Nerandomilast

Boehringer Ingelheim has peeled back the curtain on its late-stage pulmonary fibrosis programme, revealing the data behind two Phase III wins at the American Thoracic Society (ATS) meeting on Sunday.The German drugmaker previously reported that nerandomilast, its oral phosphodiesterase 4 (PDE4) inhibitor, met the primary endpoint of each trial by significantly improving absolute change from baseline in forced vital capacity (FVC) versus placebo at week 52. FIBRONEER-IPF enrolled 1,177 patients with idiopathic pulmonary fibrosis (IPF), and FIBRONEER-ILD recruited 1,176 individuals with progressive pulmonary fibrosis (PPF).A marketing application for nerandomilast in IPF is currently under priority review at the FDA, with a decision expected in the fourth quarter. Boehringer has also submitted a US regulatory filing for the PDE4 inhibitor to treat PPF.Diarrhoea drawbacksIn the two studies, patients were randomised to receive either a 9-mg or 18-mg dose of nerandomilast twice-daily, or placebo. Both the low and high dose, in each trial, met the primary endpoint. In FIBRONEER-IPF, patients in the 18-mg dose group and 9-mg dose group saw an adjusted mean change in FVC of -114.7 ml and -138.6 ml, respectively, compared with -183.5 ml for placebo. However, 41.3% of patients in the high-dose cohort, and 31.1% who received the low-dose, reported diarrhoea, versus 16% in the placebo group. The side effect led to study discontinuation in 6.1% of patients in the 18-mg group, 1.8% of the 9-mg recipients, and 0.5% of those on placebo. Oppenheimer analyst Jeff Jones previously suggested that gastrointestinal tolerability could be an issue with nerandomilast (see – Spotlight On: Another ILD win raises stakes on Boehringer’s looming full reveal).The incidence of diarrhoea was lower in the FIBRONEER-ILD trial. In the 18-mg cohort, 36.6% of patients reported the symptom, which led to a 2.6% discontinuation rate; the 9-mg cohort saw 29.5% of patients experience diarrhoea, leading to discontinuation in 1.3% of the group. Of those who received placebo, 24.7% reported diarrhea, and 0.5% discontinued treatment due to the symptom.Patients with PPF also experienced a greater benefit from nerandomilast. The 9-mg and 18-mg cohorts saw an adjusted mean change in FVC of -84.6 ml and -98.6 ml, respectively, compared with −165.8 ml for placebo. While the experimental treatment did not meet, in either trial, its composite secondary endpoint of time to first acute exacerbation, hospitalisation for a respiratory cause, or death Boehringer noted that in FIBRONEER-ILD, there were numerically fewer deaths in both treatment groups: 33 in the 9-mg cohort, 24 in the 18-mg cohort, versus 50 in the placebo arm. Shashank Deshpande, Boehringer's head of human pharma, said that IPF and PPF are "devastating conditions," with half of those diagnosed with IPF dying within five years. "Despite this stark reality…there remains a need for additional therapies," he said. "The latest efficacy, safety and tolerability data on nerandomilast points to its potential in addressing the needs of those impacted by IPF and PPF."

iStock, Mininyx Doodle At the heart of the licensing deal is CUE-501, a bispecific molecule that can selectively deplete B cells to address autoimmune and inflammatory conditions. Boehringer Ingelheim is fronting $12 million to license Cue Biopharma’s investigational B cell depletion therapy for autoimmune diseases, the German biopharma announced on Monday. The star of this back-heavy, multi-year deal is Cue’s CUE-501, a preclinical bispecific molecule that works by binding to a specific protein found on the surface of B cells. At the same time, CUE-501 also engages and activates a specific subset of killer T cells, selectively depleting B cells to suppress autoimmunity and inflammation. According to the biotech’s website , CUE-501 sidesteps the systemic activation of all T cells, which “may offer significant advantages over current cell therapy-based strategies.” For the right to develop and commercialize CUE-501, Boehringer Ingelheim is pledging up to $345 million in research, development and commercial milestones, on top of the $12 million upfront payment. Cue will also be entitled to royalties on net sales of CUE-501. In exchange for this investment, Cue will leverage its platform technologies to further develop CUE-501. Both parties may also expand the partnership to include other anti-B cell bispecifics for autoimmune indications, according to Monday’s release. Carine Boustany, Boehringer Ingelheim’s global head of Immunology and Respiratory Disease Research, said in a statement that Monday’s licensing deal is a “strategic expansion” of the company’s portfolio in the autoimmune and inflammatory space, allowing it to “deliver a more effective treatment option to patients earlier in their disease journey.” Boehringer’s immunology and inflammatory portfolio is anchored by the oral kinase inhibitor Ofev, indicated for idiopathic pulmonary fibrosis (IPF). In 2024, sales of Ofev jumped 7% to rake in approximately $4.26 billion. Meanwhile, the pharma’s asthma drug Spiriva remained one of its top sellers, with more than $1.8 billion in sales last year, despite dipping roughly 17% from the previous year. Additionally, in September 2024, Boehringer Ingelheim reported that its drug candidate nerandomilast aced the Phase III FIBRONEER-IPF study, showing significant lung function benefits in patients with IPF. At the time, the pharma revealed plans to approval application for the drug in this indication, though a specific timeline was not provided. Beyond I&I, Boehringer Ingelheim has also signed several deals in the past year. In January, the pharma entered two antibody-focused partnerships —one with Lonza’s Synaffix and another with Oxford BioTherapeutics—in oncology. In July 2024, Boehringer Ingelheim dropped $1.3 billion to acquire Nerio Therapeutics and its small molecule assets that can “reshape” the immune system to target tumors.