Major Milestone Achieved in XtalPi and Jikang Bio's Challenging GPCR-Targeted Antibody Drug Discovery Project

Today (August 3), XtalPi and Shanghai Jikang Biomedical Technology Co., Ltd. have reached a consensus on the milestone progress of the commissioned R&D project for antibody drugs targeting innovative GPCR: With the joint support of XtalPi's AI-powered antibody discovery platform XupremeHit® and Jikang Biomedical’s unique know-how transformation technology for GPCR targets, both parties have fully leveraged their respective technical advantages. The discovered antibodies meet the agreed acceptance criteria, and the project has successfully achieved a key milestone.

Background of the Cooperation Project

GPCR (G Protein-Coupled Receptor), namely G protein-coupled receptor, is a 7-transmembrane protein and the largest membrane protein family in the mammalian genome. It is not only involved in the regulation of multiple functions in the body but also closely related to the occurrence of many diseases, making it an important target for new drug development. Currently, FDA-approved drugs targeting GPCR account for only 34% of the market, most of which are small molecule drugs, while another 56% of GPCR targets remain to be developed [1].

At present, only two antibody drugs targeting GPCR have been approved for marketing. The main reasons lie in technical obstacles such as the difficulty in antigen preparation, limited exposure of antigen-binding epitopes, and the lack of functional conformation in the exposed epitopes.

AI-Powered Antibody Discovery Platform Accelerates R&D Innovation

To address the unmet clinical needs and development challenges of GPCR targets, XtalPi has established a one-stop platform called XrossXeven™, which covers AI-powered antigen design, antigen preparation and immunization, and antibody discovery.

During the target selection phase, Shanghai Jikang Biomedical Technology Co., Ltd. proposed a differentiation strategy for targets and antibodies based on systematic research of existing GPCR antibody targets, identifying candidate targets and antibody target characteristics. In the antigen preparation phase, XtalPi collaborated with Shanghai Jikang Biomedical Technology Co., Ltd. to design and prepare various types of target antigens based on structural and epitope studies of antigen GPCRs, including the use of proprietary processes to obtain high-quality NanodiscGPCR antigens, which yielded excellent post-immunization responses.

During the antibody discovery phase, XtalPi simultaneously utilized its internal hybridoma platform XtraDoma®, phage display platform XpeedPlay®, and NGS+AI analysis platform XploreSeq® to rapidly obtain multiple candidate antibody sequences targeting GPCRs in a complementary manner.

Notably, in response to the difficulty of obtaining GPCR-targeting antibodies, XtalPi's intelligent platform XploreSeq® has played a significant role in expanding the candidate antibody sequence space and discovering more specific antibody epitopes. It applies NGS technology to conduct bioinformatics analysis on millions of BCRs obtained from immunized mice. Through learning from wet-lab experimental data and multiple iterations, it selects antibodies with high affinity, cross-species binding, and excellent developability from different lineages to address the multiple challenges posed by GPCR targets.

Moreover, the AI-powered platform can significantly reduce the traditional discovery time. Compared with the 2-3 month development cycle of conventional platforms, the XploreSeq® platform is able to identify diverse lead antibodies covering the maximum number of epitopes in as little as 6 weeks, thereby increasing the success rate of downstream screening.

Currently, for the GPCR antibody discovery project of Shanghai Jikang Biomedical Technology Co., Ltd., the XtalPi XploreSeq® platform has successfully identified 20 high-affinity molecules with specific epitopes and cyno-cross reactivity, four of which are functional lead antibodies. Both parties’ functional platforms were utilized to cross-validate the biophysical properties of the antibodies, laying a solid foundation for the further development of antibody drugs.

Complementary Advantages, a Promising Future

To further optimize the lead antibody, Shanghai Jikang Biomedical Technology Co., Ltd. and XtalPi will leverage their respective strengths in 3D structure analysis and AI design to perform structural modeling of the antigen-antibody complex, optimizing the antibody's affinity and immunogenicity.

In addition, XtalPi will utilize its drug-likeness analysis platform XcelDev® to comprehensively evaluate and optimize the candidate antibodies, collaborating with Shanghai Jikang Biomedical Technology Co., Ltd. to advance the development of GPCR antibody drugs. Subsequently, Jikang Biomedical will leverage its expertise in GPCR-antibody complex structure analysis to study the molecular recognition mechanisms of the candidate antibodies, providing innovative approaches for broader GPCR antibody screening.

Editor: Muyan

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