CMC Development and Manufacturing

Our chemistry, manufacturing, and controls (CMC) development consists of two progressive steps. In the first, we use contract development and manufacturing organizations (CDMOs); in the second, we are establishing our own capabilities and infrastructure, including a manufacturing facility, which will provide us with enhanced control of material supply for both clinical trials and the commercial market, enable rapid implementation of process changes and help us achieve better long-term margins.

Our CMC department is managed by a team of experts covering the full spectrum of technical capabilities, including cell line development, cell culture and purification process development, analytical and formulation development, GMP manufacturing, quality control and assurance, as well as CMC regulatory support. Our scientists have extensive experience in both international and local biopharmaceutical companies, and have participated in a wide range of projects including monoclonal antibody and fusion protein, as well as challenging bi-specific or bi-functional molecules. 

Our in-house CMC labs specialize in cell line development and analytical development. The team actively manages a number of global and CDMOs to advance both early and late-stage biologics for IND submission as well as clinical material supply for China and global trials. We augment our in-house capabilities by out-sourcing some aspects of CMC to contract research/manufacturing organizations. In this way, we meet the quality, speed and cost-effectiveness goals set for I-Mab’s biologics projects.

Our agile and comprehensive Cell Line Development (CLD) lab aims to bridge in-house discovery and CMC out-sourcing and shorten the overall timeline from clinical candidate selection to IND filing. The CLD lab has established the following capabilities:

Evaluating developability

Developing cell lines from vector construction, clonal screening, top clone evaluation, and long-term stability studies

Producing test samples for difficult-to-express molecules

The Analytical Lab supports drug discovery, cell line development, process development and CMC technology transfer with the following capabilities:

Evaluating developability and characterizing biological molecules

Performing analytical development, analytical method transfer and qualification, and troubleshooting for CMC development

Providing fast turn-around analytical support for process development

CMC Quality Assurance

CMC quality assurance leads the establishment and maintenance of a CMC quality management system based on ICH Q8/Q9/Q10 guidelines. It provides oversight of all relevant quality activities during CMC development phases and clinical material supply by CDMOs to ensure compliance with applicable regulations (e.g., NMPA GMP (2010), US regulations found in Title 21 of the CFR, EU guidelines to GMP for human use and their annexes, and ICH guidelines, etc.)

Manufacturing Facility Planning

We believe it is advantageous that we own and control our GMP manufacturing process in order to ensure quality and secure production slots for clinical trial materials and commercial supplies. We plan to commence the construction of our own state-of-the-art biologics manufacturing facility in Hangzhou, China, by the end of 2019. At this manufacturing facility, we plan to produce drug substance and drug product for clinical or, in the future, commercial use. We expect this facility to include a pilot GMP manufacturing plant with two 500-liter and two 2,000-liter single-use bioreactors; once construction of the full commercial-scale manufacturing plant is complete it will house eight more 2,000-liter single-use bioreactors with filling and finishing lines.

Our R&D organization comprises high-caliber professionals with international biopharma experiences. 

Our high-caliber management and senior directors have an average of 14 years of global biopharma R&D experiences with extensive networks in China and the globe. 

The skillset of the team is highlighted by a combination of extensive global pharma experience, local drug development and operational experience with clinical networks in China and the United States. The team is driven by high ethical standards, clinical science and a passion for improving the lives of patients.

Non-Clinical Development

Our Non-Clinical Development team consists of seasoned scientists with extensive experience of pre-clinical development of innovative drugs in China and globally. We design and manage efficacy and safety studies using appropriate in vitro and in vivo models to support candidate selection, lead optimization and clinical development of new drugs based on the target biology and pharmacological mechanism of action.

agencies in a wide range of geographical regions, and are experienced in designing non-clinical development programs to support IND and BLA filings in both China and the rest of the world. We effectively work with non-clinical contract research organizations and leverage their capabilities for customized design and study executions, while closely monitoring the processes and progresses to ensure timely deliverables with high quality. We also provide technical support on bioanalytic and translational medicine for smooth transition from non-clinical to clinical development, and perform critical data evaluation of in/out-licensing opportunities.

Biomarker-Enabled Translational Medicine Capabilities

Our focus on developing innovative drug molecules demands the ability to apply relevant biomarkers that link drug response to treatment efficacy, which is critical for early-stage clinical trials of our investigational drugs. This translational medicine capability requires cross-functional knowledge and unique skills to link the target biology of an investigational drug to clinical responses in selected patients. We have developed proprietary and tailor-made biomarkers for each of our investigational drugs, which are used to select potential responders; predict and measure target engagement; support dose selection; and enable timely informed decisions on advancing our assets to the next phase of clinical development.

Clinical Development

Our clinical development is led by a global team of clinical scientists, industry physicians, data-management specialists, biostatisticians, clinical operation staff and drug-safety experts, who are strategically based in Shanghai, Beijing, and the US to cover Phase 1 through Phase 3 clinical trials in China, and early-stage clinical trials in the US. Our clinical team accounts for approximately 80% of our entire R&D organization’s headcount and 80% of our budget allocation.

Our clinical development team has extensive global and local drug development experience, and operational experience with clinical networks in China and the US. On top of this, our team has the ability to integrate internal core development functions encompassing regulatory affairs; translational medicine; clinical research and operations; data management; biostatistics; clinical safety and pharmacovigilance; portfolio and project management; and global drug supplies. The in-house core competencies include program strategies, regulatory affairs (with both FDA and NMPA), study design, protocol development, and KOL/PI engagement. 

We also effectively leverage external resources, including clinical contract research organizations, academic clinical centers and/or networks, and play critical roles in collaborating with our global partners, conducting technical assessments of in-licensing/out-licensing compounds to support business development priorities.

Furthermore, we have established and implemented a robust internal clinical governance system, including development governance, standard operating procedures (SOPs), protocol review committees, safety steering committee and systematic vendor assessment and management processes, all designed to safeguard patient safety and data reporting. 

Our clinical development capabilities are best demonstrated by our rapid implementation of seven ongoing clinical trials, including four Phase 1/2 and registrational trials in Greater China and three Phase 1 trials in the US within the past three years.

Medical Office

The I-Mab Medical Office delivers quality and safety commitments to our patients/clinical trial subjects. The Medical Office is responsible for supporting R&D by holistically and systematically managing quality across the organization to meet company quality objectives and ensure regulatory compliance. The Medical Office is accountable for safety monitoring and risk management of patient/clinical trial subjects throughout the product life cycle from first-in-human trials through to post-marketing. Our Medical Office footprint extends to Shanghai, Beijing and the US to support the I-Mab global organization in the following areas:

a) Establish a quality-oriented organization to ensure sustainable compliance with the laws and regulations governing drug discovery and development;

b) Establish, maintain, monitor and continue improving a Quality Management System covering all development activities;

c) Ensure the highest level of safety reporting compliance, signal detection, risk evaluation, and risk minimization measures, to ensure and maintain a favorable benefit/risk profile of I-Mab products;

d) Serve as the medical safety representative of I-Mab products and provide medical safety leadership for all clinical development programs and post-approval products;

e) Maintain efficient medical safety collaborations with business partners and contribute to the due diligence of potential partnerships as requested. 

Clinical/Medical Research

Clinical/Medical Research is composed of two teams of clinicians dedicated to drug development in oncology and immunology, disease areas in which they possess profound scientific knowledge and clinical expertise. These teams draw on their understanding of innovative compounds, development processes and the requirements for registration of new drugs to guide study design, medical training and instruction, and study oversight throughout the clinical trials to ensure patient safety and maintain data quality and integrity. They also serve as the clinical contacts for internal and external partners and stakeholders.

Early Development

Early Development represents a team of clinical scientists and clinicians who provide clinical pharmacology, pharmacometrics and other clinical support to compound development from Phase 1 to Phase 3. They lead cross-functional teams to develop and implement Clinical Pharmacology & Pharmacometrics strategies.

Clinical Operations

Clinical Operations encompass the integrated clinical trial management functions, and our Clinical Operations team has a strong clinical trial execution skillset and rich industrial experience. To advance I-Mab’s innovative pipeline, the team conducts China-focused or multi-regional clinical trials (MRCT), following specific regulatory requirements. We leverage the capabilities of clinical CROs, SMO, clinical labs, and supply depots, while providing oversight throughout the studies. The team also collaborates closely with the US clinical team for global development of I-Mab assets.

Quantitative Sciences (QS)

Our Quantitative Science (QS) group is composed of biostatistics, statistical programming and data management teams. Highly specialized in technical skills and industry practices, the QS group works closely with the Clinical/Medical Research team for clinical trial design, data collection, data analysis and interpretation. We apply cutting-edge methodologies in biostatistics and data sciences, combined with a deep understanding of regulatory guidelines, industry standards and trends, to deliver integrated quantitative evidence to support our drug development in the most efficient way.

Portfolio and Project Management Office (PMO)

Our R&D project team is structured as a cross-functional matrix that is responsible for product strategy planning and execution. Our Portfolio and Project Management Office (PMO) consists of a group of portfolio and project management professionals who are the strategic and operational leads in the cross-functional team. PMO oversees the dynamics and progress of the I-Mab portfolio and provides governance support to ensure our portfolio is highly aligned with the I-Mab mission and vision. Meanwhile, PMO implements program management principles and tools throughout the drug discovery and development processes to enable the R&D teams to deliver milestones in a timely and cost-efficient way. Cost, timeline and risk management are the three core values of PMO.

Regulatory Affairs

I-Mab’s regulatory team, split between Beijing and Shanghai, is responsible for all non-US regulatory activities. The team provides regulatory expertise and leadership for IND submissions, clinical development and eventually regulatory approval from the regulatory authorities. The team also serves as an effective channel between the company and regulatory authorities to guide the regulatory process from start to finish in the highly regulated and constantly evolving regulatory environment. 

In addition, the team provides regulatory strategy and policy interpretation for I-Mab’s in-licensing, out-licensing and clinical trial activities outside China. 

US Clinical Development Team

Located in Maryland, USA, the US clinical team works closely with other parts of the company in China to set up global trials for our key global assets. We also work closely with consultants, specialized CROs/vendors in the US for site selection, study design, regulatory interaction, and study execution to meet different regulatory requirements. In addition, we partner with the Business Development team for licensing or partnerships with other companies or academic institutes in the US.

R&D Governance

To implement global standards for drug development, we have established a robust governance regime for all stages of our R&D activities, through our internal discovery, CMC, preclinical and clinical development programs, and through product acquisition and in-licensing strategies. The R&D governance regime enables our senior management to continuously oversee and monitor the company’s R&D activities for complying with applicable laws, regulations, rules, guidelines and internal policies. The R&D governance regime was put into practice and operates independently of the Chief Executive Officer’s responsibilities.

We have established various governance and decision-making committees composed of senior representatives from the respective functional units. These committees review, discuss and determine, for instance, whether a drug candidate molecule is qualified to move forward into the next stage; which data package would be most appropriate for submission to regulatory agencies; and how clinical safety of our investigational drugs will be monitored and reported. These committees make decisions over the critical “checkpoints” of our R&D activities and include our Science Committee; IND Scientific Advisory Committee; R&D Project/Program/Portfolio Governance; Medical Safety Council; and Safety Management Team.

The I-Mab Quality Management Review (QMR) provides company-level, cross-functional management oversight of the company’s Quality Management System (QMS) and the compliance status of regulated activities to applicable laws, regulation, policies and procedures, focusing on R&D and CMC GXP activities. To ensure our Corporate Quality Plan is met, key QMS elements have been established and trends, changes, risks are identified and addressed proactively.

Our R&D Quality Council is composed of representatives from each R&D function. The R&D Quality Council is a governance body that oversees the performance of I-Mab R&D Quality Management System (QMS) and serve as the final decision-making body for critical quality issue that affects subject/patient safety, data integrity and global/local regulatory authority compliance. The R&D QMS encompasses the structure, responsibilities and procedures that enables the organization to identify, measure, control and enhance core regulated processes and activities.

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