DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemophilia B — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHemophilia B maps to a 5-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 hemophilia b 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
coagulation factor VII (F7) — F7 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5PAG · 1.36 Å · ligand (2R)-2-hydroxy-N-[[3-[5-hydroxy-4-(1H-pyrrolo[3,2-c]pyridin-2-yl)pyrazol-1-yl]phenyl]methyl]-3-methylbutanamide (7YJ). Experimental structure, not a prediction.
What the evidence adds up to
A 2006 review of gene therapy for haemophilia B noted that one patient achieved 10% of normal Factor IX activity after liver-directed gene therapy with a single-stranded adeno-associated virus vector. Expression fell at one month, likely due to an immune response to the modified cells. The review concluded that gene therapy had been successful in that patient but expression was unstable because of an immune response, and that abrogating immune responses was the next major hurdle.
A 2017 review of novel therapies for haemophilia A and B stated that none of the approaches then in development specifically addressed the challenge of dispersing treatment to the developing world.
A phase 1/2 first-in-human trial of arvenacogene sanparvovec, an AAV5 vector carrying the human Factor IX gene with the Padua mutation, enrolled 13 male patients aged 18 or older with moderately severe or severe haemophilia B (Factor IX activity ≤2%) and a documented history of at least 150 days of prior Factor IX prophylaxis. Patients received a single intravenous infusion in one of three dose cohorts: 2.5×10¹² vector genomes per kilogram (four participants), 5×10¹² vg/kg (three participants), or 2×10¹³ vg/kg (six participants). Mean Factor IX activity at 52 weeks was 26.3% (standard deviation 19.7) in cohort 1 and 35.7% (SD 17.0) in cohort 2; at 24 weeks it was 14.7% (SD 9.6) in cohort 3. Mean annualised bleeding rate was 7.2 (SD 7.8) in cohort 1, zero in cohort 2, and 1.9 (SD 3.6) at 24 weeks in cohort 3. Ten of the 13 patients discontinued Factor IX prophylaxis. Grade 1–2 adverse reactions occurred in 50% (2/4), 66.7% (2/3), and 66.7% (4/6) of participants in cohorts 1, 2, and 3 respectively. Six of 13 participants had elevated transaminase levels and 3 of 13 had infusion-related reactions. All adverse reactions resolved without sequelae. No grade 3 or higher adverse reactions and no Factor IX inhibitors were reported.
What is still missing is evidence from larger, longer, and randomised trials, data on whether the observed Factor IX expression and bleeding reduction are durable beyond one year, and any strategy for making such treatment available in settings where prophylaxis is already difficult to deliver.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2017 · 123 citations · open access
Novel approaches to hemophilia therapy: successes and challenges
AbstractNew therapies for hemophilia A and hemophilia B will likely continue to change clinical practice. Ranging from extended half-life to nonfactor products and gene therapy, these innovative approaches have the potential to enhance the standard of care by decreasing infusion frequency to increase compliance, promoting prophylaxis, offering alternatives to inhibitor patients, and easing route of administration. Each category has intrinsic challenges that may limit the broader application of these promising therapies. To date, none specifically address the challenge of dispersing treatment to the developing world.
Current Opinion in Hematology · 2006 · 54 citations
Gene therapy for hemophilia
AbstractPURPOSE OF REVIEW: This review will highlight the progress achieved in the past 2 years on using gene therapy to treat hemophilia in animals and humans. RECENT FINDINGS: There has been substantial progress in using gene therapy to treat animals with hemophilia. Novel approaches for hemophilia A in mice include expression of Factor VIII in blood cells or platelets derived from ex-vivo transduced hematopoietic stem cells, or in-vivo transfer of transposons expressing Factor VIII into endothelial cells or hepatocytes. Advances in large-animal models include the demonstration that neonatal administration of a retroviral vector expressing canine Factor VIII completely corrected hemophilia A in dogs, and that double-stranded adeno-associated virus vectors resulted in expression of Factor IX that is 28-fold that obtained using single-stranded adeno-associated virus vectors. In humans, one hemophilia B patient achieved 10% of normal activity after liver-directed gene therapy with a single-stranded adeno-associated virus vector expressing human Factor IX. Expression fell at 1 month, however, which was likely due to an immune response to the modified cells. SUMMARY: Gene therapy has been successful in a patient with hemophilia B, but expression was unstable due to an immune response. Abrogating immune responses is the next major hurdle for achieving long-lasting gene therapy.
Arvenacogene sanparvovec: A novel gene therapy for hemophilia B – results from A phase I–II first-in-human trial
AbstractAbstract Introduction: ANB-002 (INN: arvenacogene sanparvovec) is a gene construct for the therapy of hemophilia B. It utilizes an adeno-associated virus type 5 (AAV5) vector containing the human Factor IX (FIX) gene with the Padua mutation. Following a single intravenous infusion, the therapy is designed to deliver the FIX gene to hepatocytes, leading to sustained FIX protein production by the liver. Its production can potentially reduce or eliminate the need for factor replacement therapy in patients with hemophilia. Methods: ANB-002-1/SAFRAN is an ongoing, open-label, single-arm, phase 1/2 first-in-human clinical trial evaluating the safety and efficacy of arvenacogene sanparvovec in patients with moderately severe or severe hemophilia B (NCT06120582). According to eligibility criteria, male patients aged 18 years or older with moderately severe or severe hemophilia B (FIX activity ≤2%) and a documented history of at least 150 days of previous FIX prophylaxis were included. The absence of both FIX inhibitor and anti-AAV5 antibodies was confirmed for all patients before enrollment. Thirteen patients with hemophilia B received a single dose of arvenacogene sanparvovec in one of three dose cohorts (2.5×10¹² vector genomes (vg) per kilogram (kg) of body weight in four participants, 5×10¹² vg/kg in three participants and 2×10¹³ vg/kg in six participants) between May 2023 and July 2024. Results: The mean FIX activity ± standard deviation (±SD) (one-stage assay) was 26.3±19.7% at the cohort 1, 35.7±17.0% at the cohort 2 at 52 week and 14.7±9.6% at the cohort 3 at 24 week. The mean of annualized bleeding rate (ABR) was 7.2 (±7.8) at cohort 1 and there were no bleedings at cohort 2. The mean annualized bleeding rate for 24 weeks was 1.9 (±3.6) at cohort 3. Ten patients from thirteen discontinued FIX prophylaxis. Grades 1–2 adverse reactions (AR) were reported in 50% (2/4), 66.7% (2/3) and 66.7% (4/6) of participants in cohorts 1, 2 and 3 respectively. Six of thirteen participants experienced adverse reactions of elevated transaminase levels and 3 of 13 experienced infusion-related reactions. All adverse reactions cases resolved without sequelae. No AR of grade 3 or higher were reported in any of the cohorts. No FIX inhibitor was detected in all cohorts. Conclusion: A single administration of ANB-002 (arvenacogene sanparvovec) gene therapy to 13 patients with moderately severe or severe hemophilia B resulted in durable factor IX expression, sustained clinical benefit that made it possible completely discontinue the FIX prophylaxis for 10 from 13 participants. Therapy was well tolerated.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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