ASCO 2024 preview – more questions for BioNTech

BioNTech needs its cancer projects to pick up the Covid slack, but data on two bispecific antibody projects, acasunlimab and PM8002, are far from emphatic, according to just revealed ASCO abstracts.

Acasunlimab, particularly in combination with Keytruda, has been linked with liver toxicity, the new data show. On the other hand, PM8002 might be comparable to Summit’s similarly acting project ivonescimab, which was the subject of a high-profile deal with Akeso; however, Summit is much further ahead in development.

Co-stimulatory risk/reward

BioNTech and its acasunlimab partner Genmab have already revealed plans to push the anti-PD-L1 x 4-1BB MAb into phase 3 in second-line NSCLC, even as others are exiting the space.

With little data on this approach available, the ASCO poster presentation promises an insight into the partners’ confidence, and the abstract gives investors a sneak peek. 

The data come from a phase 2 trial of NSCLC patients who had progressed on a checkpoint inhibitor. The study tests acasunlimab both as monotherapy and in combination with Keytruda.

Although response rates with monotherapy looked reasonable, durability was lacklustre – something already disclosed by Genmab’s chief executive officer, Jan van der Winkel, at the Jefferies London Healthcare Conference last November. However, persistence seemed to improve with the addition of Keytruda.

Acasunlimab’s ASCO data

Note: cutoff date 9 January 2024. Source: ASCO 2024 abstract.

This could come at a cost, however. With the combo, liver-related adverse events were seen in 19% of patients, and in 13% at grade 3 or higher. Details of the planned phase 3 study haven’t yet been disclosed but, with a combo approach looking likely, the partners will have to hope they can manage toxicity.

BioNTech chases Summit

ASCO will also feature a poster on the anti-PD-L1 x VEGF bispecific antibody PM8002, which BioNTech licensed from China’s Biotheus last year. The latter group previously presented data from a Chinese phase 1/2 study in various solid tumours; this year’s ASCO will see more results from the same trial, with a focus on NSCLC.

PD-(L)1 and VEGF inhibitors are both well established in NSCLC, but it is hoped that bispecifics targeting both could lead to synergistic efficacy. The leading proponent of this approach is Summit Therapeutics, which licensed ivonescimab from Akeso for $500m in December 2022.

BioNTech will hope to challenge Summit, and the ASCO abstract data suggest that PM8002 might have similar efficacy to ivonescimab, although patient numbers are small. However, BioNTech is well behind, having disclosed plans to start global trials this year, while ivonescimab is already in US phase 3 NSCLC studies.

The ASCO abstract details results from several NSCLC cohorts receiving PM8002 monotherapy in the first and second lines. The most impressive results are from the treatment-naive cohort; indeed, the 47% ORR looks in line with the 50% response rate reported with ivonescimab monotherapy at ASCO 2022, among 54 PD-L1-positive patients.

PM8002 in NSCLC

Note: cutoff date 20 December 2023. Source: ASCO 2024 abstract.

In the second line, results with PM8002 were less emphatic. Ivonescimab has previously produced higher response rates in this setting, but it’s worth noting that this was with a chemo combo, making a cross-trial comparison inadvisable.

A Chinese phase 2/3 trial is already under way testing PM8002 plus chemo in EGFR mutant non-squamous NSCLC patients who've previously failed an EGFR-TKI.

Toxicity with PM8002 didn’t look remarkable, with 18% of patients experiencing grade 3 or higher adverse events, and 8% discontinuing therapy. The available data suggest that the project warrants further study, but overall BioNTech’s pipeline could do with some more excitement.

The ASCO annual meeting takes place in Chicago on 31 May to 4 June.