Boehringer delivers fresh blow to Nxera Pharma

That includes the Phase 2 ready lead compound NXE0048149 (“NXE’149”). No further information was provided by Boehringer Ingelheim.

All rights to the GPR52 portfolio will revert in full to Nxera Pharma together with all data and intellectual property generated under the collaboration in accordance with the terms of the Collaboration and License Option Agreement.

Christopher Cargill, CEO and President of Nxera Pharma, said: “Although we are disappointed that Boehringer Ingelheim has chosen not to proceed with the license option, its decision does not diminish the significant potential of the GPR52 agonist program, which has demonstrated highly encouraging attributes as a first-in-class approach to treating several major symptoms of schizophrenia and address the shortcomings of current treatment options.

“We are energised by the strong scientific and clinical foundations already established and see meaningful opportunity in regaining full rights. We look forward to updating the market as we advance discussions with potential partners next year.”

NXE’149 and other GPR52 agonists within the portfolio were designed by Nxera using its world-leading NxWave™ structure-based drug design platform to improve patient outcomes by simultaneously addressing positive, negative, and cognitive symptoms of schizophrenia.

A Phase 1 trial evaluating single and multiple ascending doses of NXE’149 demonstrated a highly favourable safety profile, with NXE’149 well tolerated in healthy participants across all dose levels. There were no severe or serious adverse events (AEs) and no AEs leading to discontinuation. Pharmacokinetic analyses showed dose-proportional exposure, equivalent free concentrations in plasma and cerebrospinal fluid at steady state, and a long half-life supporting once-daily dosing.

Notably, pharmacodynamic endpoints including cognitive assessments, neurophysiological measures and peripheral biomarkers provided evidence of engagement of brain circuitry relevant to the treatment of schizophrenia and related disorders.

The expression of GPR52 in brain regions associated with positive symptoms of schizophrenia (e.g. hallucinations and delusions) and those associated with cognitive dysfunction (e.g. attention and memory deficits) and negative symptoms (e.g. social withdrawal and apathy), suggest that NXE’149 may have the potential to treat all three symptom domains of schizophrenia, unlike current therapies which only treat the positive symptoms.

The benefit risk profile of NXE’149, as evidenced by the preclinical and human pharmacodynamic data, could offer patients a major new therapeutic option for their disease and support its continued clinical development.

With the program now Phase 2 ready, Nxera plans to explore strategic opportunities, including a formal out-licensing process with the intention of partnering the program with a major pharmaceutical or specialist neuroscience company in 2026.