Therapeutics · Critical care immunology
Endpoint Health
A Palo Alto company that set out to rescue sepsis drugs the field had given up on, by finding the patients they actually help. It licensed a plasma protein from Grifols, raised $52 million, and then went quiet.
The drug that was already on the shelf
Antithrombin III is not a new molecule. It is a protein purified from donated human plasma, and in the United States the FDA has approved it for one narrow use: hereditary antithrombin deficiency. Grifols, the Barcelona plasma company, makes it.
In March 1997 a multicenter phase 3 trial began testing high doses of it in severe sepsis. KyberSept enrolled 2,314 adults and ran to January 2000. The result, in JAMA in October 2001, was flat: 28 day mortality of 38.9 percent on antithrombin against 38.7 on placebo. Among patients also given heparin, bleeding rose from 13.5 to 23.8 percent.
Buried in that failure was a subgroup. Among the 698 patients given no heparin, 90 day mortality was 44.9 percent against 52.5 percent, p=0.03. A 2006 reanalysis narrowed it further: with disseminated intravascular coagulation and no heparin, an absolute 14.6 percent cut in 28 day mortality.
Sixteen years after that reanalysis, a startup asked Grifols for the molecule.
Why sepsis breaks drugs
Every sepsis company inherits the same graveyard. The only drug that ever cleared a Phase III and reached the market was Xigris, recombinant human activated protein C, approved by the FDA in 2001 on a single trial stopped early. The confirmatory trial, PROWESS-SHOCK, randomized 1,697 patients with septic shock and found 28 day mortality of 26.4 percent on drug against 24.2 on placebo. On October 25, 2011, Eli Lilly pulled Xigris from every market worldwide and halted all trials of it.
In Critical Care Medicine in 2014, Steven Opal and colleagues summarized three decades: “a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit.” Their prescription was not a better molecule but better patient selection. Derek Angus had already written that “more sophisticated selection of patients seems key if we are to most wisely test agents designed to manipulate the septic host response.”
That sentence is the thesis of Endpoint Health.
Founders who had already sold to Roche
Jason Springs met Leonardo Teixeira and Diego Rey at Cornell, where the two were PhD students and he was taking an MBA. Around 2008 they started GeneWEAVE, a rapid bacterial detection company. Springs says it took 50 to 70 pitches to get one term sheet. Roche bought GeneWEAVE in 2015 in a deal valued at $425 million.
Endpoint Health was incorporated in June 2018 and went through Y Combinator in the winter 2019 batch. Springs, Rey, Teixeira and Jeff Osborn built it on an inversion: start with patient data, work out which biological subgroup a drug actually helps, then find a drug that already exists. They called it Precision-First. It launched on July 13, 2020 with $12 million from Mayfield, Y Combinator, AME Cloud Ventures and Wireframe Ventures.
Two crowded years, then silence
Everything landed in 2022. In February, Grifols signed a global collaboration and license making it exclusive supplier of antithrombin III for sepsis, committed up to $25 million, and left Endpoint the development and commercial rights everywhere except China. In June came $52 million in equity and debt from Mayfield, Humboldt Fund, AME Cloud Ventures, Alix Ventures, the Global Health Investment Corporation and five other funds. In September, BARDA signed a $679,115 contract and Ransi Somaratne became the first chief medical officer. In October, Endpoint acquired Iconic Therapeutics and unveiled EP004, an anti tissue factor antibody, with an IND targeted for 2023.
Then the record stops. The last press release is dated October 4, 2022. The website was last archived on December 11, 2025 and no longer resolves.
What is proven, and what is still claimed
| Evidence | What the record shows | Source type |
|---|---|---|
| Grifols license | Feb 24, 2022, repeated in Grifols SEC filings. Exclusive AT-III supply, up to $25 million committed, royalties on net sales, rights global except China. “Endpoint Health will manage the clinical development, the subsequent regulatory approval process and commercialization.” | Public record |
| Regulatory status | No FDA approval, clearance or authorization for any product or test. The company said in 2022 it expected to file an IND and an IDE that year. Neither was confirmed. | Not found |
| Registered trials | Searches on Sep 24, 2026 for the company as sponsor, organization or collaborator returned zero studies. The Phase II trial the 2022 round funded was never registered. | Not found |
| Grifols pipeline | “ATIII in Sepsis (partnership with Endpoint Health)” sits in the hematology row of Grifols Form 6-K pipeline tables for 2022 and 2023. The 2024 report, filed Feb 26, 2025, lists no antithrombin sepsis program. | Public record |
| Federal funding | One contract: 75A50122C00058, signed Sep 14, 2022 by BARDA within HHS ASPR, $679,115 obligated, Sep 16, 2022 to Aug 30, 2024, for the ADRENAL secondary analysis. | Public record |
| Classifier, first result | Shock, March 2022. A 15 gene score split vasodilatory shock into innate prevalent and adaptive prevalent states. Applied retrospectively to VANISH, 28 day mortality on hydrocortisone was 43.3 percent against 14.7 on placebo in the adaptive group, reversed in the innate group, interaction p=0.028. The release called it “hypothesis-generating” pending prospective validation. | Public record |
| Classifier, replication | Critical Care and Resuscitation, June 2025. The BARDA funded substudy classified 540 ADRENAL patients. “There was no evidence of a heterogeneity of treatment effect of hydrocortisone on mortality in the 2 endotypes or in the subgroup with severe shock.” One signal ran the wrong way: “Patients with the IA-P endotype and pulmonary sepsis appear to be harmed by corticosteroids.” | Public record |
| Framing versus record | The February 2022 release said the approach identified two groups with significantly different treatment impact on 28 day mortality. The larger cohort did not reproduce it. | Differs from later record |
| EP004 | Announced Oct 4, 2022 from the Iconic Therapeutics acquisition. “EP004 is currently completing IND-enabling studies, and the company expects an IND submission in 2023.” Nothing since. | Not found |
| Operating status | Last release Oct 4, 2022. Site last archived Dec 11, 2025, unreachable Sep 24, 2026. Y Combinator lists Rey and Osborn under Former Founders. A company database records 21 staff at end 2022 and 8 in March 2026. | Independent |
Read plainly: the science was real, the partner was real, the federal money was real, and the answer came back negative. The companion test got the fairest hearing anyone could ask for, a randomized cohort five times larger than the retrospective one, and it did not hold. What never happened at all is the part the $52 million was raised for: an IND, an IDE, and a Phase II trial in the patients the test picked out.
What to watch
- Whether Grifols reassigns antithrombin III in sepsis or lets it go. It left the published Grifols pipeline between the 2023 and 2024 reports.
- Whether EP004, formerly ICON-4, resurfaces under another owner. Its sibling molecule ICON-2 became Exelixis XB002 and is in the clinic.
- Any ClinicalTrials.gov registration naming Endpoint Health.
- Any SEC filing under the company’s own name. There has never been one.
- Whether the immune endotype idea survives elsewhere. Sepsis subtyping is an active field, and one negative replication is a data point, not a verdict.
In their words
“We combine AI, therapeutics and therapy-guiding tests to rewrite the molecule-first drug development model.”
Jason Springs, co-founder and CEO, June 2022 · Company release
“We identified Antithrombin III as a potentially promising treatment for Sepsis using our proprietary AI platform and we believe we can transform the standard of care in immune-driven illnesses.”
Jason Springs, Grifols announcement, February 2022 · Partner release
“These aren’t single diseases, they’re heterogeneous syndromes, and we can see this in clinical practice”
Hector Wong, MD, Cincinnati Children’s Hospital, 2020 · Company release
“Critically ill patients require multiple therapies that may range from routine care such as fluids, to novel therapies.”
Todd Rice, MD, Vanderbilt University Medical Center, 2020 · Company release
“This research is a meaningful step towards exploring the possibility that subgroups of septic shock patients may respond differently to hydrocortisone therapy depending on their biological characteristics.”
Mitchell Levy, MD, Surviving Sepsis Campaign guideline co-author, 2022 · Company release
“a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit”
Steven Opal and colleagues, Critical Care Medicine, 2014 · Peer reviewed
“There was no evidence of a heterogeneity of treatment effect of hydrocortisone on mortality in the 2 endotypes or in the subgroup with severe shock.”
Venkatesh and colleagues, Critical Care and Resuscitation, June 2025 · Peer reviewed
Related companies
Sources
- Public recordContract 75A50122C00058, BARDA
- Public recordGrifols SA Form 6-K, 2022 report
- Public recordGrifols SA Form 6-K, 2023 report
- Public recordGrifols SA Form 6-K, 2024 report
- Public recordSponsor searches, zero studies
- Public recordHigh-dose antithrombin III in severe sepsis
- Public recordAntithrombin without heparin in sepsis with DIC
- Public recordDrotrecogin alfa in septic shock, PROWESS-SHOCK
- Public recordGene expression scoring in vasodilatory shock
- Public recordImmune endotypes, ADRENAL secondary analysis
- Peer reviewedNext generation of sepsis trial designs
- Peer reviewedDrotrecogin alfa, a sad final fizzle
- IndependentSepsis Drug Xigris Pulled From Worldwide Market
- InterviewJason Springs on GeneWEAVE and Endpoint
- PartnerGrifols and Endpoint sign AT-III sepsis deal
- CompanyEndpoint Health launches with $12 million
- CompanyEndpoint Health raises $52 million
- CompanyEP004 unveiled, Iconic Therapeutics acquired
- CompanyWebsite, about, approach and news archive
- IndependentCompany profile, employees, entity
- CompanyCorticosteroid response in septic shock
- Public recordEDGAR company and full text search
Profile researched and written by Healthcare Discovery. Last updated September 29, 2026.
