Hopes that Mirati could become the first company to succeed in targeting the “undruggable” KRAS oncology target have played a significant part in sending this company’s stock to an all-time high. But, judging by yesterday’s abstract drop for the upcoming AACR conference, the bulls will have to be patient. Both Mirati’s KRAS C12C inhibitor, MRTX1257, and Amgen’s rival AMG 510, will feature at the meeting, but there are no clinical data to report. Amgen’s three abstracts detail AMG 510’s discovery and in vivo characterisation, while Mirati has one preclinical abstract whose text has not yet been made available. Hopes were stoked by Amgen’s head of R&D, David Reese, who on an analyst call last month stated that the group was “seeing interesting early hints of clinical activity” and expected by mid-year to present “initial results … in terms of best-in-class”. These first results seem unlikely to come before Asco. MRTX1257 was Mirati’s early lead, but the current focus is on MRTX849, which has just entered phase I. Despite this early stage of development Leerink estimates that KRAS accounts for 70% of Mirati’s valuation, which today stands at a staggering $2.6bn.
| SELECTED PROJECTS AGAINST CANCERS HARBOURING KRAS MUTATIONS | ||||
|---|---|---|---|---|
| Project | Company | Mechanism | Status | Trial ID |
| AMG 510 | Amgen | KRAS G12C inhibitor | 1st in human data possible at Asco | NCT03600883 |
| TNO155 | Novartis | SHP2 inhibitor | Study in KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mut tumours | NCT03114319 |
| MRTX849 | Mirati (ex Array) | KRAS G12C inhibitor | Trial in KRAS G12C mut cancers started Jan 2019 | NCT03785249 |
| KRAS TCR | Gilead (ex Kite/NCI) | Anti-KRAS G12D engineered T-cell receptor | NCI trial starting Mar 2019 | NCT03745326 |
| Unnamed | Mirati | KRAS G12D inhibitor | Preclinical | None |
| MRTX1257 | Mirati | KRAS G12C inhibitor | Early pipeline lead | None |
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