Develop KRAS dual inhibitor! Seven months after "handing in" with AbbVie, this upstart company raised US$88.5 million in Series B financing

On July 19, Frontier Medicines, a cutting-edge small molecule drug research and development in the United States, announced the completion of a $88.5 million Series B financing. This round of financing was jointly led by Woodline Partners LP and RA Capital Management, followed by Deerfield Management Company and others. The funds obtained will be used to accelerate the pipeline research and development represented by KRAS G12C mutant inhibitors, and to develop basic technologies such as machine learning.

来源：Frontier Medicines

Founded in 2018, Frontier is a small molecule drug research and development company that targets "undrugable" proteins based on chemical proteomics research and develops precision tumor therapy. It has previously completed a US$67 million Series A financing. In 2019, Frontier was listed on the list of "Biopharmaceutical Companies" selected by the American life science media FierceBiotech.

Frontier believes that when the protein conformation changes or moves, small molecules can covalently bind to the targetable sites exposed by the protein to lock the protein's conformation. At the same time, the company is also developing protein degradation technology to add a new weapon to target "unable to drug" targets.

Specifically, Frontier uses a chemical proteomics platform (a method to understand the interactions of small molecules and proteins in a cellular environment) combined with machine learning algorithms to discover binding pockets in proteins involved in key disease pathways (that is, druggable Hotspots) and design molecules to target these pockets from a pharmacological point of view. The machine learning algorithm developed by it can use unique hotspot data to classify the relative reactivity and binding potential of a given protein in a specific region.

Frontier's machine learning/artificial intelligence engine (Source: Frontier Medicines)

The company's current leading research project targets the KRAS G12C mutant. The unique feature is that this candidate molecule can directly inhibit the activated GTP-binding KRAS G12C and the inactivated GDP-binding KRAS G12C at the same time. Drugs with this characteristic provide new treatment opportunities for patients who do not respond to or are resistant to the first generation of KRAS G12C inhibitors (which can only inhibit inactivated GDP-binding KRAS G12C).

KRAS is one of the most common mutated oncogenes in cancer, which encodes a small, membrane-bound GTPase. In normal cells, KRAS acts as a molecular switch, cycling between the inactive state (bound with GDP) and the activated state (bound with GTP). Somatic KRAS mutations can cause abnormal protein function, leading to the accumulation of active KRAS, and abnormal activation of the cell's EGFR (epithelial growth factor receptor) signaling pathway downstream.

KRAS G12C mutations account for 12%-14% of all KRAS mutations, and are most common in patients with non-small cell lung cancer, colorectal cancer, and pancreatic cancer. The first-generation KRAS G12C inhibitor exerts pharmacological activity by inhibiting the conversion of inactivated GDP-binding KRAS G12C to activated KRAS G12C.

Frontier wholly-owned pipeline (Source: Frontier Medicines)

"Finding a small molecule therapy that can inhibit both the activation and inactivation of KRAS G12C mutants is a long-awaited scientific breakthrough. Drugs with dual inhibition may have better anti-cancer effects than drugs that only target the inactive state of KRAS G12C mutants. Effect.” said Professor Frank McCormick of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF).

Frontier and AbbVie collaboration pipeline (Source: Frontier Medicines)

In addition to KRAS G12C inhibitors, Frontier's pipeline also contains candidate molecules that target other cancer targets. It is worth mentioning that, although all current projects are in the preclinical development stage, in December last year, Frontier has reached a global strategic cooperation with pharmaceutical giant AbbVie to jointly develop and commercialize protein targets for "non-drugable" proteins. Innovative small molecule drug pipeline. According to the terms of the agreement, the two parties will cooperate to promote scientific discovery and preclinical development projects for E3 ligase, immunology and oncology targets. AbbVie will pay Frontier an upfront payment of US$55 million. At the same time, Frontier is eligible for additional milestone payments that may exceed US$1 billion.

参考资料：

1# Frontier Medicines Raises $88.5 MillionSeries B Financing to Advance Precision Oncology and Targeted Protein Degradation Pipeline.（来源：Frontier Medicines）

2# Frontier Medicines and AbbVie Establish Global Partnership to Discover and Develop Novel Therapies and E3 Degraders Against Difficult-to-Drug Targets（来源：Frontier Medicines）

Reprinted from: Medicine Rubik's Cube Pro https://mp.weixin.qq.com/s/Kl1hcVVvyZwN75HiZYMBFA