Drug discovery · Transcription factors
Talus Bio
A Seattle company that strips a living human cell down to the proteins still gripping DNA, measures all of them at once by mass spectrometry, and uses the result to hunt drugs for targets that structure based methods cannot see. Everything is preclinical, and an unusual share of the evidence is public.
Proteins in tubes, and no way to measure them
A postdoc walked into a mass spectrometry lab at the University of Washington with gene regulating proteins in tubes and no way to tell what was in them.
“One day, he, more or less, walked into the lab and needed to measure a bunch of proteins in some tubes, which was pretty much the only thing I knew how to do!” Lindsay Pino told Women In Bio in 2025. She was finishing a PhD in quantitative proteomics. He was Alex Federation, a postdoc at the Altius Institute for Biomedical Sciences, a Seattle nonprofit studying gene regulation.
His assay plus her readout became Talus Bio, spun out of the university and Altius in October 2020 and through Y Combinator the next summer.
The class of target nobody can hold still
Transcription factors bind DNA and decide which genes are on. More than 1,600 are encoded in the human genome, and when they misfire they drive cancer, fibrosis, inflammation and metabolic disease. The nuclear hormone receptors behind tamoxifen and dexamethasone have been drugged for decades. Most of the rest have not, because pulling one out of a cell strips away the DNA and partner proteins that hold its shape.
“The rest are very rigid intertwined proteins that stick to DNA and there’s no spot on them to put a small molecule when they are in the cell,” Federation told Fierce Biotech in 2021. Once isolated, he added to GeekWire a year later, “they kind of just fall apart. You can’t do structural biology. You can’t do the normal experiments that you would in drug discovery.”
So Talus took the assay into the cell. Cells are dosed with compound, nuclei are caught on lectin coated magnetic beads, and salt buffers wash away everything not bound to chromatin. What remains goes to a mass spectrometer. The company has called this MARMOT, then TF-Scan, then native regulome profiling. The measurement is the same: which switches sit on DNA, and how a drug moves them.
Two scientists who kept the company
Federation trained in medicinal chemistry with Jay Bradner, an early champion of open drug discovery. Pino trained at the Broad Institute, the University of Washington and the University of Pennsylvania. Neither handed the company to a hired chief executive. The third technical pillar is Will Fondrie, head of data science, principal investigator on two NIH grants and an author on Casanovo, the transformer model that reads peptides out of mass spectra, published in Nature Communications in 2024.
Grants first, then venture, then a model
A $255,831 National Science Foundation award in 2021 paid for the first engineering. A $1.5 million pre-seed led by Fifty Years followed, then $7 million led by NFX in 2022, plus NIH awards and, in 2023, $2.3 million from the Washington State Andy Hill CARE Fund. In August 2024 Two Bear Capital led an $11.2 million round the company labeled Seed+, and a Two Bear partner joined the board.
Then came the publishing. June 2025: a preprint describing a Regulome Atlas across 36 human cell lines that detected 897 annotated transcription factors. July 2025: free profiling offered to outside labs. December 2025: a collaboration with Tokyo based PRISM BioLab. And in July 2026, a preprint introducing Ptarmigan-1, a model that places protein residues and small molecules in one shared space from sequence and flat chemistry, with no three dimensional pose: ten milliseconds per compound, and 3.4 billion compounds against 20,431 human proteins in under a day. By September 2026 the website led with structure free drug discovery, and the 2023 pipeline page returned a 404.
What is proven, and what is still claimed
| Evidence | What the record shows | Source type |
|---|---|---|
| Platform preprint | Native, Spatiotemporal Profiling of the Global Human Regulome, bioRxiv, revised Jun 25, 2025. Chromatin enrichment plus label free DIA across 36 cell lines; 897 transcription factors detected, nearly 60 percent of the human repertoire. No journal version in PubMed as of Sep 23, 2026. | Public record |
| Model preprint | Structure-free, site-resolved contrastive learning, bioRxiv, Jul 28, 2026, all authors Talus employees. Ptarmigan-1 scores a pair in 10 milliseconds against about 54 seconds for the co-folding model Boltz-2, ranks second to it on the LIT-PCBA benchmark, and holds positive enrichment on disordered targets where Boltz-2 falls to near random. Code is not released, and two newsletters covering it in August 2026 noted the absence of wet lab confirmation. | Public record |
| Therapeutic programs | AACR 2025 posters: TAL61, a covalent Brachyury inhibitor, cut tumor burden in patient derived chordoma xenografts and by more than 50 percent in Brachyury positive lung cancer models; covalent compounds against NONO lowered AR and ARv7 in prostate cancer cells. Conference data, not papers. | Company-stated |
| Clinical stage | No trial registered on ClinicalTrials.gov for Talus Bioscience or TAL61 as of Sep 23, 2026. In 2024 the company said it was advancing toward IND enabling studies in chordoma. None has been announced. | Not found |
| Federal funding | SBIR.gov lists seven awards totaling $5,394,162 through 2024, starting with NSF in 2021. NIH RePORTER adds a $1,035,634 NCATS Phase II award running July 2026 to June 2028. About $6.43 million on record. | Public record |
| Non-dilutive total | The company has said since 2023 that it holds six non-dilutive awards exceeding $7.3 million. Federal records plus $2.3 million in CARE Fund grants reach about $8.7 million, across eight federal and two state awards. | Counts differ |
| Patents | Three families assigned to Talus Bioscience: reactive cysteines in nuclear proteins, filed May 2023; extraction using volatile salts, filed Feb 2024; lectin assisted isolation of nuclei, published Dec 2025. The earlier nuclear proteome patent naming Federation, US 12,276,667, granted Apr 15, 2025, belongs to the Altius Institute. Any license is not public. | Public record |
| Published output | 24 PubMed records carry a Talus affiliation, 2022 to 2026, mostly proteomics methods and software; the GitHub organization holds 38 repositories. The atlas preprint says raw data goes to PRIDE on acceptance and matrices are available on request, so the atlas is not yet downloadable. | Public record |
| Partnership | PRISM BioLab, Dec 17, 2025, sharing discovery costs and any out-licensing profits. Earlier pharma work was never named. | Partner-stated |
Read plainly: the measurement is real and documented, the chemistry is early, and the newest claim is the least tested. Ptarmigan-1 has a strong retrospective case, including a patent only STAT6 series it recovered without having seen it, and no reported bench experiment confirming a compound it picked. Nothing has reached a patient.
What to watch
- Wet lab validation of Ptarmigan-1 predictions, and whether the model or its code is released.
- Peer reviewed versions of the two preprints, and whether the atlas data lands in PRIDE.
- A candidate nomination or an IND for the Brachyury program.
- Whether the therapeutic pipeline returns, or the business settles into platform access and partnerships.
- A new financing. The last announced round closed in August 2024, and the only Form D was filed that month.
In their words
“The rest are very rigid intertwined proteins that stick to DNA and there’s no spot on them to put a small molecule when they are in the cell.”
Alex Federation, co-founder and CEO, Fierce Biotech, 2021 · Independent
“One day, he, more or less, walked into the lab and needed to measure a bunch of proteins in some tubes, which was pretty much the only thing I knew how to do!”
Lindsay Pino, co-founder and CTO, Women In Bio, 2025 · Interview
“Instead of trying to repeatedly slam a square peg in a round hole and wondering why we can’t build new therapeutics for transcription factors, what if we just changed the way we try to do drug discovery?”
Lindsay Pino, PharmaVoice, 2023 · Interview
“Our platform has already logged over 50 million protein-compound interactions this year.”
Alex Federation, AACR release, April 2025 · Company release
“Instead of using AI to guess biology, we generate the biological data that trains better AI.”
Lindsay Pino, Regulome Summit recap, November 2025 · Company release
“The STAT6 inhibitor recovery is the part that convinced me this is real.”
Natasha Kilroy, Kiin Bio Weekly, August 2026 · Independent
“Crucially, Ptarmigan-1 does not have experimental validation at this time but the team has noted their intention to pursue this in the near future.”
Decoding Bio, BioByte 167, August 2026 · Independent
Related companies
Sources
- Public recordNative, Spatiotemporal Profiling of the Global Human Regulome
- Public recordStructure-free, site-resolved contrastive learning
- Public recordForm D, Talus Bioscience, Inc., CIK 0002033246
- Public recordSBIR.gov portfolio, Talus Bioscience Inc
- Public recordNIH RePORTER awards to Talus Bioscience, Inc.
- Public recordGoogle Patents, assignee Talus Bioscience
- Public recordPubMed affiliation search, Talus Bioscience
- Public recordCasanovo, sequence-to-sequence translation of spectra
- IndependentTalus Bio wants to knock proteins off of DNA
- IndependentSeattle startup lands $9.75M
- InterviewDrug discovery with transcription factor know-how
- InterviewNIH Innovation Zone 2024, Talus Bio
- IndependentSeattle biotech startup secures $11.2M
- IndependentTalus Bio tacks on $11M
- InterviewInspiring Women of Seattle, Lindsay Pino
- IndependentTalus Bio’s Ptarmigan-1
- IndependentBioByte 167, on Ptarmigan-1
- CompanyNew grants for transcription factor drugs
- CompanyNew funding for the AI platform
- CompanyPreclinical data at AACR 2025
- CompanyTech Access Program
- CompanyRegulome Summit 2025 recap
- PartnerCollaboration with PRISM BioLab
- CompanyTalus Bio website and YC page
Profile researched and written by Healthcare Discovery. Last updated September 29, 2026.
