Henlius and Ottimo join the bispecific bundle
Two new PD-(L)1 x VEGF projects have entered the clinic.
Two new PD-(L)1 x VEGF projects have entered the clinic.
Two new projects in the super-hot PD-(L)1 x VEGF arena are just starting human testing, according to the latest listings on clinicaltrials.gov. Shanghai Henlius’s HLX37 and Ottimo Pharma’s jankistomig are both going into solid tumour trials, but there are key differences between the assets.
HLX37, which targets PD-L1 and VEGF, recently began an early phase 1 study in China. Meanwhile, UK-based Ottimo, which only emerged from stealth mode last year, is testing its PD-1 x VEGFR2 project jankistomig in a global phase 1/2.
Jankistomig is unusual in that it wasn’t licensed from China, but rather was developed by Jonny Finlay, Ottimo’s chief scientific advisor and co-founder. It’s also the only such project specifically to hit VEGFR2, according to OncologyPipeline.
Privately held Ottimo, which closed a $140m series A venture financing round a year ago, reckons that selectivity for VEGFR2 will minimise VEGF-related side effects. The group now has a chance to put this theory to the test.
Meanwhile, HLX37 is taking a similar approach to Bristol Myers Squibb and BioNTech’s pumitamig; both target PD-L1 to anchor the therapy to tumour cells. OncologyPipeline lists around 20 PD-(L)1 x VEGF assets in the clinic.
Recently disclosed first-in-human studies*
| Project | Mechanism | Company | Trial | Scheduled start |
|---|---|---|---|---|
| DFC413 | Undisclosed radioconjugate (uses Lu-177) | Novartis | Solid tumours | 24 Nov 2025 |
| HLX37 | PD-L1 x VEGF bispecific | Shanghai Henlius | Solid tumours | 28 Nov 2025 |
| IDE892 | PRMT5 inhibitor | Ideaya | MTAP-deleted solid tumours | 15 Dec 2025 |
| QLC5513 | Likely TROP2 ADC | Qilu Pharmaceutical | + iparomlimab/tuvonralimab (PD-1 x CTLA-4 FDC) +/- chemo in solid tumourss | 30 Dec 2025 |
| ZGGS34 | MUC17 x CD28 trispecific T-cell engager | Suzhou Zelgen | MUC17+ve solid tumours | Dec 2025 |
| NW101 | PRAME engineered TCR | Neowise | HLA-A*02:01+ve solid tumours | Dec 2025 |
| Jankistomig | PD-1 x VEGFR2 bispecific MAb | Ottimo Pharma | Solid tumours | Dec 2025 |
Note: *these projects were first listed on the clinicaltrials.gov database between 3 and 11 Dec 2025.
Outside this arena, other projects entering the clinic include Ideaya’s PRMT5 inhibitor IDE892 and Suzhou Zelgen’s MUC17 x CD28 trispecific T-cell engager ZGGS34.
Ideaya had a recent blow with the loss of GSK as a partner for its Werner helicase inhibitor IDE275 and its DNA Pol theta inhibitor IDE705. However, the group has recently moved to highlight its other projects: as well as IDE892, it recently had an IND cleared for its B7-H3 and PTK7-targeting ADC IDE034, and submitted an IND for its KAT6/7 inhibitor IDE574.
The new clinical entrant, IDE892, will compete with other PRMT5 inhibitors such as Bristol Myers Squibb’s Mirati-originated BMS-986504, which is going into phase 2/3 trials in first-line MTAP-deleted NSCLC and pancreatic cancer.
Amgen was previously in the lead here with AMG 193, but still appears to be nailing down its ideal dose, while Tango recently revealed pivotal plans for its contender, vopimetostat. Other players include AstraZeneca, set to report early results soon with AZD3470.
Still, PRMT5 inhibition has largely underwhelmed so far, with Tango last year discontinuing its then lead project, the brain-penetrant PRMT5 inhibitor TNG908, after this disappointed in glioblastoma.
MUC17
There’s less competition in MUC17, where according to OncologyPipeline there’s just one other clinical-stage asset – Huadong Medicine’s ADC HDM2012 – as well as preclinical-stage T-cell engagers from Guangzhou Excelmab and Jiangsu Simcere.
Zelgen’s ZGGS34 is also a MUC17-targeting T-cell engager, but additionally hits the co-stimulatory protein CD28. However, the jury is still out on co-stimulatory approaches, while Amgen discontinued its MUC17-targeting T-cell engager AMG 199 in 2023, citing a “business decision”.
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