CN-105 · program

CN-105 for Intracerebral hemorrhage

Phase 2CompletedAegisCN LLC
  • FDA Orphan Drug

Indications for CN-105: Intracerebral hemorrhage · Phase 2 Postoperative delirium · Phase 2

The lead and original CN-105 indication, carried by AegisCN from a 48-subject Phase 1 in healthy volunteers (NCT02670824, completed 2016) through three Phase 2 trials of IV CN-105 given every 6 hours for up to 72 hours starting within 12 hours of symptom onset. CATCH (NCT03168581, n=38, six US sites, AegisCN-sponsored, subsidised by FDA orphan-products grant FD-R-5387) was open-label and reported an odds ratio of 2.69 (95% CI 1.31-5.51) for a lower 30-day modified Rankin Scale versus 1:1 matched ERICH historical controls — with no placebo arm, so the effect cannot be separated from natural recovery. The properly controlled follow-up, S-CATCH (NCT03711903, n=60, sponsored by the National Neuroscience Institute in Singapore with AegisCN as industry collaborator), finished enrolling in June 2022 and published only in June 2026: CN-105 was safe (SAEs 26.7% vs 30%) and fewer treated patients deteriorated neurologically (0% vs 10%), but the efficacy endpoint missed — favourable mRS <=3 in 77.8% vs 66.7%, p=0.35. A 240-patient placebo-controlled dose-finding Phase 2 in China (NCT06255977, Beijing Tiantan Hospital with SDM Bio Service Inc.) started 2022-08-24 with estimated completion 2024-08 but has not been updated since 2024-02-13 and now carries ClinicalTrials.gov status UNKNOWN with no results. No Phase 3 is registered and no CN-105 trial is ongoing anywhere as of July 2026.

Data current as of

Development timeline

Phase 2Aug 2017 – Jun 2026
  1. missedS-CATCH: the randomized Phase 2b in 60 Singaporean ICH patients confirmed safety but missed on 90-day functional outcome (mRS <=3 77.8% vs 66.7%, p=0.35).↗
  2. UpcomingpendingCN-CATCH, the 240-patient Chinese dose-finding Phase 2, listed an estimated primary completion of May 2024 but has produced no results and its registry record has not been updated since February 2024.
  3. China Phase 2 starts: 240-patient, 4-arm (placebo, 0.1, 0.3, 1.0 mg/kg) placebo-controlled dose-finding trial at Beijing Tiantan Hospital with SDM Bio Service Inc. Last registry update 2024-02-13; ClinicalTrials.gov status is now UNKNOWN and the estimated 2024-08 completion has passed with no results or publication.
  4. S-CATCH completes with 60 randomized (30 CN-105 / 30 placebo). This is the last patient-facing activity in the ICH program to date.
  5. metCATCH: the open-label Phase 2a in 38 ICH patients met its safety primary with no excess hematoma expansion, and showed a 30-day mRS odds ratio of 2.69 (1.31-5.51) against matched historical controls.↗
  6. CATCH completes (38 enrolled). Published Neurocrit Care 2022: safe, no hematoma expansion, OR 2.69 (1.31-5.51) for lower 30-day mRS versus matched historical controls — an uncontrolled comparison.↗
  7. S-CATCH opens in Singapore — the first randomized, double-blind, placebo-controlled test of CN-105 in ICH (NCT03711903; National Neuroscience Institute lead sponsor, AegisCN collaborator).
  8. Phase 2 entry: CATCH, an open-label multisite US proof-of-concept in acute primary supratentorial ICH, opens (NCT03168581; AegisCN lead sponsor, with Duke Clinical Research Institute and PharPoint Research).
Phase 1Dec 2015 – Jun 2017
  1. metPhase 1 in 48 healthy adults: no significant safety issues on single or repeated IV dosing, linear PK with ~3.6 h half-life and no accumulation.↗
  2. Phase 1 completed: safe in single-escalating and multiple-dose paradigms, terminal half-life ~3.6 h, linear PK without accumulation. ClinicalTrials.gov month precision (2016-08); the day is an approximation.
  3. First-in-human Phase 1 single-ascending/multiple-dose study in 48 healthy US volunteers begins (NCT02670824, AegisCN-sponsored). ClinicalTrials.gov records the start to month precision only (2015-12); the day is an approximation.

Readouts

  • 2026-06-23ReportedFull resultsmissedNCT03711903

    S-CATCH: the randomized Phase 2b in 60 Singaporean ICH patients confirmed safety but missed on 90-day functional outcome (mRS <=3 77.8% vs 66.7%, p=0.35). ↗

  • Mid-2024DelayedTopline datapendingNCT06255977

    CN-CATCH, the 240-patient Chinese dose-finding Phase 2, listed an estimated primary completion of May 2024 but has produced no results and its registry record has not been updated since February 2024.

  • 2022-02-01ReportedFull resultsmetNCT03168581

    CATCH: the open-label Phase 2a in 38 ICH patients met its safety primary with no excess hematoma expansion, and showed a 30-day mRS odds ratio of 2.69 (1.31-5.51) against matched historical controls. ↗

  • 2017-06-01ReportedFull resultsmetNCT02670824

    Phase 1 in 48 healthy adults: no significant safety issues on single or repeated IV dosing, linear PK with ~3.6 h half-life and no accumulation. ↗

Clinical trials in Intracerebral hemorrhage

NCT06255977CN-CATCHPhase 2Unknownn=240

A Multicenter, Randomized, Blind, Placebo-controlled, Dose-finding Phase II Trial Evaluating the Safety and Efficacy of the Neuroprotective Peptide CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage (CN-CATCH) — sponsor: Beijing Tiantan Hospital

Started Aug 2022· Primary completion May 2024

NCT03711903S-CATCHPhase 2Completedn=60

A Phase 2, Randomized, Double Blind, Placebo Controlled Study To Evaluate The Administration of CN-105 In Participants With Acute Supratentorial Intracerebral Hemorrhage (S-CATCH) — sponsor: National Neuroscience Institute, Singapore

Started Mar 2019· Primary completion Jun 2022

missedsecondaryFunctional outcome: modified Rankin Scale <=3 at 90 days — 77.8% vs 66.7% achieving mRS <=3 (0.35)

77.8% (CN-105) versus 66.7% (placebo) achieved mRS <=3 — no statistically significant improvement in 90-day functional outcome (p=0.35). The authors framed it as an encouraging trend warranting investigation in targeted subgroups. This is the only randomized, placebo-controlled efficacy look in ICH to date, though the trial was sized for safety.

metprimaryPrimary: safety (adverse events, serious adverse events, in-hospital / 30-day / 90-day mortality, neurological deterioration, CNS infection, hematoma extension) — SAEs 26.7% vs 30.0%; in-hospital neurological deterioration 0% vs 10%

60 patients randomized 1:1 (30 on CN-105 1.0 mg/kg IV q6h vs 30 placebo). No significant difference in serious adverse events (26.7% vs 30.0%); fewer CN-105 patients had in-hospital neurological deterioration (0% vs 10%). Safety and feasibility of acute-setting dosing were confirmed.

NCT03168581CATCHPhase 2Completedn=38

A Proof of Concept Study to Evaluate Administration of CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage (CATCH)

Started Aug 2017· Primary completion Sept 2019

metprimaryPrimary: safety and feasibility of CN-105 given within 12 h of acute primary supratentorial ICH (AEs through 90 days, in-hospital and 90-day mortality, NIHSS increase >2 from baseline persisting >24 h)

First-in-disease-state, multicenter, OPEN-LABEL trial; 38 participants at 6 US sites. Adverse events occurred at the expected rate with no increase in hematoma expansion or neurological deterioration, and pharmacokinetics were favourable.

mixedexploratoryExploratory efficacy: 30-day modified Rankin Scale versus 1:1 matched historical controls from the ERICH study — OR 2.69 (95% CI 1.31-5.51) for a lower (better) 30-day mRS

Odds ratio 2.69 (95% CI 1.31-5.51) for a lower 30-day mRS after adjustment for ICH score, sex and race/ethnicity. This is NOT a randomized comparison — an open-label arm versus matched external controls — so it is a signal, not evidence of efficacy. Recorded as 'mixed' for that reason; the subsequent randomized S-CATCH trial did not confirm it.

mixedexploratoryExploratory biomarker analysis: neuroinflammatory panel versus perihematomal edema volume — CRP r=0.56; IL-8/IL-10/MCP/MMP-9 r=-0.51 to -0.63 (0.002-0.02 (inverse markers); 0.006 (CRP))

18 ICH patients plus 16 CN-105-treated. Higher CRP was associated with larger edema volumes (p=0.006, r=0.56); IL-8, IL-10, MCP and MMP-9 were inversely associated (p=0.002-0.02, r=-0.51 to -0.63); IL1-RA, IL1-B, IL23, vWF and IL17 showed no association. Proposed as candidate surrogate endpoints — this is not a treatment-effect result.

NCT02670824Phase 1Completedn=48

Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects

Started Dec 2015· Primary completion May 2016

metsecondaryPharmacokinetics (terminal half-life, accumulation, dose linearity) — median terminal t1/2 ~3.6 h

Linear kinetics with no accumulation; median terminal elimination half-life ~3.6 h, unchanged between single and repeated dosing. The authors concluded the drug was ready for first-in-disease Phase 2 in ICH.

metprimarySafety and tolerability (adverse reactions, vital signs, ECG, clinical labs) of single escalating and repeated IV doses, 0.01-1.0 mg/kg

48 subjects randomized (36 active, 12 placebo); all completed. No significant safety issues were identified with either the single-escalating-dose or the repeated-dose regimen.

Formulations

FormulationRouteRegimenPharmacokinetics
CN-105 intravenous solution
30-minute IV infusion. Phase 1 covered 0.01-1.0 mg/kg as single escalating and repeated doses. The clinical dose carried forward is 1.0 mg/kg IV every 6 hours: in acute intracerebral hemorrhage (CATCH, S-CATCH) started within 12 hours of symptom onset and continued up to 72 hours; in the MARBLE postoperative-delirium Phase 2, escalating cohorts of 0.1 / 0.5 / 1.0 mg/kg IV every 6 hours from 1 hour before surgery through postoperative day 3 or discharge (maximum 13 doses). The China Phase 2 (NCT06255977) tested 0.1, 0.3 and 1.0 mg/kg against placebo.
IntravenousOthert½ 3.6 h · Tmax 0.5 h · F 100%

Mechanism of action (compound-wide)

CN-105 is an apolipoprotein E-mimetic pentapeptide that reproduces the polar, receptor-binding face of the apoE alpha-helical domain (apoE residues ~130-149) in a five-residue linear sequence small enough to cross the blood-brain barrier, which intact apoE does not. In the injured brain it binds LDL-receptor-family receptors on microglia, astrocytes and neurons — LRP1 (low-density lipoprotein receptor-related protein 1) is the receptor most consistently implicated — and initiates signalling that downregulates the activated, pro-inflammatory glial phenotype. In translational models this produces markedly reduced microglial activation, smaller lesion and infarct volumes, less neuronal degeneration and improved functional and survival outcomes across intracerebral hemorrhage, subarachnoid hemorrhage, ischemic stroke and traumatic brain injury. Because the mechanism is immunomodulatory rather than hemostatic or thrombolytic, CN-105 is positioned as a secondary-brain-injury therapeutic, and the same rationale underlies its Phase 2 evaluation in postoperative delirium. No quantitative binding affinity for CN-105 at LRP1 has been published in open sources, so receptor engagement is characterised qualitatively; notably, the MARBLE trial found no significant effect on CSF IL-6, IL-8, MCP-1 or G-CSF, so target engagement in humans remains undemonstrated.

TargetActionAffinity
LRP1primaryLRP1Agonist—ⓘ

← Full CN-105 compound page (identity, identifiers, all indications)

Sources

  1. A Multicenter, Randomized, Blind, Placebo-controlled, Dose-finding Phase II Trial Evaluating the Safety and Efficacy of the Neuroprotective Peptide CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage (CN-CATCH) — ClinicalTrials.gov
  2. A Phase 2, Randomized, Double Blind, Placebo Controlled Study To Evaluate The Administration of CN-105 In Participants With Acute Supratentorial Intracerebral Hemorrhage (S-CATCH) — ClinicalTrials.gov
  3. A Proof of Concept Study to Evaluate Administration of CN-105 in Patients With Acute Supratentorial Intracerebral Hemorrhage (CATCH) — ClinicalTrials.gov
  4. An Exploratory Analysis of Biomarkers of Perihematomal Edema in the CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial — Journal of Stroke and Cerebrovascular Diseases 2022, doi:10.1016/j.jstrokecerebrovasdis.2022.106600
  5. Apolipoprotein E mimetic peptide CN-105 improves outcome in a murine model of subarachnoid hemorrhage — Scientific Reports / PubMed Central
  6. CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial — Neurocritical Care 2022;36(1):216-225, doi:10.1007/s12028-021-01287-0
  7. CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage Trial in Singapore (S-CATCH): A Phase 2b, Randomized, Double-blind, Placebo-Controlled Trial — Neurocritical Care, online 2026-06-23, doi:10.1007/s12028-026-02563-7
  8. Phase 1 Randomized, Double-Blind, Placebo-Controlled Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects — Journal of Clinical Pharmacology 2017;57(6):770-776
  9. Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Escalating Dose and Repeated Doses of CN-105 in Healthy Adult Subjects — ClinicalTrials.gov
  10. Tolerability and Pharmacokinetics of Single Escalating and Repeated Doses of CN-105 in Healthy Participants — Clinical Therapeutics 2022;44(5):744-754, doi:10.1016/j.clinthera.2022.03.006