Pipeline

Therapies in development

Our research and development teams aim to target the underlying mechanisms of brain disease. We move together towards a singular goal to deliver novel therapies that redefine the standard of care for patients and address the areas in brain disease where we see the greatest need.

Hormonal / neuropeptide signaling


Project	Area
Eptinezumab (anti-CGRP mAb)¹	Migraine prevention²	Filing
Mode of Action Eptinezumab is a monoclonal immunoglobulin G1 (IgG1) antibody that binds to human calcitonin gene-related peptide (CGRP) with high specificity and high affinity for the CGRP α- and β-form. CGRP is a signaling molecule in the pathophysiology of migraine and cluster headache. *Three phase III clinical trials (SUNLIGHT, SUNRISE, and SUNSET) are related to the Asia registration activities.
Eptinezumab (anti-CGRP mAb)¹	Cluster headache	3
Mode of Action Eptinezumab is a monoclonal immunoglobulin G1 (IgG1) antibody that binds to human calcitonin gene-related peptide (CGRP) with high specificity and high affinity for the CGRP α- and β-form. CGRP is a signaling molecule in the pathophysiology of migraine and cluster headache.
Lu AG09222 (anti-PACAP mAb)³	Migraine prevention²	2
Mode of Action Lu AG09222 is an investigational monoclonal antibody designed to bind and inhibit signaling mediated by pituitary adenylate cyclase-activating polypeptide (PACAP); a neuropeptide that is implicated in migraine pathophysiology.
Lu AG13909 (anti-ACTH mAb)⁴	Neurohormonal dysfunctions	1
Mode of Action Lu AG13909 is a humanized anti-adrenocorticotropic hormone (anti-ACTH) monoclonal antibody that blocks the binding of ACTH to the melanocortin 2 receptor in the adrenal glands, thereby decreasing the neurohormonal signaling of ACTH.

Circuitry / neuronal biology


Project	Area
Brexpiprazole⁵	PTSD⁶	Filing
Mode of Action Brexpiprazole is a small molecule and a potent serotonin–dopamine activity modulator. It acts as a partial agonist at serotonin 5-HT1A and dopamine D2 receptors, and as an antagonist at serotonin 5-HT2A and noradrenaline α1B/α2C receptors. The serotonergic, dopaminergic, and especially the noradrenergic systems are believed to be involved in PTSD (post-traumatic stress disorder) symptomatology with re-experiencing, Negative cognition and mood, Avoidance and Arousal. *Life cycle management. In partnership with Otsuka Pharmaceutical Development & Commercialization, Inc.
Lu AF28996 (D1-D2 agonist)⁷	Parkinson's disease	1
Mode of Action Lu AF28996 is a small molecule with agonistic properties towards D1 and D2 receptors. Concerted D1 and D2 dopamine receptor stimulation may play an important role in motor control of Parkinson’s disease patients.
MAGLi programs⁸	Neurology	1
Mode of Action The MAGL inhibitor programs consists of several small molecules and highly selective inhibitors of monoacylglycerol lipase (MAGL), the primary enzyme responsible for the degradation of the endocannabinoid ligand 2-arachidonoylglycerol (2-AG). Enhancing the actions of 2-AG on CB1 and CB2 receptors may restore altered neuronal transmission and decrease neuroinflammation and thereby it may produce beneficial effects across a range of symptoms and related indications within Neurology.

Protein aggregation, folding and clearance


Project	Area	Phase 1	Phase 2	Phase 3
Lu AF82422 (anti-alpha-synuclein mAb)	Synucleinopathies (MSA)				2
Mode of Action Lu AF82422 is a monoclonal antibody (mAb) targeting alpha-synuclein. Misfolding, aggregation and extracellular spreading of alpha-synuclein is believed to play a major role in disease pathology and progression in Multiple System Atrophy (MSA), Parkinson’s disease and other neurodegenerative disorders.

Neuroinflammation / Neuroimmunology


Project	Area	Phase 1	Phase 2	Phase 3
Lu AG22515 (CD40L blocker)⁹	Neurology				1
Mode of Action Lu AG22515 is a CD40L blocker, which interferes with the activation of the adaptive immune response by inhibiting the CD40L/CD40 co-stimulatory interaction on immune cells; an interaction, which plays a role in the pathophysiology of several immune-mediated diseases. * CD40L/serum-albumin bispecific antibody-fragment ((scFv)2-Fab)) based on AprilBio’s SAFA™ technology platform.

CGRP: Calcitonin gene-related peptide;
Two phase III clinical trials, supporting registration in Asia, including China and Japan: SUNRISE, and SUNSET trials.
PACAP: Pituitary adenylate cyclase activating peptide;
ACTH: Adrenocorticotropic hormone. Two phase Ib trials are currently ongoing in Congenital Adrenal Hyperplasia and Cushing’s Disease. For technical reasons, the latter has been officially categorized as a Phase II trial to adhere to local requirements in Georgia;
Acts as a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors;
Post-traumatic stress disorder;
Dopamine receptor D1 and D2;
MAGLi: Monoacylglycerol lipase (“MAGlipase”) inhibitor;
Ph1b trial ongoing in TED (Thyroid Eye Disease)