NSC - Therapeutics GmBH

NSC-Therapeutics GmbH

is a semi-virtual drug development company based in St. Radegund/ Graz, Austria, specializing in therapies for Alzheimer's disease and related disorders. Their lead compound is NSC001 (also known as AF267B), a rigid, orthosteric, and highly specific muscarinic M1 receptor agonist. This compound is exclusively licensed from the Life Sciences Research Israel (LSRI). The company operates in close proximity to NeuroScios, a contract research organization with nearly 30 years of experience in organizing clinical trials for neurodegenerative and cerebrovascular disorders.

NSC-Therapeutics is led by Dr. Manfred Windisch, who brings 40 years of experience in preclinical and clinical research on Alzheimer's disease. He is supported by Dr. Abraham Fisher, the medicinal chemist who invented NSC001 and several other related M1 agonists. Preclinical studies have demonstrated that NSC001 effectively targets key AD hallmarks, including cognitive deficits, β-amyloid and tau pathologies, and α-synuclein aggregates. NSC001 also prevents neurotoxic aggregates by promoting shedding of cellular prion protein (PrPc). and modulates microglial function and neuroinflammatory responses through TREM2 ectodomain shedding. These combined effects position NSC001 as a potential multi-modal therapy for AD and related disorders. NSC001 represents a promising therapeutic candidate for AD and related neurodegenerative conditions, offering both rapid cognitive enhancement and long-term disease-modifying effects through precise modulation of the M1 mAChR. Its favorable safety profile, demonstrated in Phase 1 trials, and its multi-faceted mechanism of action position it uniquely among muscarinic agonists and M1 positive modulators, with potential efficacy across various stages of AD progression. In 2024, NSC-Therapeutics received $5 million in funding from the Alzheimer's Drug Discovery Foundation to support upcoming Phase 2 proof-of-concept clinical trials for NSC001 in patients with mild to moderate Alzheimer's disease.”

The Leading Company In Development Of Muscarinic Agonists

FAST COGNITIVE IMPROVEMENT

AND LONG TERM

DISEASE MODIFICATION:

1. Increase in alpha-Secretase activity

2. Inhibition of GSK3-beta

3. Modulation of TREM-2

4. Outstanding safety and tolerability

HIGH SELECTIVITY FOR M1-RECEPTOR
EXCELLENT ORAL BIOAVAILIBILITY
HIGH BBB PENETRATION
ABSOLUTE LINEAR PK

NSC001

A highly selective M1 muscarinic acetylcholine receptor agonist

NSC001, also known as AF267B, is a rigid, orthosteric, and highly specific muscarinic M1 receptor agonist developed by NSC-Therapeutics GmbH for the treatment of Alzheimer's disease (AD) and related neurodegenerative disorders. The compound is designed to address cognitive deficits and modify disease pathology by precisely modulating the M1 muscarinic acetylcholine receptor (mAChR).

Mechanism of Action

An extremely early event in the pathogenesis of AD is the selective degeneration of basal forebrain cholinergic nuclei leading to a deficit in acetylcholine while post-synaptic M1 muscarinic receptors (M1 mAChR) are preserved. The M1 mAChR is a fundamental player in learning and memory and a primary drug target for the treatment of memory deficits, psychosis, and disease-modifying therapy. Thus the activation of M1 mAChR is a validated therapeutic target for addressing cognitive dysfunction in both schizophrenia and Alzheimer's disease (AD), as this receptor plays a critical role in regulating cognitive deficits and disease progression. Activation of M1 mAChRs by NSC001 can:

Enhance cognitive function by stimulating cholinergic activity.
Shift amyloid precursor protein (APP) processing towards non-amyloidogenic pathways, reducing β-amyloid production.
Inhibit tau hyperphosphorylation by modulating kinases such as GSK3β.
Prevent neurotoxic aggregates by promoting shedding of cellular prion protein (PrPc).
Modulate microglial function and neuroinflammatory responses through TREM2 ectodomain shedding.
Inhibit α-synuclein oligomer aggregation.

These combined effects position NSC001 as a potential multi-modal therapy for AD and related disorders.

Clinical Studies

Safety Profile

NSC001 was already tested in 5 differnt Phase 1 Trials. So far it was well tolarated and showed a good safety profile.

Manfred Windisch, PhD

CEO and President

Manfred Windisch is CEO of NSC-Therapeutics GmbH, he founded in 2013, specialized in drug development for neurological indications, focusing on Alzheimer's disease and related disorders

He earned his PhD degree in Physiology and Biochemistry from the University of Graz, Austria, 1985. He spent several years heading a neurobiology group at the University with research in the field of brain metabolism and animal model development. He was involved for many years in research programs in Europe, North America, and Asia. He established a global network of research collaborations and stimulated scientific information exchange. 1999, he founded his first own CRO, JSW-Lifesciences, where he created transgenic and induced rodent models of neurodegenerative diseases and used these models in 60–80 pharmacological studies each year, allowing to define experimental standards to increase predictive value in preclinical drug testing.

He initiated also a clinical research group and was involved in studies in AD, MCI, PD, amyotrophic lateral sclerosis, and cerebrovascular diseases, organizing about 47 international trials from Phase 1 to Phase 3, including complex designs using state-of-the-art imaging and CSF biomarkers.

He was involved in a manyfold of important drug development programs for Alzheimer's disease, in almost all relevant therapeutic areas,

Since 2007 he has been one of the executive organizers of the prestigious AD-PD conference.

2017 he founded NSC Therapeutics, to develop NSC001, a highly specific M1-muscarinic agonist for treatment of Alzheimer's disease.

Abraham Fisher, PhD

Chief Scientific officer

Professor Abraham Fisher is a renowned scientist and artist with a distinguished career in the fields of Alzheimer's Disease (AD) and Parkinson’s Disease (PD). He is the Co-Founder and President of the groundbreaking series of International Conferences on Alzheimer’s and Parkinson’s Diseases and related neurological disorders (AD/PD™), hosted by Kenes Group. His extensive academic background includes a Ph.D. in Medicinal Chemistry from Tel Aviv University, an M.Sc. in Organic Chemistry, and a B.Sc. in Chemistry from the Hebrew University of Jerusalem.

With over 45 years of drug design and discovery expertise, Prof. Fisher is a trailblazer in advancing cholinergic treatments for CNS diseases. He has published over 170 peer-reviewed papers and book chapters and edited several key texts on AD and PD. His scientific achievements include leading complex, multicenter R&D projects and inventing over 25 global patents. He has been instrumental in developing novel treatments targeting selective M1 muscarinic receptor agonists, emphasizing their therapeutic potential for AD and PD.

Prof. Fisher’s groundbreaking work includes the creation of the “AF series” of selective M1 agonists:

AF102B (Cevimeline, EVOXACTM): The first M1-selective muscarinic agonist, FDA-approved in 2000 and approved in Japan in 2001, for treating dry mouth in Sjögren’s Syndrome.
AF267B (NSC001): A highly selective M1 receptor partial agonist under investigation for cognitive enhancement in AD and other related disorders.

His work has profoundly influenced innovative therapeutic strategies, focusing on selective receptor modulation and novel pathways in treating complex CNS disorders. Beyond his scientific contributions, Prof. Fisher is also a painter, exemplifying his versatile talents and creativity.