DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemophagocytic syndrome — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHemophagocytic syndrome maps to a 7-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hemophagocytic syndrome is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
Bruton tyrosine kinase (BTK) — BTK is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
In an open-label phase 2-3 study of 34 children with primary haemophagocytic lymphohistiocytosis, 63% of previously treated patients and 65% of all patients who received emapalumab plus dexamethasone met the primary endpoint of overall response, both significantly above the prespecified null hypothesis of 40%. Among previously treated patients, 70% proceeded to haematopoietic stem-cell transplantation; 74% were alive at last observation. Emapalumab was not associated with organ toxicity, but severe infections occurred in 10 patients and one patient discontinued due to disseminated histoplasmosis.
A retrospective chart review across 33 US hospitals identified 17 patients with malignancy-associated HLH who received at least one dose of emapalumab between 2018 and 2021. Median age at HLH diagnosis was 15 years; 59% received emapalumab in an intensive care unit, and 94% had received other HLH therapies beforehand. Emapalumab-containing regimens normalised or maintained key laboratory values in most patients, but overall survival at end of follow-up was 23.5% and 12-month survival probability from initiation was 22.1%.
A separate analysis of a large US electronic health record dataset covering 41,750 patients diagnosed with primary or secondary HLH found that emapalumab treatment rates rose from 0.73% in 2019 to 1.9% in 2024. The death rate for HLH fell from 4% in 2018 (before emapalumab was introduced) to 1.1% in 2024. Among patients not treated with emapalumab, 39% had a hospital stay longer than 14 days, compared with 13% of treated patients; 69% of treated patients had a stay of 4 to 6 days, versus 18% of untreated patients.
The evidence for emapalumab in primary HLH comes from a single-arm study with no randomised comparator. In malignancy-associated HLH, survival remains very poor and no standard dosing has been established. The population-level dataset cannot attribute falling death rates to emapalumab specifically, and the treatment rate remains low. What is still missing are randomised controlled trials, prospective data on optimal timing and dosing in secondary HLH, and reliable stratification of patients most likely to benefit.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2020 · 519 citations · open access
Emapalumab in Children with Primary Hemophagocytic Lymphohistiocytosis
AbstractBACKGROUND: Primary hemophagocytic lymphohistiocytosis is a rare syndrome characterized by immune dysregulation and hyperinflammation. It typically manifests in infancy and is associated with high mortality. METHODS: We investigated the efficacy and safety of emapalumab (a human anti-interferon-γ antibody), administered with dexamethasone, in an open-label, single-group, phase 2-3 study involving patients who had received conventional therapy before enrollment (previously treated patients) and previously untreated patients who were 18 years of age or younger and had primary hemophagocytic lymphohistiocytosis. The patients could enter a long-term follow-up study until 1 year after allogeneic hematopoietic stem-cell transplantation or until 1 year after the last dose of emapalumab, if transplantation was not performed. The planned 8-week treatment period could be shortened or extended if needed according to the timing of transplantation. The primary efficacy end point was the overall response, which was assessed in the previously treated patients according to objective clinical and laboratory criteria. RESULTS: At the cutoff date of July 20, 2017, a total of 34 patients (27 previously treated patients and 7 previously untreated patients) had received emapalumab; 26 patients completed the study. A total of 63% of the previously treated patients and 65% of the patients who received an emapalumab infusion had a response; these percentages were significantly higher than the prespecified null hypothesis of 40% (P = 0.02 and P = 0.005, respectively). In the previously treated group, 70% of the patients were able to proceed to transplantation, as were 65% of the patients who received emapalumab. At the last observation, 74% of the previously treated patients and 71% of the patients who received emapalumab were alive. Emapalumab was not associated with any organ toxicity. Severe infections developed in 10 patients during emapalumab treatment. Emapalumab was discontinued in 1 patient because of disseminated histoplasmosis. CONCLUSIONS: Emapalumab was an efficacious targeted therapy for patients with primary hemophagocytic lymphohistiocytosis. (Funded by NovImmune and the European Commission; NI-0501-04 and NI-0501-05 ClinicalTrials.gov numbers, NCT01818492 and NCT02069899.).
Emapalumab use in malignancy-associated hemophagocytic lymphohistiocytosis in the United States: the REAL-HLH study
AbstractABSTRACT: Malignancy-associated hemophagocytic lymphohistiocytosis (mHLH), a hyperinflammatory syndrome, has poor prognosis and no standard therapy. Emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon gamma, is approved for treating primary hemophagocytic lymphohistiocytosis (pHLH). REAL-HLH, a retrospective chart review conducted across 33 US hospitals, evaluated real-world treatment patterns and outcomes in patients treated with ≥1 dose of emapalumab between 20 November 2018 and 31 October 2021. Data are presented for the subset of patients with mHLH. Overall, 51 of 105 (48.6%) patients were categorized as having secondary HLH, of which 17 of 51 patients had HLH associated with an underlying malignancy (mHLH). At HLH diagnosis, the median age (range) was 15.0 (3.0-27.0) years, 6 of 14 (42.9%) patients with available data had a positive Optimized HLH Inflammatory index, indicating pathologic inflammation; 9 of 17 (52.9%) had infections; and 10 of 17 (58.8%) received emapalumab in an intensive care unit. Emapalumab was primarily initiated for treating refractory (10/17; 58.8%) or progressive (3/17, 17.7%) disease. Most patients received HLH-related therapies before (16/17; 94.1%) and/or concurrent with (15/17; 88.2%) emapalumab. Treatment with emapalumab-containing regimens normalized most key laboratory parameters and maintained normal values for others (fibrinogen [11/13; 84.6%], absolute neutrophil count [6/10; 60%], and chemokine ligand 9 [7/8; 87.5%]) per physician assessment. Overall survival at the end of follow-up and 12-month survival probability from emapalumab initiation were 23.5% and 22.1%, respectively. In conclusion, emapalumab-containing regimens normalized, improved, or maintained normal values for most laboratory parameters in patients with mHLH. Future studies are warranted to establish appropriate emapalumab dosing and utility in this high-risk population.
Journal of Human Immunity · 2025 · 0 citations · open access
Impact of Emapalumab on Patients with Hemophagocytic Lymphohistiocytosis
AbstractRationale In 2018, emapalumab was introduced for treatment of hemophagocytic lymphohistiocytosis (HLH). Emapalumab targets cytosolic and receptor-bound interferon-gamma to attenuate hyperinflammation. Methods A large limited de-identified dataset from Epic Cosmos was used to examine treatment rates with emapalumab. Demographics, length of stay, and overall death rates were analyzed. Results Since emapalumab was introduced, 41,750 patients have been diagnosed with primary or secondary HLH. Treatment with emapalumab steadily increased from 0.73% in 2019 to 1.9% in 2024. Death rate of HLH in 2018 prior to introduction of emapalumab was 4%. The death rate in 2024 was 1.1%. Prevalence of HLH was not affected by race or age. Overall prevalence across all ethnicities was 0.01%. Prevalence of HLH in patients under 10 years and between 10 to 19 years of age was 0.01%, but after age 19 years the prevalence decreased to between 0.002 and 0.006%. 39% of patients diagnosed with HLH not treated with emapalumab had a length of stay greater than 14 days compared with 13% of treated patients. Conversely, 69% of treated patients had a length of stay between 4 to 6 days, compared with 18% of untreated patients. Discussion Treatment rates of emapalumab have slowly increased since introduction but remain low despite benefits of treatment. Prevalence of HLH remains consistent among races but is lower in patients aged >20 years. Length of hospital stay was significantly reduced in patients treated with emapalumab. Death rates from HLH decreased from 4% to 1.1% in the time period since emapalumab became available.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
