MTDrug One-stop Service

Driving Innovation through Technology to Accelerate Peptide Drug Development

As an international CRDMO specializing in contract R&D and manufacturing of peptide products, Motif Biotech is dedicated to providing global partners with comprehensive services—from early-stage discovery and CMC (Chemistry, Manufacturing, and Controls) research to commercial production. Our expertise covers cosmeceutical peptides, veterinary peptides, complex peptide fragments, and high-purity impurities.

Full-Chain Technical Support to Accelerate Clinical Transformation We have established a seamless link from laboratory R&D to large-scale commercial production, ensuring high-quality project execution through a rigorous, science-driven quality management system.

Core Service Areas：
Custom Peptide API Synthesis & Process Development
Production of Intermediates and Fragment Starting Materials (FSM)
Impurity Standards Research & Characterization
Peptide Technology Transfer & Regulatory/Registration Support
CRO Services (Discovery & Preclinical)
  • Early Discovery: Synthetic route design and screening.
  • Preclinical Research: Accurate identification of Critical Quality Attributes (CQAs) and process benchmarking.
  • Safety & Analytics: Process safety risk assessment; analytical method development and optimization.
  • Characterization: Structural confirmation via spectroscopy; identification of toxic impurities.
  • Reference Standards: Preparation, analysis, and calibration of analytical controls.
  • Quality Standards: Formulation of rigorous quality specifications.
  • Pilot Production: Kilogram-scale production in glass reactors or pilot plants.
  • Stability Studies: Comprehensive stability investigations.
  • Regulatory Support: Preparation and filing of IND (Investigational New Drug) registration documents.
CDMO & CMO Services (Clinical to Commercial)
  • Clinical Phase Support (I, II, III): Continuous process improvement and optimization based on QbD (Quality by Design) concepts.
  • Quality Risk Analysis (QRA): Systematic evaluation of quality risks.
  • Analytical Validation: Development, validation, and standard formulation for raw materials, intermediates, and final APIs.
  • Process Transfer: Seamless transfer of analytical methods and API production processes.
  • Commercialization (MAH Regime): New drug registration and cGMP-compliant commercial production under the Marketing Authorization Holder (MAH) system.
  • NDA Support: Process validation for NDA declarations; writing and filing of CMC/NDA registration documents.
Technical Excellence
Multi-dimensional Synthesis:

Proficient in SPPS (Solid-Phase), LPPS (Liquid-Phase), and hybrid technologies. Extensive experience in long-chain, cyclic, and specially modified peptides.

Advanced IPC (In-Process Control)

Implementation of real-time monitoring to ensure reaction precision and minimize side reactions.

Extensive Impurity Library

A proprietary entity library of over 10 mainstream peptide varieties to support professional impurity profiling.

Quality & Compliance

Follow international mainstream audit standards to ensure high product reliability

Regulatory Compliance

Holds a "Drug Manufacturing License" (Su 20240016) issued by the Jiangsu Medical Products Administration (MPA); production follows ICH Q7 international guidelines.

International Filings

Core products hold U.S. FDA DMF filings (e.g., Tirzepatide DMF #041036, Semaglutide DMF #041860).

State-of-the-Art Facilities

4,300m² R&D and production base in Suzhou with 100+ professional labs and a planned annual output of 30kg.

Operational Efficiency
Resource Optimization

Improved resin recovery and optimized reaction conditions to maximize raw material conversion rates.

Digital Empowerment

Real-time equipment monitoring via digital management systems, increasing equipment utilization by 23%.

Lean Workforce

Refined job management and professional training to reduce labor costs and improve output efficiency.

Case Studies Revision
[Case Study 1] Etelcalcetide: Technology Transfer & Scale-up

Challenge: Balancing complex disulfide bond formation with ultra-high purity requirements.

Background: Etelcalcetide is a synthetic peptide composed of 7 D-amino acids with a cysteine-disulfide bond. Its structure poses extreme challenges for synthesis selectivity and impurity control.

Motif Solutions
Strategy A
Disulfide Bonds
Motif utilized proprietary directional oxidation technology, precisely controlling pH and oxidant titration to significantly improve ring-formation selectivity and reduce dimer formation.
Strategy B
D-Amino Acid Kinetics
Used our dual-drive technology platform to simulate parameters and optimize condensation reagents, ensuring complete coupling of D-type amino acids.
Strategy C
Cost Control
Optimized elution gradients and resin recycling via intelligent production management, reducing solvent consumption (e.g., Acetonitrile) while maintaining purity.
[Case Study 2] Semaglutide: From R&D to Commercial Scaling

Challenge: Managing a long synthesis chain and stringent impurity profiles for global compliance.

Motif Solutions
Path Optimization
Integrated SPPS and LPPS to minimize deletion peptides and racemization.
Real-time IPC
Scalpel-level monitoring at key coupling nodes to verify completeness, ensuring batch robustness and shortening purification cycles.
Impurity Profiling
Leveraging the Motif Analytical Platform, we synthesized and characterized over 10 related impurities, providing customers with comprehensive traceability reports for IND/NDA filings.
Results
Successful FDA DMF filing (#041860), 23% increase in equipment efficiency, and a 33% reduction in labor cost per gram.
[Case Study] Tirzepatide: Technology Transfer for Long-Chain Synthesis and Side-Chain Modification

Challenge: Synergizing 39-AA Long-Chain Synthesis Efficiency with Complex Site-Specific Side-Chain Modification

1. Project Background

Tirzepatide is a novel dual GIP/GLP-1 receptor agonist. Its structure consists of a 39-amino-acid linear peptide featuring a unique C20 fatty diacid side chain conjugated to a specific lysine (Lys) residue. The ultra-long amino acid sequence and the necessity for site-selective side-chain introduction pose significant challenges to synthesis conversion rates and impurity control during process scale-up.

2. Technical Difficulties & Motif’s Solutions
Challenge A
Synthesis Efficiency of the 39-AA Ultra-Long Chain
  • Difficulty: As the sequence lengthens, the coupling efficiency in Solid-Phase Peptide Synthesis (SPPS) is highly susceptible to steric hindrance, leading to the generation of hard-to-separate deletion sequences.
  • Solution: Motif Biotech employed a convergent synthesis (fragment condensation) strategy combined with high-loading resin technology. By cleaving the long chain into high-purity fragments for independent synthesis and utilizing Liquid-Phase Peptide Synthesis (LPPS) for precise assembly, we effectively bypassed the cumulative errors associated with linear synthesis, drastically improving the purity of the crude product.
Challenge B
Site-Specific Coupling of the C20 Fatty Diacid Side Chain
  • Difficulty: The side chain is structurally complex and highly hydrophobic. It requires precise, site-specific modification while ensuring that other reactive functional groups on the main chain remain unaffected.
  • Solution: We applied a rigorous Orthogonal Protection strategy, selecting side-chain protecting groups sensitive to specific deprotection reagents. Combined with an optimized solvent system, this improved the solubility and mitigated the steric hindrance of the long-chain peptide during modification, ensuring highly efficient side-chain coupling.
Challenge C
Balancing Purification and Yield for Poorly Soluble Peptides
  • Difficulty: The introduction of a bulky hydrophobic side chain drastically increases the overall hydrophobicity of the molecule, which can lead to reduced column loading capacity and poor solubility during purification.
  • Solution: We developed a temperature-controlled chromatographic purification process. By precisely regulating the mobile phase and temperature parameters, we achieved an optimal balance between high purity and overall yield while maintaining high sample loading capacity.
3. Project results
  • Regulatory Milestone: Supported the successful filing of the US FDA DMF (DMF #041036) for this product, with an impurity profile fully compliant with stringent international registration requirements.
  • Process Scale-Up: The process was smoothly scaled up from the laboratory 100-gram scale to commercial kilogram-scale batches, demonstrating high batch-to-batch consistency (low RSD).
  • Impurity Control: Specific hard-to-separate impurities (e.g., optical isomers, side-chain deletion impurities) were effectively controlled, resulting in excellent finished product release metrics.
[Case Study] Thymalfasin (Thymosin α1): High-Purity Process Optimization and Commercial Scale-Up

Challenge: Suppressing Aspartimide Side Reactions and Optimizing Cost-Efficiency

1. Project background

Thymalfasin (Thymosin α1) is an N-terminally acetylated peptide consisting of 28 amino acids, widely used for clinical immunomodulation. Its sequence contains critical aspartic acid (Asp) residues, which are highly prone to triggering aspartimide cyclization side reactions during deprotection. In the context of volume-based procurement (VBP) and fierce market competition, achieving a perfect balance between "cost reduction & efficiency enhancement" and "high purity" was the core objective of this process transfer.

2. Technical Difficulties & Motif’s Solutions
Challenge A
Suppressing Aspartimide Cyclization Side Reactions
  • Difficulty: Under basic Fmoc-deprotection conditions, the Asp-X sequence is highly susceptible to intramolecular nucleophilic attack, generating aspartimide by-products that are extremely difficult to remove via conventional chromatography, severely impacting the final yield.
  • Solution: Motif Biotech introduced Backbone Protection technology alongside an optimized deprotection system. By incorporating sterically hindering protecting groups at vulnerable key sites and utilizing milder reaction conditions, we mechanistically suppressed the formation of this characteristic impurity.
Challenge B
High-Conversion N-Terminal Acetylation
  • Difficulty: Incomplete reaction during the N-terminal acetylation step leaves trace amounts of des-acetyl impurities, creating immense pressure during downstream purification.
  • Solution: We implemented an in-situ activation capping process. Utilizing highly reactive acetylating agents combined with In-Process Control (IPC) monitoring, we ensured a conversion rate approaching 100%, cutting off the risk of des-acetyl impurity generation at the source.
Challenge C
Driving Down Manufacturing Costs for a Mature Product
  • Difficulty: As a high-volume mature API, the process is highly sensitive to solvent consumption, resin utilization, and overall manufacturing costs.
  • Solution: We comprehensively implemented green chemistry and circular processes. By integrating intelligent equipment to optimize chromatographic elution gradients and employing an efficient solvent recovery and recycling system, we significantly drove down the cost per gram while ensuring the finished product purity far exceeded pharmacopoeial standards.
3. Project Results
  • Quality Metrics: The finished product purity consistently remains at an exceptionally high level, with stringent single-impurity control that fully complies with Chinese Pharmacopoeia (ChP), United States Pharmacopeia (USP), and European Pharmacopoeia (EP) standards.
  • Efficient Delivery: Leveraging our robust process platform, we achieved a "zero-friction" technology transfer, drastically shortening the cycle from project initiation to the delivery of the first commercial-scale batch.