{
 "title": "ACD856 evidence dataset (Condor Research)",
 "version": "1.1",
 "cutoff": "2026-10-26",
 "license": "CC BY 4.0",
 "creator": "Condor Research Editorial",
 "url": "https://condorresearch.com/wp-content/uploads/evidence-cards/acd856/dataset.json",
 "data_dictionary": {
  "census[].evidence_type": "H human; A animal (with or without cells); V in vitro only; R review. Highest level present.",
  "census[].origin": "sponsor = any AlzeCure author or AlzeCure funding (criterion A); independent otherwise.",
  "census[].data_role": "primary, review_own_data, mention.",
  "human_studies[]": "One row per human study; doses omitted by editorial rule.",
  "claims[].verdict": "SUPPORTED, TRIAL_DATA, PARTIAL, CONTRADICTED, NO_SOURCE, NOT_ASSESSABLE (definitions in Table 13).",
  "vendors[]": "Anonymised public catalogue pages; URLs held by Condor Research Editorial."
 },
 "search_log": {
  "pubmed": {
   "query": "\"ACD856\"[tiab] OR \"ACD-856\"[tiab] OR \"ACD 856\"[tiab]",
   "count": 6,
   "all_fields_count": 12,
   "all_fields_note": "6 additional records were false matches on 'acd' AND '856'",
   "affiliation_query": "AlzeCure[ad]: 32 records, no further ACD856 record",
   "date": "2026-10-26"
  },
  "europepmc": {
   "query": "ACD856 OR \"ACD-856\" OR \"ACD 856\"",
   "hits": 21
  },
  "ctgov": {
   "queries": [
    "query.term=ACD856",
    "query.term=ACD-856",
    "query.intr=ACD856",
    "query.spons=AlzeCure",
    "query.term=ACD855",
    "query.intr=ponazuril (8 unrelated device trials: brand-name expansion)"
   ],
   "acd856_records": 3
  },
  "ctis": {
   "queries": [
    "ACD856",
    "ACD-856",
    "ACD855",
    "AlzeCure",
    "NeuroRestore",
    "ponazuril"
   ],
   "records": [
    "2025-522287-32-00"
   ]
  },
  "euctr": {
   "query": "AlzeCure",
   "records": [
    "2022-000902-82 (ACD440, not ACD856)"
   ],
   "note": "Adult-only phase 1 trials not displayed"
  },
  "pubchem": "Name search ACD856 / ACD-856: no record; CID 139434107 for CAS 2375424-89-6 has no ACD856 synonym",
  "patents": "Google Patents via scraping service (direct requests refused)",
  "regulators": [
   "openFDA drugsfda: no match",
   "EMA: no entry",
   "WADA 2026: S0"
  ],
  "forums": "Web-search excerpts; Reddit not queried directly",
  "date": "2026-10-26"
 },
 "census": [
  {
   "pmid": "34440640",
   "year": 2021,
   "evidence_type": "A",
   "origin": "sponsor",
   "data_role": "primary",
   "design": "Screen of about 25,000 molecules; recombinant Trk cell assays, surface plasmon resonance, kinase kinetics, rat hippocampal slices (LTP), rat microdialysis, mouse and rat memory models including 18-month-old mice",
   "species": "cells; mouse; rat",
   "n": "8 per group typical (mouse); 6 rats (microdialysis); 12 per group (rat object recognition)",
   "authors_sponsor": "7/10 employed by or holding equity in AlzeCure (conflict statement)",
   "funding": "ADDF, Vinnova, Swedish Research Council, Swedish Brain Foundation and others",
   "role": "Discovery paper: ACD855 (ponazuril) and ACD856 named as Trk PAMs; chemical structure withheld by the developer ('company confidentiality')",
   "title": "Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction.",
   "journal": "Cells",
   "doi": "10.3390/cells10081871"
  },
  {
   "pmid": "37394539",
   "year": 2023,
   "evidence_type": "A",
   "origin": "sponsor",
   "data_role": "primary",
   "design": "Forced swim test in mice and rats with ACD855, ACD856 and AC26845, ketamine and fluoxetine; rat microdialysis",
   "species": "mouse; rat",
   "n": "6-8 mice per group; 6 rats (microdialysis)",
   "authors_sponsor": "5/7 employed by AlzeCure",
   "funding": "not stated beyond employment",
   "role": "Antidepressant-like behaviour in rodents",
   "title": "Antidepressant effects of novel positive allosteric modulators of Trk-receptor mediated signaling - a potential therapeutic concept?",
   "journal": "Psychopharmacology (Berl)",
   "doi": "10.1007/s00213-023-06410-x"
  },
  {
   "pmid": "37446337",
   "year": 2023,
   "evidence_type": "A",
   "origin": "sponsor",
   "data_role": "primary",
   "design": "PC12, SH-SY5Y and primary cortical neurons (neurite outgrowth, SNAP25, pTrkB, pERK, amyloid-beta and energy-deprivation toxicity, BDNF); BDNF in brains of 3-month and 21-month-old mice; forced swim test",
   "species": "cells; mouse",
   "n": "7-8 mice per group (behaviour)",
   "authors_sponsor": "10/10 employed by AlzeCure at the time",
   "funding": "no external funding",
   "role": "Neuroprotection and BDNF data; reports about 60% TrkA activation without NGF in recombinant cells (partial agonism)",
   "title": "Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.",
   "journal": "Int J Mol Sci",
   "doi": "10.3390/ijms241311159"
  },
  {
   "pmid": "37874100",
   "year": 2023,
   "evidence_type": "H",
   "origin": "sponsor",
   "data_role": "primary",
   "design": "Phase 1, randomised, double-blind, placebo-controlled, 7 days, healthy volunteers; plasma, urine and CSF pharmacokinetics; qEEG in two cohorts",
   "species": "human",
   "n": "24 (18 active, 6 placebo)",
   "authors_sponsor": "6/10 AlzeCure; 2 CRO (CTC); 2 qEEG vendor (Siesta Group)",
   "funding": "AlzeCure",
   "role": "Only published repeated-exposure human data; qEEG as a target-engagement marker",
   "title": "Safety, Tolerability, Pharmacokinetics and Quantitative Electroencephalography Assessment of ACD856, a Novel Positive Allosteric Modulator of Trk-Receptors Following Multiple Doses in Healthy Subjects.",
   "journal": "J Prev Alzheimers Dis",
   "doi": "10.14283/jpad.2023.89"
  },
  {
   "pmid": "38353689",
   "year": 2024,
   "evidence_type": "H",
   "origin": "sponsor",
   "data_role": "primary",
   "design": "Phase 0 (open label, 6 men, sub-pharmacological exposure) and phase 1 (randomised, double-blind, placebo-controlled)",
   "species": "human",
   "n": "6 + 56 (42 active, 14 placebo)",
   "authors_sponsor": "5/7 AlzeCure (3 employees, 2 paid consultants); 2 CRO (CTC)",
   "funding": "AlzeCure; open-access fee paid by Karolinska Institutet",
   "role": "First-in-human data; also the only public report of the discontinued ACD855 human study",
   "title": "ACD856, a novel positive allosteric modulator of Trk receptors, single ascending doses in healthy subjects: Safety and pharmacokinetics.",
   "journal": "Eur J Clin Pharmacol",
   "doi": "10.1007/s00228-024-03645-1"
  },
  {
   "pmid": "39204102",
   "year": 2024,
   "evidence_type": "R",
   "origin": "sponsor",
   "data_role": "review_own_data",
   "design": "Narrative review of Trk positive allosteric modulators",
   "species": "review",
   "n": null,
   "authors_sponsor": "6/6 employed by AlzeCure",
   "funding": "no external funding",
   "role": "States that AlzeCure has not disclosed the chemical structure of ACD856 in journals",
   "title": "Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease.",
   "journal": "Pharmaceuticals (Basel)",
   "doi": "10.3390/ph17080997"
  }
 ],
 "census_fulltext_only_mentions": [
  {
   "pmid": "37631266",
   "year": 2023,
   "journal": "Pharmaceutics",
   "country": "Argentina",
   "type": "independent review"
  },
  {
   "pmid": "39174535",
   "year": 2024,
   "journal": "Signal Transduct Target Ther",
   "country": "China",
   "type": "independent review"
  },
  {
   "pmid": "41383700",
   "year": 2024,
   "journal": "Neuroprotection",
   "country": "China",
   "type": "independent review"
  },
  {
   "pmid": "40336944",
   "year": 2025,
   "journal": "Front Aging Neurosci",
   "country": "China",
   "type": "independent review (qEEG biomarkers)"
  },
  {
   "pmid": "41562905",
   "year": 2025,
   "journal": "Med Sci (Basel)",
   "country": "Russia",
   "type": "independent review"
  },
  {
   "pmid": "41053984",
   "year": 2026,
   "journal": "FEBS Open Bio",
   "country": "Finland",
   "type": "independent review"
  },
  {
   "pmid": "41596628",
   "year": 2026,
   "journal": "Int J Mol Sci",
   "country": "Japan",
   "type": "independent review"
  },
  {
   "pmid": "41599368",
   "year": 2026,
   "journal": "Molecules",
   "country": "Poland",
   "type": "independent review"
  },
  {
   "pmid": "42337959",
   "year": 2026,
   "journal": "Alzheimers Dement",
   "country": "Mexico",
   "type": "independent review"
  },
  {
   "pmid": "42041106",
   "year": 2026,
   "journal": "J Med Chem",
   "country": "Italy",
   "type": "independent review"
  }
 ],
 "related_not_counted": [
  {
   "pmid": "31857832",
   "note": "Independent patent highlight (ACS Med Chem Lett 2019) of AlzeCure's triazine filing; the source that chemistry databases cite for the 'Example 5' structure; does not name ACD856"
  },
  {
   "pmid": "35850433",
   "note": "AlzeCure-authored review of neurotrophin therapeutics (2022); ACD856 not named in title or abstract"
  },
  {
   "pmid": "42048677",
   "note": "AlzeCure paper on ACD137, a TrkA negative allosteric modulator from the same group (2026)"
  }
 ],
 "human_studies": [
  {
   "key": "ACD855-SAD",
   "compound": "ACD855 (ponazuril)",
   "phase": "1",
   "registry": "EudraCT 2018-002320-16 (not public: adult phase 1)",
   "ctgov": null,
   "population": "Healthy volunteers",
   "n": "Cohort 1 only (n not reported)",
   "design": "Phase 1, stopped after the first cohort",
   "start": "2018",
   "end": "2019",
   "status": "Prematurely terminated",
   "reg_first_post": null,
   "result": "Plasma half-life averaged 68 days against a predicted 4.6 days; development stopped",
   "channel": "Background paragraph and supplementary figure of PMID 38353689",
   "refs": [
    "38353689"
   ]
  },
  {
   "key": "microdose",
   "compound": "ACD856",
   "phase": "0",
   "registry": "NCT05783830; EudraCT 2019-003504-13",
   "ctgov": "NCT05783830",
   "population": "Healthy men",
   "n": "6",
   "design": "Open-label phase 0, sub-pharmacological exposure",
   "start": "2020-01-13",
   "end": "2020-04-18",
   "status": "Completed",
   "reg_first_post": "2023-03-24",
   "result": "Terminal half-life about 19-20 h; 8 adverse events in 4 participants, 7 judged possibly related, including one transient liver-enzyme elevation (two events of severe intensity by CTCAE) for which the authors cite strenuous exercise; no serious adverse events",
   "channel": "PMID 38353689; AAIC 2021 poster",
   "refs": [
    "38353689",
    "AAIC2021"
   ]
  },
  {
   "key": "SAD",
   "compound": "ACD856",
   "phase": "1",
   "registry": "NCT05077631; EudraCT 2020-003379-16",
   "ctgov": "NCT05077631",
   "population": "Healthy adults",
   "n": "56 (42 active, 14 placebo)",
   "design": "Randomised, double-blind, placebo-controlled",
   "start": "2021-02-15",
   "end": "2022-02-22",
   "status": "Completed",
   "reg_first_post": "2021-10-14",
   "result": "62 adverse events in 31 of 56 participants; 24 events in 13 participants on ACD856 judged possibly related, mostly mild, headache most common; no serious adverse events; exposure proportional across cohorts",
   "channel": "PMID 38353689",
   "refs": [
    "38353689",
    "CT_SAD"
   ]
  },
  {
   "key": "MAD",
   "compound": "ACD856",
   "phase": "1",
   "registry": "NCT05077501",
   "ctgov": "NCT05077501",
   "population": "Healthy adults",
   "n": "24 (18 active, 6 placebo)",
   "design": "Randomised, double-blind, placebo-controlled, 7-day study period",
   "start": "2021-09-29",
   "end": "2022-05-23",
   "status": "Completed",
   "reg_first_post": "2021-10-14",
   "result": "No serious adverse events; CSF levels rose across cohorts; qEEG: more relative theta, less fast alpha and beta power",
   "channel": "PMID 37874100; CTAD 2022 abstract",
   "refs": [
    "37874100",
    "CT_MAD"
   ]
  },
  {
   "key": "Ib",
   "compound": "ACD856",
   "phase": "1b",
   "registry": "CTIS 2025-522287-32-00",
   "ctgov": null,
   "population": "Healthy participants, 18-64 and 65+",
   "n": "40 (CTIS field)",
   "design": "Randomised, double-blind, placebo-controlled phase 1b",
   "start": "2025-10-22",
   "end": "2026-04-09",
   "status": "Ended",
   "reg_first_post": "2025-09-10",
   "result": "Company: well tolerated, no substance-related safety findings, higher blood and CSF concentrations",
   "channel": "Press releases of 20 April and 16 June 2026 only",
   "refs": [
    "CTIS",
    "PR_IB"
   ]
  },
  {
   "key": "IIa",
   "compound": "ACD856",
   "phase": "2a",
   "registry": "Not located (CTIS, ClinicalTrials.gov)",
   "ctgov": null,
   "population": "People with Alzheimer's disease (planned)",
   "n": "Not disclosed",
   "design": "Not disclosed",
   "start": "planned 2026",
   "end": null,
   "status": "Planned; EU EIC grant awarded",
   "reg_first_post": null,
   "result": "None",
   "channel": "Company reports",
   "refs": [
    "PR_EIC",
    "Q2_2026"
   ]
  }
 ],
 "analytics": {
  "date": "2026-10-26",
  "identity": {
   "tool": "RDKit 2026.09.1",
   "proton_mass": 1.007276467,
   "molecules": [
    {
     "key": "vendor_acd856",
     "name": "Structure sold as 'ACD856' (CAS 2375424-89-6; PubChem CID 139434107, 'IGF-1R modulator 1', patent Example 5)",
     "formula": "C22H17N3O4",
     "inchikey": "REYFGVMCUDWCML-UHFFFAOYSA-N",
     "mw_average": 387.4,
     "monoisotopic": 387.1219,
     "ions": {
      "[M+H]+": 388.1292,
      "[M+Na]+": 410.1111,
      "[M-H]-": 386.1146
     },
     "clogp_crippen": 2.78,
     "tpsa": 86.1,
     "hbd": 1,
     "hba": 4
    },
    {
     "key": "acd855_ponazuril",
     "name": "ACD855 = ponazuril (toltrazuril sulfone; CAS 69004-04-2; CID 3050408)",
     "formula": "C18H14F3N3O6S",
     "inchikey": "VBUNOIXRZNJNAD-UHFFFAOYSA-N",
     "mw_average": 457.39,
     "monoisotopic": 457.0555,
     "ions": {
      "[M+H]+": 458.0628,
      "[M+Na]+": 480.0448,
      "[M-H]-": 456.0483
     },
     "clogp_crippen": 1.62,
     "tpsa": 120.2,
     "hbd": 1,
     "hba": 6
    },
    {
     "key": "toltrazuril",
     "name": "Toltrazuril (CID 68591), the parent veterinary drug",
     "formula": "C18H14F3N3O4S",
     "inchikey": "OCINXEZVIIVXFU-UHFFFAOYSA-N",
     "mw_average": 425.39,
     "monoisotopic": 425.0657,
     "ions": {
      "[M+H]+": 426.073,
      "[M+Na]+": 448.0549,
      "[M-H]-": 424.0584
     },
     "clogp_crippen": 2.94,
     "tpsa": 86.1,
     "hbd": 1,
     "hba": 5
    }
   ],
   "note": "The vendor structure is computed from the PubChem record; AlzeCure has not published ACD856's structure, so these values describe what is sold, not a confirmed identity. Vendor E's formula (C9H7NO5) cannot correspond to CAS 2375424-89-6."
  },
  "safety_bounds": {
   "method": "Exact one-sided 95% upper bound for the frequency of an adverse event observed in 0 of n exposed participants (Clopper-Pearson; equals 1 - 0.05^(1/n), close to 3/n).",
   "assumptions": [
    "Phase 0 participants (n = 6) excluded: exposure was sub-pharmacological.",
    "Each participant counted once; the two phase 1 studies had separate cohorts.",
    "Phase 1b allocation not published; two scenarios shown.",
    "Bounds concern serious adverse events, of which none was reported, occurring within the exposure and follow-up of these studies (study periods of up to 7 days in published data), in healthy adults."
   ],
   "rows": [
    {
     "label": "7-day study period, published (second phase 1)",
     "n": 18,
     "upper95": 0.1533,
     "rule_of_three": 0.1667
    },
    {
     "label": "Any pharmacological exposure, published (both phase 1 studies)",
     "n": 60,
     "upper95": 0.0487,
     "rule_of_three": 0.05
    },
    {
     "label": "Published + phase 1b if all 40 received ACD856 (upper scenario)",
     "n": 100,
     "upper95": 0.0295,
     "rule_of_three": 0.03
    },
    {
     "label": "Published + phase 1b if 30 of 40 received ACD856 (assumed 3:1)",
     "n": 90,
     "upper95": 0.0327,
     "rule_of_three": 0.0333
    }
   ],
   "curve": [
    {
     "n": 5,
     "upper95": 0.4507
    },
    {
     "n": 10,
     "upper95": 0.2589
    },
    {
     "n": 15,
     "upper95": 0.181
    },
    {
     "n": 20,
     "upper95": 0.1391
    },
    {
     "n": 25,
     "upper95": 0.1129
    },
    {
     "n": 30,
     "upper95": 0.095
    },
    {
     "n": 35,
     "upper95": 0.082
    },
    {
     "n": 40,
     "upper95": 0.0722
    },
    {
     "n": 45,
     "upper95": 0.0644
    },
    {
     "n": 50,
     "upper95": 0.0582
    },
    {
     "n": 55,
     "upper95": 0.053
    },
    {
     "n": 60,
     "upper95": 0.0487
    },
    {
     "n": 65,
     "upper95": 0.045
    },
    {
     "n": 70,
     "upper95": 0.0419
    },
    {
     "n": 75,
     "upper95": 0.0392
    },
    {
     "n": 80,
     "upper95": 0.0368
    },
    {
     "n": 85,
     "upper95": 0.0346
    },
    {
     "n": 90,
     "upper95": 0.0327
    },
    {
     "n": 95,
     "upper95": 0.031
    },
    {
     "n": 100,
     "upper95": 0.0295
    },
    {
     "n": 105,
     "upper95": 0.0281
    },
    {
     "n": 110,
     "upper95": 0.0269
    },
    {
     "n": 115,
     "upper95": 0.0257
    },
    {
     "n": 120,
     "upper95": 0.0247
    },
    {
     "n": 125,
     "upper95": 0.0237
    },
    {
     "n": 130,
     "upper95": 0.0228
    },
    {
     "n": 135,
     "upper95": 0.0219
    },
    {
     "n": 140,
     "upper95": 0.0212
    },
    {
     "n": 145,
     "upper95": 0.0204
    },
    {
     "n": 150,
     "upper95": 0.0198
    },
    {
     "n": 155,
     "upper95": 0.0191
    },
    {
     "n": 160,
     "upper95": 0.0185
    },
    {
     "n": 165,
     "upper95": 0.018
    },
    {
     "n": 170,
     "upper95": 0.0175
    },
    {
     "n": 175,
     "upper95": 0.017
    },
    {
     "n": 180,
     "upper95": 0.0165
    },
    {
     "n": 185,
     "upper95": 0.0161
    },
    {
     "n": 190,
     "upper95": 0.0156
    },
    {
     "n": 195,
     "upper95": 0.0152
    },
    {
     "n": 200,
     "upper95": 0.0149
    },
    {
     "n": 205,
     "upper95": 0.0145
    },
    {
     "n": 210,
     "upper95": 0.0142
    },
    {
     "n": 215,
     "upper95": 0.0138
    },
    {
     "n": 220,
     "upper95": 0.0135
    },
    {
     "n": 225,
     "upper95": 0.0132
    },
    {
     "n": 230,
     "upper95": 0.0129
    },
    {
     "n": 235,
     "upper95": 0.0127
    },
    {
     "n": 240,
     "upper95": 0.0124
    },
    {
     "n": 245,
     "upper95": 0.0122
    },
    {
     "n": 250,
     "upper95": 0.0119
    },
    {
     "n": 255,
     "upper95": 0.0117
    },
    {
     "n": 260,
     "upper95": 0.0115
    },
    {
     "n": 265,
     "upper95": 0.0112
    },
    {
     "n": 270,
     "upper95": 0.011
    },
    {
     "n": 275,
     "upper95": 0.0108
    },
    {
     "n": 280,
     "upper95": 0.0106
    },
    {
     "n": 285,
     "upper95": 0.0105
    },
    {
     "n": 290,
     "upper95": 0.0103
    },
    {
     "n": 295,
     "upper95": 0.0101
    },
    {
     "n": 300,
     "upper95": 0.0099
    },
    {
     "n": 305,
     "upper95": 0.0098
    },
    {
     "n": 310,
     "upper95": 0.0096
    },
    {
     "n": 315,
     "upper95": 0.0095
    },
    {
     "n": 320,
     "upper95": 0.0093
    },
    {
     "n": 325,
     "upper95": 0.0092
    },
    {
     "n": 330,
     "upper95": 0.009
    },
    {
     "n": 335,
     "upper95": 0.0089
    },
    {
     "n": 340,
     "upper95": 0.0088
    },
    {
     "n": 345,
     "upper95": 0.0086
    },
    {
     "n": 350,
     "upper95": 0.0085
    },
    {
     "n": 355,
     "upper95": 0.0084
    },
    {
     "n": 360,
     "upper95": 0.0083
    },
    {
     "n": 365,
     "upper95": 0.0082
    },
    {
     "n": 370,
     "upper95": 0.0081
    },
    {
     "n": 375,
     "upper95": 0.008
    },
    {
     "n": 380,
     "upper95": 0.0079
    },
    {
     "n": 385,
     "upper95": 0.0078
    },
    {
     "n": 390,
     "upper95": 0.0077
    },
    {
     "n": 395,
     "upper95": 0.0076
    },
    {
     "n": 400,
     "upper95": 0.0075
    },
    {
     "n": 405,
     "upper95": 0.0074
    },
    {
     "n": 410,
     "upper95": 0.0073
    },
    {
     "n": 415,
     "upper95": 0.0072
    },
    {
     "n": 420,
     "upper95": 0.0071
    },
    {
     "n": 425,
     "upper95": 0.007
    },
    {
     "n": 430,
     "upper95": 0.0069
    },
    {
     "n": 435,
     "upper95": 0.0069
    },
    {
     "n": 440,
     "upper95": 0.0068
    },
    {
     "n": 445,
     "upper95": 0.0067
    },
    {
     "n": 450,
     "upper95": 0.0066
    },
    {
     "n": 455,
     "upper95": 0.0066
    },
    {
     "n": 460,
     "upper95": 0.0065
    },
    {
     "n": 465,
     "upper95": 0.0064
    },
    {
     "n": 470,
     "upper95": 0.0064
    },
    {
     "n": 475,
     "upper95": 0.0063
    },
    {
     "n": 480,
     "upper95": 0.0062
    },
    {
     "n": 485,
     "upper95": 0.0062
    },
    {
     "n": 490,
     "upper95": 0.0061
    },
    {
     "n": 495,
     "upper95": 0.006
    },
    {
     "n": 500,
     "upper95": 0.006
    }
   ]
  },
  "qeeg_detectable_effect": {
   "method": "Smallest standardised paired effect (dz) detectable with 80% power by a two-sided paired t test, n = 6 per cohort.",
   "n": 6,
   "dz_alpha_0_05": 1.43,
   "dz_alpha_0_10": 1.19,
   "dz_alpha_0_05_n_12": 0.89,
   "reading": "With six participants per cohort only very large within-person changes can be detected reliably; smaller real effects would usually be missed, and statistically significant results from samples this small tend to overstate effect size."
  },
  "registration_and_publication_lags": {
   "rows": [
    {
     "study": "microdose",
     "registry": "NCT05783830; EudraCT 2019-003504-13",
     "start": "2020-01-13",
     "end": "2020-04-18",
     "registry_first_posted": "2023-03-24",
     "registration_minus_start_days": 1166,
     "days_end_to_cutoff": 2382,
     "journal_publication": "2024-02-14",
     "days_end_to_publication": 1397
    },
    {
     "study": "SAD",
     "registry": "NCT05077631; EudraCT 2020-003379-16",
     "start": "2021-02-15",
     "end": "2022-02-22",
     "registry_first_posted": "2021-10-14",
     "registration_minus_start_days": 241,
     "days_end_to_cutoff": 1707,
     "journal_publication": "2024-02-14",
     "days_end_to_publication": 722
    },
    {
     "study": "MAD",
     "registry": "NCT05077501",
     "start": "2021-09-29",
     "end": "2022-05-23",
     "registry_first_posted": "2021-10-14",
     "registration_minus_start_days": 15,
     "days_end_to_cutoff": 1617,
     "journal_publication": "2023-07-12",
     "days_end_to_publication": 415
    },
    {
     "study": "Ib",
     "registry": "CTIS 2025-522287-32-00",
     "start": "2025-10-22",
     "end": "2026-04-09",
     "registry_first_posted": "2025-09-10",
     "registration_minus_start_days": -42,
     "days_end_to_cutoff": 200,
     "journal_publication": null,
     "days_end_to_publication": null
    }
   ],
   "note": "ClinicalTrials.gov first-posted dates and EU CTIS decision date; journal dates are first online publication. None of these trials posted results on ClinicalTrials.gov; for non-US phase 1 trials that is not required. Phase 1b results summary: none public at cut-off."
  },
  "authorship_concentration": {
   "unit": "PubMed record naming ACD856 in title/abstract (n = 6); trials counted separately",
   "criterion_A_any_author_or_funding": {
    "all": "6/6",
    "primary": "5/5",
    "human": "2/2"
   },
   "criterion_B_first_or_last_author_AlzeCure": "6/6 (first and last authors of all six records are AlzeCure employees, read from the articles' author lists)",
   "sensitivity_with_fulltext_mentions": "6/16 records if the 10 independent reviews that name ACD856 only in their full text are added; none of them reports new data",
   "trial_level": "5/5 human studies with any reported data were sponsored by AlzeCure (ACD855 phase 1, ACD856 phase 0, two ACD856 phase 1 studies, phase 1b)",
   "independent_primary_data": 0
  },
  "authorship_benchmark": {
   "method": "PubMed title/abstract records; a record counts if any printed affiliation names the originating company. Affiliations only, so lower than full-text coding (PubMed prints only the corresponding author's affiliation for the 2023 phase 1 paper).",
   "rows": [
    {
     "program": "ACD856",
     "query": "ACD856[tiab] OR \"ACD-856\"[tiab]",
     "records": 6,
     "with_originator_affiliation": 6,
     "share": 1.0
    },
    {
     "program": "Fosgonimeton (ATH-1017)",
     "query": "fosgonimeton[tiab] OR \"ATH-1017\"[tiab] OR ATH1017[tiab]",
     "records": 8,
     "with_originator_affiliation": 4,
     "share": 0.5
    },
    {
     "program": "Osavampator (TAK-653)",
     "query": "\"TAK-653\"[tiab] OR osavampator[tiab] OR \"NBI-1065845\"[tiab]",
     "records": 14,
     "with_originator_affiliation": 7,
     "share": 0.5
    }
   ],
   "date": "2026-10-26",
   "excluded": "LM11A-31 was not benchmarked: most of its papers come from its academic inventors, whose university affiliations an affiliation rule cannot link to the company."
  }
 },
 "double_coding": {
  "n": 6,
  "coder1": "manual, full text",
  "coder2": "deterministic rules on PubMed metadata, written before comparison",
  "variables": {
   "evidence_type": {
    "agreement_pct": 100,
    "kappa": 1.0,
    "disagreements": [],
    "note": null
   },
   "origin": {
    "agreement_pct": 100,
    "kappa": null,
    "disagreements": [],
    "note": "kappa undefined: both coders used a single category (all records developer-linked)"
   },
   "data_role": {
    "agreement_pct": 100,
    "kappa": 1.0,
    "disagreements": [],
    "note": null
   }
  },
  "coder2_codes": {
   "39204102": {
    "evidence_type": "R",
    "origin": "sponsor",
    "data_role": "review_own_data"
   },
   "38353689": {
    "evidence_type": "H",
    "origin": "sponsor",
    "data_role": "primary"
   },
   "37874100": {
    "evidence_type": "H",
    "origin": "sponsor",
    "data_role": "primary"
   },
   "37446337": {
    "evidence_type": "A",
    "origin": "sponsor",
    "data_role": "primary"
   },
   "37394539": {
    "evidence_type": "A",
    "origin": "sponsor",
    "data_role": "primary"
   },
   "34440640": {
    "evidence_type": "A",
    "origin": "sponsor",
    "data_role": "primary"
   }
  }
 },
 "patents": [
  {
   "publication": "WO2018115891A1",
   "applicant": "Stiftelsen AlzeCure",
   "filed": "2017-12-21",
   "subject": "Use of triazinetriones, including toltrazuril and ponazuril, as neurotrophin-receptor modulators (incl. BDNF Val66Met carriers)",
   "status": "EP withdrawn; US, AU, CA abandoned; CN, JP pending"
  },
  {
   "publication": "WO2019162702A1",
   "applicant": "AlzeCure Pharma AB",
   "filed": "2019-02-26",
   "subject": "1-aryl-3-phenyl-1,3,5-triazinane-2,4,6-triones; the 'Example 5' compound sold as ACD856 belongs here",
   "status": "EP and US active; further US application pending"
  },
  {
   "publication": "WO2020002949A1",
   "applicant": "AlzeCure Pharma AB",
   "filed": "2019-06-28 (GB priority 2018-06-28)",
   "subject": "4-substituted phenyl-triazinetriones (biphenyl series)",
   "status": "EP withdrawn; US abandoned; CN, JP pending"
  },
  {
   "publication": "WO2020002950A1",
   "applicant": "AlzeCure Pharma AB",
   "filed": "2019-06-28 (GB priority 2018-06-28)",
   "subject": "4-substituted phenyl-triazinetriones (heteroaryl-methyl series)",
   "status": "EP and US active"
  },
  {
   "publication": "WO2021038241A1",
   "applicant": "AlzeCure Pharma AB",
   "filed": "2020-08-28",
   "subject": "Further triazine derivatives",
   "status": "AU, KR active; EP, CN, JP pending; one US application abandoned, one pending"
  }
 ],
 "vendors": [
  {
   "vendor": "A",
   "type": "Research-chemical retailer (US)",
   "name_used": "ACD856",
   "cas": "2375424-89-6",
   "formula": "C22H17N3O4",
   "iupac": "1-(3-methyl-4-phenoxyphenyl)-3-phenyl-1,3,5-triazinane-2,4,6-trione",
   "observation": "Powder and PEG-400 solution; purity claim 99.8%+; no batch report linked on the page; claims to be the first seller"
  },
  {
   "vendor": "B",
   "type": "Research-chemical retailer",
   "name_used": "ACD856 (IGF-1R Modulator 1)",
   "cas": "2375424-89-6",
   "formula": "C22H17N3O4",
   "iupac": "same as A",
   "observation": "Several formats including finished capsules; batch code and one report on file; reproduces EC50 values from the 2021 paper"
  },
  {
   "vendor": "C",
   "type": "Reagent supplier (China)",
   "name_used": "ACD856 (ACD-856)",
   "cas": "not shown in excerpt",
   "formula": "not shown",
   "iupac": "structure image only",
   "observation": "States TrkC EC50 of 33 nM; the 2021 paper reports 0.33 µM"
  },
  {
   "vendor": "D",
   "type": "Bulk API trader (China)",
   "name_used": "ACD856 powder / IGF-1R modulator 1",
   "cas": "2375424-89-6",
   "formula": "C22H17N3O4",
   "iupac": "not given",
   "observation": "Kilogram packs; lists 'FDA' among certificates"
  },
  {
   "vendor": "E",
   "type": "Bulk trader (Hong Kong)",
   "name_used": "ACD-856",
   "cas": "2375424-89-6",
   "formula": "C9H7NO5 (MW 209.16)",
   "iupac": "not given",
   "observation": "Formula and mass incompatible with the CAS number it quotes"
  },
  {
   "vendor": "F",
   "type": "Catalogue reagent supplier",
   "name_used": "IGF-1R modulator 1 (does not use the name ACD856)",
   "cas": "2375424-89-6",
   "formula": "C22H17N3O4",
   "iupac": "SMILES given",
   "observation": "Cites patent WO2019162702 'Example 5'; EC50 0.34 µM (TrkA), 0.39 µM (TrkB), 0.25 µM (IGF1R), 0.29 µM (FGFR1)"
  }
 ],
 "boltaev_2017": {
  "reference": [
   [
    "BDNF",
    100,
    null,
    "reference (EC50 1.1 nM)"
   ],
   [
    "NT-4",
    73,
    6,
    "high-efficacy agonist"
   ],
   [
    "NT-3",
    16,
    4,
    "low-efficacy partial agonist"
   ],
   [
    "NGF",
    0,
    null,
    "inactive (negative control)"
   ]
  ],
  "tested": [
   "7,8-DHF",
   "LM22A-4",
   "Deoxygedunin",
   "Amitriptyline",
   "Deprenyl",
   "DMAQ-B1"
  ],
  "detection_floor_neurons_pct": 16,
  "detection_floor_engineered_cells_pct": "5-10",
  "dmaqb1": {
   "trkb_hek_pct": "16 ± 2",
   "trkb_neurons": "not detected",
   "erk_neurons_pct": 50,
   "akt_neurons_pct": 20,
   "note": "transient, peak at 15 min"
  },
  "cells": [
   "rat primary cortical neurons",
   "HEK cells expressing human TrkB",
   "differentiated SH-SY5Y",
   "U2OS PathHunter (DiscoverX)",
   "CHO NFAT-bla CellSensor"
  ],
  "readouts": [
   "TrkB phosphorylation (sandwich ELISA, Western blot)",
   "AKT and ERK1/2 phosphorylation (fixed-cell immunoassay)",
   "SHC1 recruitment reporter",
   "NFAT gene-reporter"
  ],
  "hts": [
   [
    "Library screened (BDNF at EC15, allosteric and agonist modes)",
    40000
   ],
   [
    "Primary hits",
    355
   ],
   [
    "After counterscreens",
    83
   ],
   [
    "Potential PAMs in CellSensor",
    3
   ],
   [
    "Confirmed in cortical neurons",
    0
   ]
  ],
  "platform_note": "The primary screen used the same DiscoverX PathHunter U2OS reporter format that AlzeCure used to measure ACD856 potency (Dahlström 2021).",
  "not_tested": "ACD856 and the triazinetriones were not tested (the series was disclosed in 2021)."
 },
 "comparators": [
  {
   "compound": "ACD856",
   "developer": "AlzeCure Pharma (licensed to QuantumCell, 2026)",
   "mechanism": "Positive allosteric modulator of TrkA, TrkB and TrkC (cell assays); binds the TrkA intracellular domain",
   "stage": "Phase 1 / 1b in healthy volunteers",
   "outcome": "Safety, pharmacokinetics, CSF exposure, qEEG; no efficacy trial",
   "refs": [
    "34440640",
    "37874100"
   ]
  },
  {
   "compound": "E2511",
   "developer": "Eisai",
   "mechanism": "TrkA positive modulator binding the intracellular juxtamembrane region (company data)",
   "stage": "Phase 1",
   "outcome": "Phase 1 studies in healthy volunteers, as summarised by AlzeCure's review",
   "refs": [
    "39204102"
   ]
  },
  {
   "compound": "7,8-Dihydroxyflavone",
   "developer": "Academic (Emory University)",
   "mechanism": "Reported TrkB agonist (binding to the extracellular domain)",
   "stage": "Preclinical",
   "outcome": "Independent test (Columbia and Broad groups, 2017): no reproducible TrkB phosphorylation above the study's threshold in rat cortical neurons, HEK-TrkB or SH-SY5Y cells under the conditions tested, no AKT or ERK activation in neurons, no signal in two reporter assays; also tested across concentrations and time points",
   "refs": [
    "20133810",
    "28831019",
    "24503862"
   ]
  },
  {
   "compound": "LM22A-4",
   "developer": "Academic (Stanford/UCSF)",
   "mechanism": "Reported BDNF loop-domain mimetic, TrkB partial agonist",
   "stage": "Preclinical",
   "outcome": "Same independent test, compound synthesised in-house: no TrkB phosphorylation, no AKT or ERK activation, no reporter signal",
   "refs": [
    "20407211",
    "28831019",
    "24503862"
   ]
  },
  {
   "compound": "Deoxygedunin, amitriptyline, deprenyl",
   "developer": "Various (reported TrkB activators)",
   "mechanism": "Reported to induce TrkB phosphorylation",
   "stage": "Preclinical (amitriptyline and deprenyl are approved drugs for other uses)",
   "outcome": "Same independent test: no TrkB phosphorylation and no AKT or ERK activation in neurons",
   "refs": [
    "28831019"
   ]
  },
  {
   "compound": "DMAQ-B1",
   "developer": "Academic (natural product)",
   "mechanism": "Reported Trk and insulin-receptor activator",
   "stage": "Preclinical",
   "outcome": "Same independent test: weak TrkB phosphorylation in HEK-TrkB cells (16% of BDNF), none detected in neurons; transient ERK and AKT activation in neurons",
   "refs": [
    "28831019"
   ]
  },
  {
   "compound": "LM11A-31",
   "developer": "PharmatrophiX",
   "mechanism": "p75 neurotrophin receptor modulator (not a Trk modulator)",
   "stage": "Phase 2a in Alzheimer's disease",
   "outcome": "Met its primary safety endpoint; no significant effect on cognitive tests",
   "refs": [
    "38760589"
   ]
  },
  {
   "compound": "Fosgonimeton (ATH-1017)",
   "developer": "Athira Pharma",
   "mechanism": "Positive modulator of the HGF/MET system (not Trk)",
   "stage": "Phase 2/3 (LIFT-AD)",
   "outcome": "Did not meet primary or secondary endpoints in mild-to-moderate Alzheimer's disease",
   "refs": [
    "35180125",
    "41393340"
   ]
  }
 ],
 "claims": [
  {
   "n": 1,
   "claim": "ACD856 improves memory or cognition in people",
   "where": "Forum threads",
   "verdict": "NO_SOURCE",
   "evidence": "No human study has a memory or cognition endpoint. The memory data are from mice and rats; the human trials measured safety, exposure and EEG.",
   "refs": [
    "34440640",
    "37874100"
   ]
  },
  {
   "n": 2,
   "claim": "It raises BDNF levels",
   "where": "Forum threads",
   "verdict": "PARTIAL",
   "evidence": "In cultured cortical neurons BDNF rose by about 30%, and brain BDNF rose in 21-month-old mice; in 3-month-old mice five days of exposure did not change cortical or hippocampal BDNF. No human BDNF measurement is published.",
   "refs": [
    "37446337"
   ]
  },
  {
   "n": 3,
   "claim": "It only amplifies BDNF that is already there, so it cannot overstimulate",
   "where": "Forum threads",
   "verdict": "CONTRADICTED",
   "evidence": "The developer reports about 60% TrkA activation without NGF in recombinant cells and calls this partial agonism, while noting it may reflect receptor over-expression.",
   "refs": [
    "37446337"
   ]
  },
  {
   "n": 4,
   "claim": "It is selective for Trk receptors",
   "where": "Vendor pages, forums",
   "verdict": "PARTIAL",
   "evidence": "In the same assays ACD856 was as potent at IGF1R and FGFR1 as at Trk receptors; the authors describe selectivity in efficacy, not potency.",
   "refs": [
    "34440640"
   ]
  },
  {
   "n": 5,
   "claim": "It works as an antidepressant / against anhedonia",
   "where": "Forum threads",
   "verdict": "PARTIAL",
   "evidence": "Antidepressant-like effects in the forced swim test in mice and rats. In the 7-day human trial, mood questionnaires were safety measures in healthy volunteers. No trial in depression is registered.",
   "refs": [
    "37394539",
    "37446337",
    "37874100"
   ]
  },
  {
   "n": 6,
   "claim": "It reverses age-related memory loss",
   "where": "Forum threads, vendor copy",
   "verdict": "PARTIAL",
   "evidence": "In 18-month-old mice the change was non-significant at 24 h and significant at 11 days in a passive avoidance task, in one experiment.",
   "refs": [
    "34440640"
   ]
  },
  {
   "n": 7,
   "claim": "It is neuroprotective or disease-modifying in Alzheimer's",
   "where": "Company releases, vendor copy",
   "verdict": "PARTIAL",
   "evidence": "Protection against amyloid-beta and energy deprivation in cultured neurons, from the developer. No human disease-modification data.",
   "refs": [
    "37446337"
   ]
  },
  {
   "n": 8,
   "claim": "It crosses into the brain",
   "where": "Forums, company",
   "verdict": "PARTIAL",
   "evidence": "In the second phase 1 study (24 healthy volunteers, 18 on ACD856), CSF concentrations sampled at steady state rose across cohorts: evidence of exposure in the central nervous system, not a measurement in brain tissue or of Trk engagement.",
   "refs": [
    "37874100"
   ]
  },
  {
   "n": 9,
   "claim": "Its half-life is about a day",
   "where": "Forum threads",
   "verdict": "SUPPORTED",
   "evidence": "Terminal half-life about 19-20 h in the phase 0 and second phase 1 studies.",
   "refs": [
    "38353689",
    "37874100"
   ]
  },
  {
   "n": 10,
   "claim": "It shows target engagement in humans",
   "where": "Company releases",
   "verdict": "TRIAL_DATA",
   "evidence": "qEEG changes graded across two cohorts of six; the authors state these do not allow general conclusions on neuronal activity, and no active control was used.",
   "refs": [
    "37874100"
   ]
  },
  {
   "n": 11,
   "claim": "Side effects: drowsiness, brain fog, raised heart rate",
   "where": "Forum reports",
   "verdict": "NOT_ASSESSABLE",
   "evidence": "Published studies report adverse events, mostly mild (headache most common; 24 possibly related events in 13 of 56 participants in the first phase 1 study), and no serious adverse events within study periods of up to 7 days; forum anecdotes concern unverified material and cannot be assessed.",
   "refs": [
    "38353689",
    "37874100"
   ]
  },
  {
   "n": 12,
   "claim": "Effects fade after weeks (tolerance)",
   "where": "Forum threads",
   "verdict": "NO_SOURCE",
   "evidence": "No human study with a study period longer than 7 days has been published.",
   "refs": [
    "37874100"
   ]
  },
  {
   "n": 13,
   "claim": "It helps sexual dysfunction",
   "where": "Forum threads",
   "verdict": "NO_SOURCE",
   "evidence": "No data in any species located.",
   "refs": []
  },
  {
   "n": 14,
   "claim": "It is safer than 7,8-DHF",
   "where": "Forum threads",
   "verdict": "NO_SOURCE",
   "evidence": "No head-to-head data. In an independent test, 7,8-DHF produced no detectable TrkB phosphorylation or downstream AKT/ERK activation in neurons or TrkB-expressing cells, so its claimed mechanism is itself unconfirmed.",
   "refs": [
    "28831019"
   ]
  },
  {
   "n": 15,
   "claim": "It came from a veterinary drug",
   "where": "Forum threads",
   "verdict": "SUPPORTED",
   "evidence": "The series started with ponazuril (renamed ACD855), a veterinary antiprotozoal; ACD856 is a follow-up compound.",
   "refs": [
    "34440640",
    "38353689"
   ]
  },
  {
   "n": 16,
   "claim": "It is in phase 2 / close to approval",
   "where": "Forum threads",
   "verdict": "CONTRADICTED",
   "evidence": "At the cut-off no phase 2 trial was located in CTIS or ClinicalTrials.gov; the company plans a phase 2a. No regulator has approved it.",
   "refs": [
    "CTIS",
    "CTGOV",
    "Q2_2026"
   ]
  },
  {
   "n": 17,
   "claim": "The powder sold as ACD856 is the clinical compound",
   "where": "Vendor pages",
   "verdict": "NOT_ASSESSABLE",
   "evidence": "AlzeCure has not disclosed ACD856's structure; vendors sell a patent example (CAS 2375424-89-6) under the name. The link is plausible but unconfirmed.",
   "refs": [
    "39204102",
    "31857832"
   ]
  },
  {
   "n": 18,
   "claim": "It raises serotonin and dopamine",
   "where": "Forum threads",
   "verdict": "PARTIAL",
   "evidence": "Rat hippocampal microdialysis: serotonin rose significantly; noradrenaline and dopamine showed trends (company poster).",
   "refs": [
    "AAIC2021",
    "37394539"
   ]
  }
 ],
 "claim_counts": {
  "NO_SOURCE": 4,
  "PARTIAL": 7,
  "CONTRADICTED": 2,
  "SUPPORTED": 2,
  "TRIAL_DATA": 1,
  "NOT_ASSESSABLE": 2
 },
 "financial_interest": [
  {
   "type": "direct",
   "party": "AlzeCure Pharma AB",
   "role": "Originator, sponsor of every human study, employer of most authors",
   "interest": "Licensor under the July 2026 QuantumCell agreement: USD 12 million upfront (USD 5 million of it as an equity investment), milestones and tiered royalties; company states total value above USD 2.2 billion excluding royalties",
   "refs": [
    "PR_QC",
    "Q2_2026"
   ]
  },
  {
   "type": "direct",
   "party": "QuantumCell ApS",
   "role": "Licensee of global rights to the NeuroRestore platform including ACD856",
   "interest": "Development and commercial rights; pays the above terms",
   "refs": [
    "PR_QC"
   ]
  },
  {
   "type": "direct",
   "party": "European Innovation Council (EIC Accelerator)",
   "role": "Grant funder of the planned phase 2a",
   "interest": "EUR 2.5 million grant (first payment December 2025), with a possible further investment through the EIC Fund",
   "refs": [
    "PR_EIC",
    "Q2_2026"
   ]
  },
  {
   "type": "indirect",
   "party": "QuantumCell's owners (Novo Holdings, Forbion, Lundbeck Foundation, First Spark Ventures)",
   "role": "Investors in the licensee, as listed by AlzeCure",
   "interest": "Indirect, through QuantumCell; no compound-specific figures disclosed",
   "refs": [
    "Q2_2026"
   ]
  },
  {
   "type": "indirect",
   "party": "Stiftelsen AlzeCure (AlzeCure Foundation)",
   "role": "Original assignee of the 2017 triazinetrione patent family; author affiliation in the 2021 discovery paper",
   "interest": "Indirect; holdings not quantified here",
   "refs": [
    "34440640"
   ]
  },
  {
   "type": "indirect",
   "party": "Contract organisations: CTC Clinical Trial Consultants, Siesta Group, Suven Life Sciences, Pronexus",
   "role": "Ran trials, qEEG analysis and animal studies; CTC staff co-authored both clinical papers",
   "interest": "Fee-for-service; no equity disclosed",
   "refs": [
    "38353689",
    "37874100",
    "34440640"
   ]
  },
  {
   "type": "indirect",
   "party": "Paid consultants",
   "role": "Two co-authors of the 2024 phase 1 paper are paid consultants of AlzeCure",
   "interest": "Disclosed in the article",
   "refs": [
    "38353689"
   ]
  }
 ],
 "not_attributed": "The USD 10 million upfront from Eli Lilly (June 2026) concerns AlzeCure's Alzstatin platform (ACD680), not ACD856, and is excluded.",
 "regulatory": [
  {
   "jurisdiction": "EU (EMA)",
   "status": "No marketing authorisation or application located",
   "basis": "EMA medicines search, 2026-10-26",
   "refs": [
    "EMAREP"
   ]
  },
  {
   "jurisdiction": "United States (FDA)",
   "status": "No approval located",
   "basis": "openFDA drugsfda: no match for ACD856",
   "refs": [
    "OPENFDA"
   ]
  },
  {
   "jurisdiction": "Sport (WADA)",
   "status": "Not named on the 2026 Prohibited List; an unapproved substance falls under section S0",
   "basis": "WADA 2026 List",
   "refs": [
    "WADA"
   ]
  },
  {
   "jurisdiction": "Clinical status",
   "status": "Investigational; human data from healthy volunteers only",
   "basis": "CTIS and ClinicalTrials.gov",
   "refs": [
    "CTIS",
    "CTGOV"
   ]
  }
 ],
 "timeline": [
  {
   "date": "2015",
   "category": "funding",
   "event": "Alzheimer's Drug Discovery Foundation grant cited for the screening work"
  },
  {
   "date": "2017-12-21",
   "category": "patent",
   "event": "First triazinetrione patent family filed (ponazuril and toltrazuril as Trk modulators)"
  },
  {
   "date": "2018-06-28",
   "category": "patent",
   "event": "Priority date of two follow-up patent families"
  },
  {
   "date": "2018",
   "category": "clinical",
   "event": "ACD855 (ponazuril) phase 1 study starts; stopped after cohort 1"
  },
  {
   "date": "2019-02-26",
   "category": "patent",
   "event": "Patent family containing the structure vendors sell as ACD856 filed"
  },
  {
   "date": "2020-01-13",
   "category": "clinical",
   "event": "ACD856 phase 0 study starts (6 men)"
  },
  {
   "date": "2021-02-15",
   "category": "clinical",
   "event": "First phase 1 study starts"
  },
  {
   "date": "2021-07-23",
   "category": "literature",
   "event": "Discovery paper names ACD855 and ACD856"
  },
  {
   "date": "2021-09-29",
   "category": "clinical",
   "event": "Second phase 1 study starts"
  },
  {
   "date": "2021-10-14",
   "category": "registry",
   "event": "Both phase 1 studies posted on ClinicalTrials.gov"
  },
  {
   "date": "2022-05-23",
   "category": "clinical",
   "event": "Second phase 1 study completed"
  },
  {
   "date": "2023-03-24",
   "category": "registry",
   "event": "Phase 0 study registered, about three years after it ended"
  },
  {
   "date": "2023-07-12",
   "category": "literature",
   "event": "Mecond phase 1 and qEEG paper published"
  },
  {
   "date": "2024-02-14",
   "category": "literature",
   "event": "Phase 0 and first phase 1 paper published"
  },
  {
   "date": "2025-02-17",
   "category": "corporate",
   "event": "EU EIC grant of EUR 2.5 million for a phase 2a announced"
  },
  {
   "date": "2025-10-22",
   "category": "clinical",
   "event": "Phase 1b in healthy participants starts (CTIS)"
  },
  {
   "date": "2026-04-09",
   "category": "clinical",
   "event": "Phase 1b ends"
  },
  {
   "date": "2026-06-16",
   "category": "corporate",
   "event": "Phase 1b topline by press release"
  },
  {
   "date": "2026-07-01",
   "category": "corporate",
   "event": "Global licence to QuantumCell announced"
  },
  {
   "date": "2026-10-26",
   "category": "cutoff",
   "event": "Data cut-off: no phase 2 registered"
  }
 ],
 "forum_volume": {
  "posts_unique": 104,
  "organic_last_6m": 41,
  "organic_prior_6m": 55,
  "ratio": 0.75,
  "top_subreddits": "NooTopics 69, Biohackers 11, NootropicsHelp 4",
  "note": "Condor Research reddit-trend file, 25 October 2026 (research-2026-10-25/reddit-trend/reddit.csv). Not re-queried."
 },
 "references": [
  {
   "n": 1,
   "doc": "CENSUS",
   "cita": "Condor Research census of PubMed records, this dossier (dataset.json).",
   "url": "https://condorresearch.com/wp-content/uploads/evidence-cards/acd856/dataset.json"
  },
  {
   "n": 2,
   "doc": "CTGOV",
   "cita": "ClinicalTrials.gov API v2, queries ACD856, ACD-856, ACD855, AlzeCure (sponsor), retrieved 2026-10-26.",
   "url": "https://clinicaltrials.gov/search?term=ACD856"
  },
  {
   "n": 3,
   "doc": "CTIS",
   "cita": "EU Clinical Trials Information System, trial 2025-522287-32-00 (public API record).",
   "url": "https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2025-522287-32-00"
  },
  {
   "n": 4,
   "pmid": "38353689",
   "doi": "10.1007/s00228-024-03645-1",
   "cita": "Nilsson B, Bylund J, Halldin MM et al. ACD856, a novel positive allosteric modulator of Trk receptors, single ascending doses in healthy subjects: Safety and pharmacokinetics. Eur J Clin Pharmacol. 2024;80(5):717-727.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/38353689/"
  },
  {
   "n": 5,
   "doc": "OPENFDA",
   "cita": "openFDA drugsfda endpoint, search ACD856, 2026-10-26: no matches.",
   "url": "https://api.fda.gov/drug/drugsfda.json?search=ACD856"
  },
  {
   "n": 6,
   "doc": "EMAREP",
   "cita": "European Medicines Agency, medicines search, 2026-10-26: no ACD856 entry.",
   "url": "https://www.ema.europa.eu/en/medicines"
  },
  {
   "n": 7,
   "doc": "PR_QC",
   "cita": "AlzeCure Pharma. AlzeCure Pharma enters an out-licensing and collaboration agreement with QuantumCell ApS for the NeuroRestore ACD856 project. Press release, 1 July 2026.",
   "url": "https://www.alzecurepharma.se/en/alzecure-pharma-enters-an-out-licensing-and-collaboration-agreement-with-quantumcell-aps-for-the-neurorestore-acd856-project/"
  },
  {
   "n": 8,
   "doc": "Q2_2026",
   "cita": "AlzeCure Pharma. Interim report April-June 2026.",
   "url": "https://www.alzecurepharma.se/en/wp-content/uploads/sites/2/2026/08/alzecure-q2-2026-eng-260826.pdf"
  },
  {
   "n": 9,
   "pmid": "34440640",
   "doi": "10.3390/cells10081871",
   "cita": "Dahlström M, Madjid N, Nordvall G et al. Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction. Cells. 2021;10(8).",
   "url": "https://pubmed.ncbi.nlm.nih.gov/34440640/"
  },
  {
   "n": 10,
   "pmid": "37446337",
   "doi": "10.3390/ijms241311159",
   "cita": "Parrado Fernandez C, Juric S, Backlund M et al. Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer's Disease. Int J Mol Sci. 2023;24(13).",
   "url": "https://pubmed.ncbi.nlm.nih.gov/37446337/"
  },
  {
   "n": 11,
   "pmid": "39204102",
   "doi": "10.3390/ph17080997",
   "cita": "Forsell P, Parrado Fernández C, Nilsson B et al. Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease. Pharmaceuticals (Basel). 2024;17(8).",
   "url": "https://pubmed.ncbi.nlm.nih.gov/39204102/"
  },
  {
   "n": 12,
   "doc": "PUBCHEM",
   "cita": "PubChem. CID 139434107 (IGF-1R modulator 1, CAS 2375424-89-6) and CID 3050408 (ponazuril). Name search 'ACD856' and 'ACD-856': no record.",
   "url": "https://pubchem.ncbi.nlm.nih.gov/compound/139434107"
  },
  {
   "n": 13,
   "doc": "PAT2019",
   "cita": "Nordvall G, Forsell P. Triazine derivatives for treating diseases relating to neurotrophins. WO2019162702A1.",
   "url": "https://patents.google.com/patent/WO2019162702A1/en"
  },
  {
   "n": 14,
   "doc": "VENDORS",
   "cita": "Six public vendor catalogue pages read on 2026-10-26; anonymised, URLs held by Condor Research Editorial.",
   "url": "https://condorresearch.com/research/acd856-evidence-card/#identity"
  },
  {
   "n": 15,
   "doc": "PAT2017",
   "cita": "Nordvall G, Forsell P, Sandin J. Triazinetrione derivatives and their use as modulators of neurotrophin receptor and receptor tyrosine kinases. WO2018115891A1.",
   "url": "https://patents.google.com/patent/WO2018115891A1/en"
  },
  {
   "n": 16,
   "doc": "PAT2020A",
   "cita": "Nordvall G, Forsell P. 4-substituted phenyl-1,3,5-triazine derivatives as modulators of Trk receptors. WO2020002949A1.",
   "url": "https://patents.google.com/patent/WO2020002949A1/en"
  },
  {
   "n": 17,
   "doc": "PAT2020B",
   "cita": "Nordvall G, Forsell P. 4-substituted phenyl-1,3,5-triazine derivatives as modulators of Trk receptors. WO2020002950A1.",
   "url": "https://patents.google.com/patent/WO2020002950A1/en"
  },
  {
   "n": 18,
   "doc": "PAT2021",
   "cita": "Nordvall G, Forsell P. Triazine derivatives for treating diseases relating to neurotrophins. WO2021038241A1.",
   "url": "https://patents.google.com/patent/WO2021038241A1/en"
  },
  {
   "n": 19,
   "pmid": "37394539",
   "doi": "10.1007/s00213-023-06410-x",
   "cita": "Madjid N, Lidell V, Nordvall G et al. Antidepressant effects of novel positive allosteric modulators of Trk-receptor mediated signaling - a potential therapeutic concept?. Psychopharmacology (Berl). 2023;240(8):1789-1804.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/37394539/"
  },
  {
   "n": 20,
   "doc": "AAIC2021",
   "cita": "Nordvall G, Madjid N, Backlund M, et al. ACD856, a novel positive allosteric modulator of Trk-receptors in clinical development for the treatment of Alzheimer's disease. Poster, AAIC 2021 (company copy).",
   "url": "https://www.alzecurepharma.se/en/wp-content/uploads/sites/2/2021/07/acd856-a-novel-positive-allosteric-modulator-of-trk-receptors-in-clinical-development-for-the-treatment-of-alzheimers-disease-poster-alzecure-aaic-2021-final.pdf"
  },
  {
   "n": 21,
   "pmid": "37874100",
   "doi": "10.14283/jpad.2023.89",
   "cita": "Önnestam K, Nilsson B, Rother M et al. Safety, Tolerability, Pharmacokinetics and Quantitative Electroencephalography Assessment of ACD856, a Novel Positive Allosteric Modulator of Trk-Receptors Following Multiple Doses in Healthy Subjects. J Prev Alzheimers Dis. 2023;10(4):778-789.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/37874100/"
  },
  {
   "n": 22,
   "doc": "PR_IB",
   "cita": "AlzeCure Pharma. Positive results from the Phase Ib clinical study of NeuroRestore ACD856. Press release, 16 June 2026.",
   "url": "https://www.alzecurepharma.se/en/positive-results-from-the-phase-ib-clinical-study-of-neurorestore-acd856-under-development-for-alzheimers/"
  },
  {
   "n": 23,
   "doc": "PR_EIC",
   "cita": "AlzeCure Pharma. AlzeCure receives payment of EU grant for Phase 2 clinical trial with NeuroRestore ACD856. Press release, 3 December 2025.",
   "url": "https://www.alzecurepharma.se/en/alzecure-receives-payment-of-eu-grant-for-phase-2-clinical-trial-with-neurorestore-acd856-for-alzheimers-disease/"
  },
  {
   "n": 24,
   "doc": "CT_SAD",
   "cita": "ClinicalTrials.gov NCT05077631, first phase 1 study of ACD856.",
   "url": "https://clinicaltrials.gov/study/NCT05077631"
  },
  {
   "n": 25,
   "doc": "CT_MAD",
   "cita": "ClinicalTrials.gov NCT05077501, second phase 1 study of ACD856.",
   "url": "https://clinicaltrials.gov/study/NCT05077501"
  },
  {
   "n": 26,
   "doc": "CT_MICRO",
   "cita": "ClinicalTrials.gov NCT05783830, phase 0 study of ACD856.",
   "url": "https://clinicaltrials.gov/study/NCT05783830"
  },
  {
   "n": 27,
   "doc": "PR_LPLV",
   "cita": "AlzeCure Pharma. Last patient has completed AlzeCure's Phase Ib clinical study with NeuroRestore ACD856. Press release, 20 April 2026.",
   "url": "https://www.alzecurepharma.se/en/last-patient-has-completed-alzecures-phase-ib-clinical-study-with-neurorestore-acd856/"
  },
  {
   "n": 28,
   "doc": "EUCTR",
   "cita": "EU Clinical Trials Register search 'AlzeCure' (1 result, ACD440); the register does not display adult-only phase 1 trials.",
   "url": "https://www.clinicaltrialsregister.eu/ctr-search/search?query=AlzeCure"
  },
  {
   "n": 29,
   "pmid": "20133810",
   "doi": "10.1073/pnas.0913572107",
   "cita": "Jang SW, Liu X, Yepes M et al. A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl Acad Sci U S A. 2010;107(6):2687-92.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/20133810/"
  },
  {
   "n": 30,
   "pmid": "20407211",
   "doi": "10.1172/JCI41356",
   "cita": "Massa SM, Yang T, Xie Y et al. Small molecule BDNF mimetics activate TrkB signaling and prevent neuronal degeneration in rodents. J Clin Invest. 2010;120(5):1774-85.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/20407211/"
  },
  {
   "n": 31,
   "pmid": "28831019",
   "doi": "10.1126/scisignal.aal1670",
   "cita": "Boltaev U, Meyer Y, Tolibzoda F et al. Multiplex quantitative assays indicate a need for reevaluating reported small-molecule TrkB agonists. Sci Signal. 2017;10(493).",
   "url": "https://pubmed.ncbi.nlm.nih.gov/28831019/"
  },
  {
   "n": 32,
   "pmid": "24503862",
   "doi": "10.1371/journal.pone.0087923",
   "cita": "Todd D, Gowers I, Dowler SJ et al. A monoclonal antibody TrkB receptor agonist as a potential therapeutic for Huntington's disease. PLoS One. 2014;9(2):e87923.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/24503862/"
  },
  {
   "n": 33,
   "pmid": "38760589",
   "doi": "10.1038/s41591-024-02977-w",
   "cita": "Shanks HRC, Chen K, Reiman EM et al. p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial. Nat Med. 2024;30(6):1761-1770.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/38760589/"
  },
  {
   "n": 34,
   "pmid": "35180125",
   "doi": "10.3233/JAD-215511",
   "cita": "Hua X, Church K, Walker W et al. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Positive Modulator of HGF/MET, Fosgonimeton, in Healthy Volunteers and Subjects with Alzheimer's Disease: Randomized, Placebo-Controlled, Double-Blind, Phase I Clinical Trial. J Alzheimers Dis. 2022;86(3):1399-1413.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/35180125/"
  },
  {
   "n": 35,
   "pmid": "41393340",
   "doi": "10.1177/25424823251405817",
   "cita": "Porsteinsson AP, Sabbagh M, Tariot PN et al. Fosgonimeton in mild-to-moderate Alzheimer's disease. J Alzheimers Dis Rep. 2025;9:25424823251405817.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/41393340/"
  },
  {
   "n": 36,
   "doc": "FORUMS",
   "cita": "Public forum threads (r/NooTopics, r/cognitivescience, r/PSSD, r/NootropicsDepot) read as web-search excerpts on 2026-10-26; volume from Condor Research's Reddit trend file of 25 October 2026. Personal regimens are not reproduced.",
   "url": "https://www.reddit.com/r/NooTopics/"
  },
  {
   "n": 37,
   "pmid": "31857832",
   "doi": "10.1021/acsmedchemlett.9b00506",
   "cita": "Kargbo RB. Modulation of Tropomyosin Receptor Kinase for the Treatment of Neurotrophin Diseases: Alzheimer's, Huntington's and Parkinson's. ACS Med Chem Lett. 2019;10(12):1590-1591.",
   "url": "https://pubmed.ncbi.nlm.nih.gov/31857832/"
  },
  {
   "n": 38,
   "doc": "WADA",
   "cita": "World Anti-Doping Agency. 2026 Prohibited List (section S0, non-approved substances).",
   "url": "https://www.wada-ama.org/en/prohibited-list"
  }
 ],
 "changelog": [
  {
   "version": "1.0",
   "date": "2026-10-26",
   "change": "First version."
  },
  {
   "version": "1.1",
   "date": "2026-10-26",
   "change": "Boltaev et al. 2017 read in full: comparator rows for 7,8-DHF and LM22A-4 made specific, three further reported TrkB activators added, Figure 5 (TrkB activation by reported agonists and the independent screen) added, link to ACD856 assay platform stated; Todd et al. 2014 cited."
  }
 ]
}