Oncology therapeutics · Click chemistry
Shasqi
The first company to run a click chemistry reaction inside a living human being. Its lead drug passed every safety bar it was set, then missed the one that decides whether a cancer drug continues, and the company has rebuilt around a second version of the idea.
Two buckles
In October 2020 two patients were injected with a clear gel, made from modified sodium hyaluronate, directly into a tumor. Over the days that followed an inert version of doxorubicin went into a vein. The gel carried one half of a chemical pair, the drug the other. Where the two met they snapped together and released active chemotherapy at the tumor.
Nothing else in the body was supposed to take part. The two halves, a tetrazine and a trans-cyclooctene, do not exist in human biology, so they have almost nothing to react with except each other. Shasqi called it the first use of click chemistry in a human being, and no one has contested the claim since.
Two years later the Royal Swedish Academy of Sciences gave the 2022 Nobel Prize in Chemistry to Carolyn R. Bertozzi, Morten Meldal and K. Barry Sharpless “for the development of click chemistry and bioorthogonal chemistry.” Bertozzi took the reaction into living organisms. Shasqi, which had seven people when it filed its IND, had already taken it into patients.
The one percent problem
Systemic cancer drugs are wasteful in a specific and expensive way. Very little of the dose reaches the tumor; the rest circulates, degrades and does damage. Antibody drug conjugates tie the targeting antibody and the toxic payload into one molecule and still deliver only a sliver of it. Mejía Oneto puts it at “less than 1% of the ADC dose actually reaches the tumor,” and says the same holds for small molecules and biologics.
Doxorubicin makes the cost of that waste easy to see. It works against many solid tumors, and patients can take roughly seven doses in a lifetime before cardiac damage becomes the limiting factor. The ceiling is not the cancer. The ceiling is the heart.
The CAPAC idea is to break the molecule in two. Put one clickable half at the tumor. Infuse the other, chemically muzzled, into the bloodstream. Let the reaction happen only where the first half waits. If that works the dose ceiling moves, because the drug is only fully a drug at one address.
A surgeon and a chemist
Mejía Oneto came at the problem sideways. He holds a PhD in organic chemistry from Emory and an MD from the University of Minnesota, and was an orthopedic surgery resident at UC Davis when he started thinking about it. He could place a metal implant to the millimeter and could not aim a drug at all.
The chemistry came from Maksim Royzen at the University at Albany, who had been developing the tetrazine and trans-cyclooctene pairing since his postdoctoral work. The two connected in 2013, and the founding patents run through both universities.
When Shasqi began is not settled. Y Combinator lists it in the Winter 2015 batch. Mejía Oneto's own YC biography says he joined in 2015 with a company called Tambo and that Shasqi was its 2018 spinoff. UC Davis wrote in 2020 that he launched Shasqi in 2018. A June 2025 company release says he founded it in 2014. Four versions, all on the record.
What the trial actually found
The registered study, NCT04106492, ran from August 2020 to September 2023 at eight sites including MD Anderson, Stanford, City of Hope and Chris O'Brien Lifehouse in Sydney. Phase 1 enrolled 39 patients. Phase 2a enrolled 14 more with soft tissue sarcoma. Fifty three in total, which is what the registry records as actual enrollment.
The safety result was remarkable. Patients tolerated SQ3370 at up to 15 times the conventional doxorubicin dose with no dose limiting toxicities and mild myelosuppression. Twelve times conventional became the Phase 2 dose. Immune profiling showed cytotoxic CD8 positive T cell expansion in tumors and in circulation, in sarcomas that are usually immunologically quiet.
The efficacy result was not. In Phase 2a the unconfirmed objective response rate was 14.3 percent, two of fourteen patients, with a disease control rate of 71.4 percent. The authors write that the study was terminated because the prespecified criterion for continuing, a response rate better than standard doxorubicin, was not met.
The second version
Shasqi's answer was to change the targeting half, not the chemistry. Injecting a gel only works if a needle can safely reach the tumor. The company now infuses an antibody fragment carrying the clickable group, lets it bind and lets the excess clear, then infuses the payload. The lead target is CEACAM5, overexpressed in lung, gastric, pancreatic and colorectal cancers, paired with an attenuated MMAE protodrug.
Johnson & Johnson Enterprise Innovation signed a research collaboration in June 2023 and expanded it that October. The board added Pamela M. Klein and Mark McCamish in January 2024, and in October 2025 Roger Dansey, formerly chief development officer at Pfizer Oncology and chief medical officer at Seagen. That is a board assembled for a drug that has not yet reached patients.
What is proven, and what is still claimed
| Evidence | What the record shows | Source type |
|---|---|---|
| The chemistry works in people | Clinical Cancer Research, September 2025, and the June 2025 medRxiv preprint report the first in vivo click chemistry reaction in a clinical setting. Safety held at 8.9 times the veterinary dose in dogs and 15 times the conventional dose in patients, with no dose limiting toxicities. | Public record |
| Registered trial status | NCT04106492, Phase 1/2a, sponsor Shasqi, Inc. Started Aug 1, 2020. Actual enrollment 53. Primary completion Sep 7, 2023. Status: terminated. | Public record |
| Why it stopped | The preprint states it plainly: “The study was terminated as the prespecified criteria for study continuation of ORR greater than that of standard Dox was not met.” | Public record |
| How the result was announced | The June 16, 2025 company release announcing that publication leads with the 12 fold dose and the immune response. It does not mention the termination, or that the response rate matched standard doxorubicin. | Differs from the paper |
| Company stage | October 2023 release: “a clinical stage biotech company”. June 2025 release: “a preclinical biotechnology company”. The YC directory still puts the lead asset in Phase 2. | Descriptions disagree |
| Federal funding | Five NCI SBIR R44 projects, Mejía Oneto as principal investigator, eleven award year records, FY2021 to FY2026, totaling $10,233,607. The newest runs to Aug 31, 2027. | Public record |
| Position in the field | Veraxa Biotech's August 2026 prospectus states: “Only two small biotech companies pursue such approaches, TagWorks and Shasqi, which have both progressed into clinical studies.” Telix names Shasqi Inc among its sarcoma competitors in its FY2025 annual report. | Public record |
| Next clinical program | In March 2025 the company said it would finish preclinical work that year and start clinical trials in 2026. As of September 22, 2026 no new Shasqi-sponsored study appears on ClinicalTrials.gov. | Not found |
Read plainly: Shasqi proved the hard part and lost on the easy part. A bioorthogonal reaction can be run inside a person, the products are tolerated, and twelve to fifteen times a standard chemotherapy dose can be given without the toxicity that dose normally carries. Then the tumors responded about as often as they do to ordinary doxorubicin. A platform validated and a product discontinued, in one dataset. Whether the pivot to antibody fragments and a stronger payload turns the first result into the second is the remaining question.
What to watch
- A new trial registration. The company said in March 2025 that clinical trials would begin in 2026, and none is registered as of September 22, 2026.
- Whether the Johnson & Johnson collaboration, signed June 2023 and expanded October 2023, produces a named candidate. No financial terms have been disclosed.
- Human data on the CEACAM5 and MMAE combination. Everything published so far is preclinical.
In their words
“Shasqi is founded on the belief that one day we will be able to beat cancer without poisoning our bodies.”
José M. Mejía Oneto, founder and CEO, October 2020 release · Company release
“I think it's extremely unique that a seven-person company can file an IND.”
José M. Mejía Oneto to PharmaVoice, 2022 · Interview
“The world of research and the world of manufacturing were transformed through the application of click chemistry, and now I think the world of therapeutics is also going to be transformed by the use of this,”
José M. Mejía Oneto to PharmaVoice, 2022 · Interview
“The significance of this work expands far beyond the current study, as it demonstrates that click chemistry can be harnessed inside the human body to redefine how therapeutics are activated in the body,”
Carolyn Bertozzi, 2022 Nobel laureate, in the June 2025 release · Company release
“Now we have the proof of concept that click chemistry really works in vivo.”
David Bauer, University of Missouri, to The Scientist, 2025 · Independent
“While the initial focus has been on the biopolymer approach, we have most recently pivoted to using an approach similar to antibody-drug conjugates (ADCs), wherein the click chemistry component is localized at the tumor using an antibody fragment,”
José M. Mejía Oneto, University at Albany, March 2025 · University newsroom
Related companies
Sources
- Public recordClinicalTrials.gov NCT04106492
- Public recordNIH RePORTER, five NCI SBIR R44 projects
- Public recordNobel Prize in Chemistry 2022, press release
- Public recordFirst-in-Class Click Chemistry Based Cancer Therapeutic
- Public recordSQ3370 Phase 1/2a preprint
- Public recordVeraxa Biotech Holding AG, Form 424B5
- IndependentNobel-winning click chemistry in humans
- IndependentShasqi snatches $50M
- IndependentClick Chemistry Applications in Oncology
- IndependentShasqi and the ADC 1% problem
- IndependentNIH-Funded Cancer Drug Delivery Platform
- IndependentUC Davis startup in clinical trials
- CompanyClick chemistry breakthrough release
- CompanyLandmark study release
- CompanyBoard appointment releases, Jan 2024 and Oct 2025
- CompanyWebsite, pipeline, YC directory profile
Profile researched and written by Healthcare Discovery. Last updated September 29, 2026.
