First-in-class TDP-43 antibody developed using SurpraAntigen™ platform
The only TDP-43 antibody with reported in vivo activity
Advancing the anti-TDP-43 antibody towards clinical development is the latest in a series of important milestones already achieved this year in the Company’s cutting-edge therapeutic and diagnostic programs targeting TDP-43 – which are amongst the most comprehensive in the field. TDP-43 pathology is strongly associated with cognitive decline and episodic memory loss in neurodegenerative diseases. Effectively slowing or stopping the spread of TDP-43 pathology throughout the brain could provide the first TDP-43 targeted therapeutic approach for treating conditions such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), where almost half of all FTLD cases exhibit TDP-43 pathology with significant market potential for AC Immune’s TDP-43 antibody. Other indications include limbic-predominant age-related TDP-43 encephalopathy (LATE), and sub-populations of argyrophilic grain disease and Lewy Body Dementia.
Additionally, pathological aggregation of TDP-43 has emerged as an important co-pathology in Alzheimer’s disease linked to disease severity and occurring in ~50% of patients. Recognition that neurodegenerative diseases are driven by a complex interplay of pathologies highlights that successful treatments and cures will likely require combination therapy powered by precision medicine. This diversified approach is pioneered by
“The Company’s success is driven in part by our proprietary SupraAntigen™ platform, which has already produced therapeutic monoclonal antibody candidates targeting Abeta and Tau that were successfully out-licensed to leading pharmaceutical companies and are currently advancing in multiple Phase 2 clinical studies. Advancement of the anti-TDP-43 antibody further validates the continuing productivity of this platform, which, together with our Morphomer™ platform for small molecule development, are responsible for discovery and development of our maturing pipeline of first-in-class or best-in-class therapeutic and diagnostic candidates.”
TDP-43 is an RNA/DNA-binding protein that functions primarily in the nucleus as a regulator of gene transcription and RNA metabolism. TDP-43 pathology has been shown to start from a focal point in the brain and spread to other brain regions with disease progression. Antibody-mediated clearance of pathological TDP-43 therefore represents an attractive strategy for therapeutic intervention – potentially slowing the spread by blocking the ability of pathological TDP-43 to seed aggregation in neighboring healthy cells. The anti-TDP-43 antibody binds all forms of TDP-43 with high affinity and is the only antibody with reported in vivo activity. Proof-of-concept data presented at the 2020 AAT-AD/PD™ Conference demonstrated anti-TDP-43 antibody’s ability to mitigate TDP-43 neuropathology in a mouse model of TDP-43 proteinopathies.
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Source: AC Immune SA