Switzerland-based Molecular Partners reported that an experimental ensovibep being developed for the treatment and prevention of COVID-19 infection remains fully functional in the presence of the Omicron (B.1.1.529) variant of the SARS-CoV-2 coronavirus.

According to in vitro studies in a pseudoviral system mimicking the Omicron variant, ensovibep retained high neutralizing activity comparable to that against the original non-mutant SARS-CoV-2. Thus, while the half-maximal inhibitory concentration (IC50) of ensovibep against the latter is 1.6 ng/ml, in the case of Omicron it only increases by a factor of 1.3–1.4 to 2.1–2.2 ng/ml.

The neutralizing activity of ensovibep against all other strains of coronavirus, including the variants of concern such as Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2), is very high: IC50 falls within a narrow range of 1–8 ng/ml.

  • In comparison, the monoclonal antibody Xevudy (sotrovimab, VIR-7831, GSK4182136) promoted by GlaxoSmithKline and Vir Biotechnology and positioned as one of the best for fighting all coronavirus mutations, requires significantly higher concentrations to neutralize SARS-CoV-2 variants: IC50 is between 51 and 187 ng/ml.

Sotrovimab Is Effective Against Omicron Variant of Coronavirus

A monoclonal antibody developed by GlaxoSmithKline and Vir Biotechnology successfully counteracts a new strain of SARS-CoV-2.

Ensovibep is undergoing clinical validation in partnership with Novartis.

  • Ensovibep’s clinical successes, announced in January 2022, have boosted Molecular Partners’ stock price as Novartis looks to buy global rights to the drug and secure early regulatory approval for its intravenous use in COVID-19 treatment. A clinical trial of a subcutaneous formulation of ensovibep is planned in the meantime.
  • Novartis acquired the global rights to ensovibep from Molecular Partners. The financial terms of the deal involve a milestone payment of 150 million Swiss francs ($156 million) and a 22% royalty on sales of the ready-to-use drug (in high-income countries).


Ensovibep for COVID-19: Clinical Trial

The EMPATHY (NCT04828161) phase 2/3 (randomized, double-blind, placebo-controlled, multicenter, international) clinical trial is examining the efficacy and safety of intravenously administered ensovibep among ambulatory adult patients with mild-to-moderate COVID-19 whose symptoms manifested within 7 days before study entry.

The hypothesis being tested is whether ensovibep can keep COVID-19 infection from worsening and thereby reduce the risk of hospitalization or death from its complications.

An analysis of data from 400 patients found that all three doses of ensovibep (75, 225, and 600 mg) provided a statistically significant reduction in viral load within 8 days of a single use of the drug when compared to placebo.

Administration of ensovibep resulted in a 78% reduction in the risk of hospitalization, emergency room visits, and/or death relative to placebo. The risk of hospitalization and/or death was reduced by a relative 87%.

Ensovibep accelerated patients’ recovery, shortening the time to clinically meaningful improvements.


Ensovibep: Mechanism of Action

Ensovibep (MP0420), a DARPin compound being developed for the treatment and prevention of COVID-19 infection, targets multiple parts of the SARS-CoV-2 coronavirus.

  • DARPin (designed ankyrin repeat protein) is a small (15 kDa; one-tenth the size of a typical antibody) genetically engineered protein — an antibody mimetic that exhibits highly specific and high-affinity binding to a protein target. Different DARPin proteins can be linked to each other in a single molecule so that it performs several functions simultaneously.

Ensovibep is a trispecific DARPin molecule: it includes three DARPin domains that target the same epitope of the receptor-binding domain (RBD) of the S protein trimers but do so via different antigen-binding amino acid sequences. Ensovibep, by binding RBD, prevents its conformational change (promotes the premature transition of S protein to a post-fusion conformation) necessary for SARS-CoV-2 penetration into infected cells, which it does by binding to angiotensin-converting enzyme 2 (ACE2) receptors on their surface.

Ensovibep resists coronavirus mutations through so-called cooperative binding: even if one of the three RBD-binding domains in the DARPin molecule loses its ability due to mutations, it is still supported by the other RBD-binding domains.

Due to the two DARPin domains connected to ensovibep, which bind serum albumin, the elimination half-life is significantly prolonged, which suggests a prolonged therapeutic effect.

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The intravenous formulation of ensovibep is in clinical trials. A subcutaneous formulation of ensovibep is in the preclinical stage of development.


Omicron Variant: Latest Scientific News, Findings, Evidence, and Developments

Up-to-date scientific information about the new Omicron variant of SARS-CoV-2/COVID-19.



Ensovibep clinical results call. EMPATHY Part A. Molecular Partners, January 10, 2022. [PDF]

Molecular Partners. Corporate presentation, May 2022. [PDF]

SARS-CoV-2 Omicron and pan-variant neutralization activity of Ensovibep: a DARPin therapeutic candidate for treatment of COVID-19. ISAR-ICAR2022. [PDF]

Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants. bioRxiv, December 17, 2021. [PDF]

Pre-clinical data of ensovibep, a multi-specific DARPin therapeutic with high potency against all frequent SARS-CoV-2 variants. Molecular Partners, October 20, 2021. [PDF]

EMPATHY: A ph2-3 randomized, placebo-controlled trial evaluating safety and efficacy of ensovibep in ambulatory COVID-19 patients. ISIRV-WHO Conference, October 19, 2021. [PDF]

Safety, tolerability and pharmacokinetics of ensovibep in patients with mild to moderate COVID-19: Preliminary report of a phase 2a, open-label, single dose escalation study. 8th ESWI Influenza Conference, December 6, 2021. [PDF]

Ensovibep, a potential antiviral COVID-19 treatment, is safe and well tolerated in healthy volunteers: Preliminary safety and PK results from a phase 1, multi-part, ascending, single-dose study. 8th ESWI Influenza Conference, December 6, 2021. [PDF]

Molecular Partners. Corporate presentation, November 2021. [PDF]

Highly potent anti-SARS-CoV-2 multivalent DARPin therapeutic candidates. bioRxiv, July 21, 2021. [PDF]

Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs. April 27, 2021. [PDF]

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