Capabilities Presentation

October 2010

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Presentation Outline

• Overview of Particle Sciences

• Corporate Partnerships

• Licensed Technologies

• Development Model

• Select Technologies

• Select Current Projects

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Introduction

• CRO servicing Pharmaceutical and Biotech companies

• Providing formulation/drug delivery, analytical services and clinical trial material production

• Founded in 1991, privately held, profitable

• Bethlehem, PA, 15,000 sq ft, 40+ employees

• Comprehensive formulations approach

• State-of-the-art chemical and physical characterization methodologies

• cGLP/cGMP, analytical/bioanalytical laboratories

• cGMP clinical trial materials production for both sterile and non-sterile products

• Full ICH stability programs

• Dedicated highly potent compound handling infrastructure

• DEA licensed, FDA registered

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Broad Base of Experience

• MD and PhD’s in: Physical Chemistry, Medicinal Chemistry, Synthetic Organic Chemistry, Material Science, Biomaterials, Analytical Chemistry, Colloids and Polymers, Physical Bioorganic Chemistry ……

• Director level oversight of analytical, quality, formulation, clinical and cGMP production groups

• Broad industry experience: international, large/small Pharma, biotech, government, not-for-profit

– Small molecules, oligos, peptides, proteins

– Multiple therapeutic areas

• Multiple commercialized technologies

• > 100 patents pending / issued ranging from nanoparticles to medical devices

• Regulatory, US and foreign CMC section support

• Technology transfer of multiple technologies

• Nanoparticle design

• Instrument/device design

• Many peer reviewed publications

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Particle Sciences’ Role

• From post-discovery through clinical development• Work under multiple models• Prefer to be an integrated member of the team• Routine work through true innovation/invention

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Integrated Approach

• Full development program management• Multiple integrated disciplines

– Formulation– Analytical/Characterization– Regulatory support– Production

• Responsive• Interactive / Open• Clients ranging from early venture-backed companies to

not-for-profit to large Pharma• Track record of innovation and of developing

commercializable technologies

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Formulation/Process Equipment

• Hydraulic and electric injection molders (lab and pilot scale)

• Compounder / Extruder (lab and pilot scale)

• Pelletizer

• Class 10,000 and Class 100 clean rooms

• Laminar flow hoods

• Laboratory homogenizer

• Admixer

• Microfluidics® high pressure homogenizer

• Microfluidics Reaction Technology™ system, MRT

• Three ultrasonic dispersers / Homogenizers with in-line capability

• High energy media mill

• Two 1.5 liter jacketed double planetary mixer with vacuum

• Two mini-spray dryers with organic solvent capability

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Formulation/Process Equipment

• Several micronizers with sanitary collector capability

• Augmented Drip Casting ADC™

• Roller mill

• Laboratory homogenizers

• Lyophilizers

• Bench-scale tangential flow filtration unit

• Three 500 gallon jacketed stainless tanks

• Three 100 gallon self-fired stainless tanks

• Glass-lined jacketed and pressurized reactor

• Cooling tower with 2 heat exchangers

• USP water treatment system

• Multiple stability chambers

• Autoclave

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Analytical / Bioanalytical Tools

• HPLC, UPLC• Microwave extraction• LC/MS Ion Trap• LC/MS Triple Quads• NMR, SEM, XRPD by third parties• UV/Vis• FTIR• DSC• Microscopic image analysis• Raman imaging with particle size/morphology integration • Fluorophotometer• Percutaneous absorption (IVRT)• ELISA• USP Dissolution Apparatus• Karl Fischer – Volumetric and Coulometric

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Physical Characterization

• Particle Sizing– Laser light scattering (DLS)– Fraunhofer diffraction (wet/dry)– X-ray and photo disc centrifuge sedimentometry– Optical counting (SPOS)– Image analysis

• High Throughput Particle Size Analysis (DLS)– Screening for protein stability / aggregation

• Zeta Potential– Electrophoretic light scattering– Phase analysis light scattering– Streaming potential

• Rheology– Oscillating rheometer– Rotational viscometer– Tack & compressive force

• Raman with particle size/morphology analysis• Advanced Instruments 3320 Osmometer• Shimadzu DSC-60• Kruss Contact Angle/Surface Energy Measuring

System G10• Turbiscan sedimentation-stability analyzer

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ICH Stability

• ICH Stability– Long term & accelerated conditions (T/RH controlled chambers)

• 25 °C/60% RH, 30 °C/65% RH, 40 °C/75% RH

– Photostability

– Stress stability 50 °C/85% RH

– Freeze / Thaw

• Custom Programs

• Developmental Stability Studies– Homogeneity via Raman spectroscopy

– Forced degradation

• MSn structure elucidation

• API/Drug Product

– API/Excipient compatibility via

• DSC

• HPLC

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Corporate Partnerships

Through partnerships, PSI strives to bring best of breed technology to bear on Clients’ projects. For example:

• Leading medical polymer supplier to streamline supply chain and offer new chemistries

• Microfluidics:

– Best in class high pressure homogenizers

– MRT for controlled precipitation of nanoparticles

• Horiba: collaborating to integrate optical microscopic imaging system (Clemex) with Raman spectroscopy (XploRA) to meet coming regulatory demands

• Malvern: collaborating on high throughput DLS system (APS) to speed large molecule formulation and stability screening

• IES Engineers: serve as PSI’s Chemical Hygiene Office, band compounds, and evaluate new processes from an EHS perspective

• Lehigh University: Development of novel bio-based surfactants to enhance drug solubility and penetration

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Licensed Technologies

• PSI believes in a multi-platform approach to best address our client’s challenges.

• PSI uses standard technologies, actively develops its own delivery technologies and in-licenses where strategic.

• Examples of recently in-licensed technologies include:

– Proprietary solid solution technology using GRAS amphiphilic polymers

– PEGylated cationic polymers: family of compounds with a wide range of uses – freedom to operate an important aspect of this portfolio

– Naturally derived biodegradable polymers: green materials suitable for sustained release IM/SC/IP dosage forms

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Development Model

• Technology centered to drive efficiency

– PSI has developed a skill/knowledge set around various technologies that enhance drug delivery

– PSI applies these technologies to a variety of dosage forms

• Solubility Program: leveraging Hansen Solubility Parameters and a proprietary solvent database spanning a wide range to accurately determine HSP values for a given material

• Design of Experiments: PSI has institutionalized use of JMP software for screening, characterization, and optimization studies as part of QbD program

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Particle/Microcapsule Design

• Extensive experience in particulate

design

• Company-wide core competency for

15 years

– Multiple successful efforts with large

commercial entities

– Ph.D. work of several staff members

– Both physical and chemical methods

• Production

– Scaled to 100,000’s kg per year

– Nanoparticle production

– Surface modification

– Microencapsulation

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Select Technologies- Spray Drying

• Bucchi B-290 (2)• Capable of handling aqueous and non-aqueous

systems

• Increases bioavailability by converting API into amorphous state, nanoparticles, or a combination of these two forms

• Good for Biopharmaceutical Classification Systems II and IV molecules

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Select Technologies- Augmented Drip Casting

• Applications: taste masking, capsules, pediatric dosage forms, combination products, highly controlled IM/SQ release

• Uniform, solid microspheres or core-shell microcapsules

• 10’s to 100’s in diameter

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Select Technologies- Hot Melt Extrusion

• Haake compounder/extruder

• Leistritz 18 mm twin screw extruder

• Increases bioavailability by converting API into amorphous state, molecular solution, nanoparticles, or a combination of all three

• Good for Biopharmaceutical Classification Systems II and IV molecules

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Select Technologies- Drug Eluting Devices

• Increasing demand

– Patent extension

– Local and systemic delivery

– Improved pharmacokinetics• Chronic systemic

• Local high concentrations

– Improved compliance

• Thermoplastic (EVA, PU)

• Thermoset (reactive silicones)

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Select Current Projects

ANDA program for intravaginal ring

• Multinational Pharma contracted PSI to conduct complete

development program for contraceptive intravaginal ring

– PSI has infrastructure to handle highly potent compounds,

including hormones

• After scale up, PSI will transfer manufacturing technology

to Client

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Select Current Projects

Pediculicide: Phase I (III in 2010)

• Complete formulation semi-solid (on/off shampoo)– High aesthetic demand

– Desired increase in efficacy

• API method development

• Drug product method development

• Participate in preclinical and clinical testing protocol design

• Production of GLP and GMP materials

• Full stability program

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Mucosal delivery of ARV’s: Phase II (III in 2011)• Complete formulation of multiple semi-solid formats

– High aesthetic demand• Multiple consumer tests

– Expensive API(s)• Inexpensive formula/applicator

– Demanding stability profile

• Scale up and all analytical method development

• Production of tox and clinical materials

• Full stability program

• Extensive regulatory support

• Extensive external laboratory coordination

Select Current Projects

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Select Current Projects

Novel ophthalmic excipient

• PSI developed novel cationic PEGylated excipients for

multiple applications, including ophthalmic

• Phase I for dry eye has demonstrated statistically significant

advantage for tear break up compared to commercial

product

• Several Companies are interested in a variety of potential

applications – dry eye, incorporation of excipient into

devices, stabilization of antibodies…

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Novel Dermal Filler

• Issue: Novel modified polysaccharide technology for sub-

dermal filler gel containing biodegradable microparticles

• Resolution: Transferred in polymer technology (chemistry

and processing), and developed prototype gel formulations

and microparticles.

• Outcome: GLP formulations prepared for mini-pig tolerability

study. Good study outcome. Technology available for

license.

Select Current Projects

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Select Current Projects

Improved bioavailability of an oral chemotherapeutic

• Issue: Repurposed potent, BCS II API with poor (1%) oral

bioavailability, CTM required for P1 trial, and route to

conversion of dosage form to an oral solid

• Resolution: Reformulate using both nanoparticle and

microemulsion approaches for eventual conversion into

solid dosage form

• Outcome: Produced CTM from successful candidates

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Select Current Projects

Oncology agent with novel MOA for IV administration

• Issue: toxicity of particulate formulations developed by three

different academic institutions

– Full characterization of academic formulations showed they

were not what they were purported to be

• Resolution: filled in gaps in preformulation studies which

guided evaluation of several nanoparticulate approaches

• Outcome: two lead formulations are in tox testing and look

promising with best tox profile of any formulation to date.

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Select Current Projects

Oncology agent for IV/oral administration use

• Issues: API has liver toxicity; Client requested development of

IV product that could be ultimately administered orally

– Home run is reduced liver tox and good oral BA

• Resolution: target nanoparticle formulation with stealth coating

• Outcome: Six formulations ready for in vitro testing.

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Select Current Projects

Taste-masking of pediatric oral Neuroblastoma agent

• Issues: API (BCS II) may have bad taste and is susceptible

to acid hydrolysis

• Resolution: evaluated several methods for taste masking

and enteric coating

• Outcome: formulations based on complex coacervation,

emulsion, and augmented drip casting methods are ready

for Client in vitro testing.

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Select Current Projects

Oncology agent for IV administration

• Issues: API is BCS II and intravenous administration is

required; Client’s original drug delivery CRO was

unresponsive, expensive, did not freely share data, and

would not supply tox batch

• Resolution: Nanocrystal approach evaluated

• Outcome: formulation at requested concentration (25%

API) developed with mean particle size of ~100 nm, with

good stability and amenable to lyophilization – evaluation

of gamma sterilization of lyophile underway.

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Select Current Projects

Cytotoxic agent for SC administration

• Issues: Client wants to match innovator IV PK profile with

SC administration. API is highly potent, BCS II, and

susceptible to hydrolysis. Client wants to incorporate

proprietary polymer into formulation.

• Resolution: nanoparticle approaches for this API including

milling in non-aqueous vehicles and production of

lyophilized material that can be reconstituted with vehicle

containing proprietary polymer

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Select Current Projects

Anti-neoplastic nanoparticle for intrathecal delivery

• Process characterization and scale up of University-

originated technology

– Develop analytic methods

– Characterize product

– Support CMC of compassionate use IND

– Produce sterile CTM

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Summary

• Technology driven CRO

• Seasoned staff

• Multiple platforms centered around drug delivery– Nano- / Micro-particles

– Drug-eluting devices (Combination Products)

– Polymer solutions

• Full analytical, bioanalytical and stability support

• Clinical trial materials manufacturing