Peptide NCEs and Generics

Development and Manufacturing

CGMP

With more than a decade of committed service to the peptide industry, CPC Scientific is a trusted provider of high-quality peptides to researchers and pharmaceutical companies all over the world. The CPC Group is comprised of peptide experts who have actively pursued peptide design and large scale manufacturing for more than 30 years, so your project is in good hands.

CPC Scientific is the ideal peptide partner for all of your CGMP needs, from concept to commercial.

CONTENTS3 INTRODUCTION

4 CGMP OVERVIEW

6 GENERIC PEPTIDES

7 DMF SCHEDULE

9 CERTIFICATIONS AND AUDITS

10 MANUFACTURING CAPACITY

11 MANUFACTURING EQUIPMENT

12 QUALITY PROGRAM

14 PARTNERING WITH CPC SCIENTIFIC

16 PEPTIVAC™ NEOANTIGEN PEPTIDES

17 CGMP PRODUCT CITATIONS

19 CONTACT INFORMATION

THIS IS THE LAST PEPTIDE BROCHURE YOU’LL NEED TO REVIEW.No matter the stage or scale of your project, CPC Scientific has the facilities and proven experience to meet your needs.

We invite you to review empirical evidence in the pages ahead. We welcome your closest scrutiny because, frankly, if we meet our own exacting standards, we stand ready to take on the scientific world.

If you have any questions, please feel free to call a consultant at:

(408)734-3800Toll-Free:

(877)272-7241

cpcscientific.com3

Analytical Method Development and Validation | Quality Assurance & Regulatory support

• SPPS, LPPS, ligation chemistry and fragment condensation methodologies

• All protecting strategies (Boc, Fmoc, Cbz) can be used

• Innovative purification and isolation techniques employed

• Process development and scale-up competence insures a robust commercial process

• Complex sequences and peptide modifications adapted to large-scale production

E X P E R T I S E

COMPLETE PRODUCT LIFE-CYCLE SUPPORT

OVERVIEW

PROCESS SCALE-UP PROCESS VALIDATION

COMMERCIALMANUFACTURING

DiscoveryCommercial

PhaseClinical

Phase IIIClinical Phase II

Pre-Clinical Phase

Clinical Phase I

PROCESS DEVELOPMENT

US-BASED CGMP PROJECTSBY CLINICAL TESTING PHASE

0 5 10 15 20 25 30 35 40

Phase I

Phase II

Phase III

54

G E N E R I CP E P T I D E SCPC Scientific offers a variety of generic peptides for use as active pharmaceutical ingredients (APIs), which are utilized in the treatment of various diseases including cancer, diabetes, obesity, and multiple sclerosis. Our CGMP manufacturing facility employs a rigorous quality and EHS system to insure global compliance, including the stringent requirements of the United States, European Union, China, and Japan.

In addition, we fully support our pharmaceutical customers with required regulatory documentation including Drug Master Files (DMFs).

NAME SEQUENCE/INDICATION DMFLeuprolide Acetate

pGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt | Indications: Prostate Cancer, Endometriosis, Uterine Leiomyomata, Precocious Puberty, Breast Cancer.

MFDS: 2018/04US FDA: 2015/04CFDA: Approved in 2009

Triptorelin Acetate

pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 | Indication: Hormone-responsive cancers such as prostate cancer or breast cancer, Precocious Puberty, Estrogen-Dependent Conditions (e.g., Endometriosis or Uterine Fibroids), Assisted Reproduction.

CFDA: 2014/03CFDA: Y20170001090

Exenatide Acetate

H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 | Indication: Diabetes.

CFDA: 2015/12CFDA: Y20170001378

Terlipressin Acetate

H-Gly-Gly-Gly-Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH2 (disulfide bridge) | Indication: An analogue of vasopressin, BLeeding Esophageal Varices, Septic Shock, Hepatorenal Syndrome, cardiovascular (low blood pressure.).

EMA: 2019/09CFDA: 2019/09

Cetrorelix Acetate

Ac-D-Nal-D-Cpa-D-Pal-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH2 | Indication: IVF. CFDA: 2019/08

Triptorelin Pamoate

pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2 | Indication: Endometriosis, Uterine Fibroids, Premature Puberty. Symptoms of Prostate Cancer and ART.

CFDA: 2020/03

Teduglutide H-His-Gly-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-OH | Indication: Short Bowel Syndrome.

CFDA: 2020/08

Degarelix Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(L-Hor)-D-4Aph(Cbm)-Leu-Lys(iPr)-Pro-D-Ala-NH2 | Indication: Prostate Cancer.

CFDA: TBD

Buserelin Acetate

pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt | Indication: Prostate and Breast Cancers.

CFDA: TBD

Liraglutide Acetate

H-His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys(γ-Glu-palmitoyl)-Glu-Phe-Ile-Ala-Trp-Leu-Val-Arg-Gly-Arg-Gly-OH | Indication: Diabetes (type II).

CFDA: 2020/02

DMF SCHEDULE

BROWSE OURPEPTIDE CATALOG

www.cpcscientific.com

76

CERTIFICATIONS AND AUDITS

• FDA (US): Audited

• EMA (EU): Audited

• MFDS (Korea): Audited

• NMPA (China): Audited

• ISO 9001 Certified

• ISO 13485 Certified

CGMP COMPLIANCECPC’s CGMP program strictly adheres to CGMP guidelines including:• Code of Federal Regulations Part 210/211 (21

CFR 210/211)

• ICH Q7 (International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Harmonised Tripartite Guideline Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Q7)

We were the FIRST peptide CMO in Asia to be inspected by the

U S F D A

4 USFDA INSPECTIONSNO FORM-483 OBSERVATIONS

9

MANUFACTURINGCAPACITY

• 750,000 sq. ft. CGMP Manufacturing space

• 17 CGMP Peptide Synthesis Suites by 2019

• CGMP batch sizes from gram scale to multi-kilogram scale (20kg/batch)

• Qualified air and water systems

• IQ, OQ, PQ qualified equipment

• Class 100K and 10K clean rooms

Large-Scale CGMP Manufacturing Equipment

0 5 10 15 20

Tray Lyophilizer: 1,000L

Tray Lyophilizer: 500L

Tray Lyophilizer: 150L

30" Column

20" Column

12" Column

Reactors: 500L

Reactors: 200L

GMP Peptide Synthesis Suites

Now End of 2019 Neoantigen Suites

C

1110

QUALITYPROGRAM

• Appearance: white to off-white solid

• Solubility: Clear solution at a predefined concentration

• Purity (HPLC, UPLC): 95-99% specific to phase of development

• Molecular weight (MS)

• AAA (Amino Acid Analysis): ±10% of theoretical

• Peptide content: ≥70%

• Counter-ion content

• Moisture content (Karl Fisher): ≤10%

• Residual Solvent Content: GC-MS

• Residual trifluoroacetic acid: ≤0.1%

• Bioburden: Report Aerobic and Spore Count, USP guidelines

• Endotoxin: Report LAL (Gel Clot), USP guidelines

• Elemental Analysis (ICP-MS): Report results for the following metals: Sb, As, Bi, Cd, Cu, Pb, Hg, Mo, Ag, SnOu

r CGM

P sp

ecifi

catio

ns a

nd te

sting

pr

oced

ures

can i

nclud

e the

follo

wing

:

• Phase appropriate control systems consulting

• CMC compilation• DMF compilation and

submission• Annual product reviews

• Batch record review• Document management & control• Deviations/Investigations• CAPA follow up and tracking• Complaint management• Product release

QUALITY ASSURANCE REGULATORY SUPPORT

• In-process, release and environmental control testing

• Standard release testing performed in-house

• Audited contract laboratories available for additional testing

• Method development and validation, formal method transfer

• Stability studies (ICH) and forced degradation

A dedicated, in-house Quality Department verifies full CGMP compliance throughout production, as well as testing and documentation standards in accordance with the most stringent FDA requirements.

13

CPC provides all required regulatory support for your peptide APIs:

• Phase-appropriate consulting and control systems

• Information necessary for chemistry, manufacturing, and controls (CMC) compilation for Investigatory New Drug (IND) and New Drug Application (NDA) submissions

• Drug Master File (DMF) compillation and submission

• Annual product reviews

REGULATORY S U P P O R T

OUR EXPERIENCE IS AT YOUR DISPOSAL

YOUR SUCCESS IS OUR SUCCESS. Your dedicated contacts will know your project as

well as you do, and they’ll keep you in the loop.

PARTNERINGWITH CPC

Research & Development • ProductionQuality Control • Quality Assurance • Logistics

Founded in 2001, CPC Scientific is a globally-recognized CDMO. The CPC Group is comprised of peptide experts who have actively pursued peptide design and largescale manufacturing for more than 30 years, so your project is in good hands. We work directly with leaders in the biotechnology and pharmaceutical industries to help bring life-changing therapeutics and diagnostics to market.

1514

ASY*-FITC was synthesized using good manufacturing practice (GMP) methods (CPC Scientific, Inc.). Stability was evaluated on high-performance liquid chromatography (HPLC) and mass spectrometry. Aliquots of peptide (0.8 mg) were stored at −20 °C as lyophilized powder in single-use amber vials for protection from light.”

H2NHN

NH

HN

NH

HN

NH

HN

O

O

OHO

OH

O

CONH2O

O

OH

CO2HO

OHNO

HN

NHO

CO2H

HN

S

HN

O

O

HO

CO2H

HO

Joshi, Bishnu P., et al. “Multimodal endoscope can quantifywide-field fluorescence detection of Barrett’s neoplasia”. Endoscopy 48.02 (2016): A1-A13.

“SCIENCEVSCANCER

WITH THESE CHALLENGES IN MIND, WE’VE LAUNCHED OUR PEPTIVAC™ NEOANTIGEN MANUFACTURING PLATFORM.

The individualized nature of neoantigen immunotherapy requires 10-30 CGMP-grade peptides designed and produced for each patient. This process represents a significant paradigm shift in the need for multiple unique peptide sequences, the rapidity of synthesis, quality control, and prompt release.

SPEED MATTERS.Most projects complete in3-4 WEEKS

• 3 Dedicated Neoantigen CGMP Suites

• Rapid Manufacturing, QC, & Release

• Most Projects Completed in 3-4 Weeks

• Affordable Pricing for small-scale CGMP projects

• Automated & Manual Synthesis

• Flexible & Adaptable Synthetic Approaches to Improve Success Rate

SPEED+PRECISION=PEPTIVAC™

NEOANTIGEN PEPTIDE PRODUCTION WITH CPC SCIENTIFIC

To reach a neoantigen specialist, email:

Sales@CPCscientific.com

Nakagawa, Mayumi. “Recall Antigen for Promoting T-Helper Type 1 Response.” U.S. Patent Application 15/552,285, filed February 15, 2018.

Nakagawa, Mayumi. “Hpv e6 protein t cell epitopes and uses thereof.” U.S. Patent Application No. 14/566,604, filed August 13, 2015.

Saenz, Rebecca, et al. “TLR4-dependent activation of dendritic cells by an HMGB1-derived peptide adjuvant.” J Transl Med 12 (2014): 211.

Wang, Xuelian, et al. “Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine.” Vaccine 31.49 (2013): 5806-5813.

Sturm, Matthew B., et al. “Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: first-in-human results.” Science Translational

and many more...

CGMP CITATIONS

1716

1245 Reamwood Avenue Sunnyvale, CA 94089

In mid-2019, we’ll be moving to:160 East Tasman Drive, Suite 200

San Jose, CA 95134

408-734-3800 toll-free: 877-272-7241

CPCScientific.com sales@cpcscientific.com

WE LOOK FORWARDTO WORKING WITH YOU.

19