Esmo 2020 movers – antibody drug conjugates dominate the news flow

Pre-conference deals were ultimately responsible for the substantial share price gains notched up by the two biggest winners of Esmo – Immunomedics and Seattle Genetics. The data presented at the cancer meeting help to explain why these groups attracted attention in the first place.

Other notable stock market moves include Exelixis’s bounce on the Checkmate-9ER data, which put Cabometyx back in the game in first-line renal cancer, and advances from Cardiff Oncology and Mersana, which stand out among the small caps. With Pieris the only clear loser, biotech can probably conclude that Esmo was a positive force for the sector this year.

Perhaps this was to be expected, considering that demand for biopharma stocks remains very buoyant, notwithstanding something of a pullback this week. To find the biggest moves among Esmo-presenting stocks Evaluate Vantage tracked share price gains or losses from the close on September 11, ahead of the release of most of the abstracts, to the close on the September 21, the final day of the conference.

Leaders

Gilead’s takeout of Immunomedics was announced in the middle of this period, triggering the latter’s 102% surge. But Esmo also saw full results from the Ascent trial, which no doubt helped persuade Gilead to pull the trigger on the deal (Gilead’s cancer ambitions stretch to $21bn, September 14, 2020).

The study tested Trodelvy in metastatic triple-negative breast cancer. Despite having already received a median of four lines of therapy, patients given the Trop-2 targeting antibody drug conjugate experienced a 5.4 month overall survival advantage over those given single-agent chemo (HR of 0.48; p<0.0001).

Data in bladder cancer were less encouraging. In the Trophy-U-01 trial Trodelvy’s overall response came in at 27%; patients had progressed after chemotherapy and a checkpoint inhibitor.

Seattle and Astellas’s rival ADC, Padcev, is approved in this setting on a 44% ORR. Further putting the boot in, these partners announced the early termination for efficacy of the confirmatory EV-301 study, just as Esmo got under way.

Seattle also received an Esmo boost from presentation of full results of the InnovaTV 204 trial of tisotumab vedotin, a separate ADC project, in advanced metastatic cervical cancer. ORR of 24% among 101 patients and median overall survival of 12.1 months has persuaded the company and partner Genmab to seek accelerated approval.

The Esmo period also saw a substantial deal from Seattle: a collaboration with Merck & Co over two separate assets, including the ADC ladiratuzumab vedotin. Little surprise then that Seattle emerged as an Esmo victor (Seattle benefits from Merck's long shot, September 15, 2020).

The extent to which ADCs were on show over this period certainly confirms that this technology has finally come of age. Whether the Esmo data from Immunomedics justifies the price tag to which Gilead agreed is another question entirely. 

Others receiving an Esmo boost included Exelixis and Bristol Myers Squibb, which look to have clawed back their position in first-line renal cancer with a combination of their respective drugs, Cabometyx and Opdivo. Bristol shares actually fell over the Esmo period, though it is harder to discern the impact of these conferences on big pharma stocks.

Lilly looks to have benefited from a prime spot at Sunday’s presidential session for the MonarchE study, which found that Verzenio reduced the risk of cancer recurrence in high-risk early-stage breast cancer patients. This is a new market for CDK4&6 inhibitors, and one that Pfizer has been ruled out of: the failed Pallas trial in the setting also featured at Esmo.

Among the small caps Cardiff Oncology rose on mounting hopes for onvansertib, which tangentially competes in the KRAS space. The PLK1 inhibitor does not target KRAS directly – PLK1 is described as a master regulator of mitosis which has synthetic lethality with KRAS-mutated colorectal cancer.

Esmo saw efficacy data from nine patients, four of whom had partial response and a further four stable disease, with one proceeding to curative surgery followed by no evidence of disease. The company’s valuation has ballooned more than tenfold since initial data at AACR earlier this year first piqued interest in the company, which has since changed its name from Trovagene.

KRAS cooling

A leading KRAS contender, Amgen, failed to ignite much new excitement among investors with sotorasib, however, despite the data also being published in the New England Journal of Medicine.

Mersana provided more news on the ADC front: response rates to XMT-1536 were similar to those reported at Asco earlier this year, albeit in a few more patients. After a remarkable run the company’s market cap now sits at a staggering $1.6bn, leaving little room for disappointment.

Blueprint’s rise was largely down to non-Esmo data on Ayvakit in systemic mastocytosis; however, the company did attract some attention with preclinical data on what it describes as a fourth-generation EGFR inhibitor. BLU-945 has been designed to block several resistance mechanisms, including those used by tumours use to evade Tagrisso, Astrazeneca’s leading EGFR TKI.

The project is due to go into the clinic next year and Blueprint’s work in EGFR lung cancer is likely to become a major focus in the coming years. Several companies continue to work on projects that they hope will improve response rates in this lung cancer niche; J&J’s bispecific approach was also on show at Esmo, although work here is also early.

Elsewhere, innovative Chinese companies continue to become more visible at global cancer conferences, with both Innovent and Beigene receiving Esmo-period share prices boosts, and presenting several new datasets.

Beigene in particular attracted attention with its combo trial of a PD-L1 and PD-1 inhibitor; data in urothelial cancer contained some intriguing hints of efficacy, although it is not yet clear whether the company will push on any further with this approach.

Finally to Pieris, which appears to have been the biggest casualty of Esmo. Phase I data with its 4-1BB/HER2 bispecific PRS-343 disappointed, despite the company's best efforts to talk up the results. ORR reached 12% with PRS-343 monotherapy and 11% when the project was combined with Roche’s Tecentriq. 

PRS-343 is on hold while Pieris carries out further studies requested by the FDA; perhaps investors see little reason to carry on.