Takeda Pharmaceutical said Tuesday it has committed up to a staggering $6 billion—including $4 billion upfront—to acquire from Nimbus Therapeutics a candidate for multiple autoimmune diseases that is Phase III-bound in psoriasis after showing positive mid-stage results last month.

NDI-034858 is an oral, selective allosteric inhibitor of tyrosine kinase 2 (TYK2), which Takeda will rename TAK-279 when the deal is completed—something Takeda expects by the end of its 2022 fiscal year on March 31, 2023.

Also in 2023, Takeda plans to launch a Phase III trial of TAK-279 in psoriasis. Last month, Numbus released positive topline results showing the drug to have met the primary efficacy endpoint in a Phase IIb trial (NCT04999839) by generating what the company called a statistically significant greater proportion of patients reaching PASI-75 (a 75% improvement in skin lesions as measured by the Psoriasis Area and Severity Index) compared to placebo at 12 weeks.

Takeda said data from the Phase IIb psoriasis trial will be presented at an unspecified future medical conference “early in 2023.”

“After having seen the NDI-034858 Phase IIb data, particularly the PASI scores, we are excited by the differentiation of this molecule within the TYK2 class, and we believe in its broad potential for people with autoimmune diseases,” Andy Plump, MD, PhD, Takeda’s president of research & development, said in a statement. “This program further expands Takeda’s GI clinical programs and therapeutic focus.”

Takeda’s therapeutic areas of focus include gastroenterology, along with oncology, rare disease, neuroscience, plasma-derived therapies, and vaccines.

The Phase IIb trial evaluated NDI-034858/TAK-279 in 259 patients with moderate-to-severe plaque psoriasis. The randomized, multicenter, double-blind, placebo-controlled study assessed four dosages of NDI-034858 taken orally once daily.

Nimbus added that it achieved additional endpoints in the trial, and had shown that the safety of NDI-034858 was consistent with other leading allosteric TYK2 inhibitors.

In addition to psoriasis, Takeda reasons, TAK-279 could show best-in-class efficacy and safety in autoimmune diseases that include inflammatory bowel disease (IBD), systemic lupus erythematosus—and psoriatic arthritis, where Nimbus has been evaluating NDI-034858 in an ongoing Phase IIb trial (NCT05153148) with an estimated primary completion date of May 2023.

Takeda said it will study TAK-279 in IBD—something Nimbus said last month it planned to do—as well as other unspecified autoimmune diseases. One of those may be lupus, in which Nimbus also said last month it planned to study the drug.

Broad development program

“We are confident we can execute a broad development program and deliver a best-in-class therapy for these patients, given Takeda’s strong background in immune-mediated diseases, including inflammatory bowel disease,” stated Christophe Weber, Takeda’s president and CEO.

“Adding this TYK2 inhibitor to our late-stage pipeline gives Takeda an exciting program that has the potential to significantly expand our portfolio and patient impact, while enhancing our growth strategy beyond Entyvio®, Weber added.

Takeda is eager to develop new drugs to recoup the losses it expects when Entyvio (vedolizumab) loses patent exclusivity in Europe in May 2025, followed by the United States in May 2026.

Entyvio—Takeda’s biggest-selling product—generated ¥521.8 billion ($3.848 billion) in sales in Takeda’s last full fiscal year, which ended March 31, 2022, up 21.5% from ¥429.3 billion ($3.166 billion) a year earlier. Since then, Entyvio has racked up ¥646.6 billion ($4.768 billion) in the first half of the company’s current fiscal year, up 35% from ¥255.9 billion ($1.887 million) in AprilSeptember 2021.

Entyvio is an integrin receptor antagonist indicated for moderately to severely active ulcerative colitis and moderately to severely active Crohn’s disease, both in adults.

TYK2 is a signal-transducing kinase that mediates immune signaling and has shown importance to both adaptive and innate immune cells. The TYK2 protein catalyzes the phosphorylation and activation of STAT proteins downstream of the IL-23, IL-12, and type I interferon receptors, among several cytokine receptors.

According to Nimbus, human genetic studies have shown that mutations in TYK2 that reduce kinase activity and downstream signaling are protective in a large number of autoimmune and inflammatory diseases, including psoriasis. Inhibition of TYK2 is expected to impact psoriasis pathogenesis primarily through its effects on the IL-23/Th17/Th22 axis.

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