Weekly New Drug Insights: Mabwell's Second-Gen ADC Patent Published; Nectin-4 ADC Data at ESMO Highly Anticipated

Review of New Drug Market Performance This Week: From September 4, 2023 to September 8, 2023, the top 5 companies in terms of increase in the new drug sector are: Adagene (14.5%), Antengene (5.8%), I-Mab (3.2%), Betta Pharmaceuticals (3.1%), and Simcere Pharmaceutical (2.6%). The top 5 companies in terms of decrease are: Kintor Pharmaceutical (-10.9%), Endoluminal Sciences (-9.4%), Yonsei Biopharmaceuticals (-7.9%), RemeGen (-7.8%), and Zelgen Biopharmaceuticals (-7.4%).

Key Analysis of the New Drug Industry This Week: Recently, Mabwell disclosed its second-generation ADC technology patent. In this patent, Mabwell revealed the design concept of its second-generation ADC drugs. According to Mabwell's ADC patent, its second-generation ADC technology mainly optimizes the linker, toxin Dxd, and the release unit GGFG in the Daiichi Sankyo technology platform, which is expected to bring differentiated competitive advantages. Currently, Mabwell has already deployed ADC products targeting Trop-2, B7H3, and other targets based on the above technology.

In contrast, Mabwell's second-generation ADC has a structure similar to Daiichi Sankyo's DXd series of ADC drugs:

1) The connector part differs from the traditional MC connector. Instead, it adopts a design that has been successfully applied in Nectin-4 ADC 9MW2821, which can simultaneously connect two -SH groups exposed after disulfide bond cleavage, enabling site-specific conjugation with high uniformity (DAR value is generally 4).

2) The release unit is different from the GGFG4 peptide, instead using a PEG-other amino acid peptide segment (e.g., valine-alanine);

3) The payload is also an exatecan analog, but it differs significantly from Dxd and varies greatly from the modifications made by other companies in China targeting Dxd.

Based on the first and second-generation ADC technology platforms, Mabwell has currently laid out multiple drugs in the ADC field, with three novel ADC drugs (targeting Nectin-4, TROP2, and B7-H3 respectively) entering the clinical development stage. Among them, Nectin-4ADC 9MW2821, based on the first-generation ADC technology, is the fastest-progressing Nectin-4ADC in China, with positive clinical data already disclosed; the company expects to disclose the latest data of Nectin-4ADC in the form of an oral presentation at the ESMO 2023 conference, and the relevant data is worth looking forward to.

This Week's New Drug Approvals & Acceptance Status:

This week in China, 5 new drugs or new indications were approved for marketing, 46 new drugs received IND approval, 22 new drug INDs were accepted, and 7 new drug NDAs were accepted.

This Week's TOP 3 Focus in China's New Drug Industry:

(1) On September 6, CSPC Pharmaceutical Group's new RANKL antibody drug Nalousumab was approved for marketing by the NMPA for the treatment of adult patients with giant cell tumor of bone who are not eligible for surgical resection or for whom surgical resection may lead to severe functional impairment.

(2) On September 8, the official website of the National Medical Products Administration of China announced that the Recombinant Factor VIII for Injection applied by Ronsen Pharmaceutical, a subsidiary of Tian Tan Bio, has been officially approved.

(3) On September 7, Luye Pharma announced that its self-developed innovative formulation, injectable goserelin microspheres, had been approved by the China National Medical Products Administration for a new indication, intended for premenopausal and perimenopausal women with breast cancer who are suitable for hormone therapy.

This Week's TOP 3 Focus in the Overseas New Drug Industry:

(1) On September 4, Seagen and Genmab jointly announced that the Phase III clinical trial innovaTV301 of the TFADC new drug Tivdak for the treatment of recurrent or refractory cervical cancer met the primary endpoint of OS in the interim analysis, significantly prolonging OS compared to chemotherapy.

(2) On September 6, Johnson & Johnson announced that the Phase III clinical trial MARIPOSA-2 of EGFR/cMET bispecific antibody Amivantamab + chemotherapy +/- Lazertinib for the treatment of Osimertinib resistance had reached the primary endpoint of PFS, bringing a clinically meaningful improvement in PFS for post-Osimertinib treatment.

(3) On September 7, Alnylam announced that the phase II clinical trial KARDIA-1 of AGT siRNA therapy Zilebesiran for the treatment of hypertension had met its primary endpoint, with a significant dose-dependent reduction in 24-hour average systolic blood pressure at 3 months of treatment.

Risk Warning: The risk of clinical trial progress being slower than expected, the risk of clinical trial results being less favorable than expected, the risk of changes in pharmaceutical policies, and the risk of patent disputes for innovative drugs.