Today, Vigil Neuroscience announced that it had failed to achieve positive results from the phase 2 IGNITE open-label trial. This specific study was evaluating the use of the fully human monoclonal antibody TREM2 agonist for the treatment of patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). This specific rare neurological disorder is characterized by white matter of the brain wasting away, which in turn causes the formation of lesions on a person’s brain. Consider that the cause for ALSP is a mutation of the CSF1R gene that occurs. In turn, such a mutation leads to microglial dysfunction. The hope is that with TREM2 and CSF1R signaling pathways having the same signaling as DAP12/SYK, iluzanebart could increase signaling of this pathway to make up for the loss of CSF1R and mitigate as much microglial dysfunction as possible.
Unfortunately, this theory of using the fully human monoclonal antibody TREM2 agonist iluzanebart to treat this rare neurological disorder didn’t pan out as expected. Not much was released in the way of clinical data, just the company noting that there was no positive impact on biomarker or efficacy endpoints to warrant further investigation of it. It also noted that it would discontinue the phase 2 long-term extension study as well (previously noted beforehand). There was a positive item in the press release, but it was primarily with respect to safety and tolerability. It was revealed that both the 20 mg/kg and 40 mg/kg dose cohorts were favorable.
The negative is that this program is no longer in place, and there can be no shareholder value generated from the development of iluzanebart for ALSP. On the flip side, this means nothing in terms of the deal that Vigil had made with big pharma Sanofi back on May 21st of 2025, which is that it agreed to be acquired for $470 million. In essence, shareholders of Vigil would receive up to $10.00 per share in cash. This is to be broken down in terms of $8.00 per share in cash upon closing of this acquisition and then a non-tradeable contingent value right (CVR) of $2.00 per share in cash following the first commercial sale of VG-3927. This leads me to the next point, which is that the acquisition was solely because of the oral small molecule TREM2 agonist VG-3927. It had nothing at all to do with Iluzanebart in the slightest.
With that being said, the acquisition is expected to close in Q3 of 2025. As far as iluzanebart goes, with the buyout in play, Vigil agreed to hand the rights of this drug back to Amgen. It is not clear when this drug will be handed back to this other big pharma, but it should happen slightly before Sanofi completes its acquisition of Vigil. It remains to be seen if a small molecule TREM2 agonist such as VG-3927 can be successful in treating patients with Alzheimer’s disease (AD). However, it is a phase 2-ready clinical drug in the targeting of these patients, and Sanofi appears to be on board in testing it out, considering it chose to acquire Vigil for it.
The hope was that its drug could be used to activate TREM2 in immune brain cells (microglia) found in these patients. The mode of action was not to directly target the C1FR dysfunction found in ALSP but instead to indirectly affect it. That is, TREM2 activation was to lead to cells having a resistant nature to being tampered with, controlling the amount of inflammation present, and lastly, reducing the amount of cell death happening in these patients. Unfortunately, this mechanism of action (MOA) was not proven.