcription

1 Introduction to Enteris BioPharma

2 Enteris BioPharma Intelligent Solutions for Oral Drug Delivery Privately held, New Jersey based biotech company Owned solely by Victory Park Capital, a large Chicago based investment firm Clinically validated oral formulation technology, Peptelligence TM Offers formulation solution for peptides and challenging small molecules Extensive scientific know-how and R&D experience Proven GMP tablet manufacturing capabilities 2

3 Clinically Validated Oral Delivery Technology Clinically validated oral peptide delivery technology Positive Phase 3 oral Calcitonin: Osteoporosis (1) Positive Phase 2 oral PTH: Osteoporosis (2) Positive Phase 2 oral Calcitonin: Osteopenia (3) Positive Phase 1 oral CR845: Neuropathic Pain (4) Sponsored preclinical peptide programs 15 ongoing or completed formulation programs (1) Tarsa Therapeutics, Inc. (JBMR 27, No.8, 2012, ) (2) Unigene Laboratories, Inc. (Bone 53, 2013, ) (Clin Pharm 52, No. 6, 2013) (3) Tarsa Therapeutics, Inc. (ASBMR, 2012) 3 (4) Cara Therapeutics, Inc. (data on file)

4 Potential Commercial Benefits of Peptelligence TM Increases product uptake and utilization vs. injectable or other routes of administration Increased physician starts; fewer patient refusals Enhanced patient compliance Better patient outcomes Protects and extends product exclusivity and commercial life Provides compelling differentiation in competitive markets Adds extra layer of robust IP protection until 2030 Refreshes and extends commercial life of products 4

5 Oral Peptide Delivery Challenges to oral peptide delivery GI tract is designed to degrade peptides Susceptibility to acid degradation and protease digestion Low permeability through the intestinal cell layer Inter- and intra-subject variability Variability due to food effects and poor patient compliance with dosing regimen Peptelligence TM solution to these challenges Minimizes food effect Reduces peptide degradation Increases paracellular transport No modification of the peptide required 5

6 Permeability Oral Small Molecule Delivery Challenges to oral small molecule delivery Solubility or dissolution limited absorption Poor permeability due to interaction with efflux transporters or other mechanisms Low bioavailability resulting in increased variability First pass clearance by the intestine and liver following absorption Peptelligence TM solution for BCS Class II, III and IV compounds I Simple solid oral dosage form (tablet or capsule) III Increase local concentration or add permeation enhancers Solubility II Increase particle surface area or include co-solvents or surfactants IV Combine the strategies for II and III 6

7 Peptelligence TM Solution to Oral Drug Delivery Enteric coat prevents tablet from opening in stomach at low ph Enteric coat dissolves at neutral ph in the small intestine Protease inhibitor, permeability enhancers and API released API absorbed across intestinal wall via paracellular transport Peptelligence TM orally delivers intact, biologically active API into systemic circulation Efficacy has been demonstrated for compounds varying in size, charge, hydrophobicity, stability and therapeutic indications 7

8 Excipient Safety Profile Protease Inhibitor: Organic Acid Pharmaceutically accepted ingredient Transport Enhancer: Acyl Carnitine Scope of non-clinical safety package has been confirmed by FDA Genotoxicity and respiratory toxicity completed 6 month rat toxicology study completed 9 month dog toxicology study completed Part of tablet formulation in 12 clinical studies (328 subjects ) Drug Master File (Type V Safety Data) available for crossreference All other Excipients (Tablet Fillers) Pharmaceutically accepted ingredients 8

9 Tableting Capabilities Identified coated organic acid as compatible excipient with peptides and small molecules Simple and scaleable manufacturing process Optimized release characteristics and bioavailability Demonstrated room temperature stability of tablet for at least 9 months for several peptides Supplied CTM for Phase 1 and Phase 2 studies 9

10 Peptelligence TM Peptide Bioavailability Formulated vs. Unformulated Program Type Effect of Formulation on the Bioavailability of Various Peptides in Pre-Clinical Animal Models No. of Amino Acids Sponsored 4 39 Study Type Ranges of Unformulated Bioavailability (%) for 12 Peptides Ranges of Formulated Bioavailability * (%) for 12 peptides Rat Dog <LOD ** * in each case the percent bioavailability of the formulated peptide was higher than unformulated ** LOD = limit of detection 10

11 CR845 (ng/ml) Phase 1 Oral CR845 Study CR845 Demonstrated 16% Oral Bioavailability N = 8/group 0.5 mg 1 mg 3 mg 10 mg Time (hours) Mean + SEM 11

12 Peptide (pg/ml) PTH Phase 2 Study Reproducible PK Profile: Mean Values at Week 0 and Week PTH(1-31)amide (5 mg), wk 0 PTH(1-31)amide (5 mg), wk Time* (minutes) Time relative to Tmax 12

13 Mean % Change LS-BMD Phase 3 Oral sct Study Phase 3 Study for Oral sct: Primary Endpoint (Change in LS BMD) Achieved 3.00 p= p= p=ns p<0.001* p=0.014* 0.5 p=ns* rsct Tablet Nasal Spray Placebo 13

14 BCS Class III Small Molecule Case Study Currently approved only for IV infusion as a last resort antibiotic therapy 100mg loading dose, followed by 50mg every 12hrs, duration ranging from 5 to 14 days Must be dosed in the clinic BCS Class III Very high solubility in water: >295 mg/ml at all ph ranging from 1 14 Very poor permeability: Oral formulations explored to date exhibit a limit of approx. 5 %F PeptelligenceTM uniquely suited to enable oral formulation with suitable F Oral therapy offers out of clinic dosing Reduced overall healthcare costs Strategy: Initiate dosing by IV titration, then discharge with oral therapy 14

15 Plasma Tigecycline (mcg/ml) BCS Class III Small Molecule Rat Study Animals dosed via intraduodenal administration to simulate oral dosing (0.64 mg/kg IV or 4.8 mg/kg ID) IV ID PBS ID 100mM CA, 26mM LLC ID 400mM CA, 26mM LLC Time (hrs) 15

16 BCS Class III Small Molecule Study Summary Small molecule rat study %F for unformulated ID dose: 1.6 to 2.76% %F of formulated ID dosing increased by 10 to 20 fold Peptelligence TM achieved high oral bioavailability where other formulation technologies have failed 16

17 Partnering with Enteris Enteris is dedicated to building long term strategic relationship to solve challenging formulation issues with our proprietary oral delivery platform, Peptelligence TM Peptelligence TM offers the turn-key oral formulation solution Development and execution of a robust formulation strategy Fully optimized GMP clinical trial materials Value added drug presentation Extensive IP protection until

18 Enteris BioPharma Intelligent Solutions for Oral Drug Delivery Enteris has effectively addressed both permeability and solubility challenges with a simple, elegant and scalable solution Peptelligence TM has demonstrated a track record of clinical success across a range of compounds and therapeutic indications Enteris offers robust IP protection, regulatory CMC support and finished, solid dosage formulations for preclinical and early phase clinical studies 18

19 Introduction to Enteris BioPharma