HPK1 therapy (Ryvu Therapeutics)

Courtesy Tomohiro Ohsumi/Getty Images Two weeks after Nimbus Therapeutics reported positive Phase IIb data for NDI-034858, Takeda is acquiring both the therapy and Nimbus Lakshmi, a wholly owned subsidiary, in a potentially $6 billion deal. The therapy is an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor being developed to treat autoimmune diseases. The Phase IIb readout in late November was for moderate-to-severe plaque psoriasis. In the Phase IIb study of 259 patients, NDI-034858 met the primary efficacy endpoint, demonstrating a statistically significant higher number of patients hitting a 75% improvement in skin lesions. The measurement was via the Psoriasis Area and Severity Index (PASI-75) compared to placebo at 12 weeks. Under the terms of the deal, Takeda will pay Nimbus $4 billion upfront. There are two additional sales milestones of $1 billion each when or if annual net sales of the drug reach $4 and $5 billion. Jeb Keiper, CEO of Nimbus, told BioSpace Nimbus' goal is to design breakthrough medicines and take them through clinical development and then to "collaborate with multinational pharma companies that can accelerate [the medicines] forward through commercialization." This isn't the first large deal for Nimbus. In 2016, the company's lead clinical program, firsocostat in NASH, which was acquired by Gilead Sciences. The FDA approved Bristol Myers Squibb’s Sotyktu (deucravacitinib), a first-in-class, oral TYK2 inhibitor for moderate-to-severe plaque psoriasis in September. Nimbus and Takeda believe NDI-034858 has the potential to compete effectively against Sotyktu in the marketplace, despite being significantly behind in getting to market. Earlier projections have estimated Sotyktu could hit $4 billion in annual sales. A Takeda spokesperson told BioSpace that adding the TYK2 inhibitor to its pipeline gives Takeda the opportunity to expand its portfolio, as well as its GI clinical programs and therapeutic focus. A private company, Nimbus raised $125 million in mid-September, with new investors Bain Capital Life Sciences and SV Health Investors joining an existing stable of prominent investors. Those funds supported the Phase IIb trial of NDI-034858 as well as the launch of the psoriasis Phase II trial and additional Phase IIb trials of the drug in inflammatory bowel disease and lupus. Now, with an additional $4 billion, the company has plenty of funds to advance the ongoing Phase I/II trials of NDI-101150, its hematopoietic progenitor kinase 1 (HPK1) inhibitor in solid tumors. It also has preclinical programs targeting Casitas B-lineage lymphoma b (Cbl-b) and Werner syndrome helicate (WRN).

- Nimbus to receive $4 billion in upfront cash, and up to $2 billion in commercial milestone payments - - NDI-034858 has potential best-in-class pro new therapeutic class of selective allosteric TYK2 inhibitors for immune-mediated diseases - BOSTON--(BUSINESS WIRE)-- Nimbus Therapeutics, LLC (“Nimbus Therapeutics” or “Nimbus”), a clinical-stage company that designs and develops breakthrough medicines through its powerful computational drug discovery engine, today announced that it has signed a definitive agreement under which Takeda (TSE:4502/NYSE:TAK) will acquire Nimbus Lakshmi, Inc., a wholly-owned subsidiary of Nimbus Therapeutics, and its tyrosine kinase 2 (TYK2) inhibitor NDI-034858. NDI-034858 is an oral, selective allosteric TYK2 inhibitor being evaluated for the treatment of multiple autoimmune diseases following successful recent Phase 2b results in psoriasis. “Nimbus’ allosteric TYK2 inhibitor has the potential to be a best-in-class medicine in multiple disease areas, and we are confident that Takeda’s commitment and capabilities will enable NDI-034858 to reach its full value to patients,” said Jeb Keiper, M.S., MBA, Chief Executive Officer of Nimbus. “The proposed acquisition highlights Nimbus’ ability to discover and develop high-value investigational medicines leveraging our computational structure-based drug design and development engine. We will continue to advance other exciting target programs in our R&D pipeline — including our selective HPK1 inhibitor, currently in a Phase 1/2 study in patients with solid tumors — as we have done since our founding in 2009.” Under the terms of the agreement, Takeda will pay Nimbus Therapeutics $4 billion upfront, and sales-based milestone payments up to $2 billion. The transaction is expected to be finalized in the first half of 2023. Closing of the transaction is contingent on completion of review under antitrust laws, including the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976. Nimbus Therapeutics will retain ownership of its other research and development subsidiaries. Takeda will be solely responsible for future development and commercialization of NDI-034858 and other TYK2 inhibitors. J.P. Morgan Securities LLC is acting as exclusive financial advisor to Nimbus Therapeutics and Goodwin Procter LLP is serving as its legal advisor. About NDI-034858 NDI-034858 is an allosteric TYK2 inhibitor discovered and developed by Nimbus Therapeutics that is being evaluated for the treatment of multiple autoimmune diseases. In preclinical studies, NDI-034858 has demonstrated exceptional functional selectivity and wide therapeutic margins. In Phase 1 studies, NDI-034858 showed a good tolerability profile, a dose-dependent trend in exploratory clinical activity and a pharmacokinetic pro for once-daily solid oral dosing. Results from Nimbus’ Phase 2b clinical trial in patients with moderate-to-severe plaque psoriasis demonstrated a significantly greater proportion of patients in the study achieving the primary endpoint of PASI-75 (a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index) compared to placebo after twelve weeks of treatment. Data from this trial will be presented at an upcoming medical conference. In addition to psoriasis, NDI-034858 is in an ongoing Phase 2b trial in active psoriatic arthritis (NCT05153148). About Nimbus Therapeutics Nimbus Therapeutics is a clinical-stage, structure-based drug discovery company developing novel small molecule medicines designed to act against well-validated but difficult-to-drug targets implicated in multiple human diseases. Nimbus combines leading-edge computational technologies with a tailored array of machine learning-based predictive modeling approaches. Nimbus’ pipeline includes clinical-stage programs targeting TYK2 and HPK1 (NCT05128487), as well as a diverse portfolio of preclinical programs focused on cancer, inflammatory and autoimmune conditions and metabolic diseases. Nimbus is headquartered in Boston, MA. To learn more about Nimbus, please visit .