In-house Programs

Our emerging pipeline of in-house programs comprises drug candidates advancing through various stages of early development and preclinical studies with a focus on core therapeutic areas including neurology, gastro-intestinal, inflammatory and other indications. Our plan is to advance only the highest quality programs from our proprietary pipeline to clinical development, with the intent to eventually commercialize selected products in designated markets ourselves.

PHASE 1b (voluntarily suspended)

Muscarinic M1 agonist

CANDIDATE: HTL0018318

INDICATION: Neurology diseases

MODALITY: Small molecule

WHOLLY-OWNED BY:


HTL0018318 is a first-in-class, selective small molecule muscarinic M1 receptor agonist in clinical development as a potential new symptomatic treatment of cognition in neurodegenerative disorders, principally Alzheimer’s disease. HTL0018318 works through the cholinergic pathway but has a different mechanism of action than available acetyl-cholinesterase inhibitors.

HTL0018318 was designed to be selective for M1 receptors and to avoid unwanted side effects and off-target binding seen with previous poorly selective muscarinic agonists, such as xanomeline.

HTL0018318 completed a Phase 1b patient study conducted and sponsored by us to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics as an adjunct to standard cholinesterase inhibitor therapy (donepezil) in patients with mild to moderate Alzheimer’s disease.

In September 2018, Sosei Heptares, together with AbbVie (formerly Allergan), decided to voluntarily suspend clinical development activities with HTL0018318 pending the investigation of an unexpected toxicology finding in an animal study involving non-human primates.

In January 2021, Sosei Heptares regained the worldwide rights to its muscarinic agonist programs.

 

+ Clinical Trials

+ Press Releases

PHASE 1

Muscarinic M4 agonist

CANDIDATE: HTL0016878

INDICATION: Schizophrenia / Alzheimer’s

MODALITY: Small molecule

WHOLLY-OWNED BY:


HTL0016878 is a first-in-class, selective and orally available, small molecule muscarinic M4 receptor agonist being advanced through clinical development as a potential new treatment for neurobehavioural symptoms associated with Alzheimer’s disease. HTL0016878 has been designed to work through a different mechanism of action than available antipsychotics. The high selectivity of HTL0016878 offers the possibility for an improved safety profile over previous non-selective muscarinic receptor agonists.

HTL0016878 is in a Phase 1 double-blind, randomized first-in-human clinical study being conducted in the U.K. by us and funded by AbbVie (formerly Allergan) to assess safety, tolerability and pharmacokinetics of single and multiple oral doses of HTL0016878 in healthy volunteers.

In January 2021, Sosei Heptares regained the worldwide rights to its muscarinic agonist programs.

 

+ Clinical Trials

+ Press Releases

PHASE1

SSTR agonist

INDICATION: Endocrine/Neuroendocrine disorders

MODALITY: Peptide

WHOLLY-OWNED BY:


Sosei Heptares group is advancing a novel somatostatin (SSTR) peptide agonist for the treatment of endocrine disorders. Preclinical studies of our agent to date  have demonstrated unique selectivity in comparison to approved drugs with the potential for improved side effect and pharmacokinetic profiles.

+ Publications

PHASE 2 (clinical development suspended)

Muscarinic M1 agonist (DLB)

CANDIDATE: HTL0018318

INDICATION: Dementia with Lewy Bodies (DLB)

MODALITY: Small molecule

WHOLLY-OWNED BY:


HTL0018318 is a first-in-class, selective, small molecule muscarinic M1 receptor agonist under clinical investigation as a potential new symptomatic treatment for cognitive impairment in patients with Alzheimer’s disease (AD) and other dementias, including dementia with Lewy bodies (DLB).

DLB is the second most common form of degenerative dementia after AD and relates to dementia associated with the presence of Lewy bodies (abnormal deposits of a protein called alpha-synuclein) in the brain that affect behaviour, cognition and movement. In DLB, loss of presynaptic cholinergic (acetylcholine-producing) neurons is thought to be a key driver of disease symptoms. As in AD, postsynaptic neurons and muscarinic receptors in DLB are preserved, which presents an important opportunity for a selective M1 agonist-based approach.

DLB affects up to an estimated 20-30% of all dementia patients. In Japan, this represents approximately 920,000 individuals, and in the U.S. approximately 1.4 million individuals. There are no approved therapies for DLB in the U.S. or Europe, while branded donepezil (Aricept®, Eisai) is conditionally approved in Japan.

Under an amendment to the original 2016 global R&D and commercialization partnership with Allergan, we gained a license to develop and promote HTL0018318 in Japan as a potential new treatment for patients with DLB. HTL0018318 was about to commence a Phase 2a clinical study in Japan, however in September 2018, we decided to voluntarily suspend clinical development activities with HTL0018318 pending the investigation of an unexpected toxicology finding.  A thorough investigation of these findings is still ongoing. While the Group remains committed to continuing its program in Japan focused on developing new therapies for dementia with Lewy bodies (“DLB”), it decided to withdraw the planned Phase 2 trial of HTL0018318 in DLB patients in Japan (NCT#03592862). Start-up activities for this DLB study were underway when development of the HTL0018318 compound was suspended in September 2018 and consequently, studies were put on hold. The Group expects a different clinical trial approach will be required in the future and has taken this decision to minimize unnecessary expenditure on clinical trial activities. The Group plans to resubmit a new clinical trial notification for HTL0018318 (or another novel M1 agonist) to the Japanese Pharmaceuticals and Medical Devices Agency (“PMDA”) in the future. 

+ Clinical Trials

+ Press Releases

Preclinical

GLP-1 antagonist

INDICATION: Endocrine diseases

MODALITY: Peptide

WHOLLY-OWNED BY:


Emerging In-House Programs

Preclinical

H4 antagonist

INDICATION: Atopic dermatitis

MODALITY: Small molecule

WHOLLY-OWNED BY:


Sosei Heptares is advancing a novel small molecule H4 receptor antagonist for the treatment of atopic dermatitis (AD). The H4 receptor is a clinically validated target in AD and pruritis (itch) and our preclinical studies to date with our leading candidate demonstrate efficacy in human primary immune cells and an excellent safety profile in early toxicology studies.

Preclinical

EP4 antagonist

INDICATION: Immuno-oncology

MODALITY: Small molecule

WHOLLY-OWNED BY:


Sosei Heptares is advancing a novel, highly selective and potent antagonist of the EP4 receptor to mediate PGE2 immunosuppression in the tumor microenvironment within oncology. 

Preclinical

GLP-2 agonist

INDICATION: Intestinal failure

MODALITY: Peptide

WHOLLY-OWNED BY:


Sosei Heptares is advancing a potent glucagon-like peptide-2 (GLP-2) agonist for the treatment of intestinal disorders. GLP-2 is a clinically validated target involved in pathways that stimulate mucosal growth, improve intestinal permeability, nutrient absorption and mesenteric blood flow.

Preclinical

GPR52 agonist

INDICATION: Neurology diseases

MODALITY: Small molecule

WHOLLY-OWNED BY:


Sosei Heptares is advancing a GPR52 agonist as a potential therapy to address positive symptoms, negative symptoms and cognitive impairment in schizophrenia and other psychosis disorders, without adverse effects typically associated with antipsychotics.

Preclinical

PAR2 mAb

INDICATION: Atopic dermatitis

MODALITY: Monoclonal antibody

WHOLLY-OWNED BY:


Arising from its alliance with MorphoSys, Sosei Heptares is progressing a PAR-2-neutralizing mAb for the treatment of atopic dermatitis where reductions in pruritus (itch) and inflammation and normalization in skin barrier function are predicted. Strong literature data demonstrates that PAR-2 neutralization is also likely to be beneficial in a wide variety of disease situations including inflammatory bowel disease, pain (acute or chronic, itch, neuropathic, cancer, inflammatory, migraine), asthma.

Pre-discovery and Discovery Programs

We are advancing multiple additional In-House Programs through Pre-Discovery and Discovery.