Genor goes one better

Not to be outdone by Akeso/Summit's ivonescimab, which has spawned a multitude of follow-on bispecifics, Genor Biopharma aims to go one better, combining activity at PD-1 and VEGF with CTLA-4 blockade in a project coded GB268. This has just started a phase 1 study in solid tumours, the latest listings on the clinicaltrials.gov registry reveal.

Also among the first-time entrants into human studies is a pair of molecules that aim to improve on Johnson & Johnson's Rybrevant by using an ADC rather than a naked bispecific MAb format. And the private backers of the US biotech Avenzo Therapeutics will note a new entrant from Akeso with a bispecific ADC that will challenge a similarly acting project on which Avenzo recently took out an option.

Ongoing interest in ivonescimab and PD-(L)1 x VEGF bispecifics was recently highlighted by Akeso's latest apparent win, in the Harmoni-6 chemo combo trial in first-line NSCLC. Despite some caveats Summit stock rose strongly, and other players in this field, including BioNTech, Instil Bio and Merck & Co, will be watching carefully.

Now Genor has emerged as a new clinical player with the trispecific GB268. It's possible that adding CTLA-4 blockade into the mix could dial up efficacy, but in the absence of a strong scientific rationale that finds a way to restrict such activity to tumour cells the toxicity of such a molecule might make GB268 a non-starter.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 10 and 18 Apr 2025.

Rybrevant has become a drug on which J&J has pinned much of its future growth, but its sales have yet to suggest that it's on a trajectory to hit that company's $5bn revenue forecast.

Several companies, most prominently AstraZeneca with AZD9592, are combining Rybrevant's activity at EGFR and cMet in an ADC format. They are now being joined by Novatim Immune's KY-0301 and Hansoh Pharma's HS-20122, a pair of ADCs due to enter their first-in-human trials in May.

A similar effort with an ADC modality comes from Hangzhou DAC's anti-Steap1 project DXC008, a new challenger to Amgen's similarly acting T-cell engager xaluritamig, which started phase 3 last year. Meanwhile, Amgen's Five-Prime-derived anti-FGFR2b MAb bemarituzumab sees a new phase 1 player in Chia Tai Tianqing's similarly acting MAb TQB2210.

But perhaps the most intriguing new clinical-stage challenger is Akeso's AK146D1, an ADC that targets Nectin-4 and TROP2. Last November another Chinese ADC specialist, VelaVigo, attracted Avenzo as a potential ex-China partner for its own anti-Nectin-4 x TROP2 asset, VBC103, and subsequently closed a $50m pre-series A funding round.

Avenzo is a private US biotech that has also licensed other projects from China. Its deal with VelaVigo is an ex-China option that, if exercised, would entail the payment of $50m in up-front and near-term milestones.