Teropavimab + Zinlirvimab

Drug information

Drug's link(s)

Not provided

Generic name

Teropavimab and Zinlirvimab

Brand names

Not provided

Compound type

Biotherapeutic

Drug class/category

2 bNAbs targeting gp120 on HIV-1 envelope

Summary

Teropavimab (GS-5423; 3BNC117-LS) and zinlirvimab (GS-2872; 10-1074-LS) are a long-acting combination of the broadly neutralising antibodies (bNAbs) 3BNC117 and 10-1074 currently in clinical development for the treatment of HIV-1 infection. The crystallisable fragment domains of both teropavimab and zinlirvimab contain two directed amino acid substitutions termed “LS” (residues N434S and M428L) resulting in long-acting bNAbs with improved efficacy and half-life. Teropavimab functions by targeting the CD4-binding site of the HIV-1 envelope glycoprotein gp120, while zinlirvimab targets the HIV-1 envelope V3 glycan supersite. These interactions mechanistically disrupt the initial entry of HIV-1 virions into the host CD4+ cell, which is an essential step in HIV infection.

Approval status

Unknown

Regulatory authorities

Unknown

Therapeutic area(s)

Use case(s)

Treatment

Administration route

Intravenous, Subcutaneous

Associated long-acting platforms

Broadly neutralising monoclonal antibody

Use of drug

Ease of administration

Administered by a nurse
Administered by a specialty health worker

Frequency of administration

Not provided

User acceptance

Not provided

Dosage

Available dose and strength

Not provided

Maximum dose

Not provided

Recommended dosing regimen

Not provided

Additional comments

Not provided

Dosage link(s)

Not provided

Associated compounds, formulations and regimens

Not provided

Associated technologies

Not provided

Additional information

Not provided

Developer(s)

Originator

United States

Gilead

Gilead Sciences, Inc. is a multinational biopharmaceutical company that develops and manufactures innovative medicines for life-threatening diseases, including anti-viral therapeutics for HIV/AIDS, Hepatitis B, Hepatitis C and Covid-19. Headquartered in Foster City, California, Gilead was originally founded in 1987 and is currently listed on both the S&P 500 and the NASDAQ Biotechnology Index.

Drug structure

Scale-up and manufacturing prospects

Scale-up prospects

Production scale up and manufacturing requirements for therapeutic monoclonal antibody products are primarily related to formulation stability, pharmacokinetic suitability and maintenance of quality attributes. The industrial manufacture of high-concentration broadly neutralising antibody (bNAb) formulations for parenteral administration can introduce production challenges regarding aggregation propensity and formulation viscosity. Exploratory process optimisations such as bNAb co-formulation and multi-specific antibody composition have the potential to reduce overall manufacturing costs.

Tentative equipment list for manufacturing

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. 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.

Manufacturing

Biological activity of bNAbs is highly dependant on their chemical, conformational and structural stability. Reduced glycosylation of bNAbs during manufacture and chemical degradation processes such as deamidation can result in increased aggregation, loss of activity and diminished solubility. Degradation may occur at any stage throughout the manufacturing process including bioprocessing, purification, product delivery and storage. Considerations to increase formulation stability may include pH optimisation and the addition of suitable excipients (e.g. surfactants, stabilizers and buffers).

Specific analytical instrument required for characterization of formulation

Formulation characterisation for single-entity bNAb production include capillary isoelectric focusing and ion-exchange chromatography for identification of post-translational modifications, subvisible particle quantitation, thermal DSC, size-exclusion chromatography for measurement of concentration dependent aggregation rates and capillary electrophoresis for antibody fragmentation and clipping. Co-formulated bNAbs in mixture may utilise SE-HPLC, capillary electrophoresis sodium dodecyl sulphate, dynamic light scattering, microflow imaging and multi-attribute method mass spectrometry analysis.

Excipients & delivery device(s)

Proprietary excipients used

Not provided

Novel excipients or existing excipients at a concentration above Inactive Ingredient Database (IID) for the specified route of administration

Not provided

Residual solvents used

Not provided

Delivery device(s)

No delivery device

Safety, Efficacy and Evidence Summary

Safety

Not provided

Efficacy

Not provided

Evidence Summary

Not provided

References and relevant studies

Not provided

Description

Zinlirvimab+Teropamivimab combination

Brief description

Zinlirvimab variants + combination with Teropamivimab (Heavy chain e.g. SEQ 59-61)

Representative patent

WO2020056145