ESMO 2024 preview – Summit and BioNTech battle again

This year’s ASCO meeting saw a showdown between two PD-(L)1 x VEGF-targeting bispecifics, from Summit/Akeso and BioNTech/Biotheus, and this looks set to be repeated at ESMO in September. While the main battleground has so far been NSCLC, the European congress will see a face off in triple-negative breast cancer, according to titles unveiled last week.

Meanwhile, among other biological approaches to be presented at ESMO, MAGE-A4 and cytokines will feature, although these are areas in which disappointments have outweighed successes.

PD-(L)1 x VEGF face off

Both Summit and BioNTech hope that targeting PD-(L)1 and VEGF with one molecule will offer safety and efficacy advantages over the tried-and-tested approach of giving a checkpoint inhibitor and a VEGF blocker like Avastin separately.

They're taking a slightly different tack, with Summit’s ivonescimab targeting PD-1, found on T cells, and BioNTech’s BNT327 hitting PD-L1, expressed on tumours. Investors will be looking for any early clues suggesting which of these two approaches might work best.

ESMO will feature studies of both MAbs plus chemo in first-line TNBC. There are already some data here on BNT327, from a Chinese 1/2 trial presented at SABCS last December just after BioNTech licensed the project. With an 8 October cutoff, among 42 patients, there was a 79% ORR and median PFS of 9.2 months.

Biotheus has begun a Chinese phase 3 in first-line TNBC. BioNTech has said it plans to start global trials of BNT327 this year.

Ivonescimab is behind in this setting, with no TNBC data available yet. Akeso’s phase 2 first-line Chinese trial is also testing its anti-CD47 MAb ligufalimab; investigator-sponsored mid-stage studies in neoadjuvant TNBC are additionally under way.

New iMAGE?

ESMO will see the first data on Immatics’ and Bristol Myers Squibb’s MAGE-A4/8-targeting TCR-based T-cell engager, IMA401. There have been numerous failures in MAGE-A4, although Roche hasn’t given up here with what could be a similar approach, while Adaptimmune’s anti-MAGE-A4 engineered TCR afami-cel awaits an approval decision by 4 August.

Bristol only paid $150m up front to license IMA401, making this a low-stakes bet for the big pharma. Immatics has been in the spotlight this year for its anti-PRAME T-cell receptor project IMA203.

Cytokine-based approaches could also do with some good news; at ESMO the US/South Korean firm NeoImmuneTech will be flying the flag with efineptakin alfa (NT-17), an IL-7 fusion protein. The study in question recruited large B-cell lymphoma patients who had already received CD19-directed Car-T therapy; safety and biomarker data were presented at ASH in 2022.

NeoImmuneTech claims that efineptakin alfa is the only clinical-stage, long-acting human IL-7. Various groups have been been pursuing IL-7, but recent setbacks include Medikine terminating the phase 1 study of its fusion protein MDK-703, citing a “corporate decision”, and disappointing data with Cytheris’s recombinant human IL-7 CYT107 plus Tecentriq at last year’s ESMO. BioNTech’s BNT152, an mRNA project designed to spur the patient’s body to make IL-7, is still in play.

Several novel targets will feature at ESMO: Bristol Myers Squibb’s BMS-986012 and GV20 Therapeutics’ GV20-0251 are the only assets to hit fucosyl-GM1 and IGSF8 respectively, according to OncologyPipeline.

Meanwhile, Sanofi and Biond Biologics’ SAR444881 is one of only a handful of clinical-stage ILT2-targeting projects, in addition to Agenus’s AGEN1571 and NGM Biopharmaceuticals’ NGM707 (which also hits ILT4).

Selected ESMO 2024 oral presentations featuring biologicals

Source: ESMO.

ESMO will take place in Barcelona, Spain, on 13-17 September 2024.