After vaccines and antiviral approaches to tackling the Covid-19 pandemic, it’s time for antibodies to take their turn in the spotlight. This week Lilly seized the lead in this space, starting the first clinical trial of an antibody designed to treat the novel coronavirus.
LY-CoV555, derived from a deal with Abcellera, targets Covid-19’s Spike protein, meaning that unlike projects aiming to reduce the infection’s complications it takes direct aim at the virus itself. While at present this is the only clinical-stage antibody against Covid-19, it will not retain this monopoly for long.
The Spike protein-targeting approach is similar to that of several of Lilly’s competitors. The protein is present on the virus surface, and the virus uses it to dock with the Ace2 receptor on target cells, allowing it to be internalised and infect.
The next project into the clinic with this mechanism could come from Vir’s partnership with Glaxosmithkline, which has so far identified two lead MAbs. Also keenly awaited are a multi-antibody cocktail from Regeneron, and a project under way at Astrazeneca, all of which could be studied in patients within the next few months.
The hope is that these antibodies can prevent the virus docking, or hit another part of it that leads to antibody-mediated destruction.
The last two are noteworthy because they are based in part on plasma derived from patients who have recovered from Covid-19 infection. This approach, it might be surmised, could provide a broader range of targets, some of which might provide a more efficient way of targeting the virus than hitting the Spike protein.
|Selected antibodies and related biologicals in development for Covid-19|
|Companies||Lead, if identified||Mechanistic approach||Clinical development?|
|Lilly/Abcellera||LY-CoV555||IgG1 MAb vs Spike protein||Safety study in hospitalised subjects|
|Sab Biotherapeutics||SAB-185||Polyclonal||Clinical trial due mid-2020|
|Regeneron||REGN-COV2||Multi-Ab cocktail, incl from recovered patients||Clinical trial due Jun 2020|
|Celltrion||CT-P59||MAb vs Spike protein receptor binding domain||Clinical trial due Jul 2020|
|Glaxosmithkline/Vir||VIR-7831 & VIR-7832||MAbs vs Spike protein||Clinical trial in Jul-Sep 2020|
|Astrazeneca||–||MAbs, incl based on recovered patients||Clinical trial in Jul-Sep 2020|
|Sorrento||STI-1499||Fully human MAb vs Spike protein||Clinical trial due Q3 2020|
|Brill Bio||–||Fully human MAb||Clinical trial due Q3 2020|
|Yumab||–||MAbs, incl based on recovered patients||Clinical trial due H2 2020|
|Molecular Partners||–||Darpin proteins||Clinical trial due H2 2020|
|Systimmune||SI-F019||Bivalent Ace2 fusion protein vs Spike protein||IND filing due 2020|
|Lilly/Junshi||JS016||Fully human MAb vs Spike protein||–|
|Atreca/Beigene/IGM||–||IgM & IgA MAbs vs novel epitopes||–|
|Amgen/Adaptive||–||MAbs based on recovered patients||–|
|Ossianix||–||Single-domain VNAR MAbs vs Spike protein||–|
|Sorrento||STI-4398||Ace2-Fc protein vs Spike protein||–|
|Sorrento/Mabpharm||STI-4920||Bispecific vs 2 domains on Spike protein||–|
|Note: excludes anti-IL6, anti-GM-CSF and other MAbs not directly targeting Covid-19.|
The Spike protein is also used as the target for most of the industry’s vaccine approaches seeking to prime the immune system, and indeed Regeneron has suggested that REGN-COV2 could also have a prophylactic role.
And there are other biologicals already in clinical development, such as MAbs against cytokines, GM-CSF and angiopoietin 2, but these are not considered here as they aim to treat the effects of Covid-19, such as cytokine elevations and respiratory complications, rather that the virus itself.
Though many projects have the same target in common, there is additional variability in antibody structure.
For instance, while most are based on IgG, a tie-up between Atreca, Beigene and IGM Biosciences is looking at those derived from IgM and IgA, which, the companies argue, have more binding domains and hence greater binding power than IgG.
A separate tie-up Vir has with Xencor looks to develop MAbs with an engineered Fc domain to give an extended half-life, and a similar thinking lies behind the so-called Darpins in development by Molecular Partners.
There are also bispecific approaches and fusion proteins, for instance SI-F019, in development by Systimmune, a private US group focusing on MAbs, bispecifics and antibody-dug conjugates. This combines two proteins each mimicking Ace2, aiming to take up the relevant binding sites on Covid-19 and prevent its interaction with the endogenous Ace2 receptor.
While many companies are making claims about the superiority of their respective approaches, these are of course all based on animal or in vitro data, and no comparison will be possible until the first clinical trials read out.
After Lilly’s clinical study, primarily testing safety, pharmacokinetics and pharmacodynamics, the designs of competitor trials will be watched with interest.
This article has been updated to reflect Celltrion's choice of CT-P59 as a lead.