Allogeneic Hematopoietic Stem Cell Transplantation With Briquilimab-Based Conditioning in Participants With GATA2 Deficiency

1. Is the biology right?

• Somatic driver evidence: no · None of IMPDH1, IMPDH2, FKBP1A, KIT has somatic-mutation evidence in GATA2 deficiency with susceptibility to MDS/AML

  Rule: Open Targets has somatic-mutation evidence for the target in this cancer. Source: Open Targets: IMPDH1 in GATA2 deficiency with susceptibility to MDS/AML, 2026-11-11
• Human genetic evidence: no · No germline or somatic evidence for IMPDH1, IMPDH2, FKBP1A, KIT in GATA2 deficiency with susceptibility to MDS/AML

  Rule: Any germline or somatic human genetic evidence for the target in this cancer, counted apart from animal-model and literature evidence. Source: Open Targets: IMPDH1 in GATA2 deficiency with susceptibility to MDS/AML, 2026-11-11
• Pediatric target: yes · KIT on the FDA list

  Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets); membership alone neither requires nor waives a study. Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
• Haematologic cancer: no · Solid tumour

  Rule: From the indication, or the registry conditions when no indication matches. Source: ClinicalTrials.gov NCT05907746, 2026-11-11

  Published context: Likelihood of approval from phase 1: 7.5% haematologic vs 4.6% solid (BIO / Informa / QLS 2021, 2011–2020). Population-level, not a prediction.

• Background therapy: Cyclophosphamide, Fludarabine: standard agents, not counted in these flags.
• IMPDH1 (via Mycophenolate Mofetil): Evidence types in GATA2 deficiency with susceptibility to MDS/AML: clinical. Datasources: clinical_precedence. · Open Targets: IMPDH1 in GATA2 deficiency with susceptibility to MDS/AML
• IMPDH2 (via Mycophenolate Mofetil): Evidence types in GATA2 deficiency with susceptibility to MDS/AML: clinical. Datasources: clinical_precedence. · Open Targets: IMPDH2 in GATA2 deficiency with susceptibility to MDS/AML
• FKBP1A (via Tacrolimus): Evidence types in GATA2 deficiency with susceptibility to MDS/AML: clinical. Datasources: clinical_precedence. · Open Targets: FKBP1A in GATA2 deficiency with susceptibility to MDS/AML
• KIT (via Briquilimab): Evidence types in GATA2 deficiency with susceptibility to MDS/AML: clinical. Datasources: clinical_precedence. · Open Targets: KIT in GATA2 deficiency with susceptibility to MDS/AML

• Not loaded on this app yet: Normal-tissue expression in vital organs. Source: Human Protein Atlas (ticket 36).
• Not loaded on this app yet: Pan-essential in cell lines. Source: DepMap (ticket 36).
• Not loaded on this app yet: Approved drug on this target. Source: Drugs@FDA (ticket 30).

2. Can the result be trusted?

• Randomised: no · Non-randomised

  Rule: Registry allocation field. Source: ClinicalTrials.gov NCT05907746, 2026-11-11
• Small denominator: yes · 13 enrolled; each patient moves a rate by 100 ÷ 13 = 7.7 points

  Rule: Enrolment under 30; the arithmetic is shown, not a benchmark. Source: ClinicalTrials.gov NCT05907746, 2026-11-11
• Primary endpoint is overall survival: no · Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment b…; Percentage of Evaluable Participants With GATA-binding Factor 2 (GATA2) Deficiency With Sustained Donor Engraftment b…

  Rule: A registered primary outcome measure names overall survival. Source: ClinicalTrials.gov NCT05907746, 2026-11-11

  Published context: Non-OS primary endpoint: odds ratio 2.79 for a positive phase 3 (Otsuka 2021, 400 phase 3 oncology trials, to 2020). Shown with the next figure: a surrogate is easier to hit, and often a weak guide to survival.

  Published context: 52% of surrogate-to-OS correlations are low (Prasad 2015, published to 2014). Shown with the figure above.
• Results overdue: no · Results posted 2026-05-29

  Rule: Primary completion (actual) more than 12 months ago and no results posted to the registry. Source: ClinicalTrials.gov NCT05907746, 2026-11-11

• Not loaded on this app yet: Treated and evaluable counts, assessor, confirmed response, follow-up and data cutoff. Source: Readout extraction (ticket 32).
• Not loaded on this app yet: Primary endpoint changed between registry versions. Source: Registry versions in the store (ticket 32).

3. What must it beat?

• Not loaded on this app yet: Control-arm result and approved therapies for the same segment, with label links. Source: Drugs@FDA, FDA labels and readouts (tickets 30, 32).

4. Too crowded, or too late?

• Stopped on this target: 241 terminated, withdrawn or suspended trials of drugs against IMPDH1; 15 of the 200 most recent give no reason. Reasons are quoted as the registry gives them on the target page. · IMPDH1: what already stopped

• Not loaded on this app yet: Programs on the target by phase and months behind the leader. Source: Programs and Drugs@FDA (ticket 33).

5. Can it be approved, and stay approved?

• Single-country: yes · The only site is in United States

  Rule: All listed sites are in one country; the share of US sites is shown. Source: ClinicalTrials.gov NCT05907746, 2026-11-11
• EU paediatric investigation plan: yes · EMA/PE/0000232771 (tacrolimus, Treatment of vernal keratoconjunctivitis): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 21 Mar 2025; EMEA-001642-PIP02-20 (tacrolimus, Prevention of solid organ transplant rejection;Treatment of solid organ transplant rejection): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 17 Mar 2021

  Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
• EU orphan designation: yes · EU/3/22/2733 positive 9 Dec 2022: Treatment in haematopoietic stem cell transplantation; EU/3/17/1912 positive 23 Aug 2017: Treatment of pulmonary arterial hypertension

  Rule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
• Authorised in the EU: yes · Advagraf: authorised since 23 Apr 2007; CellCept: authorised since 14 Feb 1996; Mycophenolate mofetil Teva: authorised since 21 Feb 2008; Myfenax: authorised since 21 Feb 2008; +6 more

  Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
• FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the link

  Rule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
• FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of Mycophenolate Mofetil, Tacrolimus, Post-Transplant Cyclophosphamide, Briquilimab

  Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
• Registered studies open to children: yes · 652 interventional studies of Mycophenolate Mofetil, Tacrolimus, Post-Transplant Cyclophosphamide, Briquilimab include patients under 18; 124 are recruiting, not yet recruiting or active

  Rule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11

• Caveat: Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where the sites are is a fact about the record, not a judgement of its quality.
• Rare pediatric disease voucher: FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. · FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs

• Not loaded on this app yet: Precedent approvals for target, modality and endpoint; accelerated-approval status. Source: Drugs@FDA and FDA accelerated-approval tables (ticket 30).

6. Can the sponsor finish?

• Sponsor: National Cancer Institute (NCI) (academic or other) · ClinicalTrials.gov NCT05907746
• principal investigator: Danielle E Pregent-Arnold, M.D., National Cancer Institute (NCI) · Person page

• Not loaded on this app yet: Filed cash, quarterly spend and the runway arithmetic. Source: SEC XBRL company facts (ticket 37).
• Not loaded on this app yet: Sponsor's completed vs stopped oncology trials and results-reporting record. Source: Registry, by company (ticket 37).

What public data cannot tell you

Public records cannot show: sales forecasts; a probability of success for this asset; full deal terms and net prices; FDA designations and action dates before approval (shown only as company-reported); clinical holds unless the company disclosed them; manufacturing; patents on unapproved drugs; whether preclinical findings have been replicated.