• 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
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
12/26
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
14/26
Nasopharynx
Oropharynx
Trachea
Carina
Main bronchus
Bronchi
Alveoli
NASAL & INHALATION DELIVERY
Technologies for Controlled Release of DrugsSmall Molecule and Peptides Dosage Forms Created
15/26
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
16/26
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
18/26
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
21/26
PROCESS SUITE EXPERIENCE
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
23/26
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
24/26
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
25/26
OUR EXPERTISE
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