Therapeutics & drug discovery · Rare pediatric neurodegeneration

Circumvent Pharmaceuticals

A Portland, Oregon drug discovery company using one rare, fatal childhood brain disease as the proving ground for a small molecule it hopes will eventually reach more common neurodegenerative conditions. Seven federal grants have funded the work since 2017. No clinical trial has started yet.

Six to twelve months

Children with CLN1 Batten Disease, also called infantile neuronal ceroid lipofuscinosis, look healthy at birth. According to a 2018 conference poster from Circumvent, symptoms typically begin between six and twelve months of age, progress to seizures and loss of cognitive and motor skills between five and ten years, and end in death, usually between ten and fifteen years. There is no approved treatment. Families are offered palliative care.

Circumvent is a small company built around a single hypothesis: that a small molecule can substitute for the enzyme these children are missing, and that the same biology might matter far beyond this one rare disease.

The problem

CLN1 is caused by mutations in the gene for palmitoyl protein thioesterase 1, or PPT1, an enzyme that normally strips a fatty molecule called palmitate off proteins inside brain cells. Without it, palmitoylated proteins pile up inside lysosomes as a fatty waste product called ceroid. A 2021 NIH grant abstract put the US patient population at fewer than 1 in 100,000. There is no disease-modifying therapy on the market for any patient.

Circumvent's compound, N-tert-butylhydroxylamine, known as NtBuHA and given the internal codes CIRC825 and, in the company's more recent grant filings, CIRC827, is designed to chemically mimic the missing PPT1 activity and clear the ceroid buildup. The molecule was not discovered in-house. According to the company's own 2018 conference materials, NtBuHA was “selected for development based on studies performed at the NIH on PPT1 knockout mice,” work associated with NICHD investigator Anil Mukherjee, who is listed among Circumvent's partners on the company's website.

Founders

Circumvent states on a 2018 conference poster that it is “a drug discovery and development company founded in 2015 and based in Portland, Oregon,” and that it is focused “on small molecule therapies for Infantile Neuronal Ceroid Lipofuscinosis (INCL or CLN1 Batten Disease) with a mission to improve the quality of life of Batten patients.” That poster names Andrew Lim as president and chief executive, Devin Wiley, M.D., Ph.D., as chief medical officer and head of research and development, and Samy Hamdouche as chief business officer, working with Robert Steiner, M.D., a Batten disease clinician then at the University of Wisconsin, Madison.

The company's first NIH SBIR grant, a $198,790 Phase I award in 2017, listed Andrew Lim as principal investigator. Leadership on the science shifted over time in the public grant record: Devin Wiley was principal investigator on the 2021 Phase II award, and Daniel Chelsky, listed by other sources as chief scientific officer, has been principal investigator on every NIH award since a 2022 continuation. The company's website lists roughly two dozen names under investors and partners, including scientists, clinicians and the founding executives, without specifying current roles for most of them.

A decade of federal funding, no trial yet

NIH RePORTER records, corroborated by independent HHS TAGGS award data, show seven SBIR and STTR grants to Circumvent Pharmaceuticals Inc. between fiscal 2017 and fiscal 2026: a $198,790 Phase I award in 2017 to derisk NtBuHA; a $1,441,757 Phase II award in 2021 to complete IND-enabling chemistry, formulation and toxicology work; a $304,787 STTR award the same year to build a blood-based assay for monitoring treatment; a separate $507,284 award in 2021 to test whether the same palmitoylation biology applies to Alzheimer's disease; a $1,449,910 Phase II continuation in 2022; and two further continuations, $1,244,790 in 2025 and $1,219,273 in 2026, aimed at finishing GLP toxicology and safety pharmacology work and preparing both an FDA Investigational New Drug filing and a Clinical Trial Application with European regulators. SBIR.gov's own portfolio page for the company separately rolls this up as 3 Phase I awards and 2 Phase II awards totaling $5,147,318, first award year 2017, and lists 4 employees.

The science behind the compound has been published. A 2024 paper in Molecular Genetics and Metabolism, co-authored by Circumvent scientists Zach Fyke, Rachel Johansson, Anna I. Scott, Devin Wiley and Daniel Chelsky along with outside researchers, reported that NtBuHA reduced buildup of the fatty waste material, cut neuroinflammation, reduced seizures and normalized motor function in a CLN1 mouse model. No results in human patients have been published, and no clinical trial for the compound is registered on ClinicalTrials.gov.

What is proven, and what is still claimed

Read plainly: the public record shows a small, federally funded preclinical program with real mouse data behind it, run for almost a decade on grant money rather than disclosed venture capital. The step that would matter most to patients, a filed IND and a first-in-human trial, has not happened yet. The company's own 2025 and 2026 grant language describes that step as still in progress.

What to watch

• Whether Circumvent files an FDA Investigational New Drug application and an EMA Clinical Trial Application for CIRC827, the stated goal of its current NIH grant.
• A first registered clinical trial in CLN1 Batten Disease patients.
• Whether the Alzheimer's disease palmitoylation work, funded separately by NIA, produces a second pipeline program.
• Confirmation, one way or another, of the reported June 2025 seed round.

In their words

Related companies

• Nectome: Also in Therapeutics. A laboratory result independent judges verified, attached to a commercial plan MIT cancelled, neuroscientists attacked, and the company has since rewritten
• Origami Therapeutics: Also in Therapeutics. A small San Diego company designing oral pills that strip the mutant huntingtin protein out of brain cells while leaving the normal protein alone
• 1910 Genetics: Also in Therapeutics. A Boston biotech that runs small and large molecule drug discovery through one AI platform, backed by a five-year commercial partnership with Microsoft
• Promakhos Therapeutics: Also in Therapeutics. A two-person Boston biotech building an oral small molecule meant to switch the innate immune system back on in Crohn’s disease

Sources

1. Public recordNIH RePORTER, award 1R43NS100233-01NINDS · 2017
2. Public recordNIH RePORTER, award 1R44NS120360-01A1NINDS · 2021
3. Public recordNIH RePORTER, award 1R41HD105560-01NICHD · 2021
4. Public recordNIH RePORTER, award 1R43AG072984-01NIA · 2021
5. Public recordNIH RePORTER, award 5R44NS120360-02NINDS · 2022
6. Public recordNIH RePORTER, award 2R44NS120360-03NINDS · 2025
7. Public recordNIH RePORTER, award 5R44NS120360-04NINDS · 2026
8. Public recordHHS TAGGS award history, R44NS120360HHS · accessed Sep 2026
9. Public recordSBIR.gov company portfolio, Circumvent PharmaceuticalsSBIR.gov
10. IndependentReduction of neuroinflammation and seizures in a mouse model of CLN1 batten disease using the small molecule enzyme mimetic, N-Tert-butyl hydroxylamineMolecular Genetics and Metabolism, Fyke Z et al · Jul 2024
11. CompanyCircumvent Pharmaceuticals: Preclinical and Discovery Programs for CLN1 Batten Disease, conference posterBDSRA · 2018
12. CompanyCircumvent Pharmaceuticals website, About and Patients pagesAccessed Sep 2026
13. AggregatorCircumvent funding, team and investors profileStartup Intros · accessed Sep 2026
14. IndependentCircumvent org chart listingThe Org · accessed Sep 2026