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 offBoth 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 biologicalsProjectCompanyMechanismTrialAbstractEfineptakin alfa (NT-I7)NeoImmuneTechrhIL-7/Fc fusion proteinDLBCL post CD19 Car-T807MOBMS-986012Bristol Myers SquibbAnti-fucosyl-GM1 MAbES-SCLC ph21786MOSAR444881/ BND22Sanofi/ Biond BiologicsAnti-ILT2 MAb+/-Keytruda or Erbitux990OIvonescimabSummit/ AkesoAnti-PD-1 x VEGF MAbChemo combo in 1L TNBC347MOBNT327/ PM8002BioNTech/ BiotheusAnti-PD-L1 x VEGF MAbAbraxane combo in 1L TNBC348MOGV20-0251GV20 TherapeuticsAnti-IGSF8 MAbSolid tumours1000MOIMA401Immatics/BMSMAGE-A4/8 x CD3 MAbPh1 dose escalation1001MOBNT211BioNTechClaudin6 Car-T + mRNAClaudin6+ solid tumours611OSource: ESMO.ESMO will take place in Barcelona, Spain, on 13-17 September 2024.