A fourth challenger from DualityBio and BioNTech

Fresh from securing GSK as a second important partner for its ADC projects, DualityBio has released the first small-cell lung cancer data from a global solid tumour trial of BNT324, the anti-B7-H3 ADC it licensed to BioNTech in April 2023, and which entered the clinic a year ago.

One irony, in this complex area of multiple deals between western and Chinese companies, is that the data position BNT324 as a direct challenger to GSK's own anti-B7-H3 ADC, GSK5764227, licensed from Hansoh Pharma last year. Overall the results validate B7-H3 as a SCLC target that now features four key players – one of which, MediLink's YL201, is notable for being unpartnered.

It was YL201 that impressed at ESMO in September, putting up mid-stage data in relapsed SCLC that featured a 61% ORR, rivalling GSK5764227 and the other similarly acting ADC here, Merck & Co/Daiichi Sankyo's ifinatamab deruxtecan. If noting else, the latest DualityBio/BioNTech data could see more western companies take an interest in partnering with MediLink.

Similar response rates

The headline number for BNT324, as revealed at the ESMO Asia conference on Friday, was an ORR of 70% in SCLC. However, that number is unconfirmed, concerns just the 9mg/kg dose, and comprises only patients who hadn't received prior treatment with topoisomerase inhibitors.

Among all 73 SCLC patients the ORR number – still unconfirmed – was 56% across two BNT324 doses (6mg/kg and 9mg/kg); this looks similar to the 55% ifinatamab deruxtecan yielded in the Ideate-Lung01 trial, and the low-60% ORR numbers put up by YL201 and GSK5764227.

All four ADCs comprise topoisomerase inhibitor payloads, and the 70% subgroup ORR cited by DualityBio is more evidence that patients can become resistant to an ADC's payload. This applies even when considering the administration of two ADCs that target different antigens – in the case of SCLC these might be DLL3 and B7-H3 – but a similar payload.

The phase 1/2 trial that was the subject of the ESMO Asia presentation included other solid cancers beyond SCLC, but the SCLC data were the most important. In other tumour types unconfirmed ORRs included 28% in castration-resistant prostate cancer (32 patients), 22% in non-squamous NSCLC (41), 25% in hepatocellular carcinoma (12) and 75% in cervical cancer (four).

A battle between four anti-B7-H3 ADCs

Notes: *12.0mg/kg; **8mg/kg; ^includes unconfirmed responses. Source: OncologyPipeline.

While SCLC comprised the largest dataset, and one that allows a handy cross-trial comparison, it isn't the only potential target for ADCs against B7-H3. Indeed, phase 3 trials include MediLink's YL201 in nasopharyngeal cancer and ifina-dxd in oesophageal, while DualityBio and BioNTech plan to start phase 1/2 studies combining BNT327 with the anti-PD-L1 x VEGF MAb BNT327 in SCLC and NSCLC next year.

BioNTech is DualityBio's partner for BNT324, as well as for ADCs targeting HER2 and TROP2. Meanwhile, earlier this week GSK paid $30m for rights to DB-1324, an ADC with an undisclosed gastrointestinal target that might be Claudin18.2, after licensing GSK5764227, as well as the anti-B7-H4 ADC GSK5733584, from Hansoh last year.

Meanwhile, Merck's rights to ifina-dxd stem from a monster ADC tie-up with Daiichi struck on the eve of last year's ESMO. A final twist is that MediLink and BioNTech are already partners, but on an anti-HER3 ADC coded YL202.

MediLink now needs to strike while the B7-H3 iron is hot.