Vigil Neuroscience is a biotechnology company focused on developing precision-based therapies targeting microglia dysfunction to treat rare and common neurodegenerative diseases.
Why did Vigil Neuroscience choose to focus on rare diseases, particularly adult-onset leukoencephalopathy (ALSP)?
We decided to focus on ALSP because it aligns with our dual approach: targeting microglia and using a precision-based strategy for neurodegeneration. This approach mirrors the advancements seen in oncology, where genetic precision has revolutionized therapies. Neuro-inflammation, particularly in the central nervous system, represents a frontier in drug discovery, and our focus on microglia—a key component of the brain's immune system—allows us to target diseases with strong genetic and mechanistic associations. Microglia act as the brain's "cleaning crew," responding to damage and maintaining health, making them central to our work.
ALSP, caused by mutations in the CSF1R receptor, results in reduced microglia numbers and functionality. Our approach leverages the shared signaling pathway of CSF1R and TREM2 receptors, over-activating TREM2 to compensate for this deficiency. Early clinical data from a small cohort (six patients) shows promising biomarker improvements, crucial in this fast-progressing disease where traditional long studies are not feasible. Moreover, our work with biomarkers helps streamline proof of concept, a vital aspect in addressing this rare, underdiagnosed disease that significantly impacts patients in their prime adult years.
What challenges exist in commercializing treatments for rare diseases?
Commercializing rare disease treatments presents unique challenges, such as low disease awareness and underdiagnosis. Only 30% of ALSP patients are properly diagnosed, partly because the condition was only identified about 12 years ago. To address this, we prioritized building relationships with the patient community from day one, creating awareness through initiatives like the "ALSP Aware" website and partnerships with organizations like Sisters’ Hope Foundation. Engaging patients and caregivers has been essential to understanding the disease's biology and its most troublesome symptoms, enabling us to design patient-centric clinical studies.
Additionally, we launched a natural history study over three years ago, which has provided invaluable insights into disease progression and biomarker correlations. These efforts help ensure that once a treatment is ready for commercialization, we have a well-informed and engaged patient community. Drawing on my rare disease experience, I have seen how robust patient engagement transforms initial skepticism into broad support, as demonstrated by the evolution of treatments for hereditary angioedema, which now has multiple approved therapies.
Can the learnings from ALSP research be applied to other neurodegenerative diseases?
Yes, our work on ALSP could extend to other conditions, particularly those involving microglia dysfunction. We currently have two modalities in development: our antibody program for ALSP and a first-in-class small molecule TREM2 agonist. While the antibody targets rare diseases, the oral small molecule is positioned for larger indications, such as Alzheimer’s disease, where it can address broader patient populations. The knowledge gained from early trials informs our broader pipeline strategy.
TREM2 activation has potential implications for other diseases like frontotemporal dementia (FTD) and Parkinson's. Microglia dysfunction plays a central role in these conditions, and activating TREM2 could restore their neuroprotective functions, allowing them to respond to damage and clear debris in the brain. This dual-modality strategy positions us to expand our reach into both rare and more common neurodegenerative diseases.
What is the timeline for key clinical readouts and developments at Vigil?
For ALSP, we anticipate final Phase 2 study results in the first half of 2025. These results will be crucial, especially as we have had productive discussions with the FDA, which indicated the possibility of accelerated approval for this indication. Regarding our small molecule TREM2 agonist, Phase 1 data is expected in the first quarter of 2025. The next six months will be pivotal as we evaluate these programs' progress and decide on the next steps for development.
These readouts mark significant milestones for us as a company. With only 65 people, we are driven by our mission to deliver transformative therapies. By leveraging both our precision-based approach and dual TREM2 modalities, we aim to make a meaningful impact in the field of neurodegeneration.
What does the recently announced partnership with Sanofi mean for Vigil Neuroscience?
The Sanofi partnership, which includes a $40 million equity investment, is a validation of our approach and the potential of our small molecule program. This strategic investment supports our research and development efforts and grants Sanofi an exclusive right of first negotiation for a global license of our TREM2 program. A defined trigger mechanism determines the timeline for this potential partnership, ensuring clarity for both parties.
This collaboration reflects the growing excitement around next-generation Alzheimer’s therapies. While existing anti-A-beta antibodies show some promise, they reduce cognitive decline by only about 30%. Our TREM2 agonist represents a complementary approach, targeting neuro-inflammation to unlock further therapeutic potential. The partnership aligns our strengths with Sanofi’s resources, paving the way for broader commercialization efforts, especially in larger indications like Alzheimer’s disease.
What progress do you hope to share next year?
By this time next year, we aim to share the outcomes of our ALSP Phase 2 study and the Phase 1 results for our TREM2 agonist. These milestones will be crucial as we advance our programs, particularly given the potential for accelerated approval in ALSP. Additionally, we will continue refining our strategy to expand the pipeline, leveraging insights from our dual TREM2 modalities to target broader neurodegenerative conditions.
Looking ahead, our focus remains on delivering transformative therapies to patients as efficiently as possible. Our precision-based approach and commitment to patient engagement position us uniquely to make significant strides in the field of neurodegeneration, with exciting developments on the horizon for 2025.
