RE:RE:RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse eventsPfizer has 12 ADCs in its pipeline that fall into one of four categories: vedotin ADCs; ADCs employing TOPO1 inhibitor payloads; next-gen auristatin ADCs with potentially improved tolerability; and ADCs with novel payload mechanisms of action. https://www.fiercebiotech.com/biotech/after-covid-decline-pfizer-builds-out-cancer-pipeline-and-leans-adcs
Pfizer yesterday offered a mechanistic rationale, claiming that vedotin-based ADCs were especially good at combining with PD-(L)1 blockade, and would thus be pushed into early lines of treatment.
That said, the group isn’t ignoring the massive industry trend, driven by Daiichi Sankyo, to develop ADCs using topoisomerase 1 payloads, and its R&D portfolio features plenty of these too. Accordingly, one of the two Adcetris follow-ons (PF-08046044) uses topoisomerase 1, while the other (PF-08046045) a payload Pfizer calls a novel tripeptide auristatin. In PD-(L)1 blockade Pfizer’s most advanced focus is on the SC MAb sasanlimab (Pfizer's PD-1 checkpoint inhibitor), but now two ADCs are in play too: PF-08046054 uses a vedotin payload, while the warhead on PF-08046037 is a TLR7 agonist. The latter seems to be derived from preclinical work Seagen had published on TLR7/8 agonist payloads, meaning that the entire ADC pipeline Pfizer highlighted yesterday had either been licensed in or acquired through Seagen.
https://www.oncologypipeline.com/apexonco/pfizer-takes-multiple-shots-goal
For example: PF-08046054 - SGNPDL-1V is under development for the treatment of advanced solid tumors including non-small cell lung cancer (NSCLC), gastric cancer, ovarian cancer, melanoma, head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer, esophageal squamous cell carcinoma (SCC). The drug candidate comprises of PD-(L)1 antibody conjugated with monomethyl auristatin E (MMAE). The drug candidate targets cells expressing PD-(L)1 and developed based on antibody-drug conjugate (ADC) technology. It is administered through intravenous route. https://www.pharmaceutical-technology.com/data-insights/pf-08046054-pfizer-triple-negative-breast-cancer-tnbc-likelihood-of-approval/
https://twitter.com/jq1234t/status/1763391687856926962/photo/1 PF-06940434 in combination with anti-PD-1 https://clinicaltrials.gov/study/NCT04152018 PF-07104091 is a novel CDK2-selective inhibitor under investigation in pts with selected advanced or metastatic solid tumors - in heavily pretreated HR+ HER2- mBC pts who progressed on prior CDK4/6 inhibitors.