Esmo 2021 – Mirati bids to be belle of the ball

World Lung is not yet over, but biopharma investors already have the next oncology conference to contend with; Esmo starts on Thursday, and the titles of all its presentations, including late-breakers, have been made available.

From these it is clear that the meeting, taking place solely in virtual format, will again have a focus on big biopharma and immune checkpoint blockade. That said, biotech watchers have several catalysts to look forward to, the most important of which appears to be a late-breaker revealing an update on Mirati’s Kras blocker adagrasib in colorectal cancer.

Adagrasib is notable for having fallen behind Amgen’s Lumakras, which secured speedy US approval for Kras-mutated lung cancer while Mirati, boasting an $8.5bn valuation, will not even file until late this year. However, while that filing is likely to include NSCLC, it is colorectal cancer that could turn out to be a trump card.

In NSCLC the two agents seem evenly matched, showing remission rates of 35-45%, but Amgen has effectively given up with Lumakras in colorectal cancer after reporting an ORR of just 7%. At its last update the colorectal cancer cohort of Mirati’s Krystal-1 study was showing ORR of 17%, so clearly investors will be hoping for a significant improvement on this number.

Other biotech-relevant oral presentations include a late-breaking clinical update on Faron’s Clevegen in solid tumours, preliminary clinical activity of Syros’s oral CDK7 inhibitor SY-5609, and phase 1 data on Redx’s lead asset, the Porcupine inhibitor RXC004.

Another late-breaker will reveal the first data on Spectrum’s poziotinib in front-line Her2 exon 20 insertion NSCLC; other cohorts of the project’s Zenith20 study have yielded two misses, in relapsed and front-line EGFR exon 20 insertion NSCLC, and one hit, in relapsed Her2 exon 20 patients. This space is competitive.

Biotech investors are also tracking an update on Astrazeneca’s Wee1 inhibitor adavosertib, which after years of development could at last show activity thanks to a focus on biomarker-defined subgroups. The Esmo oral session looks at TP53 and Ras-mutated colorectal cancer, and the data will be of note to other Wee1 players, including Zentalis and Nuvation Bio.

Investors can look forward to most oral abstracts going live later this week, with slide decks and full presentations becoming available as they happen. Late-breaker embargoes will not lift until Saturday in most cases.

First movers

Meanwhile, all of the meeting’s posters have just been made available today, resulting in the first Esmo-specific stock market moves.

Leap Therapeutics climbed 20% this morning after boasting a 68% ORR for DKN-01, even though this anti-dickkopf-1 MAb had been combined with tislelizumab, and the poster reveals four patient deaths, a fact Leap’s press release omits. Adaptimmune opened flat on a poster covering the Surpass study of ADP-A2M4CD8, a next-generation version of afami-cel, showing a 36% ORR.

Macrogenics’ posters on Margenza combos and MGC018 revealed little new. And Esmo’s first casualty appears to be Silverback Therapeutics, off 24% today on a poster of its anti-Her2 MAb/TLR8 conjugate agonist SBT6050 showing just one partial response among 14 Her2-positive solid tumours.

All that said Esmo remains an oncology meeting whose greatest focus is on large-practice-changing studies of drugs, many of which are already marketed by big biopharma companies. For those interested in the growing dominance of Merck & Co’s Keytruda, and challenges against it by Bristol Myers Squibb’s Opdivo, Astra’s Imfinzi and Cstone/EQRX’s sugemalimab, the Esmo late-breakers will not disappoint.

Esmo 2021 will take place in virtual format between September 16 and 21.

Also download for free our recent update on developments in the PD-(L)1 inhibitor space.