Particle-based Product Development Partnership Overview Phosphorex - PowerPoint PPT Presentation

Particle-based Product Development Partnership Overview

Phosphorex Snapshot • A Contract development and manufacturing (CDMO), founded in 2005 • 12,000 ft 2 facility with GLP space in Hopkinton, MA – Wet chemistry and Analytical labs – Pilot and process development with cleanroom suites – Capability of tech transfer to GMP • Focus on particle technology and formulation development – Pharmaceuticals – Medical devices – Diagnostics • Experienced team composed of experts in particle technologies with broad cross- functional experiences • Work across all stages: innovation, early stage, optimization, scale up and GLP • Flexible business model • Mission is to help clients to reduce cost and shorten the time to clinic 2

Core Competency: Development and manufacturing of microparticles and nanoparticles • A large variety – Polymeric microspheres and nanoparticles (biodegradable and non-degradable) – Lipid and liposome nanoparticles – Functionalized nanoparticles • Functionalize particle surface to enable antibody or ligand conjugation – EDC chemistry – Click chemistry • Various particle size range for selection – 15 – 100 nm – 100 – 500 nm 0.5 – 20 m m – 20 – 500 m m – – can be uniform/monodispersed if required • Can be color-stained, fluorescently labeled or API-loaded • Robust process – Reproducibility – Scalability – GLP manufacturing • Applications – diagnostic – pharmaceutical 3

Sustained Release, Long-Acting Injectables • Reduce dose frequency – API is released to environment slowly to maintain therapeutic level for extended period (weeks to months) – Improve patient compliance and enhance efficacy • Extend biological half-lives of API – Protect protein/peptide from enzymatic degradation • Biocompatible and biodegradable material – PLGA, PLA and PCL are used extensively as drug delivery carriers 90 – Low toxicity and high drug encapsulation capabilities enabled 80 multiple sustained release products in marketplace Cumulative Release (%) 70 • Flexible administration method 60 50 – SC or IM 40 – Topical administration within specific tissue/organ 30 • Suitable for delivery of broad therapeutics 20 10 – Small molecule, peptide, protein, nucleic acid, etc. 0 0 5 10 15 20 25 30 Time (Days) 4

Nanoparticles for Various Applications – Prolong circulation and decrease dosing frequency – Deliver drug to desired organ, tissue or cell – Concentrate API within targeted tissue and extend half life – Enhance blood-brain barrier crossing – Protect drug from premature degradation – Increase potency and decrease systemic toxicity – Enhance intracellular uptake of macromolecular therapeutics 5

Liposome and Lipid-Based Nanoparticles (LNP) • LNP advantages – High rate of transfer through cell membrane – Endosome escape capability via lipid-fusion mechanism • Useful for delivery of – Small-molecule chemotherapeutics – Peptides and proteins – ASO, siRNA, mRNA, pDNA - encapsulated with high loading efficiency • Potential vaccine adjuvant • Help cross blood-brain barrier • Transfection agent for gene delivery 6

Fully Integrated Approach: From Prototyping to Clinic Formulation Design and Scale Up and GLP GMP via Tech Transfer Prototyping • Interactively work with partner • Scale up, process development • Strategic partnership with to identify critical parameters, and optimization of large- CMO discuss pros/cons scale formulations • Technology transfer to CMO • Design and fabricate various • GLP batches to support IND- • Oversight and technical prototype particles enabling, pre-clinical studies support during manufacturing • Optimization of small-scale • Pilot process at a scale of clinical materials formulation. finalized for tech transfer • Troubleshooting as needed 7

Partner in Pharmaceutical Development • Over 15 years of experiences in developing and manufacturing microparticles and nanoparticles, advancing products into the clinic • Helped 65 life sciences companies (16 large pharma & biotech) develop their products • Completed 35 preclinical and clinical projects collaborating with Pharma/Biotech/Academia • Integrated approach shortens the time to clinic • Experiences, know-hows and innovation 8