Ipsen Spent Big Bucks on Two Preclinical ADC Products This Year (US$10 Billion, RMB 700 Million). What Attracted Ipsen to These Two Products That Are Worth So Much Even Before Entering Clinical Trials? The two products are STRO-003 targeting ROR-1 acquired from Sutro for US$900 million in April and FS001 with a potential total deal value of US$1.03 billion reached with AmMax Bio in July.New Drug Intelligence DatabaseSTRO-003 is a next-generation ROR1 (receptor tyrosine kinase-like orphan receptor 1) targeted ADC. This ADC uses exatecan as the payload, with a β-glucuronidase-cleavable linker. The drug employs Sutro’s proprietary non-natural amino acid site-specific conjugation technology, incorporating eight pAMF (containing azide nnAA-azidomethyl-L-phenylalanine) into the antibody, achieving a DAR value of 8 through site-specific conjugation.STRO-003 Demonstrates Potent Cytotoxic Activity in ROR1-Positive NTERA-2 Cells, While the Isotype Control Antibody-Drug Conjugate (ADC) Shows No Activity. The Cytotoxicity is Specific and Can Be Blocked by a Competitive Anti-ROR1 Antibody. No Cytotoxicity Was Observed in ROR1-Negative MCF-7 Cells. (B) STRO-003 Induced Robust Antitumor Activity in the ROR1-Expressing Breast Cancer Model MDA-MB-231. When Tested at the Same Dose, the Isotype ADC Control Showed No Antitumor Activity.
Ntera-2 cells expressing ROR1 were co-cultured with human PBMCs after treatment with STRO-003 to evaluate the immunostimulatory potential induced by immunogenic cell death (ICD). Both STRO-003 and free exatecan demonstrated potent tumor cell killing effects in this assay, while the control ADC or unconjugated anti-ROR1 antibody had no effect. As cell viability decreased, calreticulin was detected on the surface of cells treated with STRO-003 and exatecan, consistent with immunogenic cell death. Cells treated with STRO-003 or exatecan strongly induced monocyte activation, as evidenced by the induction of CD86 expression. The unconjugated anti-ROR1 antibody or non-targeting ADC showed no activity. These results indicate that EXD can activate immune cells.STRO-003 Demonstrates Promising Therapeutic Effects in PDX Models of Lung Cancer and Triple-Negative Breast Cancer, Indicating Its Potential in Treating Tumors with High ROR1 Expression.In the challenge experiment, CT26 cells were treated in vitro with doxorubicin, cisplatin, or exatecan, causing 50-75% of the cells to die or undergo apoptosis. The treated CT26 cells were injected into the right abdomen of untreated mice. Seven days later, untreated CT26 cells were injected into the contralateral abdomen of the vaccinated mice as a challenge, and tumor growth was monitored for up to 4 weeks. In the case of true ICD induction, no tumor growth was observed at the challenge site, indicating that the ADC also has a tumor vaccine effect.In summary, the reasons why Ipsen is interested in STRO-003 are approximately: 1) excellent anti-tumor activity; 2) ability to activate immune cells, converting cold tumors into hot tumors; 3) potential to act as a tumor vaccine.Yu Yan's $1.03 billion in funding, including upfront payments, development, regulatory, and commercialization milestone payments, as well as tiered royalties on global sales following successful development and regulatory approval, is relatively cheaper than STRO-003.In its publicly available patent WO2023207475, FS001 is described as a GPC3 antibody, while some suggest its target is the ITGA2 target mentioned in patent WO2024001669. However, during the early development of FS001, Professor Huang Chaolan conducted extensive research on whether this target could be druggable, indicating that it is likely a very novel target. A bold speculation would be that the target is ITGA2, and the mention of FS001 targeting GPC3 in patent WO2023207475 might have been a misleading move or possibly due to a later change in the project numbering by the company.WO2023207475: GPC3 antibody alone cannot be used to kill tumor cells in vitro, while GPC3 conjugated with MMAE/DXD in ADC demonstrates excellent tumor-killing effects.WO2024001669 patent: Cells with high expression of the ITGA2 target include cholangiocarcinoma, pancreatic cancer, epidermal cancer, and colorectal cancer, among others.The same ITGA2 target still has weak monoclonal antibody activity but excellent ADC cellular activity.FS001 is co-developed by Yugene and Shijian Biotech's ZW-Fit™ platform, but the specific linker-payload used has not been disclosed yet.Yuyan Bio onlyA young team of more than 20 people spent over two years developing a promising drug, which has given many small biotech companies great confidence. Small yet efficient companies, free from the need for large-scale operations, can achieve significant results without the traditionally assumed "10 years and $1 billion," as long as they are on the right track. In an unfavorable economic climate, it is a wise choice for small pharmaceutical enterprises to sell part of their pipelines to secure funding for the development of other pipelines. Of course, the ongoing pipelines must also be key projects. Cutting off some subpar pipelines reflects strategic prioritization, which is perhaps one reason why many pharmaceutical companies have seen their stock prices rise after downsizing through layoffs.To promote communication and innovation in the antibody industry,October 16-17, 2024The 7th Golden Autumn October Antibody Industry Development ConferenceAs scheduled. The conference aims to provide researchers with an interactive communication platform, which will help promote the further development of the antibody industry.Time:October 16-17, 2024
Location: Shanghai(Hotel Direction Notice)
Scale:600-800 people
Organizer:Biological Products Circle, Antibody Circle
Speech Support:Entegris, Resveld, AS ONE CORPORATION
Conference Fee:Free FREE!(Only charge100YuanRegistration deposit (including participation in learning sessions, tea breaks, and conference materials; the deposit is non-refundable). First come, first served, until fully booked.！
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