AL009 – multi-SIGLEC – Oncology

AL009 is a first-in-class multi Siglec inhibitor that works to enhance both the innate and adaptive immune system response to tumors by blocking a critical glycan checkpoint pathway that drives immune inhibition. This product candidate is being developed in oncology and could also have potential therapeutic application for neurodegenerative disorders.

AL008 SIRP-alpha – Oncology

AL008 is a novel immuno-oncology antibody aimed at activating the innate immune system. AL008 works through a unique dual mechanism: it targets the CD47-SIRP-alpha pathway, a potent survival pathway co-opted by tumors to evade the innate immune system, to relieve immune suppression, while also engaging Fc gamma, an activating receptor to promote immune-stimulatory pathways that drive anti-tumor immunity. 

AL008 is being developed in China by Innovent.

AL044 – MS4A – Alzheimer’s disease

AL044 targets MS4A, a major risk gene for Alzheimer’s disease that encodes a transmembrane receptor protein that is expressed selectively in microglia in the brain and is associated with control of microglia functionality and potential viability. AL044 was designed to counteract the risk variants of MS4A4A and to functionally convert the risk variants of MS4A4A to the protective variant.

AL003 – SIGLEC 3 – Alzheimer’s disease

AL003 focuses on modulating check-point receptors on the brain’s immune cells, targeting sialic acid binding Ig-like lectin 3 (SIGLEC 3), a genetic risk factor for Alzheimer’s disease. SIGLEC 3 is an inhibitory receptor expressed primarily on cells of myeloid lineage including microglia. AL003 is intended to bock the function of SIGLEC3 to increase the activity of the microglia. The Phase 1b study of AL003 in 12 Alzheimer’s disease patients is intended to assess the safety and tolerability of multiple doses of AL003.

AL003 is being developed in collaboration with AbbVie.

AL002 – TREM2 – Alzheimer’s disease

Research suggests that reduction of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) functionality may lead to Alzheimer’s disease and other forms of dementia. AL002 is intended to counteract this decreased functionality by optimizing TREM2 signaling to improve microglia activity. The randomized, controlled Phase 2 study, INVOKE-2, in patients with early Alzheimer’s disease, will enroll approximately 265 participants and assess AL002’s impact on disease progression, as well as changes in multiple fluid and imaging biomarkers. AL002 is being developed in collaboration with AbbVie.

AL101 – PGRN – Neurodegenerative diseases

AL101 is designed to increase progranulin levels for the treatment of more prevalent neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Mutations that moderately reduce the expression levels of PGRN have been shown to increase the risk of developing Alzheimer’s disease and Parkinson’s disease, and increased PGRN levels have been demonstrated to be protective for these diseases in animal models. 

AL101 is currently being studied in a Phase 1 clinical trial of healthy volunteers designed to assess safety, tolerability and pharmacokinetics and pharmacodynamics. AL101 is being developed in collaboration with GSK.

AL001 – Amyotrophic lateral sclerosis with a C9orf72 mutation – Phase 2

We are conducting a randomized, controlled Phase 2 clinical study of AL001 in people with amyotrophic lateral sclerosis (ALS) who carry a C9orf72 mutation. 

Excess aggregation of TDP-43 in brain cells is thought to lead to neuronal cell death and is associated with multiple neurodegenerative diseases. Increasing progranulin levels has been shown to reverse and be protective against TDP-43 pathology in multiple models of neurodegeneration, including ALS, where 95% of patients with ALS have TDP-43 pathology.

ALS is the first of several potential indications beyond frontotemporal dementia where we believe AL001 may have a positive impact on brain health by elevating progranulin levels.

AL001 – Frontotemporal dementia with a C9orf72 mutation – Phase 2

utation (FTD-C9orf).  FTD-C9orf72 is associated with abnormal accumulation of the protein TDP-43, which is also a hallmark in FTD. The Phase 2 study, which also includes a cohort of patients with progranulin mutations (FTD-GRN) was designed to assess the safety and tolerability of chronic dosing of AL001 and is also measuring biomarkers of disease and potential clinical activity.

AL001 – Frontotemporal dementia with a progranulin mutation – Phase 3

AL001 modulates progranulin (PGRN), a key regulator of immune activity in the brain with genetic links to multiple neurodegenerative disorders. We are initially developing AL001 for frontotemporal dementia (FTD) with progranulin mutation (FTD-GRN). The global INFRONT-3 Phase 3 clinical trial is currently enrolling both at-risk and symptomatic participants with FTD-GRN

AL001 is being developed in collaboration with GSK.

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