ULK1

Ono Pharmaceutical agreed to acquire Deciphera Pharmaceuticals for $25.60 per share in cash, representing a total equity value of $2.4 billion, bolstering the Japanese firm’s oncology portfolio. Deciphera’s sole marketed product is the KIT inhibitor Qinlock (ripretinib), whilst its pipeline includes the CSF1R inhibitor vimseltinib and the ULK inhibitor DCC-3116.Gyo Sagara, chief executive of Ono, said “we expect that this acquisition…will not only expand Ono's target oncology portfolio, but also accelerate Ono's business development in the [US] and Europe, and strengthen kinase drug discovery research.”Qinlock is approved in the US, EU and more than 40 markets as a fourth-line  treatment for gastrointestinal stromal tumours (GIST). However, efforts to expand its use in earlier settings fell flat in 2021 when the drug failed to significantly prolong progression-free survival (PFS) in the Phase III INTRIGUE study against Pfizer's Sutent (sunitinib) in patients with second-line GIST.Deciphera is currently investigating Qinlock in the late-stage INSIGHT trial for second-line GIST patients with mutations in KIT exon 11 and 17 and/or 18 and the absence of mutations in KIT exon 9, 13, and/or 14. Meanwhile, vimseltinib is expected to be filed with regulators later this year after meeting the primary endpoint of the Phase III MOTION study in patients with tenosynovial giant cell tumours not amenable to surgery.The boards of both companies have unanimously approved the transaction, which is expected to close in the third quarter. The price of the deal represents a premium of 74.7% over Deciphera’s closing share price on April 26.

Endeavor BioMedicines has raised $101m in a Series B funding round to advance its clinical-stage precision medicine pipeline. Ally Bridge Group and Avidity Partners led the financing round with new investors including Perceptive Advisors, Piper Heartland Healthcare Capital and Revelation Partners among others taking part. Furthermore, current investors Omega Funds and Longitude Capital also made investments. As part of the funding, Andrew Lam from Ally Bridge Group and Monal Mehta from Avidity Partners will be appointed to the board. Related Endeavor intends to use the funds for advancing its pipeline programmes, which include ENV-101 (taladegib) and ENV-201. An orally available, small-molecule inhibitor of the PTCH1 receptor in the Hedgehog signalling pathway, ENV-101 is being developed to treat cancer and idiopathic pulmonary fibrosis (IPF). The company stated that ENV-101 was found to have greater clinical efficacy and safety in approximately 200 participants enrolled on six already concluded studies. Precision therapy methods for ENV-101 in various PTCH1- driven cancer types and in IPF are being analysed by the company. ENV-201 is a small molecule ULK1/2 inhibitor to treat KRAS-driven cancers. The clinical-stage biotechnology company anticipates concluding investigational new drug (IND)-enabling trials and progress the programme into the clinic in 2023. Endeavor BioMedicines co-founder, CEO and chairman John Hood said: “Endeavor BioMedicines is developing precision medicines targeting the genetic culprits of cancer and fibrosis. “Researchers have investigated Hedgehog and ULK1 signalling pathways over the last decade, but now we have the understanding and capability to identify the patients who will benefit most from them. “The capital raised from a committed, top-tier investor syndicate enables us to deliver the right drug to the right patients in order to get the best clinical outcome.”

San Diego-based Endeavor BioMedicines closed on a Series B financing worth $101 million. The round was led by Ally Bridge Group and Avidity Partners, joined by new investors Perceptive Advisors, Piper Heartland Healthcare Capital, Revelation Partners, funds managed by Tekla Capital Management, and funds and accounts advised by T. Rowe Price Associates. Existing investors also participated — Omega Funds and Longitude Capital. Endeavor focuses on precision medicines for cancer and fibrosis. The company plans to use the monies raised to advance its pipeline, including taladegib (ENV-101), a small molecule inhibitor of the PTCH1 receptor in the Hedgehog signaling pathway for cancer and idiopathic pulmonary fibrosis (IPF). A second top pipeline product is ENV-201, a possible best-in-class small ULK1/2 inhibitor for KRAS-driven cancers. ENV-101 was initially being developed for patients with basal cell carcinoma (BCC) but has been expanded to multiple cancer types driven by PTCH1 in addition to IPF. “Endeavor BioMedicines is developing precision medicines targeting the genetic culprits of cancer and fibrosis,” said John Hood, co-founder, chief executive officer and chairman of Endeavor. “Researchers have investigated Hedgehog and ULK1 signaling pathways over the last decade, but now we have the understanding and capability to identify the patients who will benefit most from them. The capital raised from a committed, top-tier investor syndicate enables us to deliver the right drug to the right patients in order to get the best clinical outcome.” As part of the financing deal, Andrew Lam with Ally and Monal Mehta with Avidity will join the board of directors, joining John Hood, Bernard Davitian of Omega Fund and Patrick Enright of Longitude. On September 22, 2021, Endeavor dosed the first patient in its Phase II study of taladegib for IDF. It is a randomized, placebo-controlled, multi-center trial designed to evaluate the efficacy and safety of the drug by itself in mild to moderate IPF. It is being run in the Asia-Pacific region and will enroll about 60 participants, 30 patients in each arm. The participants will receive either a placebo or taladegib as a daily oral dose for 12 weeks of treatment. After treatment, they will be followed for another six weeks. The primary endpoints include change from baseline in frequency and severity of adverse events and key vital sign measurements. Secondary measures include Forced Vital Capacity, FEV1 and other lung function measures. Depending on the study results, they hope to run a Phase II trial of the drug in combination with standard of care sometime this year. Earlier that month, Endeavor in-licensed a ULK1/2 inhibitor program from the Salk Institute for Biological Studies and Sanford Burnham Prebys. The drug inhibits ULK1/2, an enzyme crucial in a cellular recycling process known as autophagy linked to drug resistance in RAS- and LKB1-mutated cancers. LKB1 mutations are observed in about 15% of all non-small cell lung cancer patients and a significant number of people with other types of cancers, including colorectal carcinoma. The company officially launched in January 2021 with a $62 million Series A financing led by Omega Funds, Longitude Capital and Endeavor’s management. It was co-founded by Hood, who previously founded and acted as chief executive officer of Impact Biomedicines until Celgene acquired it in 2018. Miguel de los Rios is Endeavor’s co-founder and chief scientific officer; he previously was chief executive officer of Rift Biotherapeutics.