Biotechnology & drug discovery · Transcription factors

Arpeggio Bio

A Boulder, Colorado biotech that read the transcriptome to find drugs for targets long called undruggable. It raised money from 2019 through late 2025, then wound down in the summer of 2026 after its lead cancer program could not clear a safety hurdle.

Dark DNA

Joey Azofeifa was a computer science PhD student in Robin Dowell's lab at CU Boulder, working on the part of the genome that does not code for protein, what he called the dark portion of the genome. Ninety nine percent of the human genome is not protein coding, yet scientists were learning that space was not blank.

Azofeifa had picked up a technique called global nuclear run on sequencing, or GRO seq, that let him watch RNA being transcribed within minutes of a stimulus, rather than the 12 to 24 hours older RNA sequencing required. "The problem is that if you wait 12 or 24 hours, a lot of things that have changed are secondary or tertiary and quaternary effects," he said in 2018. He teamed up with Tim Read, another Dowell lab graduate, and with Dowell herself, to turn the idea into a company.

The problem

Transcription factors are the proteins that turn genes on and off. They sit at the center of diseases from cancer to chronic kidney disease to neurodegeneration, and drug companies have mostly treated them as undruggable, since many lack the pocket a small molecule can grab onto. Arpeggio's bet was to measure what a drug does to the whole transcriptional network, rather than one target, then use that map to find molecules other companies could not see. Its GRETA platform combined nascent RNA sequencing with machine learning to flag the genes that matter for a drug's success or failure within minutes of exposure.

Founders

Azofeifa became CEO, Read became CTO, and Laura Norris joined as chief operating officer. Dowell, a CU Boulder professor and co-founder, held a patent on assessing transcription factor activity that the company licensed through CU's technology transfer process. "I think a company like Arpeggio comes out of the fact that intersections between fields gives rise to ideas that wouldn't have been conceived without those intersections," Dowell said. The science had already cleared peer review: Azofeifa, Read, Dowell and two co-authors published "Enhancer RNA profiling predicts transcription factor activity" in Genome Research in March 2018, a method Arpeggio would later commercialize.

From service business to drug pipeline

Arpeggio's first customer was FORMA Therapeutics, a Celgene partnered oncology company, which in March 2018 agreed to use Arpeggio's platform to study its drug candidates. By January 2020 the company said it had worked with more than twenty biotech and pharmaceutical companies, including four of the world's top ten, and closed a $3.2 million seed round oversubscribed by more than $2 million. Azofeifa was named to the 2020 Forbes 30 Under 30 list in healthcare that same month.

By September 2022 that partner count had grown past forty, including Forma, Intrinsic Medicine and Treventis, according to the company. The model paired two revenue lines: selling transcriptome intelligence to pharma partners, and building Arpeggio's own pipeline with half the proceeds of a new $17 million Series A led by Builders VC, with Khosla Ventures, TechU Ventures, FundersClub, Tencent and others participating. "This drug we identified with our technology is killing and melting down really hard to treat cancers" in mice, Azofeifa told BizWest.

Builders VC general partner Amit Mehta explained the firm's bet this way: "Health care is primed to benefit from a disrupting system like Arpeggio's, which has so much potential to help further our understanding of how drugs interact with each individual taking them."

The company kept raising. SEC filings show a new offering opened in November 2025 targeting more than $35 million, with just over $20 million sold within two weeks. The lead program by then was a molecular glue degrader aimed at NRF2, a transcription factor governing detoxifying and anti inflammatory defenses, in KEAP1 mutant non small cell lung cancer, with plans to expand into neurodegeneration and chronic kidney disease.

The final chord

Eight months after that November 2025 raise, Arpeggio's leadership decided to wind the company down. In a LinkedIn post reported by Fierce Biotech in August 2026, Azofeifa said the Nrf2 program had begun to "unravel" over the preceding months. "Our lead drug program … represented years of novel science," the CEO wrote. "But in the end, we were unable to separate the molecule's efficacy from an off-target liability."

He called the founding idea, restoring a whole biological system rather than blocking a single target, "beautiful," while acknowledging the "numerous challenges" it carried. The company's website went offline around the same time, and it is unclear how many of its roughly thirteen employees were affected.

What is proven, and what is still claimed

Read plainly, Arpeggio built a real scientific method, published it, and sold it as a service to dozens of pharma partners before trying to become a drug company itself. The Forma deal is documented; the J&J partnership and the melanoma degrader exist only on the company's marketing page and do not match its own pipeline page or its final statement. The company never entered a clinical trial, and it is gone before any claim about human data could be tested.

What to watch

• Whether Arpeggio's patents, GRETA platform or NRF2 chemistry are licensed or sold to another company.
• Any amended Form D closing out the November 2025 offering, which had $15.3 million of its $35.3 million target unsold at the wind down.
• Whether Azofeifa, Read or Norris start a successor company, as often happens after a platform biotech's shutdown.

In their words

Arpeggio Bio funding profile on HVCFHealthcare Venture Capital Fund

Related companies

• Talus Bio: Also in Drug Discovery and Delivery. 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
• General Proximity: Also in Drug Discovery and Delivery. A San Francisco biotech built on one idea: most disease driving proteins can be controlled, not just blocked, given the right partner protein
• Sixfold Bioscience: Also in Drug Discovery and Delivery. A London company that set out to deliver RNA drugs everywhere except the liver
• Algen Biotechnologies: Also in Drug Discovery and Delivery. A CRISPR and machine learning platform for choosing drug targets, spun out of Jennifer Doudna’s Berkeley lab in 2018

Sources

1. Public recordEnhancer RNA profiling predicts transcription factor activityGenome Research, Azofeifa et al · Mar 1, 2018
2. Public recordSEC EDGAR Form D filings, Arpeggio Biosciences, Inc., CIK 0001786698SEC · 2019 to 2025
3. IndependentBioscience start-up sheds light on ‘dark DNA’Colorado Arts and Sciences Magazine, Alison Gilchrist · May 3, 2018
4. IndependentFORMA Therapeutics Collaborates with Arpeggio Biosciences to Explore Translational Utility of Drug CandidatesBioSpace, Nick Paul Taylor · Mar 26, 2018
5. IndependentCelgene-partnered Forma teams with Arpeggio to understand drug-target interactionsFierce Biotech, Angus Liu · Mar 29, 2018
6. CompanyCU Boulder startup Arpeggio Bio raises $3.2 Million in seed funding and CEO named to 2020 Forbes 30 Under 30 List in HealthcareVenture Partners at CU Boulder, Mallory Richardson · Jan 17, 2020
7. IndependentArpeggio Bioscience raises $17M Series A to bolster drug trialsBoulder Daily Camera, Lucas High · Sep 7, 2022
8. IndependentArpeggio Biosciences rakes in $17M to measure the transcriptomeMedCity News, Katie Adams · Sep 7, 2022
9. CompanyArpeggio Biosciences raises $20M in latest offeringVenture Partners at CU Boulder, via BizWest · Nov 25, 2025
10. IndependentArpeggio plays final chord as biotech disbands on poor prospects for Nrf2 programFierce Biotech, James Waldron · Aug 10, 2026
11. CompanyArpeggio Biosciences Inc. startup portfolio pageVenture Partners at CU Boulder · updated May 19, 2026
12. CompanyArpeggio Bio company listingY Combinator · accessed Sep 21, 2026