Built on 25 years of structural innovation to optimize potency, brain penetration, and selectivity
GSM-779690T
A next-generation GSM with best-in-class properties
Over 25 years, researchers evaluated hundreds of GSM analogues to optimize potency, selectivity, brain penetration and oral bioavailability.
Engineered with best-in-class properties, GSM-779690T is Acta’s lead investigational drug candidate.
Clinical stage
Advancing to phase 1 clinical trial
Modality
Oral small molecule
Design objective
Early intervention & long-duration disease modification
Mechanism of action
Selective gamma-secretase modulation
Strong scientific foundation
Decades of scientific research and innovation
25 years
Pioneering GSM research
GSM-779690T builds on research led by GSM inventors Dr. Rudolph E. Tanzi and the late Dr. Steven L. Wagner.
Collaborative Strength
Massachusetts General Hospital
Harvard Medical School
University of California, San Diego
Best-in-Class
High potency
Exceptional brain penetration
Once-daily oral candidate
Phase One Candidate
Built from approximately $70M in preclinical development
Mechanism of action
Designed to rebalance
amyloid-beta in the brain
GSMs intervene earlier in the disease process by reducing the production of toxic amyloid-beta 42 (Aβ42) before plaques form while promoting levels of the neuroprotective peptides, amyloid-beta 37 (Aβ37) and amyloid-beta 38 (Aβ38), which reduce plaque formation. Importantly, unlike earlier gamma-secretase inhibitors (GSIs), which broadly block the enzyme’s activity, GSMs selectively modulate gamma-secretase while preserving its normal biological functions. By restoring a healthier amyloid-beta balance, GSM-779690T could be both a treatment for Alzheimer’s disease and a potential preventive therapy for the millions who are at-risk for developing the disease.
Differentiated clinical profile
Potency
5.3 nM Aβ42 potency
Brain penetration
Approximately 1:1 brain-to-plasma ratio
Oral delivery
Orally bioavailable across multiple species
Highly selective modulation
Modulates gamma-secretase with no negative effect on alternative substrate processing at concentrations up to 20,000 micromolar (μM)
GSM-779690T rebalances amyloid-beta production
Aβ42 ↓
Aggregation-prone
Aβ38 ↑
Shorter peptide
Aβ37 ↑
Shorter peptide
Decreases levels of Aβ42 that drive plaque formation
Increases levels of Aβ37 and Aβ38 that interfere with plaque formation
Differentiated preclinical profile
Exceptional in-vitro and in-vivo potency
Potential for best-in-class
Single-digit nanomolar potency
Exceptional preclinical potency in-vitro translated to potent activity in-vivo
Near 1:1 brain-to-plasma ratio
Sustained brain penetration across all time points in a single-dose mouse model
Orally bioavailable
Excellent drug-like properties confirmed in multiple species
No detectable Notch inhibition
No inhibition of gamma-secretase essential functioning at concentrations up to 20,000 nM