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Hunting for antibodies to combat COVID‑19

Antibodies produced by the body in response to infectious pathogens such as SARS-CoV-2 are at the center of the fight against COVID-19. The vaccines in development seek to train the immune system to produce neutralizing antibodies that can protect people against infection (Biopharma Dealmakers, B18, June 2020), while antibodies produced in people who have been infected with SARS-CoV-2 can be the basis for diagnostic tests, as well as starting points for the development of antibody products that could be used for prevention or treatment. In this feature, with the help of data from DealForma we look at the application of antibodies in the development of both diagnostics and treatments for the COVID-19 pandemic, with a focus on some of the partnerships established to accelerate development.

Diagnostic testing for COVID-19

The diagnostic tests for COVID-19 in use at present fall largely into two groups: those that detect viral nucleic acid sequences and those that detect antibodies to SARS-CoV-2 produced by the immune system in people who have been infected. Nucleic acid-based tests are the simplest to develop and are highly accurate. Globally, these tests have been heavily used from early on in the pandemic. However, they only pick up active infections, whereas immunoassays that detect antibodies that patients have produced in response to SARS-CoV-2 have the potential to identify people who have been infected (perhaps unknowingly) and recovered. The downside of immunoassays is that they are more challenging to develop, and the readouts may be affected by the complex nature of immune responses to infection.

Fig. 1 | Partnering deals by diagnostic type in development to target COVID-19 (February – July 2020). More than a fifth of the deals were focused upon antibody-based diagnostics. Source: DealForma, July 2020.

Spurred by the need for speed and scale, companies and academic institutions developing both types of diagnostics for COVID-19 have been active in partnering. According to data from DealForma, more than 70 deals involving the development of diagnostics for COVID-19 have been made since February (Fig. 1). The majority of the deals were focused on the development of nucleic acid-based tests, but there were also several notable deals related to antibody-based diagnostics (Table 1). As with vaccines in development for COVID-19 (Biopharma Dealmakers, B18, June 2020), the US Biomedical Advanced Research and Development Authority (BARDA) has been a key player in such partnerships.

Table 1 | Selected partnering deals announced for the development of diagnostics involving antibodies for COVID-19 (February–July 2020). Source: DealForma, July 2020.

Table 2 | Selected partnering deals announced for the development of treatments involving antibodies for COVID-19 (February–July 2020). Source: public press releases.

Antibodies as treatments

In parallel with the pursuit of diagnostic tests, a number of biopharma companies are searching for antibodies as treatments against SARS-CoV-2, harnessing the wealth of expertise and manufacturing capabilities that has been built up through the development of highly successful monoclonal antibody(mAb)-based therapies for cancer and immune disorders.

Antibodies developed to treat infectious diseases have historically been few and far between, owing to factors such as the availability of small-molecule drugs and vaccines. However, given the novelty of SARS-CoV-2—with no vaccine available yet and the only near-term options for small-molecule drugs being the repurposing of compounds, such as remdesivir, that have been developed for other diseases—antibodies have attracted intense interest as potential treatments for COVID-19. Furthermore, antibodies could be used in prevention strategies until a vaccine is successfully developed and be valuable afterwards for various groups for whom vaccines are not applicable, such as immunocompromised patients.

The antibodies in development originate from analysis of the blood of people who have recovered from SARS-CoV-2 infection, who presumably have raised an effective immune response against the coronavirus. Although convalescent plasma itself could be used as a therapy, it has key limitations linked to manufacturing at scale, batch-to-batch variability and the need for blood type matching. Consequently, efforts to harness antibodies as COVID-19 therapies have largely focused on identifying suitable neutralizing antibodies in convalescent plasma and optimizing them as therapies. The aim for such mAbs is to block viral entry into cells by binding to the spike protein of SARS-CoV-2 (Fig. 2).

Fig. 2 | Antibodies in the battle against COVID-19. Mode of action of therapeutic monoclonal antibodies for treatment or prevention of COVID-19. Antibodies that bind to the viral spike protein can block the interactions with the cellular receptor angiotensin-converting enzyme 2 (ACE2), inhibiting viral entry. Some regions of the antibody such as the Fc region can be specifically engineered to improve the characteristics of therapeutic mAbs. mAbs, monoclonal antibodies; CH, constant heavy domain; CL, constant light domain; Fab, fragment antigen-binding; Fc, fragment crystallizable; FcR, Fc receptor; VH, variable heavy domain; V-L, variable light domain.

Biopharma companies working on mAbs for COVID-19 include Regeneron, Vir, Lilly, AstraZeneca, Amgen and the Adimab spin-out Adagio Therapeutics, and partnerships are prominent in accelerating their efforts. Some of the companies, such as Vir and Regeneron, already have well-established platforms for identifying and optimizing suitable mAbs, and their partnerships have focused on development of their candidates with partners that can offer large-scale manufacturing and commercialization capabilities.

For example, in April, Vir and GlaxoSmithKline (GSK) entered a collaboration to accelerate the development of two neutralizing mAbs identified by the Vir platform, VIR-7831 and VIR-7832, with GSK making a $250 million equity investment in Vir (Table 1). And in July, Regeneron announced a $450 million contract awarded by BARDA to manufacture and supply REGN-COV2, a cocktail of two neutralizing mAbs identified by Regeneron that is in phase 2/3 trials for the treatment of COVID-19 and a phase 3 trial for the prevention of SARS-CoV-2 infection.

Other large companies have partnered with academic institutions and biotech companies to gain access to promising potential mAb candidates. One of the earliest deals of this type was penned in March when Lilly partnered with the biotech AbCellera to co-develop antibody therapeutics based on screening the blood of one of the first US patients to recover from COVID-19. Lilly initiated a phase 3 trial of LY-CoV555, the lead mAb candidate identified from this collaboration, in partnership with the National Institute of Allergy and Infectious Diseases in August. Lilly also partnered with the Chinese biotech Junshi Biosciences on COVID-19 mAbs in May 2020, with Junshi maintaining all rights within China and Lilly having an exclusive license outside of China. Phase 1 trials of their neutralizing mAb JS016 commenced in June. Another large company, Amgen, partnered with the biotech Adaptive Biotechnologies to develop COVID-19-neutralizing mAbs in April 2020.

Academia has also been a source of many therapeutic candidates and chosen to collaborate to further their developments. In June 2020, AstraZeneca licensed two neutralizing mAbs from Vanderbilt University, building on a research collaboration first initiated in April 2020, and AbbVie partnered with Harbour BioMed, Utrecht University and Erasmus Medical Center to develop a neutralizing mAb known as 47D11.

In addition to traditional partnerships, the escalating pandemic has triggered the formation of larger, never-seen-before collaborative efforts to combat the virus, including mAb therapies. These partnerships include Operation Warp Speed (a joint effort announced in May this year, between US agencies including the Centers for Disease Control and Prevention (CDC), the FDA, the NIH and BARDA); the COVID R&D alliance, which brings more than 20 pharmaceutical companies together to accelerate promising therapeutics for COVID-19; and the COVID-19 Clinical Trials Alliance, which connects sites, sponsors and CROs to speed up drug and vaccine development against COVID-19. All of these partnerships underline the magnitude of the problem and the motivation of the industry to work together and share resources to accelerate the development of countermeasures.

doi: https://doi.org/10.1038/d43747-020-01115-y

Acknowledgements

We would like to acknowledge DealForma for the use of its COVID-19 diagnostic deals data.

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