VL-2397

Cyclic Antifungal PeptideRx: InvestigationalCompound: Investigational

Also known as: Acremonium persicinum antifungal peptide, ASP2397, VL-2397

Educational Only — Not medical advice. Consult a qualified clinician before using any peptide.

Source VL-2397 at Peptiology

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Summary

VL-2397 (also called ASP2397 or GR‑2397) is an investigational cyclic antifungal peptide delivered by intravenous infusion. It is being developed for the treatment of invasive aspergillosis, including infections caused by azole‑resistant strains, and shows pre‑clinical activity against other moulds and yeasts such as Fusarium and Candida glabrata.

Mechanism of Action

VL‑2397 is a siderophore‑like molecule that mimics ferrichrome but contains three amino‑acid changes and an aluminum chelate. It enters fungal cells via the Sit1 transporter, a protein absent in human cells, providing fungal specificity. The exact intracellular target remains unknown, but the drug’s rapid fungicidal effect is linked to this unique uptake pathway.

What the Research Shows

Pre‑clinical work demonstrated rapid fungicidal activity of VL‑2397 against Aspergillus fumigatus, including azole‑resistant isolates, and efficacy in several animal models of invasive aspergillosis, even when treatment was delayed 24 h. In vitro screens have shown activity against Candida auris, Fusarium solani and Candida glabrata. A first‑in‑human phase 1 study in healthy adults evaluated single and multiple ascending intravenous doses (3–1,200 mg). The drug was well‑tolerated, with only mild infusion‑site reactions, no serious adverse events, and pharmacokinetics showing less‑than‑proportional exposure increase and no accumulation over seven daily doses. Renal excretion accounted for up to 47 % of unchanged drug. No efficacy data in infected patients have yet been published.

Reported Benefits

VL‑2397 offers a novel mechanism that bypasses common resistance pathways, showing activity against azole‑resistant Aspergillus and a broad spectrum of other pathogenic fungi in laboratory and animal studies. The phase 1 trial reported a favorable safety and tolerability profile, no drug accumulation, and predictable renal clearance, supporting further clinical development. Its rapid fungicidal action may provide an advantage over slower‑acting agents.

Limitations of the Evidence

Evidence of clinical efficacy is limited to pre‑clinical models; no patient outcome data are available. The precise intracellular target is still unidentified, which may affect predictability of resistance development. Human data are confined to healthy volunteers, so safety in immunocompromised patients remains uncertain. VL‑2397 is still investigational and has not received regulatory approval for any indication.

Safety Considerations

In the phase 1 study, the most common drug‑related adverse events were mild, self‑limited infusion‑site reactions. No serious adverse events, clinically significant vital‑sign changes, ECG abnormalities, or laboratory abnormalities were observed. Renal elimination is a major clearance pathway, suggesting monitoring of renal function may be prudent in future patient studies. Overall, the safety profile to date appears acceptable, but larger patient trials are needed.

How It Is Administered

VL‑2397 has been administered intravenously as a short infusion in single‑dose and once‑daily (q24 h) multiple‑dose regimens up to 1,200 mg for seven consecutive days in healthy volunteers. Formulation details have not been disclosed in the published abstracts.

Routes of Administration

Intravenous

Goals & Uses

  • Treatment of invasive aspergillosisAntifungalModerate
  • Treatment of azole-resistant Aspergillus infectionsAntifungal TherapyModerate
  • Other invasive mold infectionsAntifungal TherapyLow
  • Invasive aspergillosisAntifungalModerate
  • Salvage therapy for refractory invasive aspergillosisAntifungal TherapyLow

Contraindications

  • Severe hepatic impairmentOrganModerateLiver function concerns
  • Known hypersensitivity to VL-2397AllergyHigh
  • Known hypersensitivity to VL-2397 or any component of the formulationAllergyHigh

Adverse Effects

  • HypokalemiaElectrolyteUncommon
  • HeadacheNeurologicUncommonPain in the head or upper neck
  • NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
  • Elevated liver enzymes (transaminases)HepaticUncommon
  • Elevated liver enzymesHepaticUnknownIncrease in AST/ALT or other hepatic markers
  • Infusion-related reactionsHypersensitivityCommon

Drug Interactions

  • Strong CYP3A4 inhibitors/inducersLow
  • Other nephrotoxic agentsModerate
  • CYP450 substratesLow

Population Constraints

  • Pediatric patientsAgeRelative
  • Immunocompromised patientsImmunologicRelative
  • Pregnant womenReproductiveRelative
  • Patients with severe renal impairmentOrgan ImpairmentRelative
  • Pediatric patients <12 yearsAgeRelative

Regulatory Status

  • European UnionInvestigationalClinical trial authorization granted.
  • United StatesInvestigationalIND in place; Phase 2/3 trials ongoing.
  • United KingdomInvestigationalUnder MHRA clinical trial oversight.

Currently in Phase 2/3 clinical trials; not approved in any jurisdiction.

Evidence & Sources

Frequently Asked Questions

What type of fungal infections is VL‑2397 being developed to treat?

VL‑2397 is being investigated primarily for invasive aspergillosis, including infections caused by azole‑resistant Aspergillus species. Pre‑clinical data also show activity against Fusarium, Candida glabrata and Candida auris.

How does VL‑2397 get into fungal cells?

The peptide mimics a siderophore and is taken up through the fungal‑specific Sit1 transporter, which is not present in human cells. This selective uptake underlies its fungal specificity.

Has VL‑2397 been tested in patients with fungal infections?

To date, only a phase 1 safety study in healthy adults has been published. No clinical efficacy trials in infected patients have been reported in the available literature.

What adverse effects have been observed so far?

The phase 1 trial reported mild infusion‑site reactions as the most common drug‑related event. No serious adverse events, significant laboratory changes, or vital‑sign abnormalities were noted.

How is VL‑2397 administered?

All published studies used intravenous infusion, including single doses and daily infusions for up to seven days. Specific formulation details have not been disclosed.

What is VL-2397?

VL-2397 (also called ASP2397 or GR‑2397) is an investigational cyclic antifungal peptide delivered by intravenous infusion. It is being developed for the treatment of invasive aspergillosis, including infections caused by azole‑resistant strains, and shows pre‑clinical activity against other moulds and yeasts such as Fusarium and Candida glabrata.

What is VL-2397 used for?

VL-2397 is educationally associated with: Treatment of invasive aspergillosis, Treatment of azole-resistant Aspergillus infections, Other invasive mold infections, Invasive aspergillosis, Salvage therapy for refractory invasive aspergillosis. Educational only — not medical advice.

How is VL-2397 administered?

Recorded routes of administration: Intravenous.

What are the potential side effects of VL-2397?

Reported adverse effects include: Hypokalemia, Headache, Nausea, Elevated liver enzymes (transaminases), Elevated liver enzymes, Infusion-related reactions. This list is not exhaustive — consult a qualified clinician.

Who should avoid VL-2397?

Recorded contraindications: Severe hepatic impairment, Known hypersensitivity to VL-2397, Known hypersensitivity to VL-2397 or any component of the formulation. Consult a qualified clinician before use.

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