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Triple meeting 2023 preview – firsts for Amgen and Novartis

But Repare and Black Diamond still have rebuilding to do.

Nuvalent stole the headlines around the upcoming Triple Meeting, but there was plenty of other action amid yesterday’s abstract drop. 

Presentations to look out for include first-in-human data with Amgen’s PRMT5 inhibitor AMG 193 and Novartis’s WRN blocker HRO761. Meanwhile, Repare and Black Diamond, which will also have a presence at the meeting, have a way to go to convince investors about their respective reinventions.

KRAS commitment

And Lilly, which has made some recent canny investments outside oncology, announced three new preclinical programmes, including a KRAS G12D inhibitor. Lilly also promises preclinical data on a new ADC project against Nectin-4, an asset arising from the group's acquisition of Emergence Therapeutics in June.

KRAS is already a very popular target, and Nectin-4 is heading that way. Another KRAS player, Revolution Medicines, will be at the Triple Meeting (EORTC-NCI-AACR) with its G12C and multi-RAS inhibitors. 

That company’s projects target the active, GTP-bound form of RAS, or RAS(ON). Revolution believes that its KRAS G12C inhibitor could be differentiated from existing drugs in this class, and it hopes that the multi-RAS inhibitor could have broad potential. However, competition is fierce.

Amgen joins Mirati

Plenty of others are looking at PRMT5 inhibition, but Amgen is one of the most advanced players here. Data on its contender, AMG 193, will come hot on the heels of Mirati’s results with MRTX1719 in August. 

AMG 193’s showing will also be important to Ideaya Biosciences, whose MAT2A inhibitor IDE397 is being trialled in combination with the Amgen asset.

Less crowded is WRN inhibition, where Novartis’s hopes rest on HRO761. According to OncologyPipeline, the only other clinical-stage asset that shares this mechanism is Roche’s RO7589831, also in phase 1.

Black Diamond's rollercoaster

Competition was a likely reason behind Black Diamond’s shift to a fourth-generation EGFR inhibitor, BDTX-1535, in April. That company was swiftly rewarded by a bump in its share price following initial clinical data in NSCLC in June

However, its stock has come off since; next up for the group will be results with BDTX-1535 in glioblastoma, due at the Triple Meeting. 

Repare’s main focus now is the PKMYT1 inhibitor lunresertib, following the licensing to Roche in June 2022 of its ATR inhibitor camonsertib. But early data with lunresertib this June failed to move the needle; the company has said it is now focused on a combination approach. Lunresertib is already being trialled alongside camonsertib in the Mythic trial, to be presented at the Triple Meeting.

 

Notable abstracts at the Triple Meeting

ProjectCompanyTargetPresentation details
AMG 193AmgenPRMT5First-in-human data in MTAP-null solid tumours (NCT05094336)
HRO761NovartisWRNFirst-in-human data in microsatellite instability high cancers (NCT05838768)
LunresertibRepare TherapeuticsPKMYT1Updated data from ph1 Mythic trial +/- camonsertib in tumours with CCNE1 amplification or FBXW7 or PPP2R1A alterations (NCT04855656)
BDTX-1535Black Diamond TherapeuticsEGFRDose-escalation data from ph1 trial in NSCLC & glioblastoma (NCT05256290)
RMC-6291Revolution MedicinesKRAS G12CInitial efficacy data from ph1 trial in KRAS G12C-mutated solid tumours (NCT05462717)
RMC-6236Revolution MedicinesRAS (multi)Safety & PK data from ph1 trial in KRAS-mutated solid tumours (NCT05379985)
LY3962673LillyKRAS G12DPreclinical data
Etx-22LillyNectin-4Preclinical data

Source: EORTC-NCI-AACR (Triple Meeting)