Biotechnology & therapeutics · Cellular senescence

Dorian Therapeutics

A Stanford spinout that built small molecule blockers of USP16, the enzyme that strips a silencing mark off histone H2A, and pointed them at the arthritic knee. The work never left the laboratory. Altos Labs bought the company in May 2025.

One mark on one histone

Every cell keeps chemical marks that tell it which genes to read. One is a single ubiquitin molecule parked on histone H2A at lysine 119. It is a silencing mark, and it holds shut a block of genes that drive a cell into senescence, the state in which a cell stops dividing and refuses to die.

An enzyme called USP16 takes that mark off.

In 2013, in Michael Clarke’s laboratory at Stanford, Maddalena Adorno worked out what happens when a body carries too much of it. Down syndrome comes from a third copy of chromosome 21, and the USP16 gene sits on chromosome 21. In Ts65Dn mice, trisomic for 132 genes homologous to genes on human chromosome 21, the extra dose of Usp16 reduced the self-renewal of blood stem cells and the expansion of mammary epithelial cells, neural progenitors and fibroblasts. The paper ran in Nature on September 11, 2013.

Five years later Adorno and Benedetta Nicolis di Robilant, a postdoctoral researcher from the same Stanford institute, left to turn that observation into a drug company.

Why the verb mattered

Senescent cells accumulate with age and leak inflammatory signals into the tissue around them. The dominant idea in the field has been senolytics: kill those cells and let the tissue recover.

Unity Biotechnology tested that idea in the same joint Dorian was aiming at. UBX0101, a p53 and MDM2 interaction inhibitor, went into 183 patients with moderate to severe painful osteoarthritis of the knee, given as one injection into the joint at 0.5, 2.0 or 4.0 mg. On August 17, 2020, Unity reported the 12 week result. There “was no statistically significant difference” between any arm and placebo on WOMAC-A, the standard pain scale. Placebo improved by 1.017 points. The 4.0 mg arm improved by 1.019, with a p value of 0.9870. Unity dropped the program, and its shares fell about 60 percent that morning.

Dorian proposed a different verb. Rather than killing senescent cells, its compounds were meant to keep cells from turning senescent in the first place and to restore the self-renewal of the stem cells beside them. The company coined a name for the class: senoblockers.

Two postdocs and a licence

Adorno and Nicolis di Robilant met at Stanford School of Medicine and worked together for several years before founding Dorian in 2018. They took it through Y Combinator in the Summer 2018 batch and through StartX, and licensed the underlying invention out of the university. Adorno became chief executive, Nicolis di Robilant chief scientific officer. The laboratories sat in San Carlos, California, and the team stayed small: Y Combinator’s directory lists eight people.

The backers were named by the company rather than by any filing: Y Combinator, StartX, Longevity Capital, Blumberg Capital, Pacific 8 Ventures and Boom Capital. The board, by contrast, is documented in other companies’ SEC filings. Jeff George, a former chief executive of Sandoz and of Alcon, appears in 908 Devices proxy statements as a director of Dorian Therapeutics, described there as “a pre-clinical biotech firm in the cellular anti-senescence field”. Aya Jakobovits, the founding chief executive of Kite Pharma, appears as a Dorian director in Adicet Bio proxy statements.

The knee, and then the exit

In September 2021 the National Institute on Aging began funding the osteoarthritis program through a U44 cooperative agreement with Adorno as principal investigator. Across four fiscal years it paid $4,178,124. A separate National Cancer Institute award of $335,648, with Nicolis di Robilant as principal investigator, funded a second idea: that T cells age the equivalent of 30 years during CAR-T manufacturing, and that blocking USP16 might keep them young enough to work against solid tumours. The two awards together came to $4,513,772, more federal money than Dorian ever disclosed from investors.

In May 2021 the company engaged HitGen, a Shanghai listed firm, to screen DNA encoded libraries against its targets for an undisclosed payment plus milestones. That chemistry produced DT-201. At the 2024 OARSI world congress, Dorian scientists reported with collaborators at Rottapharm Biotech and the University of Milano Bicocca that DT-201 inhibits USP16 with an IC50 below 5 nM, and that a single injection into the joint eased mechanical allodynia in a rat medial meniscal tear model.

That is where the public science stops. No trial of a Dorian compound is registered on ClinicalTrials.gov. On May 21, 2025 the San Francisco Business Times reported that Altos Labs, the cellular rejuvenation company launched in 2022 with $3 billion from Jeff Bezos, Yuri Milner, ARCH Venture Partners and others, had bought Dorian. Terms were not disclosed. Adorno announced it on LinkedIn. The address doriantherapeutics.com now serves the Altos Labs website.

What is proven, and what is still claimed

Read plainly: the biology behind Dorian is real, peer reviewed and, in its strongest form, academic. The Nature and eLife papers came out of a Stanford laboratory and used genetic tools, not drugs. DT-201 itself appears only in two conference abstracts, in cells and in rats. What Dorian built in seven years was a credible target, a nanomolar inhibitor, $4.5 million of federal confidence and a rat knee that hurt less. That is a long way from a medicine.

What to watch

• Whether Altos Labs advances DT-201 or the USP16 chemistry at all. Altos has not registered a clinical trial of any kind.
• Whether the 2023 and 2024 OARSI abstracts ever become full peer reviewed papers with the complete data behind them.
• Whether the patent family is maintained. Google Patents lists WO2021042073A1 as Ceased, with its usual caveat about that label.

In their words

Dorian Therapeutics funding profile on HVCFHealthcare Venture Capital Fund

Related companies

• dNovo: Shared investor: Precursor. A Stanford trained biologist's direct reprogramming system once grew human hair on the backs of lab mice
• Alixia: Also in Therapeutics. A San Francisco drug discovery company that treats a tumor as an ecosystem rather than as a single mutation
• Endpoint Health: Also in Therapeutics. A Palo Alto company that set out to rescue sepsis drugs the field had given up on, by finding the patients they actually help
• Catena Biosciences: Also in Therapeutics. A UC Berkeley spinout that uses an engineered tyrosinase to weld two proteins together through their native amino acids, now aimed at antibody drug conjugates carrying

Sources

1. Public recordNIH RePORTER, NIA award U44 AG074108 and NCI award R43 CA265636NIH · FY2021 to FY2024
2. Public recordUsp16 contributes to somatic stem-cell defects in Down’s syndromeNature · Sep 11, 2013
3. Public recordInhibiting USP16 rescues stem cell aging and memory in an Alzheimer’s modeleLife 11:e66037 · Mar 21, 2022
4. Public recordSuppression of usp16 reverses aging features in osteoarthritis modelsOsteoarthritis and Cartilage, OARSI abstract · 2023
5. Public recordInhibition of USP16 ameliorates pain and cartilage degeneration in models of osteoarthritisOsteoarthritis and Cartilage, OARSI abstract 430 · 2024
6. Public recordPatent application WO2021042073A1, modulating cellular agingWIPO, via Google Patents · priority Aug 29, 2019
7. Public record908 Devices proxy statement, director biography of Jeff GeorgeSEC EDGAR · Apr 29, 2021
8. Public recordAdicet Bio proxy statement, director biography of Aya JakobovitsSEC EDGAR · Apr 21, 2022
9. Public recordUNITY Biotechnology 12 week data, UBX0101 Phase 2 in knee osteoarthritisGlobeNewswire · Aug 17, 2020
10. IndependentAltos Labs buys small biotech with Stanford rootsSan Francisco Business Times, Ron Leuty · May 21, 2025
11. IndependentAltos Labs snaps up Dorian TherapeuticsLongevity.Technology, Danny Sullivan · May 23, 2025
12. IndependentAltos Labs broadens scope to senotherapeutics via acquisitionFight Aging!, Reason · May 30, 2025
13. IndependentUnity drops leading program after flop, shares in freefallFierce Biotech, Ben Adams · Aug 17, 2020
14. CompanyDorian and HitGen announce research collaborationHitGen and Business Wire · May 24, 2021
15. CompanyDorian Therapeutics company page, batch and statusY Combinator directory · accessed Sep 22, 2026