CSL040 / CSL Behring - LARVOL DELTA

CSL040 Ameliorates Primary Graft Dysfunction in a Pre-Clinical Model of Lung Transplantation (ISHLT 2026) - "Recipients received mycophenolate mofetil (MMF) with or without CSL040 at escalating doses. Compared to TP10 and anti-C5 therapies, CSL040 offers superior mechanistic coverage, durable efficacy, and clinical readiness. These findings strongly support advancing CSL040 into clinical trials for PGD prevention."

Preclinical • Cardiovascular • Reperfusion Injury • Transplantation

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects (clinicaltrials.gov) - P1 | N=62 | Completed | Sponsor: CSL Behring | Recruiting ➔ Completed

First-in-human • Trial completion

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: CSL Behring | Trial completion date: May 2026 ➔ Dec 2025

Trial completion date

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: CSL Behring | Trial completion date: Apr 2025 ➔ May 2026 | Trial primary completion date: Apr 2025 ➔ Feb 2026

Trial completion date • Trial primary completion date

Preclinical safety and efficacy of the recombinant CR1 drug product CSL040 in rats and cynomolgus monkeys. (PubMed, Toxicol Appl Pharmacol) - "These non-clinical studies with CSL040 demonstrated PD activity consistent with its mode of action, adequate PK properties, and a safety profile supporting a phase 1 clinical strategy. A small follow-up study comparing the PK/PD effects of CSL040 following IV and subcutaneous (SC) administration also suggested that the latter route of administration might be a viable alternative to IV administration."

Journal • Preclinical

Mechanistic insights into complement pathway inhibition by CR1 domain duplication. (PubMed, J Biol Chem) - "We have previously used our knowledge of this domain structure to identify CSL040, a soluble extracellular fragment of CR1 containing the long homologous repeat (LHR) domains A, B, and C. CSL040 retains the ability to bind both C3b and C4b but is also a more potent complement inhibitor than other recombinant CR1-based therapeutics...Interestingly, multiplication of the C4b-binding LHR-A domain resulted in only minor increases in classical/lectin pathway inhibitory activity. The CR1 duplication variants characterized in these in vitro potency assays, as well as in affinity in solution C3b and C4b binding assays, not only provides an opportunity to identify new therapeutic molecules, but also additional mechanistic insights to the multiple interactions between CR1 and C3b/C4b."

Journal

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: CSL Behring | Trial completion date: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Immunology • Primary Immunodeficiency • CRP

The Molecular Mechanisms of Complement Receptor 1-It Is Complicated. (PubMed, Biomolecules) - "Evidence for the interaction of CR1 with additional ligands such as C1q will also be reviewed. Finally, we will bring the mechanistic understanding of CR1 activity together to provide an explanation for the differential complement pathway inhibition recently observed with CSL040, a soluble CR1-based therapeutic candidate in pre-clinical development."

Journal • Review

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: CSL Behring | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Primary Immunodeficiency • CRP

First-In-Human Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Escalating Single And Multiple Doses Of CSL040 In Healthy Subjects (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: CSL Behring

New P1 trial • Immunology • Primary Immunodeficiency • CRP