Cortexa Weekly— May 18th 2025
Cortexa Progress
A New Phase of Execution: Funding, Focus, and Forward Motion
We’re entering a new chapter—one grounded in discipline, strategy, and scientific execution. Rather than chasing headlines, Cortexa Therapeutics is focused on building a lean, results-driven pipeline that moves with urgency and precision.
Our near-term goal: to generate robust in vitro(test tube models) data on a small suite of novel compounds targeting our mechanism, something that's increasingly implicated in neurodegeneration and synaptic dysfunction. These early experiments will help us narrow the field to one or two optimized candidates.
To do that, we’re preparing to synthesize 4–6 analogs of our lead compound and run detailed potency, selectivity, and toxicity screens. If the data looks strong, we’ll move into initial in vivo(mice models) validation—keeping timelines tight, costs controlled, and milestones crystal clear.
We're currently finalizing a financing round to support this work, while also exploring strategic partnerships and grant opportunities. Every step we take is designed to minimize burn while maximizing translational impact.
Docking Breakthrough
Our chemist has made significant headway validating the computational methods we’ll use to design and select our novel compound.
Until now, we’ve had a major hurdle: finding a reliable docking protocol that can accurately model how our lead molecule, interacts with its receptor target. Without this, designing analogs with improved potency and specificity would’ve been guesswork.
To solve this, he’s been rigorously validating our docking pipeline using three key experiments:
Re-docking: He successfully confirmed that our docking tool can reproduce the known binding pose of our lead within an acceptable range—an essential benchmark that builds confidence in future analog modeling.
Scoring-Potency Correlation: By comparing docking scores with real-world potency data (IC50 values), he demonstrated a meaningful correlation, showing that our system ranks stronger binders more accurately.
Active Enrichment: He tested whether the algorithm could distinguish real binders from lookalike molecules that don’t actually bind—and it did, enriching for true actives far above random chance.
In plain terms, we’re working on building a smarter way to predict which of our future compounds are most likely to work—before spending time and money testing them in the lab. Think of it like perfecting a recipe before going to the baker: we’ve tested and tuned every ingredient so when it’s time to actually make the cake, we’re confident it’ll turn out right the first time. It saves time, avoids waste, and gets us to the final product faster.
This validation work lays the groundwork for a smarter, more targeted approach to analog design. Rather than blindly testing hundreds of compounds, we can now prioritize those most likely to succeed based on well-supported computational predictions.
Stay tuned—we’ll be sharing more about our lead series and in vitro plans soon.
Cortexa Dispatch
This week, I’m taking a brief break from discussing my research to reflect on a powerful historical example that reshaped modern medicine.
What Diabetes Looked Like Before Insulin: A Historical Lens on Therapeutic Breakthroughs
Before 1921, a diagnosis of Type 1 diabetes was a slow-moving death sentence. There was no way to regulate blood sugar, no medication to halt the body’s metabolic unraveling. Children and young adults—typically diagnosed between ages 5 and 25—would waste away, losing weight rapidly, falling into comas, and dying within months or even weeks. In 1919, for example, a 10-year-old child with newly diagnosed diabetes could expect to live no more than a year or two. The only known treatment was starvation: patients were placed on extreme caloric restriction, consuming as little as 400–800 calories per day. While this sometimes bought a few extra months of life, it came at the cost of severe weakness, stunted growth, and profound suffering.
Then came insulin. When Banting, Best, Collip, and Macleod first isolated it and began testing it in 1921–22, it was nothing short of a miracle. Children on the brink of death were brought back to life. Skeletal bodies filled out. Energy returned. It transformed not only individual lives, but the very idea of what medicine could do.
But here’s what’s less often discussed: the early researchers weren’t trying to fix every downstream symptom of diabetes. They weren’t focused on the retinopathy, the kidney disease, the vascular complications that would eventually define long-term diabetes care. They were zeroed in on a single upstream cause—insufficient insulin—and proved that if you get the biology right at the root, everything else can change downstream.
This is the kind of thinking that guides Cortexa. We’re not trying to patch every symptom of ALS. We’re not chasing inflammation, protein pathology, oxidative stress, or axon guidance just because they show up downstream. We’re going after what we believe to be one of the root mechanisms: pathological activation of calcium permeable receptors and the cascade of synaptic toxicity that follows. Just like early insulin therapy, we’re betting that fixing the upstream driver can change the whole disease trajectory.
Progress will come in phases. But history tells us that the biggest therapeutic leaps often come from simple, well-targeted interventions that hit the right biology—at the right point in the system.
We’ll be back next week with more updates on our pipeline. For now, we’re honoring the scientific clarity and conviction that changed the fate of millions—and channeling that same spirit into what we’re building here.
Join the Movement
We’re building Cortexa one block at a time. From molecular design to real-world deployment. Whether you’re here as a scientist, supporter, or someone affected by ALS: your presence matters.
