Specialist
Executive at Suzhou MediLink Therapeutics Ltd
Agenda
- Antibody drug conjugate (ADC) R&D barriers – linker technologies, antibody design, cytotoxic payload and conjugation process, plus domestic and foreign pharmaceutical companies’ technology platforms
- Clinical research challenges, plus China's Center for Drug Evaluation and the US Food and Drug Administration review and approval
- Anti-TROP-2 and anti-HER2 ADC clinical research progress at home and abroad, plus clinical data analysis
- R&D team demand and personnel structure, plus domestic and foreign pharmaceutical companies’ team competency comparison
Questions
1.
There are over 10 antibody drug conjugates (ADCs) approved for marketing around the world. China also has some ADCs ready for marketing. The popular targets of ADCs include HER2 (human epidermal growth factor receptor 2), Trop-2 (trophoblast cell-surface antigen 2) and CD20 (cluster of differentiate 20). How popular is each target among domestic researches? How is the competition in the market segments of each target?
2.
Let’s talk about the technical barriers of ADCs. What are the requirements for the druggability of antibodies? What are the characteristics and risks of antibodies such as the four subclasses of immunoglobulin G (IgG)? What is the progress of current researches?
3.
What about the druggability risks of antibodies, such as immunogenicity? How does the industry manage the risks?
4.
How to evaluate a linker technology? Which indicators can we refer to? Could you brief us on the small molecule shedding rate in blood circulation and different types of linkers?
5.
What is the popular development direction of site-specific conjugation technology? What are the advantages and disadvantages of technical routes such as enzyme catalysis and the introduction of unnatural amino acids?
6.
Can polyvalent conjugation technology be compared with site-specific conjugation technology? Is it a technological upgrade?
7.
The leading ADCs have different DARs. How to understand the DAR of an ADC? What is the normal range of the DAR? How does the DAR affect the efficacy and safety of an ADC?
8.
Can you introduce the CMC challenges confronting ADCs? Are the technology platforms of China’s CDMOs mature enough to meet the industry’s needs? You just mentioned WuXi Biologics’ DAR4 ADC. How mature are its conjugation process and purification process beyond DAR4 ADC?
9.
Can you detail the ADC R&D process and related costs? What must be determined in phase I, phase II and phase III clinical trials, respectively? Can you compare the R&D cost and cycle of ADCs with those of small molecular drugs and monoclonal antibody drugs?
10.
What is the difference between China’s CDE and the US FDA in the rationale and experience with regard to ADC approval? For example, what do the two regulators pay major attention to in terms of drug design and clinical trials?
11.
Can you compare the competitive advantages of the anti-HER2 ADC DS-8201 with those of Roche’s T-DM1 in structures, indications, some revealed therapeutic effects and safety? Can you share with us the latest progress of ADCs with the two drugs as an example?
12.
Compared with T-DM1 and DS-8201, what are the features of RemeGen’s RC48? Among the published research achievements about RC48, which are particularly noteworthy?
13.
What are the core advantages of RemeGen’s ADC technology platform?
14.
In addition to RemeGen, which players in the anti-HER2 ADC market segment are you optimistic about? Which achievements in 2021-22 deserve our attention?
15.
Can you comment on the R&D progress of anti-TROP-2 ADCs in China? Compared with Daiichi Sankyo, which domestic players progress rapidly in R&D or deserve our attention?
16.
Can you give an introduction to some targets like the epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor? Which targets deserve our attention or are promising at home and abroad?
17.
You mentioned some information about Hengrui Pharmaceuticals. As a leading innovative drug company in China, it has submitted clinical trial applications for five ADCs. It didn’t enter the ADC market early. Can you comment on its technology platforms, pipeline planning and clinical progress?
18.
What’s the ideal personnel structure of biotech companies that carry out ADC R&D? What are the requirements on the background and development experience of personnel? What kinds of talent are in shortage?
19.
Many biotech companies publicise their own technology platforms. For biotech companies that produce ADCs, which technology platforms have existence value? According to which dimensions should their technology platforms be assessed?
20.
In addition to RemeGen, which domestic players are likely to achieve commercialisation? What do you think of the competitive landscape in terms of R&D progress?
21.
RemeGen progresses more rapidly than other domestic players and has acquired the product launch approval. Do doctors show interest in or acceptance of RemeGen’s ADCs in the clinical treatment process? Can you comment on domestic doctors’ cognition of ADCs?
22.
The CMC cost of ADCs is relatively high. Will ADCs have cost advantages over popular innovative drugs, such as PD-1 antibodies, or popular bispecific antibody drugs in the future?
