Development of antibody conjugates that use a STING agonist payload might be given a second wind after Daiichi Sankyo's revelation that it plans to take one into the clinic later this fiscal year. In its earnings presentation on Thursday the Japanese company presented DS3610, a molecule that combines its "original STING agonists" with an antibody, and incorporates Fc region modification to reduce risk of cytokine release. The target of the MAb employed by DS3610 hasn't been disclosed; moreover, Daiichi wasn't widely known to have worked on STING agonists in the past. Neither STING agonists – where Pfizer's PF-07820435 is a notable discontinuation – nor STING-based ADCs have had an easy ride. The latter saw three deals in 2022, involving Merck KGaA and Mersana, Exelixis and Ryvu, and GSK and Mersana, but Takeda subsequently discontinued plozalizumab plevistinag after this showed futility in phase 1/2, while Mersana's calotatug ginistinag spent seven months on clinical hold in 2023 after a fatal drug-related adverse event. When DS3610 enters the clinic it and calota-G will be the only two STING-payload ADCs in human trials, according to OncologyPipeline. ADCs using STING agonist payloadsProjectCompanyTarget(s)StatusCalotatug ginistinagMersana (GSK acquired option in 2022)HER2Ph1 resumed after clinical holdDS3610DaiichiUndisclosedStarting ph1 in H2 fiscal 2025JAB-BX500JacobioCD73Preclinical (IND filing delayed from 2024 to 2025)JAB-BX467JacobioHER2Preclinical (IND filing delayed from 2024 to 2026)PSMA-E7766 ADCEisaiPSMAPreclinical data at SITC 2024IMGS-501ImmunoGenesisPD-L1 x PD-L2PreclinicalUnnamedExelixis/ RyvuUndisclosedPreclinical, 2022 dealM-Immunosynthen ADCMerck KGaA/ MersanaUndisclosedPreclinical, 2022 dealPlozalizumab plevistinagTakedaCCR2Discontinued after showing futility in ph1/2IMSA201ImmuneSensorEGFRDiscontinued in preclinicalST Her2-IACS8803Silverback (now merged into ARS)HER2Discontinued in preclinicalXMT-2175 & XMT-2068MersanaUndisclosedDiscontinued in preclinicalSource: OncologyPipeline.
Development of antibody conjugates that use a STING agonist payload might be given a second wind after Daiichi Sankyo's revelation that it plans to take one into the clinic later this fiscal year. In its earnings presentation on Thursday the Japanese company presented DS3610, a molecule that combines its "original STING agonists" with an antibody, and incorporates Fc region modification to reduce risk of cytokine release. The target of the MAb employed by DS3610 hasn't been disclosed; moreover, Daiichi wasn't widely known to have worked on STING agonists in the past. Neither STING agonists – where Pfizer's PF-07820435 is a notable discontinuation – nor STING-based ADCs have had an easy ride. The latter saw three deals in 2022, involving Merck KGaA and Mersana, Exelixis and Ryvu, and GSK and Mersana, but Takeda subsequently discontinued plozalizumab plevistinag after this showed futility in phase 1/2, while Mersana's calotatug ginistinag spent seven months on clinical hold in 2023 after a fatal drug-related adverse event. When DS3610 enters the clinic it and calota-G will be the only two STING-payload ADCs in human trials, according to OncologyPipeline.
ADCs using STING agonist payloads
| Project | Company | Target(s) | Status |
|---|
| Calotatug ginistinag | Mersana (GSK acquired option in 2022) | HER2 | Ph1 resumed after clinical hold |
| DS3610 | Daiichi | Undisclosed | Starting ph1 in H2 fiscal 2025 |
| JAB-BX500 | Jacobio | CD73 | Preclinical (IND filing delayed from 2024 to 2025) |
| JAB-BX467 | Jacobio | HER2 | Preclinical (IND filing delayed from 2024 to 2026) |
| PSMA-E7766 ADC | Eisai | PSMA | Preclinical data at SITC 2024 |
| IMGS-501 | ImmunoGenesis | PD-L1 x PD-L2 | Preclinical |
| Unnamed | Exelixis/ Ryvu | Undisclosed | Preclinical, 2022 deal |
| M-Immunosynthen ADC | Merck KGaA/ Mersana | Undisclosed | Preclinical, 2022 deal |
| Plozalizumab plevistinag | Takeda | CCR2 | Discontinued after showing futility in ph1/2 |
| IMSA201 | ImmuneSensor | EGFR | Discontinued in preclinical |
| ST Her2-IACS8803 | Silverback (now merged into ARS) | HER2 | Discontinued in preclinical |
| XMT-2175 & XMT-2068 | Mersana | Undisclosed | Discontinued in preclinical |
