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 2 (voluntarily 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.

+ Clinical Trials
- NCT02958696: Relative Bioavailability of HTL0018318 Oral Aqueous Solution Versus Capsules
- NCT03592862: A Study to Assess Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies (DLB) 
- NCT03198624: Pharmacokinetics of Oral Capsule in Healthy Japanese vs. Caucasian Subjects (HTL0018318)
- NCT03456349: Multi-centre Study of HTL0018318 in Patients as an add-on to Standard-of-care

+ Press Releases
- 18 Sep: Sosei Provides Update on HTL0018318
- 9 Nov 2017: Sosei to Advance Clinical Development in Japan of HTL0018318 in Patients with Dementia with Lewy Bodies (DLB) 

 

PHASE1

mGlu5 NAM

CANDIDATE: HTL0014242

INDICATION: Neurology Indications

MODALITY: Small molecule

WHOLLY-OWNED BY:


HTL0014242 is a potent and selective mGlu5 small molecule negative-allosteric modulator (NAM) discovered by us as a potential treatment for certain neurological orders. Preclinical studies of our agent to date offer significantly increased potency over the most advanced clinical agent, with an encouraging profile for an orally delivered drug.

+ Publications
- 30 Jul 2015: Fragment and Structure-Based Drug Discovery for a Class C GPCR: Discovery of the mGlu5 negative allosteric modulator HTL14242 (3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile)
- 1 Feb 2015: Structures of mGluRs shed light on the challenges of drug development of allosteric modulators
- 31 Jul 2014: Structure of class C GPCR metabotropic glutamate receptor 5 transmembrane domain

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

- 20 Feb 2019: Sosei Heptares starts new clinical development program - First subject dosed in Phase I study of HTL0030310, a selective SSTR5 (somatostatin 5) receptor agonist in development to treat endocrine disorders

Preclinical

CGRP antagonist

CANDIDATE: HTL0022562

INDICATION: Migraine

MODALITY: Small molecule

WHOLLY-OWNED BY:


Preclinical

GLP-1 antagonist

INDICATION: Metabolic diseases

MODALITY: Peptide

WHOLLY-OWNED BY:


Sosei Heptares group is developing a potent glucagon-like peptide-1 (GLP-1) antagonist for the treatment of severe hypoglycaemia in rare diseases, which are associated with poor clinical outcomes including long-term nerve and brain damage.

+ Press Releases
- 25 Apr 2016: Sosei Subsidiary Heptares Scientists Solve Structures of GLP-1 and Glucagon Receptors Enabling Structure-Based Design for Metabolic Disease

+ Publications
- 8 Jun 2017: Crystal structure of the GLP-1 receptor bound to a peptide agonist

Preclinical

GLP-2 agonist

INDICATION: Intestinal failure

MODALITY: Peptide

WHOLLY-OWNED BY:


Sosei Heptares is developing 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.

Early Discovery Targets

Discovery

OX-1 antagonist

INDICATION: Cocaine-use disorders

MODALITY: Small molecule

WHOLLY-OWNED BY:


Sosei Heptares, supported by the National Institute on Drug Abuse of the National Institutes of Health under award number R01DA039553, are developing selective orexin 1 receptor (OX1R) antagonists for the treatment of cocaine-use disorders. This is an area of high unmet need, as currently there are no FDA or EMA-approved medications for the treatment of cocaine-use disorders.

+ Press Releases
- 28 Sept 2015: Sosei Heptares awarded $5.5 million Research & Development Grant from the US National Institute on Drug Abuse

Discovery

Apelin agonist

INDICATION: Pulmonary Arterial Hypertension

MODALITY: Peptide

WHOLLY-OWNED BY:


Sosei Heptares is developing a novel apelin receptor (APLNR) peptide agonist for the treatment pulmonary arterial hypertension (PAH), a serious medical condition of increased blood pressure within the arteries of the lungs leading to heart failure and ultimately death.

Discovery

GPR35 agonist

INDICATION: Inflammatory bowel disease

MODALITY: Small molecule

WHOLLY-OWNED BY:


Sosei Heptares is developing a novel GPR35 selective agonist for the treatment of inflammatory bowel disease, a chronic gastrointestinal disease with high unmet needs. The agent displays minimal systemic exposure and is aimed to act locally in the inflamed gut.

Discovery

EP4 agonist

INDICATION: Inflammatory bowel disease

MODALITY: Small molecule

WHOLLY-OWNED BY:


Sosei Heptares is developing a novel EP4 selective agonist for the treatment of inflammatory bowel disease. The agent displays minimal systemic exposure and is aimed to act locally in the gut to effectively suppress inflammation.

Discovery

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.

Discovery

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 through discovery 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.