01/27 PHARM R&D CENTER OF EXCELLENCE

• Specialists in injectable drug formulations and combination drug product development

• From solution injectable to complex formulation design (immediate and extended- release)

• Drug product R&D for small molecule, peptide, and protein from research to commercialization

• Extensive experience in biologics, drug development, device, and delivery technologies

• Highly-qualified Ph.D. scientists working in state-of-the-art R&D lab in heart of San Diego

02/27 CONTRACTED DRUG PRODUCT R&D

• Leveraging a deep understanding of molecular properties, formulation, device • Integrating delivery system R&D projects into your development program • Optimizing target product profile to enhance value proposition

Discovery Support Drug Product Development Integration with device • Lead molecule profiling • Formulation design • Device identification • Clinical candidate evaluation • Drug product development • Formulation compatibility • Biologic half-life extension • Analytical methods • Device product development

03/27 R&D LAB CAPABILITIES

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) • Translation of innovative technologies from research to clinic

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

04/27 LEADERS WITH DEEP DOMAIN EXPERIENCE

Chris Rhodes, Ph.D. Sharon Lee Rhodes, Ph.D. Dave Litzinger, Ph.D. President & CEO Executive Vice President Scientific Advisor Founded Drug Delivery Sharon is a proven strategic Over 22 years of drug Experts in 2014 after 20 leader with a potent discovery and years in biotech and drug combination of skills in the development experience, delivery companies in technical, corporate, including technical and both technical and academic and non-profit leadership roles. executive leadership roles. arenas.

Lawrence D’Souza, Ph.D. Laxma Reddy, Ph.D. Shu Fen Wen, Ph.D. Scientific Director Scientific Director Scientific Advisor Discovery, Chemical and Formulation and Process Drug Product Development, Process Development, Development, Small Manufacturing Formulation Molecules and Biologics Over 30 years of late stage Organic chemist with Protein biophysical chemist product development discovery and early with experience in experience and device development experience in extended-release integration. small molecule, peptide, and drug delivery product protein synthesis. development.

05/27 PHARMA LEADERSHIP EXPERIENCE BASE

Our Leaders Have Worked at These Companies Our Leaders Developed These Products

06/27 SUPPORT ACROSS DRUG DEVELOPMENT

LEAD MOLECULE SELECTION SOLUTION FORMULATION • Peptides • 5C in a Vial • Small Molecules • Lyophilized • Frozen Solution

DEVICE INTEGRATION LIFE-CYCLE • Pre-filled Syringe MANAGEMENT • Cartridge • Reformulation • Pen • Long-Acting System • Auto-Injector • Non-Injectable Delivery (Oral, Nasal, Pulmonary) 07/27 MOLECULE AND DELIVERY EXPERIENCE

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

Small Molecules Peptides Proteins Oligos Antibody • IV, SC • SC • SC • SC • SC • Nasal • Inhalation • Nasal • Oral • Nasal • Ocular • Oral

13/27 COMPONENTS OF TYPICAL LAB PROJECTS

Lead Molecule Delivery System Drug Product Development Selection Selection

Analytical Analytical Formulation Analytical Development Delivery System Research Development Development Methods Stability Feasibility Development Qualification Assessment Formulation Device Lead Process Selection and Technology Preformulation Molecule PK Screening Development Development Transfer Design Scale Up GMP Mfg.

Molecule Design Delivery System Design Drug Product Design Peptide/Protein Variants Aqueous or Non-Aqueous Vehicle Pen/Auto-Injector Conjugates for Half-Life Sustained Release Formulation Pre-Filled Syringe Triggered or Targeted Systems Nasal/Ocular Drops/Spray

08/27 PRODUCT DEVELOPMENT SUPPORT

Contracted Fee for Service Proprietary Delivery Technology

Developability Assessment SubQ Biologics™ Pharmaceutical Development Modulate solubility & dissolution Solutions and Suspensions Alter subcutaneous absorption Aqueous and Non-aqueous systems Improve PK profile and ISR Scale from 1 ml to 10 liter batch size Stability and Preclinical Supplies Analytical Development Long-Acting Technology HPLC Stability Indicating Methods Proteins Content assay and impurity profiles Peptides Various drug product specific QC tests Oligonucleotides Delivery Systems Antibodies PLGA Microspheres and Implants Nanoparticles and Liposomes Extended-release Suspensions IP License Agreement Nasal and Pulmonary

09/27 EXTENDED-RELEASE INJECTABLE APPROACH

Liposome for Drug Delivery Daily Weekly Monthly Quarterly Protective layer DNA against immune destruction Suspension

Homing peptide Liposome

In Situ Gel-Forming System Drug crystallized Lipid-soluble drug in aqueous fluid in bilayer Lipid bilayer Microsphere

Non-Aqueous Solution/ Suspension

Implant

10/27 EXTENDED-RELEASE INJECTABLE PROGRAMS

Compound Type MW (kDa) Injection Frequency Liposome Salt* Gel Microsphere Suspension Small Molecule <1, several Monthly and longer  Peptide 1 Weekly to Monthly    Peptide 2 3 to 4 Months   Peptide 3, 4 Daily  Peptide 4 Weekly to Monthly   Peptide 4, 5 Weekly to Monthly    Insulin 6 Daily to Weekly   Oligonucleotide 8 Daily to Weekly  Oligonucleotide 10 Daily to Weekly triple combination  Protein 15 Weekly   Protein 50 Weekly   Antibody 150 Weekly to Monthly 

*Note: Biologics salt forms are based on proprietary SubQ BiologicsTM technology

11/27 FORM SELECTION & PARTICLE SUSPENSION

Salt or Co-crystal Dry Ball mill Micro-particle Suspension

Form Or Wet Bead mill Selection Drug Substance: Insoluble Crystal Form Free base or acid <0.01 mg/ml at 37C PBS Low rate of saturation solubility

Nano-particle Suspension Horizontal oscillatory ball mill for small scale grinding Tube Roller for low energy grinding Vertical planetary ball mill for high energy grinding

12/27 ORAL AND TOPICAL FORMULATIONS

Capsule Capabilities at Controlled Release Oral Formulations DDE Labs Through KYDES Partnership

Hand-filled Capsule batches Tablet Processes • Powder blends • Direct compression Oral Controlled Release • Microparticle-filled • Dry granulation • Instant release • Microsphere-filled • Wet granulation • Sustained release • Nanoparticle formulations • Enteric coating • Enteric or delayed release • Oil-based suspensions • Bi-layer and mini tablets • Permeation enhancing for Topical peptides Capsules • Transdermal cream • Powder blends • Topical Spray • Microparticle-filled • Microsphere-filled

14/27 NASAL & INHALATION EXPERIENCE

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

Formulation and analytical development Nasopharynx • Dosage forms: solution, suspension, and dry powder Carina Oropharynx Main bronchus • Chemical and physical stability Trachea

Drug product device assessment Bronchi • Dose delivery/content uniformity Alveoli • Particle/droplet size distribution Device • Spray pattern Spray pattern Plume geometry • Plume geometry Formulation Analytical • Leachable and extractable Drug Product

15/27 STATE-OF-THE-ART DRUG PRODUCT LAB

16/27 DDE LABS EQUIPMENT & CAPABILITIES

Analytical Development Manufacturing Suite • 17 HPLC (diode array UV Vis, fluorescence, ELSD, RID) • 3 Laminar flow hoods (ISO 5 certified) • UV/Vis & fluorescence plate readers and nanodrop • Vestibule for gowning • Particle size analyzer (laser diffraction, 1µM – 500 µM) • Material handling: depyrogenation oven, autoclave, • Dynamic light scattering / zeta potential (1 nm – 10 µM) chemical fume hood • Stability Chambers certified and monitored (ICH 25ºC/60RH, 40ºC/75RH, 2-8ºC, -20ºC, -80ºC) Bioanalytical Development • Osmometer and Viscometer for characterization • MSD ELISA for bioanalysis • Scanning electron micrograph, visual microscopy • Gel electrophoresis imager for imaging protein gels Formulation and Process Development Chemistry and Chemical Development • Microfluidizer, homogenizer, emulsifiers • Organic synthesis reactors • 37C incubators for In vitro release testing for extended- Rotary evaporator release injectables (water bath and shake-flask) • • Jacketed reaction vessels • Instron Injection force measurement • Manifold lyophilizer • Nano assembler for nanoparticle & liposome • FPLCs for protein purification • Shelf–stoppering lyophilizer for cycle development • Preparatory HPLC • Ball mill, tube roller, planetary ball mill for grinding • Salt, co-crystal, and prodrug selection • Capsule hand-fill for powder and liquid formulations • 2 laminar flow hoods for development work 17/27 MANUFACTURING AND PROCESS SUITE

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 18/27 PROCESS SUITE EXPERIENCE

Manufactured over 200 batches in the past 5 years Batch size 1 mL to 2 liters (Capability to go to 20 liter batches) 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

19/27 5 YEARS, 60 CLIENTS & GROWING

Molecules Oligonucleotide • Over 5 years, 39 lab projects / 38 consulting projects Small Molecule

• 90% of clients in US / remainder EU and JP

Protein • 6 multinational corporations Peptide • Over the last 3 years

Programs • Average of 22 clients each year (17 lab / 5 consulting) Immediate Sustained Release Release Injections Injections • Yearly average of 11 new clients and 11 repeat clients

• 2/3 business yearly from repeat clients Preformulation Nasal • 80% business from clinical and commercial companies Oral Lead Selection Topical Ocular Transdermal 20/27 39 LAB PROJECT CLIENTS IN 5 YEARS

21/27 38 CONSULTING CLIENTS IN 5 YEARS

22/27 PARTNERSHIP OPTIONS

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

23/27 R&D COLLABORATIVE PARTNERS

Client Type of Project Scope of Lab Work SENSULIN DDE is responsible for • Develop liposomal glucose-responsive insulin drug delivery system full R&D Program • Formulation, Process, Analytical, PK / BA • Drug Development Team Leadership (Mfg., Reg, Tox, Clin, BD) DIAVACS DDE runs Product • Develop oligonucleotide nano-particle drug delivery system Development • Formulation, Process, Analytical, In vitro cell culture model, in vivo Program POC ABVANCE DDE runs Product • Develop Insulin Pump Co-Formulation, Process, Analytical, PK/BA Development Program VERU DDE developed the • Small Volume Subcutaneous 3-month PLGA-gel Depot Injection product formulation in partnership with Veru

24/27 PARTNER PATENT & PUBLICATION SUPPORT

Veru Healthcare • Compositions and Methods for Long Term Release of Gonadotropin-Releasing Hormone (GnRH) Antagonists, US 15/885,464 • ASCO presentation on preclinical results Aileron Therapeutics • Peptidomimetic macrocycles and formulations thereof, US 20160101145 A1 Abvance Therapeutics • Systems, Compositions, and Methods for Treating Diabetes, Allan Cherrington, Soumitra Ghosh, Christopher A. Rhodes, Jui-Chen Lin, Patent Application US2018016647 filed March 2, 2017 Iogen LLC • Emolient topical disinfectants, WO 2018/017645 A1 • ”Enhanced topical delivery of non-complexed molecular iodine...”,Intl J Pharm 554(2019)81-86

25/27 OUR EXPERTISE

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

26/27 27/27 LAB CASE STUDIES — PRE-MARKET

PRECLINICAL Small Organic • Topical Ocular Formulation for a Diagnostic, Analytical, PK Formulation LEAD Protein • Process, Formulation, Analytical, Tech Transfer SELECTION PEGylation • CMC and Drug Development Team Consulting (Mfg., Reg, Tox) PHASE 1 Small Organic • IV Injection Formulation, Analytical, CMC Formulation PHASE 2 Peptide • Optimize IV Aqueous Formulation Stability Formulation • CMC Consulting PHASE 3 Peptide • Life Cycle Support, Immediate Release to Extended-Release Re-formulation Injection • CMC Consulting

XX/27 LAB CASE STUDIES — POST-MARKET

ANDA Peptide • Process, Analytical, and Tech Transfer Formulation • CMC and Drug Development Team Consulting (Mfg., Reg, Tox, BD) COMMERCIAL Protein • Analytical, PK/BA, Solution, Particulate Suspension, ISR Re-formulation Improvement • Defined Product Life Cycle Plan as Consulting Team COMMERCIAL Oligonucleotide • Nanoparticle Development, Process Development, Analytical, Re-formulation Scale-Up for Delivery Improvement COMMERCIAL Small Molecule • Long-Acting Injectable, Small Molecule, Particle Suspension Re-formulation Formulation

XX/27 CONSULTING CASE STUDIES

Project Type Program Scope DUE DILIGENCE Peptide Phase 1 Asset CMC Due diligence for VC investment Peptide/Microneedle Phase 3 CMC Due diligence for company acquisition Biologics Oral Delivery Due diligence for VC investment LIFE CYCLE PLANNING Protein in Commercial Product Recommend life cycle options for product improvement DELIVERY TECH ASSESS Biologics Polymer Delivery Evaluate drug delivery polymer applications to biologics Cell Penetrating Peptide Evaluate therapeutics applications for CPP delivery Small Molecule Oral Delivery Recommend therapeutics for oral delivery system Biologics Oral Delivery Evaluate oral delivery as leader of advisory board Biologics Ocular Delivery Evaluate ocular drug delivery technologies for biologics CMC SUPPORT Biologics Ocular Delivery Advise R&D program for biologics ocular drug delivery Peptide R&D Project Evaluate formulations and guide R&D program Peptide Drug Delivery Advise CMC team for delivery system development Long-Acting Injectable Advise CMC team for delivery system development XX/27 ADVISORS AND EXPERTS

William Vincek, Ph.D. Will Clodfelter, M.B.A. President Pharma CMC, formerly SVP Market & Device Development Development, Alpharma, Guilford Pharmaceuticals, GSK, Merck Mark Longer, Ph.D. Phil Duffy Regulatory Strategy Operations consultant in life sciences, previously SVP Pacira, VP at Ligand and Schein Bayer Nelson Lugo, M.B.A. Manufacturing Solomon Steiner, Ph.D. Serial entrepreneur, previously CEO and Founder Bill Van Antwerp of Perosphere, Biodel, Mannkind, and Emisphere Device and Diagnostics R&D Technologies

XX/27 BUSINESS ADVISORS

Dan Bradbury Pharma Advisor CEO Equilium, Chairman BioBrit, Former Amylin CEO

Donald Rindell Business Advisor Principal, Camino International, corporate strategy and business development

Eddie Rodriguez Legal Advisor Attorney at Troutman Sanders, corporate and legal advisor

Magda Marquet Contract Services Advisor Founder of Althea and Althea DX, successful sterile manufacturing

XX/27