⚡TL;DR
Gate Bioscience is a San Francisco biotech company developing a novel class of orally-available ‘molecular gate’ drugs designed to eliminate disease-causing secreted proteins at their source.
🧬 Molecular bouncers at work. Molecular Gates are pills that selectively block the secretion of disease-causing proteins from cells. Like a molecular nightclub bouncer.
💊 New class of drugs. This approach blends the benefits of small-molecule and large-molecule therapies, opening treatment possibilities for diseases once deemed untreatable…and improving options for many more.
🚀 Starting with Prion Disease. Gate Bioscience is leading the charge. Their first target: Prion Disease, a rare, universally fatal condition without a treatment today. And that’s just the beginning.
🙌 Why We Say Hell Yeah. Building a platform that can solve thousands of diseases is a massive undertaking, and the team is not losing focus on the human impact of their efforts. By focusing their first program on curing Prion Disease now, the team is actively racing to save real patients - including Sonia Vallabh, one of the most inspiring personal stories in medicine.
Sec61 - the passageway through which many of the proteins in the body transit.
💊 ⛩️ What are Molecular Gates?
There are ~4,000 proteins that pass through a single exit doorway (Sec61) on their way out of the cell, hundreds of which can cause disease. Up until now, to treat any of these types of diseases, you need to use a biological injectable drug.💉🩸😖
While these proteins are all different, they get made by the cell in the same way, thus creating a common vulnerability. Gate has created a mechanism to attack this shared vulnerability for the first time: molecules instructed to block the transit of a specific disease-causing protein through the Sec61 channel while allowing others to pass. “Don’t let this protein through!” the molecule says firmly in a deep voice. The cell recognizes the blocked protein is out of place and degrades it.
Think of this as a turbocharged nightclub bouncer blocking the entrance. (A very unfortunate flashback to our 20s: Friday nights, frosted tips, striped button-downs, leather shoes…and - amazingly - still getting rejected by every bouncer in sight.) This novel mechanism can be purposed to target each protein individually, opening up a treatment option for potentially hundreds of diseases.
Also awesome, these molecular gates are delivered in pill form, which is obviously more convenient, less ‘needle-y,’ and more globally accessible than injections.
Stepping on through that gate
(Dan swears that’s a song lyric, but we can’t find any record of it)
Gate Bioscience has rapidly built momentum: in July 2025 they entered a major collaboration and licensing agreement with Eli Lilly to discover and develop molecular-gate medicines leveraging Lilly’s small-molecule expertise.
In December, they closed a $65 million Series B, led by new investor Forbion alongside Lilly (as strategic investor) and existing backers A16Z, GV, ARCH Venture Partners and Versant Ventures - bringing total capital raised to approximately $135 million.
With this funding, Gate is moving its lead molecular-gate programs into IND-enabling studies and toward Phase 1 clinical trials.
⚡Why we said hell yeah!
OK so we kind of spilled the beans in our description of Molecular Gates - we couldn’t help ourselves. But keep reading for the DOUBLE hell yeah.
(Summarizing) Molecular Gates are magic pills for diseases that today need injectables: better for patients and more accessible for the world. ⚡Hell yeah for Magic Pills! 💊🎩🪄🧙
🎵Just keep on stepping on through that gate!🎶
⚡⚡Double hell yeah!
Convenient magic pills are incredibly exciting, but it’s extra cool that Molecular Gates might be the best, if not only, way to even treat certain diseases. This is evident in Gate’s commitment to delivering a cure for Prion Disease (aka Creutzfeldt-Jakob Disease). Prion Disease is a rapidly progressing neurodegenerative disease that today has no treatment and is universally fatal, with a median survival time of 1 year from symptom onset. Gate Bioscience is making fast, promising progress toward a Molecular Gate for Prion Disease - a pill that would keep Sonia Vallabh alive.
Please read this mind-bending, inspiring story of Sonia and her husband Eric. After watching her mother die from the rare brain disease in 2010, Sonia learned she carried the same Prion genetic mutation. In response, she and her husband Eric quit their jobs, earned their PhDs, and became the world's leading Prion scientists, working together toward a cure at the Broad Institute (Harvard + MIT). Gate works in close partnership with this remarkable couple, and we've had the privilege of witnessing their collaborative quest to find a cure for Sonia.
"There's a date in the future when Sonia will get the first dose of the drug that's going to save her life," Eric says. "What can I do today that brings that date closer to the present?”
Eric and Sonia prepare materials for an experiment measuring prion protein in spinal fluid. (Kayana Szymczak for NPR)
Dive in Deeper
How Molecular Gates Work (in Gate’s words): Blocking Disease-Causing Proteins at Their Origin
Andreessen Horowitz on "Investing in Gate Bio"
“Can new drugs stop deadly set of brain-eating diseases?” (Science, March 22nd 2024). Molecular Gates & alternative approaches.
Podcasts featuring Gate’s CEO, Jordi Mata-Fink
Engage with Gate
Let us know if you’re interested in a Hell Yeah ⚡ Field Trip to Gate’s lab in San Francisco. We’re gauging interest & exploring how we could put together an afternoon with the Gate team to learn more about Molecular Gates, drug discovery, and other 🤯 topics. (Did you know you can freeze proteins to visualize the interaction of molecules and proteins? Blows our mind too.)
We’re also gathering interest in pre-orders of these Gate sweatshirts. We’ll donate 50% of profits to the CJD Foundation. We expect these to cost ~$60 each. Email us at [email protected] if you’re interested.
Disclosure: We have a financial, advisory, or other professional relationship with this company.
Hit us up if you’d like to learn more or if you have suggestions for future features.
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Don’t forget: life’s too short to be an Eeyore.
