Our programs pair innovative therapeutics with Modular Delivery (MODEL) platform Delivery Modules to increase their exposure to CNS targets. We also pursue programs that leverage established mechanisms of action to enable more efficacious and/or convenient therapeutics for patients.
Our current lead candidate, ALIA-1758, is an anti-pyroglutamate amyloid beta (3pE-Aβ) antibody in-licensed from Janssen with an approved IND and expected Phase 1 clinical trial initiation in Q2 of 2024. Aliada is also pursuing programs in other neurological disorders.
ALIA-1758
Aliada’s ALIA-1758 has the potential to be a best-in-class therapy for the treatment of patients with Alzheimer’s disease (AD).
MODEL platform-enabled by Aliada to harness transport via TfR, ALIA-1758’s strong target binder properties and improved CNS delivery offers the potential to achieve robust reduction of brain amyloid burden at lower dosage levels than other antibodies in this class. Consequently, a convenient monthly subcutaneous low-dose regimen could improve access to therapy for more patients with AD.
A high-value program in its own right, ALIA-1758’s advancement also provides an opportunity to establish clinical proof-of-principle for the MODEL platform.
High-affinity 3pE-Aβ binders enable lower predicted efficacious dosage levels compared to competitors, and target the plaque form of Aβ rather than earlier stages of aggregation.
An optimized Fc domain increases half-life, reduces effector function and leads to clearance of bound antibodies through a mechanism that reduces pro-inflammatory cytokine release and immune exhaustion (see "Novel antibody clearance mechanism" below).
The anti-TfR Delivery Module transports 3pE-Aβ antibodies into the brain at a higher concentration than naked antibodies, leading to more efficient target clearance. The proprietary scFv design also confers increased stability, reduced aggregation and lower manufacturing cost.
Novel antibody clearance mechanism
When transporting a therapeutic antibody cargo such as ALIA-1758, MODEL utilizes an optimized Fc domain that prevents clearance by traditional immune activation pathways. Clearance is instead accomplished through lysosomal destruction via a process known as non-classical phagocytosis. Preclinical data suggest that this unique clearance pathway results in lower levels of cytokine release and other inflammatory markers; in addition to the lower projected human efficacious dose and potential for subcutaneous dosing, a differentiated inflammatory profile may provide a further beneficial clinical profile relative to currently approved and clinical stage amyloid-targeting antibodies.
Future Directions
Aliada is advancing wholly-owned programs in therapeutic areas that offer the potential to leverage the versatility of our MODEL platform. We have selected targets and are conducting discovery in several areas, and expect to share more information as these programs progress.
Partner Programs
We are excited to partner with Chiesi Global Rare Diseases on a co-development research collaboration to develop improved therapeutics for patients living with lysosomal storage disorders who currently lack treatments that can readily access the brain. This partnership focuses on multiple enzyme cargoes modified with our MODEL platform through in vivo studies that will test Delivery Modules harnessing transferrin and CD98 receptors.
Aliada is passionate about collaborating in future development projects involving delivery of a wide range of modalities including antibodies, RNA therapeutics, enzymes and other therapeutic cargoes. Please contact our team if you are interested in exploring a partnership.
