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NIA Small Business Showcase: Allyx Therapeutics, Inc.

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Alzheimer’s disease (AD) is a critical unmet need, as there remain no conclusive disease-modifying treatments available to slow disease progression. Synapse dysfunction and loss is the key cellular pathology that drives neuronal connectivity failure and cognitive decline during the stages of mild cognitive impairment (MCI) and early AD. Synapse dysfunction and loss is initially triggered and further accelerated by the overlapping molecular hallmarks of disease, including amyloid beta, tau, and immune mediators.

Allyx Therapeutics, Inc. logo

ALX-001 (BMS-984923) is an orally bioavailable small molecule that acts as a silent allosteric modulator of metabotropic glutamate receptor 5 (mGluR5). The cellular prion protein (PrPC) and mGluR5 synaptic receptor complex resides at the nexus of these multiple molecular pathologies and triggers an intracellular synaptic cascade, resulting in dysfunction and loss. ALX-001 selectively blocks this pathological activation of synapse damage via direct inhibition of amyloid beta oligomer toxicity, reducing intracellular tau hyperphosphorylation and preventing complement component 1q (C1q) recruitment to reduce microglial mediated synaptic pruning.

In the United States, 6 million patients are currently suffering from AD. Small-molecule drugs aimed at masking symptoms of AD that do nothing to slow progression reached peak worldwide revenues of more than $4 billion.

ALX-001 is a silent allosteric modulator of mGluR5 that selectively blocks the pathogenic activation of the receptor while preserving the physiological glutamate signaling that is required for normal cognition. As such, ALX-001 has a wide therapeutic window that can saturate the receptor without causing on-target toxicity and cognitive impairment. This program is thus differentiated from other mGluR5 programs, which primarily aim to develop negative allosteric modulators. In addition, this compound acts downstream of multiple disease hallmarks of AD by intervening directly at the synapse with a target present in physiological concentrations and druggable with an orally bioavailable small molecule.

Company Milestones


  • First quarter (Q1) 2021: Activation of an investigational new drug (IND) with the U.S. Food and Drug Administration (FDA)
  • Q1 2021: First-in-human dose upon launch of a Phase 1a single ascending dose (SAD) study
  • Q2 2022: Top-line results from the Phase 1a study
  • Q3 2022: Initiation of the Phase 1b study


  • Q2 2019: Closing of pre-seed financing
  • Q1 2021: Completion of the in-licensing agreement of the mGluR5 program from Bristol Myers Squibb and Yale University
  • Q2 2021: Closing of Series A financing

Financial Overview

Allyx Therapeutics, Inc. raised $7.6 million in Series A funding led by Bristol Myers Squibb, Elm Street Ventures, and Spring Mountain Capital. Additional investors include Harrington Discovery Institute, Life Science Angels, and Connecticut Innovations. Pre-clinical development and early clinical development were funded though non-dilutive grants from NIA. In addition, Allyx has received NIA Small Business Innovation Research (SBIR) funding to develop an anti-PrPC monoclonal antibody, which is currently in the IND-enabling stage.

Intellectual Property

Allyx’s lead candidate, ALX-001, retains a robust package of composition of matter and method of use protection.

Product Development and Regulatory Strategy

ALX-001 possesses an active IND with the FDA and is currently under evaluation in a Phase 1a SAD safety study in aged healthy volunteers. Not only does this study provide insight into safety, tolerability, and pharmacokinetics, but it includes a radioligand displacement sub-study to directly measure receptor occupancy at escalating doses. Upon completion of this study, ALX-001 will be evaluated in a Phase 1b study that will first look at 10-day repeat dose safety in aged healthy volunteers, then a 28-day repeat dose safety study in patients with AD to confirm safety, tolerability, and target engagement at the predicted efficacious dose. Upon confirming safety and tolerability at the steady state, Allyx will pursue a 12-month proof-of-concept study to evaluate the effect of ALX-001 treatment on synaptic biomarkers and cognition.

Commercialization Strategy

The goal of Allyx is to progress ALX-001 through a Phase 2a study to establish mechanistic proof of concept by leveraging biomarkers to demonstrate synapse preservation. The company believes that the result of this study will be a key gating factor for completing a partnership or out-licensing agreement. Allyx intends to identify a partner or licensee with capabilities for running the larger Phase 2 and Phase 3 study aimed at securing accelerated approval with the FDA.

Company Details

Allyx Therapeutics website

New Haven, CT

Industry: Therapeutics

Management Team:

  • Chief Executive Officer: Stephen Bloch, M.D.
  • Chief Operating Officer: Timothy Siegert, Ph.D.

Point of Contact:
Timothy Siegert, Ph.D.
Email Timothy Siegert
(908) 432-2845

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