Abbisko Therapeutics Co. Ltd. and Allist Pharmaceuticals Co. Ltd. signed an exclusive licensing deal that gives Allist rights to develop, manufacture and commercialize Abbisko’s ABK-3376, an EGFR tyrosine kinase inhibitor (TKI) for $188 million plus royalties.

Under the terms of the deal, Allist gains rights to the preclinical candidate in China, including Hong Kong, Macau and Taiwan, and the license could be expanded to include other territories for a limited time.

In exchange, Abbisko will receive an undisclosed up-front payment and potential development and commercial milestones up to $187.9 million plus tiered sales-based royalties.

Internally discovered and developed by Abbisko, ABK-3376 is a small-molecule fourth-generation EGFR inhibitor that is brain-penetrating and can inhibit exon 21 (L858R) mutations or exon 19 deletion (19DEL) mutations with acquired C797S mutations.

Abbisko Chief Scientific Officer Zhui Chen told BioWorld that there is no new generation of targeted therapy drugs that are effective for non-small-cell lung cancer (NSCLC) carrying EGFR-C797S drug-resistant mutations.

Third-generation EGFR inhibitors are already on the market for NSCLC patients with EGFR mutations. Like Allist’s furmonertinib, they gradually have moved into first-line treatment for patients carrying primary EGFR mutations, mainly 19DEL or L858R mutations. Even so, these third-generation EGFR inhibitors are likely to meet resistance at the C797S position, he said.

“That’s why we developed this fourth-generation molecule to overcome that resistance,” he said, noting that ABK-3376 has the capability to overcome both the primary mutations along with the acquired C797S mutation, “which is the main goal of this molecule.”

“There have been more than a dozen fourth-generation EGFR inhibitors in development, but our compound stands out, and that is why Allist acquired this molecule,” he said.

Based on its preclinical profile, ABK-3376 has three major advantages, he said.

Firstly, it has broad equivalent potency against all these mutations. “Other compounds will have better potency against one mutation but not the others, but we have uniform potency against all of these,” he said.

Secondly, it has better selectivity over EGFR wild-type, which translates into fewer side effects.

And, thirdly, the molecule has good brain penetration, which is important because many lung cancer patients eventually metastasize into the brain.

“The main reason for out-licensing is that it needs to be combined with a third-generation inhibitor if we want to move into first-line therapy to dominate the market. Therefore, we had to find a partner with a third-generation EGFR, and Allist was one of the three that had one, and likely the best one,” Chen said.

Furmonertinib is one of the fastest-growing third-generation EGFR inhibitors in China, and it recently entered China’s National Reimbursement Drug List.

Shanghai-based Allist only has one approved asset, Chen said, so it needs to add more assets to its pipeline, and the company was looking at this next-generation asset, “so these combination synergies were a significant factor,” he said.

Furmonertinib met its primary endpoint in a phase III trial in April 2022, demonstrating longer progression-free survival vs. first-generation EGFR TKI Iressa (gefitinib, Astrazeneca plc) as first-line therapy for locally advanced or metastatic EGFR mutation-positive NSCLC.

China’s oncology drugs market is expected to reach $12.7 billion by 2026, growing at a compound annual growth rate of 8.7% from $6.5 billion in 2018, according to Allied Market Research. There are around 4 million new cancer cases in China each year, with 18.1% from lung cancer.

Abbisko, also of Shanghai, has 15 programs in its pipeline, two of which were in-licensed and the rest were internally discovered and developed. Seven programs are now in the clinic.

In late January, the U.S. FDA granted breakthrough therapy designation to Abbisko’s colony-stimulating factor 1 receptor (CSF-1R) inhibitor, pimicotinib, for patients with tenosynovial giant cell tumors (TGCT) who are not able to have surgery.

Internally discovered and developed by Abbisko, pimicotinib (ABSK-021) is an orally bioavailable, selective, small molecule. Previous studies have shown that blocking the CSF-1R signaling pathway could modulate and change macrophage functions, and potentially treat many macrophage-dependent human diseases.

Pimicotinib is being actively investigated as a treatment for TGCT and chronic graft-vs.-host disease, with a number of additional indications being investigated via combination trials, he said.

China’s NMPA designated pimicotinib as a breakthrough therapy in July 2022. Currently, there are no highly selective CSF-1R inhibitors approved in China, and for those TGCT patients not able to have surgery, there is currently no approved drug available in China.

“We’re excited because this is one of the very few Chinese self-discovered compounds that received breakthrough therapy from both U.S. and Chinese regulators,” he said, noting that pimicotinib will enter phase III trials in both China and the U.S. in 2023.

By Tamra Sami

Link：www.bioworld.com/articles/694806-abbisko-out-licenses-preclinical-egfr-candidate-to-allist-for-188m