Drug name
Last update: Aug 2026CIS43LS (mAb)
Developer(s)
Drug information
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CIS43LS
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Biotherapeutic
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CIS43LS (VRC-MALMAB0100-00-AB) is a long-acting human IgG1 monoclonal antibody in clinical development for the prevention of P. falciparum malaria. The Fc region of CIS43LS contains two site-directed mutagenesis substitutions at amino acid residues N457S and M451L (termed “LS”) to extend its efficacy and half-life. CIS43 was originally isolated from a clinical trial participant inoculated with an attenuated P. falciparum whole-sporozoite vaccine, and functions by targeting the highly conserved junctional NPDP epitope of the P. falciparum circumsporozoite protein essential for hepatocyte infection and parasite motility. Recent studies have shown that a single dose of CIS43LS provides high levels of malarial prophylaxis for 8 weeks, and may offer additional protection for up to 6 months.
Unknown
Unknown
Therapeutic area(s)
- Malaria
- Prevention
Administration route
Subcutaneous, Intravenous
Associated long-acting platforms
Monoclonal Antibody
Use of drug
- Administered by a nurse
- Administered by a specialty health worker
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Dosage
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Associated compounds, formulations and regimens
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Associated technologies
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Additional information
Developer(s)
Leidos Biomedical Research
Leidos Biomedical Research, Inc. is a research company that operates the Frederick National Laboratory for Cancer Research on behalf of the National Cancer Institute. Based in Frederick, Maryland, the laboratory develops technological solutions for HIV/AIDs, emerging infectious diseases and oncology, in addition to providing scientific support to several national institutes including the NIAID.
Drug structure
Scale-up and manufacturing prospects
Manufacturing requirements and production scale-up for therapeutic monoclonal antibodies (mAbs) is primarily focused on pharmacokinetic suitability, formulation stability and overall maintenance of product quality. In addition, industrial bioprocessing steps can introduce further challenges regarding mAb formulation viscosity and aggregation propensity.
Industrial bioreactor vessel with a production volume capacity of between 5-25kL. Continuous disc stack centrifuges for bioreactor harvesting with subsequent membrane and depth filtration for supernatant clarification. Recombinant protein-A chromatography or other suitable affinity capture apparatus followed by two chromatographic polishing steps such as cation- and anion-exchange. Ultrafiltration membrane system to concentrate and formulate the final product.
MAbs are highly dependent on their structural, chemical and conformational stability for biological activity. Chemical degradation of mAbs during manufacture can lead to the generation of product variants and complex impurity profiles resulting from a wide range of processes, including: N-linked glycosylation, isomerisation, fragmentation, deamidation, oxidation and C-terminal lysine clipping. Additionally prior to packaging, the final product requires close monitoring for the presence of residual contaminants such as endotoxins and pro-inflammatory peptidoglycans.
Formulation characterisation steps for therapeutic mAb products include (but are not limited to): (1) Identification of post-translational modifications using ion-exchange chromatography and capillary isoelectric focusing, (2) Measurement of concentration dependent aggregation rates via thermal differential scanning calorimetry, sub-visible particle quantitation and size-exclusion chromatography, and (3) Antibody clipping and fragmentation detection by capillary electrophoresis.
Excipients & delivery device(s)
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No delivery device
Safety, Efficacy and Evidence Summary
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CIS43 antibody and M428L and N434S mutations (CIS43LS)
Antibodies and antigen binding fragments that specifically bind to P. falciparum circumsporozoite protein and neutralize P. falciparum are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. The disclosed antibodies, antigen binding fragments, nucleic acids and vectors can be used, for example, to inhibit a P. falciparum infection.
WO2018148660
Compound
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES (NIH); SANARIA INC
Not provided
February 12, 2038
Granted in the US, withdrawn in EPO member states