Esmo 2019 makes for a disappointing read-across to biotech

An analysis of stock market movers during the period of this year’s Esmo congress gives biotech watchers little cause for happiness.

This year’s instalment of Europe’s largest oncology-focused medical congress was another big pharma affair, with the battle between Glaxosmithkline and Astrazeneca/Merck & Co’s Parp inhibitors dominating the agenda. The job for many biotech investors was to figure out the read-across to their favourite stocks.

A case in point was Mirati, which fell 17% on Amgen’s disappointing AMG 510 data, marking a pause in investors’ love affair with Kras targeting. True, the congress coincided with a tough trading period as a whole, but it is incredible that there was only one biotech winner, Seattle Genetics, whose market cap gained a remarkable $2bn over the weekend.

This analysis compares the share prices of Esmo-relevant biopharma companies at market close last Thursday, a day before the most important abstracts were unveiled, and close of play yesterday, formally the meeting’s last day.

Selected Esmo 2019 stocks: biggest risers
Company Price change* Relevant data at Esmo Vantage coverage
Seattle Genetics 18% Enfortumab combo data & tucatinib PD-L1 status moves centre stage in bladder cancer
Hutchison China Meditech 16% Surufatinb in neuroendocrine tumours  
Faron 7% Clevegen in colorectal cancer  
Merck KGaA 1% Various Esmo 2019 preview – Parps on parade
Glaxosmithkline 1% Zejula in ovarian cancer maintenance Glaxo’s Parp ambitions get a boost
Bristol-Myers Squibb 1% Opdivo in liver cancer & more TMB NSCLC analyses Opdivo could have done better in liver cancer
Deciphera 1% Ripretinib in Invictus GIST study  
Roche 0% Imvigor-130 survival readout PD-L1 status moves centre stage in bladder cancer
Incyte 0% Pemigatinib in cholangiocarcinoma Targeted bile duct treatment pits Incyte against Agios
Turning Point 0% Reprotrectinib in Ros1-positive cancers  
Note: difference between closing prices on Oct 1 and Sep 26.

It might seem strange that Seattle surged on remission rate data in a phase I bladder cancer trial for enfortumab vedotin, a project already filed for accelerated approval, and one that has generated survival data in a highly impressive though uncontrolled phase II trial, EV-201.

But the filing is for second-line use, whereas Seattle’s Esmo data came from the front-line cohort of EV-103, a study combining the nectin-4 inhibitor with Keytruda. In the 45 evaluable PD-L1-positive and negative subjects the confirmed overall remission rate was 71%, with six complete remissions.

Waterfall plot from 1st-line bladder cancer subjects given enfortumab and Keytruda in EV-103. Source: Dr Christopher Hoimes & Esmo.

The potential of immunotherapy in platinum-eligible non-PD-L1 expressing bladder cancer has been thrown into doubt by Roche’s Imvigor-130 trial, from which interim overall survival curves were released for the first time at Esmo. The hint from EV-103 is that checkpoint blockade combined with enfortumab could be the answer.

Seattle was also helped by remission data in colorectal cancer in a trial of tucatinib, acquired through the $614m buyout of Cascadian Therapeutics. The only other significant riser was Hutchison China Meditech, presenting PFS data with surufatinib/sulfatinib in neuroendocrine tumours, though the period also coincided with an offering of stock by its holding company.

Away from big pharma’s immunotherapy trials, targeted treatments like surufatinib had a strong Esmo presence, but biotech came away empty-handed. Deciphera revealed a remarkable PFS advantage for ripretinib in the phase III Invictus trial, while Turning Point presented impressive response rates backing reprotrectinib in Ros1-positive cancers, but both stocks barely crept up.

Selected Esmo 2019 stocks: biggest fallers
Company Price change* Relevant data at Esmo Vantage coverage
G1 Therapeutics (32%) Trilaciclib in TNBC Breast cancer verdict brings G1 down to earth
Calithera (20%) Remission rates with INCB001158  
Aravive (17%) AVB-S6-500 in 2L ovarian cancer  
Mirati (17%) None Kras springs a leak
Immunomedics (12%) Sacituzumab in 2L bladder cancer PD-L1 status moves centre stage in bladder cancer
Adaptimmune (8%) ADP-A2M4 in synovial sarcoma  
Beigene (7%) Tislelizumab in bladder cancer  
Astrazeneca (4%) Lynparza in ovarian & prostate cancers Lynparza pushes Parps forward again
Zymeworks (2%) ZW25 in Her2-expressing tumours  
Agios (1%) Tibsovo in cholangiocarcinoma Targeted bile duct treatment pits Incyte against Agios
Amgen (1%) AMG 510 in colorectal & appendiceal tumours Kras springs a leak
Abbvie (1%) Veliparib in ovarian & breast cancers Too little too late for Abbvie and veliparib?
Pfizer (1%) Beacon CRC study Pfizer’s Beacon presents a doublet vs triplet conundrum
Novartis (1%) Kisqali in Moanleesa-3 trial  
Lilly (1%) Verzenio in Monarch-2 trial Thyroid results strengthen selpercatinib's case
Basilea (1%) Derazantinib in cholangiocarcinoma Targeted bile duct treatment pits Incyte against Agios
Pharmamar (1%) Zepsyre in 2/3L mesothelioma Mesothelioma trials contend with super-fast disease progression
Merck & Co 0% Keytruda in (neo)adjuvant TNBC Keynote-522 stokes adjuvant hopes for Keytruda
Clovis 0% Triton2 prostate cancer study Clovis is running out of waves to catch
Note: difference between closing prices on 1 Oct and 26 Sep.

At the opposite end of the scale Mirati crashed 17%, notwithstanding Leerink analysts playing up AMG 510’s disappointing 8% remission rate in colorectal cancer as “opening the door for Mirati to best”. Mirati had tended to trade up on previous reports of Amgen’s data – positive or negative – but the trick did not work this time around.

G1 Therapeutics was the biggest loser, as an Esmo presenter rubbished trilaciclib’s supposed survival benefit in breast cancer. And Immunomedics fell 12%, owing more to a further delay relating to sacituzumab’s complete response letter in breast cancer than to its admittedly positive result in bladder cancer.

As for the big story of Esmo – the three-way battle of Parp inhibitors – this was probably won by Lynparza, thanks to the cannily designed Profound study in prostate cancer, though in the ovarian setting Zejula might have the strongest dataset, vindicating Glaxosmithkline’s $5.1bn purchase of its maker, Tesaro.

Though Clovis was unmoved its Parp, Rubraca, also has an intriguing prostate cancer dataset. The worry is that this is too little, too late for the heavily indebted biotech.

A collection of all the Vantage stories from the Esmo 2019 can be found here. Next year’s congress takes place in Madrid on September 18-22.

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