Boehringer Ingelheim and Sosei Heptares join forces to develop first-in-class treatments targeting all symptoms of schizophrenia

  • Single-target agreement focused on development of novel, small molecule agonists of GPR52 discovered by Sosei Heptares with the potential to simultaneously address positive, negative and cognitive symptoms of schizophrenia
  • Sosei Heptares will receive EUR 25 million upfront from Boehringer Ingelheim and is eligible for an option exercise payment of EUR 60 million and further milestone payments totaling up to EUR 670 million plus tiered royalties

Ingelheim, Germany, Tokyo, Japan and Cambridge, UK, 11 March 2024 Today, Boehringer Ingelheim and Sosei Group Corporation (“Sosei Heptares”; TSE: 4565) announced they have entered a global collaboration and exclusive option-to-license agreement. At the center is a joint mission to develop and commercialize Sosei Heptares’ portfolio of first-in-class GPR52 agonists, a novel G protein-coupled receptor (GPCR) target, with the intent to improve patient outcomes by simultaneously addressing positive, negative, and cognitive symptoms of schizophrenia1,2,3.

Schizophrenia is a serious condition that affects about 1 in 100 people worldwide4. It is characterized by three clusters of symptoms5,6:

  • ‘Positive’ symptoms – such as psychosis, delusions and hallucinations
  • ‘Negative’ symptoms – such as social withdrawal and apathy
  • Cognitive symptoms – such as attention, planning and memory deficits

The impact of these symptoms on people’s ability to cope with normal day-to-day life is significant and the related burden on carers and society at large is substantial, especially since the age of onset of the disease is typically in the 20s7. While ‘positive’ symptoms can be stabilized with antipsychotics, some of which can have side effects, there are currently no approved medicines for ‘negative’ or cognitive symptoms.

The development of a new schizophrenia treatment targeting GPR52 has the potential to address all three aspects of schizophrenia1,2 providing a novel precision treatment. This is based on the location of the receptor in the two areas of the brain that drive the positive (the striatum) and the negative and cognitive symptoms (the prefrontal cortex). The GPR52 agonism calms the striatum while boosting frontal cortical function, which achieves further precision in treatment8.

“We’re very excited to enter this partnership with Sosei Heptares with this novel approach, which aims to address a huge unmet need of those living with schizophrenia. This partnership is highly complementary to our other development programs aiming to bring a new precision medicine approach to the treatment of mental health disorders with therapies, which we hope will transform the lives of those living with schizophrenia,” states Hugh Marston, Global Head CNS Discovery Research at Boehringer Ingelheim.

Matt Barnes, President of Heptares Therapeutics and Head of UK R&D at Sosei Heptares, commented: “This collaboration highlights the significant potential GPR52 has shown in preclinical research as a novel, first in class target for the treatment of schizophrenia and related neurological disorders. We’re delighted to partner with Boehringer Ingelheim and leverage its leading expertise in neurological disease research and innovation. Together, we will focus on accelerating the development of this highly innovative program, which is currently in a Phase 1 clinical study, towards patients in need.”

About the Agreement
Sosei Heptares will receive an upfront payment of EUR 25 million from Boehringer Ingelheim upon signing and is eligible for an option exercise payment of EUR 60 million and further development, regulatory and commercialization milestone payments totaling up to EUR 670 million plus customary tiered royalties for a clinical-stage asset on future Boehringer Ingelheim product sales.

Under the terms of the agreement, Boehringer Ingelheim has the exclusive option to license Sosei Heptares’ portfolio of GPR52 agonists following the completion of Sosei Heptares’ ongoing Phase 1 and subsequent Phase 1b trial and further Phase 2 enabling activities with HTL0048149, a first-in-class GPR52 agonist. Sosei Heptares will retain control and act as sponsor of these trials until option exercise, estimated in 2025. The licensed portfolio will include HTL0048149 as well as multiple differentiated back-up compounds designed by Sosei Heptares using its StaR® technology and structure-based drug design (SBDD) platform.


About GPR52 and HTL0048149
GPR52 is an orphan G protein-coupled receptor (GPCR) highly expressed in the brain, especially in the striatum and the prefrontal cortex, and represents a potential emerging therapeutic target for a range of neurological and neuropsychiatric disorders9.

Sosei Heptares has developed a portfolio of selective GPR52 agonists and modulators leveraging proprietary insights from its StaR® technology SBDD platform, the most advanced of which (HTL0048149) entered a first-in-human clinical trial in 202310.

HTL’149 has been designed to selectively target GPR52 as a once-daily, oral drug with an antipsychotic and pro-cognitive profile. Uniquely, HTL‘149 aims to treat positive symptoms (e.g. psychosis, delusions, hallucinations), negative symptoms (e.g. social withdrawal and apathy) and cognitive impairment (e.g. attention, planning and memory deficits) associated with schizophrenia and to minimize adverse effects associated with some of the available antipsychotic drugs9,11,12,13.

Through this novel mechanism of action, HTL’149 aims to address the significant proportion of schizophrenia patients who do not respond to existing treatments or are unable to tolerate some of the side effects of antipsychotics, which potentially results in a lack of compliance to antipsychotic treatments. Furthermore, current antipsychotic drugs do not effectively treat the negative or cognitive symptoms of disease.

HTL‘149 is under investigation in a Phase 1a/b randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study to assess its safety, pharmacokinetics, and pharmacodynamics in healthy volunteers aged 18-55 years. The trial is being conducted in the UK and initial data are expected in 20259,14.

About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that transform lives, today and for generations to come. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term, sustainable perspective. More than 53,000 employees serve over 130 markets in the two business units Human Pharma and Animal Health. Learn more at (global) or (for UK)

Boehringer Ingelheim has an innovative mental health pipeline focused on precision psychiatry approaches in indications of high unmet patient need. In pivotal trials, it includes a glycine transporter type-1 (GlyT1) inhibitor with iclepertin, addressing cognitive impairment associated with schizophrenia (CIAS) (NCT04846868, NCT04846881)15,16 and a prescription digital therapeutic (PDT), CT-155, for people experiencing negative symptoms of schizophrenia (NCT05838625 )17.

About Sosei Heptares
Sosei Heptares is a fully integrated biopharmaceutical company focused on bringing life-changing medicines based on world-class science to patients globally. Our vision is to become one of Japan’s global biopharmaceutical champions.

Our global business combines our world-leading GPCR-targeted StaR® technology, structure-based drug design and early development capabilities in the UK with a highly experienced clinical development capability and a commercial operation in Japan. We are leveraging these capabilities to generate and advance a broad and deep pipeline of novel medicines across multiple therapeutic areas, including neurology, immunology, gastroenterology and inflammatory diseases. We intend to develop these opportunities for patients in Japan and globally both internally and through our partnerships with global biopharmaceutical companies and emerging technology companies.

Sosei Heptares operates from key locations in Tokyo and Osaka (Japan), London and Cambridge (UK), Basel (Switzerland) and Seoul (South Korea).

“Sosei Heptares” is the corporate brand and trademark of Sosei Group Corporation, which is listed on the Tokyo Stock Exchange (ticker: 4565). Sosei, Heptares, the logo and StaR® are trademarks of Sosei Group companies.

For more information, please visit
LinkedIn: @soseiheptaresco | X: @soseiheptaresco | YouTube: @soseiheptaresco


For Boehringer Ingelheim
Reinhard Malin, Innovation Unit Comms, Corp. Affairs
+49 6132 77 90815 |,
Linda Ruckel, Innovation Unit Comms, Corp. Affairs
+1 (203) 791-6672 |,

For Sosei Heptares
Kentaro Tahara, VP Investor Relations and Corporate Strategy
Shinichiro Nishishita, VP Investor Relations, Head of Regulatory Disclosures
Maya Bennison, Communications Manager
+81 (0)3 5210 3399 | +44 (0)1223 949390 |

MEDiSTRAVA Consulting (for International Media)
Mark Swallow, Frazer Hall, Erica Hollingsworth
+44 (0)203 928 6900 |

Sosei Heptares Forward-looking statements
This press release contains forward-looking statements, including statements about the discovery, development, and commercialization of products. Various risks may cause Sosei Group Corporation’s actual results to differ materially from those expressed or implied by the forward-looking statements, including: adverse results in clinical development programs; failure to obtain patent protection for inventions; commercial limitations imposed by patents owned or controlled by third parties; dependence upon strategic alliance partners to develop and commercialize products and services; difficulties or delays in obtaining regulatory approvals to market products and services resulting from development efforts; the requirement for substantial funding to conduct research and development and to expand commercialization activities; and product initiatives by competitors. As a result of these factors, prospective investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.


1 Komatsu H et al., Anatomical Transcriptome of G Protein-Coupled Receptors Leads to the Identification of a Novel Therapeutic Candidate GPR52 for Psychiatric Disorders., PLoS One (2014), 9(2), e90134/1-e90134/16, 16 pp.,

2 Setoh m et al., Discovery of the First Potent and Orally Available Agonist of the Orphan G-Protein-Coupled Receptor 52., J. Med. Chem. 2014, 57, 12, 5226–5237, June 2, 2014,

3 Komatsu, H. Novel Therapeutic GPCRs for Psychiatric Disorders, Int. J. Mol. Sci. 2015, 16, 14109-14121; doi:

4 Dixon L What It Will Take to Make Coordinated Specialty Care Available to Anyone Experiencing Early Schizophrenia: Getting Over the Hump. JAMA Psychiatry. 2017;74(1):7–8. doi:10.1001/jamapsychiatry.2016.2665

5 Owen M et al., Schizophrenia. The Lancet. Volume 388, Issue 10039, 2–8 July 2016, Pages 86-97,

6 Roth RM et Al., Schizophrenia Research, Volume 98, Issues 1–3, January 2008, Pages 232-238,

7 Bleuler, M. Demential Praecox or the Group of Schizophrenias. (International Universities Press, New York, 1950).

8 Wang P et al., Discovery of Potent and Brain-Penetrant GPR52 Agonist that Suppresses Psychostimulant Behavior, J Med Chem. 2020 Nov 25; 63(22): 13951–13972,

9 Felsing et al., Structure Activity Relationships of Novel GPR52 Agonists that Suppress Psychostimulant Behavior, The FASEB Journal Volume 35, Issue S1,

10Press release - Sosei Heptares

11 Newcomer, J. W. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review CNS Drugs 2005, 19 (Suppl. 1) 1– 93.

12 Casey, D. E. Metabolic issues and cardiovascular disease in patients with psychiatric disorders Am. J. Med. 2005, 118 (Suppl. 2) 15S– 22S.

13 Taylor, D. M. Antipsychotics and QT prolongation Acta Psychiatr. Scand. 2003, 107, 85– 957Antipsychotics and QT prolongationTaylor, D. M.Acta Psychiatrica Scandinavica (2003), 107 (2), 85-95.





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