Mirati data to test whether biotech can challenge Amgen in KRAS quest

• Cancer researchers and biotech investors will soon find out whether Mirati Therapeutics can challenge Amgen in the race to develop a drug targeting a mutant gene previously thought to be “undruggable.”
• Later this month, Mirati will unveil preclinical and initial clinical data from a Phase 1 study testing its experimental cancer drug MRTX849, which binds to a protein created by the KRAS gene. KRAS mutations, which are found in many lung, colorectal and pancreatic cancers, spur cell growth and cancer progression.
• Amgen has set the bar high for Mirati, presenting clinical results in June and again this fall that showed its experimental drug AMG 510 shrunk tumors in patients with both lung and colorectal cancers. Amgen’s data are the most promising to emerge in decades of KRAS research and sent shares in both biotechs higher.

Mirati is now valued at more than $3 billion, more that twice what the San Diego-based biotech was worth when 2019 began.
Yet investors in the company know little more about Mirati’s KRAS inhibitor than they did in January, when a Phase 1 study testing the drug began.
Instead, much of that stock appreciation is tied to investors reacting to promising early results for Amgen’s competing drug, the first to show a compelling clinical profile in KRAS-driven cancers.

Credit: Ned Pagliarulo / BioPharma Dive, market data

For decades, efforts to target KRAS came up short, mostly due to difficulties in designing a drug that binds to the relevant protein
Amgen, Mirati and others are trying a new approach that involves binding a small molecule inhibitor to a shallow “pocket” on a form of KRAS dubbed G12C.
The results for AMG 510 put Amgen out in front, but Mirati could prove itself competitive. The smaller biotech will disclose first results for MRTX849 on Oct. 28 at the AACR-NCI-EORTC International, or “Triple,” Conference in Boston.
Mirati’s chief scientific officer will present preclinical data while Pasi Janne, a director of thoracic oncology at the Dana-Farber Cancer Institute will unveil initial clinical findings in an oral presentation.
While the number of patients from whom response data is collected will likely be few, shares in Mirati could trade up by as much as 70% if results look promising or fall by up to 60% if disappointing, wrote SVB Leerink analyst Andrew Berens in a Oct. 18 note to clients.
Mirati designed the Phase 1 study to quickly escalate drug doses, so Berens believes the first look on Oct. 28 will include data on higher, possibly more effective doses of MRTX849.
Treatment with the high dose of Amgen’s drug led to tumor responses in a little more than half of the 13 patients tested, a high bar for Mirati to match.
In order for Mirati to convince investors its drug is better, data would need to show initial response rates of greater than 60% of lung cancer patients, according to Berens. A response rate around 50% would suggest efficacy “on par or not materially worse than AMG 510,” he wrote.
Mirati has competition in chasing Amgen, though. Johnson & Johnson and Boehringer Ingelheim recently began Phase 1 testing of their own KRAS inhibitors, and other drugs are in or nearing testing.
For decades, KRAS has been cancer research’s “white whale.” Success from Mirati could go some ways to convincing researchers and investors that Amgen’s breakthough can be repeated.

A wave of new KRAS efforts enters the clinic

Drug	Developer	Status
AMG 510	Amgen	Data presented at WCLC, ESMO
MRTX849	Mirati Therapeutics	Initial data presentation set for Oct. 28
mRNA-5671	Moderna, Merck & Co.	First patient dosed in Phase 1
KRAS TCR	NCI, Gilead	Phase 1 study begun in May
ARS-3248	Johnson & Johnson, Wellspring	Phase 1 study begun in July
BI 1701963	Boehringer Ingelheim	Phase 1 study begun in October
BBP454	BridgeBio	Preclinical development
AZD4785	AstraZeneca, Ionis	Discontinued after Phase 1

SOURCE: Companies, clinicaltrials.gov

https://www.biopharmadive.com/news/mirati-kras-first-data-challenge-amgen/565352/