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• Specialists in combination drug product development

• Complex formulation design and device integration

• Extensive experience in biologics drug development

• Highly-qualified Ph.D. scientists

• 6,000 sq. ft. R&D lab, including process suite for clean fill

02/26

CENTER OF EXCELLENCE

Drug Product Development• Formulation design • Drug product development• Analytical methods

• Leveraging a deep understanding of molecular properties, formulation, and device• Integrating delivery system R&D projects into your development program

• Optimizing target product profile to enhance value proposition

Discovery Support• Lead molecule profiling• Clinical candidate

evaluation• Biologic half-life extension

Device Selection• Device identification• Integration with formulation• Combination product

development

03/26

DELIVERY SYSTEMS

Pharmaceutical R&D Laboratory• Formulation, analytical, process, chemistry, device development• Specialists in complex drug product development• Peptide and small molecule chemistry, conjugation (e.g., PEGylation)• Lead candidate selection, optimizing pharmaceutical properties

Drug Product Development Strategic Partnership• Strategic product development and hands-on technical support• Participation in CMC teams (analytical, formulation, chemistry, device)• Ideation and translation of innovative technologies from research to clinic

Partnering to Develop New Delivery Technologies• Sustained release injectable delivery technology• Self assembling delivery technology• Oral capsule device for targeted delivery

04/26

LAB CAPABILITIES

LEADERSHIP

05/26

Companies Our Leaders Have Worked With Products Our Leaders Have Worked On

06/26

LEADERSHIP EXPERIENCE BASE

07/26

Peptide

Protein

Small MoleculeOligonucleotide

MoleculesSustained Release

Injections

Nasal

Oral

Topical OcularTransdermal

Lead Selection

Preformulation

Immediate Release

Injections

Programs

Infectious Diseases

Alzheimer's Disease

Cardiovascular

OphthalmologyDiabetes

Oncology

Endrocrinology

HematologyInflamatory

Diseases

Pain Relief

Therapeutic Area

Public US

Private US

International

Partners

PROJECT EXPERIENCE

08/26

Analytical Research

Development Assessment

AnalyticalDevelopment

Preformulation

Delivery System Feasibility

Formulation PK Screening

Formulation Development

Technology Transfer

GMP Mfg.

Lead Molecule Selection

Delivery System Selection

Drug Product Development

Molecule DesignPeptide/Protein VariantsConjugates for Half-Life

Delivery System DesignAqueous or Non-Aqueous VehicleSustained Release FormulationTriggered or Targeted Systems

Drug Product DesignPen/Auto-InjectorPre-Filled Syringe

Nasal/Ocular Drops/Spray

Lead Molecule Design

Development Stability

Process Development

Scale Up

Analytical Methods

Qualification

Device Selection and Development

LAB CAPABILITIES

09/26

Suspension

Liposome

In Situ Gel-Forming System

Microsphere

Non-Aqueous Solution/ Suspension

Implant

Daily Weekly Monthly QuarterlyProtective layer against immune destruction

DNA

Homing peptide

Lipid-soluble drugin bilayer

Lipid bilayer

Drug crystallized in aqueous fluid

Liposome for Drug Delivery

SUSTAINED RELEASEFORMULATION APPROACHES

Various includingReversible PEG

10/26

Acylation(albumin binder)

Carbohydrate analogues

Poly AminoAcid Fusions

PEGylation

Albumin or Fc Fusion(FcRn recycling)

Daily Weekly Monthly

HESylation, Glycosylation

XTEN, ELP, PASylation

SUSTAINED RELEASECONJUGATE APPROACHES

Compound Type MW (kDa) Injection Frequency Liposome Salt Gel Microsphere

Peptide 1 Weekly to Monthly Peptide 1 Weekly to Monthly Peptide 2 >4 Months Peptide 3 Daily Peptide 4 Daily Peptide 4 Weekly to Monthly Peptide 4 Weekly to Monthly Peptide 5 Weekly to Monthly Insulin 6 Daily to Weekly

Oligonucleotide 10 Weekly Oligonucleotide 10 Weekly Oligonucleotide 10 Weekly

Protein 15 Weekly Protein 50 Weekly

11/26

SUSTAINED RELEASE TECHNOLOGIESCOMPOUNDS EVALUATED

Lead Molecule Selection and Molecular Design• Structural modifications to improve physio-chemical

properties and extend half-life• Amino acid variants for site-specific conjugation• Mutation series and Fc fusions

Non covalent modifications to alter properties• Salts and complexes to slow dissolution

Recombinant protein expression, peptide and oligonucleotide synthesis

Structural characterization, stability, and degradation products identification

Insulin Hexamer PEGylated Protein

Exenatide Macugen12/26

SPECIALISTS IN BIOLOGICS

~ 1K Da ~ 10K Da ~ 100K Da

Small Molecules

• IV, SC• Nasal• Oral

Peptides

• SC• Inhalation• Nasal• Ocular• Oral

Proteins

• SC• Nasal

Oligos

• SC

Antibody

• SC

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ROUTE OF ADMISSION

Non-invasive delivery for small molecule, peptide, and protein• Painless, no needles or injections• Easy administration by patient or caregiver

Formulation and analytical development • Dosage forms: solution, suspension, and dry powder• Chemical and physical stability

Drug product device assessment• Dose delivery/content uniformity• Particle/droplet size distribution• Spray pattern• Plume geometry• Leachable and extractable

Drug Product

Formulation

Device

Analytical

Olfactory epithelium

Respiratory region

Spray pattern Plume geometry

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Nasopharynx

Oropharynx

Trachea

Carina

Main bronchus

Bronchi

Alveoli

NASAL & INHALATION DELIVERY

Technologies for Controlled Release of DrugsSmall Molecule and Peptides Dosage Forms Created

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Tablets

• Bi-layer Tablets• Mini Tablets

Capsules

• Powder blends• Microparticle-filled• Microsphere-filled

Tablet Processes• Direct compression• Dry granulation• Wet granulation• Enteric coating

Oral Controlled Release

• Instant release• Sustained release• Enteric or delayed release

Topical

• Transdermal cream• Topical Spray

PARTNERSHIP WITH KYDES

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Chemical Instability• Deamidation –

Asn and Gln residues• Oxidation – Met residues• Degradation, ligation

(adduct formation)

Solubility Issues• pH, temperature,

buffer composition, ionic strength, etc.

Injection Site Reaction Issues

• Precipitation, extreme pH, osmolality, needle size, etc.

Gelation Issues• pH, temperature,

buffer composition, ionic strength, etc.

DELIVERY CHALLENGES SOLVED

Project Specific Work• Shorter well-defined projects• Typically 3 to 9 months• Confidential project definition• Payment milestones

Dedicated R&D Team• Longer term and broader projects• Typically 1 to 3 years• Dedicated resources for program• Regular quarterly or monthly payments

17/26

PARTNERSHIP OPTIONS

Aileron chemistry and formulation composition• Peptidomimetic macrocycles and formulations

thereof US 20160101145 A1

Client applications not yet published• Chemical responsive formulation• Nasal formulation for infection• Sustained release peptide formulation• Co-formulation of peptides

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PARTNER PATENT SUPPORT

ANALYTICAL

• High Performance Liquid Chromatography (HPLC) with diode array, fluorescence, and molecular weight detection for formulation characterization, in vitro release, and stability

• Ultraviolet-visible spectrophotometry (UV/Vis), fluorescence, and absorbance based plate readers for concentration, plasma compatibility, and solubility screening

• Particle size analyzer (laser diffraction) and dynamic light scattering for hydrodynamic radii estimation

• Injection force measurement using Instron

• Stability Chambers certified and monitored (ICH conditions 25ºC/60RH, 40ºC/75RH, 2-8ºC, -20ºC, -80ºC)

• SEM for microsphere visualization

FORMULATION

• Osmometer and Viscometer for characterization• Microfluidizer• Extruder

PROCESS

• Tray lyophilizer for cycle development• Laminar flow hood, depyrogenation oven, and

autoclave in the clean room for preclinical and stability sample preparation

BIOANALYTICAL

• MSD ELISA for bioanalysis• Gel electrophoresis imager for imaging protein gels

CHEMISTRY

• Fast protein liquid chromatography (FPLC) for protein purification

• Rotavap19/26

EQUIPMENT SETUP R&D AND PRODUCT DEVELOPMENT

Test Article Preparation –Research to Toxicity Studies

Restricted Access – Training Required

Suite meets ISO Class 7

Laminar Flow Hoods• ISO Class 5 annual certification

Quality System Guidelines• Sterile Technique, Cleaning

Documentation System• Process Batch Records

20/26

PROCESS SUITE

Manufactured over 200 batches in the past 4 years

Batch size 800 µL to 2 liters

Batch records and suite preparation signed off ahead of fill

Batch release testing with Certificate of Analysis• Concentration, purity, pH, osmolarity, endotoxin, and others

Formulation composition and process• Aqueous and non-aqueous solutions and suspensions• Liposomes, microspheres, gels, salts, and others

Formulation and fill finish manufacturing• 24 month shelf life now supporting phase 2 program• Stability studies to support ANDA filing• Several development studies for toxicology and clinical formulation selection

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PROCESS SUITE EXPERIENCE

22/26

FACILITY

David Litzinger, Ph.D.Dave has over 22 years of drug discovery and development experience, including technical and leadership roles in CMC and other functional areas in pharmaceutical and biotech companies.

William Vincek, Ph.D. President Pharma CMC, formerly SVP Development, Alpharma, Guilford Pharmaceuticals, GSK, Merck

Phil Duffy Operations consultant in life sciences, previously SVP Pacira, VP at Ligand and Schein Bayer

Solomon Steiner, Ph.D. CEO Perosphere Inc., previously CEO and Founder of Biodel, Mannkind, and Emisphere Technologies

Will Clodfelter, M.B.A.Market & Device Development

Mark Longer, Ph.D.Regulatory Strategy

Nelson Lugo, M.B.A.Manufacturing

Bill Van AntwerpDevice and Diagnostics R&D

Molly Holman, Ph.D., J.D.Intellectual Property, Legal

James Matriano, Ph.D.Bioanalytical

Michelle NeohMarket Research

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TECHNICAL ADVISORS

Dan BradburyPharma AdvisorFormer Amylin CEO, Chairman BioBrit, advisor to startups

Donald RindellBusiness AdvisorPrincipal, Camino International, corporate strategy and business development

Eddie RodriguezLegal AdvisorAttorney at Troutman Sanders, corporate and legal advisor

Magda MarquetContract Services AdvisorFounder of Althea and Althea DX, successful sterile manufacturing

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BUSINESS ADVISORS

Combination Drug Product Development• Peptide and protein development• Lead molecule profiling and half-life extension• Subcutaneous and ocular formulation design and development• Sustained release injectable formulations• Device design and development• Translation from research through clinical and commercialization

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OUR EXPERTISE

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