Theseus Pharmaceuticals put a brave face on the death of a patient revealed at ASCO in a trial of its leas asset, THE-630, but just over a month later reality has bitten. Yesterday it scrapped development of this pan-KIT inhibitor in gastrointestinal stromal tumours because of dose-limiting toxicities. The death reported at Asco, from myocardial infarction, might have been easy enough to dismiss – the patient had received eight prior therapies and had comorbidities – but now comes disclosure of hand-foot reactions, which have limited Theseus’s ability to dose THE-630 high enough to see whether it can yield meaningful efficacy. The group is now pivoting to THE-349, a so-called fourth-generation mutant EGFR-targeting kinase inhibitor aiming to improve on Astrazeneca’s blockbuster Tagrisso in lung cancer. As a recent Stifel note pointed out, this is a hot and potentially lucrative area, but competition is already fierce: Tagrisso, both on and off-label, has set a high bar, and many biotech competitors are playing for a slice of the pie. Theseus does not even plan to file an IND for THE-349 until the fourth quarter of this year, and its stock lost 72% today. 4th-generation* projects targeting mutant EGFRCompanyProjectStatusNoteBlueprintBLU-945Ph1/2 Symphony, +/- TagrissoAsco 2023 data showed ORR 10% (4/41)Black Diamond TherapeuticsBDTX-1535Ph1 NCT05256290First data, from NSCLC cohort, impressed in Jun 2023J Ints BioJIN-A02Ph1/2 NCT05394831Pharmacokinetic data publishedBridge BiotherapeuticsBBT-176Ph1/2 NCT04820023Pharmacokinetic data publishedC4 TherapeuticsCFT8919**PreclinicalIND cleared Jul 2023BlueprintBLU-525Preclinical Boehringer IngelheimBI-732Preclinical TheseusTHE-349PreclinicalIND filing due Q4 2023Scorpion TherapeuticsSTX-241PreclinicalIND filing due H1 2024Notes: *definition assumes that Iressa & Tarceva are 1st-generation, Gilotrif & Vizimpro are 2nd-generation, Tagrisso, nazartinib & others are 3rd-generation; 4th-generation implies activity in escape mutations developed in response to Tagrisso treatment, C797S and/or other "rare" EGFR mutations; **degrder project, as all others are TKIs. Source: Stifel.
Theseus Pharmaceuticals put a brave face on the death of a patient revealed at ASCO in a trial of its leas asset, THE-630, but just over a month later reality has bitten. Yesterday it scrapped development of this pan-KIT inhibitor in gastrointestinal stromal tumours because of dose-limiting toxicities. The death reported at Asco, from myocardial infarction, might have been easy enough to dismiss – the patient had received eight prior therapies and had comorbidities – but now comes disclosure of hand-foot reactions, which have limited Theseus’s ability to dose THE-630 high enough to see whether it can yield meaningful efficacy. The group is now pivoting to THE-349, a so-called fourth-generation mutant EGFR-targeting kinase inhibitor aiming to improve on Astrazeneca’s blockbuster Tagrisso in lung cancer. As a recent Stifel note pointed out, this is a hot and potentially lucrative area, but competition is already fierce: Tagrisso, both on and off-label, has set a high bar, and many biotech competitors are playing for a slice of the pie. Theseus does not even plan to file an IND for THE-349 until the fourth quarter of this year, and its stock lost 72% today.
4th-generation* projects targeting mutant EGFR
