Antiviral Alliances in the Shadow of COVID-19
With 102 coronavirus-associated alliances to date, COVID-19 has quickly become the largest category of disease indications for antiviral alliances.
The biopharma industry has unique visibility and responsibility in this time of the COVID-19 pandemic. With capital markets severely constrained for an indefinite period, the industry is turning to alliances with singular focus and creativity. Antiviral alliances, both new and repurposed to address coronavirus, are leading the way.
To understand the terms of biopharma antiviral agreements, and provide a resource to those having access to similarly situated modalities, we reviewed several hundred antiviral agreements signed over the past decade, including approximately 100 that pertain directly to coronavirus detection, treatment or prophylaxis.
For purposes of this analysis, we looked at antiviral agreements commenced since January 2010 based on one or more of the following: (i) press release, (ii) financial notes disclosure, or (iii) SEC-filed contract. We found 577 such agreements, all of which are listed in the All Antivirals spreadsheet accompanying this article. Importantly, we identified 102 agreements that were specifically-related to coronaviruses (COVID-19, SARS or MERS), all of which are listed in the Coronavirus spreadsheet also accompanying this article. In each instance, we noted the following agreement terms and collateral information where available:
- Deal Type – There are 26 deal types used in BiosciDB; definitions are here
- Deal Size – Summation of all upfront, R&D and milestone payments, including any equity or loan payments, to be paid to the R&D Licensor (individual payment amounts and Financial Term Explanations are at the far right of the spreadsheet)
- Stage at Signing – One or more of the following: Diagnostic, Regent, Discovery, Lead Molecule, Preclinical, Phase I, Phase II, Phase III, Filed, Approved, Formulation, Orphan Indication
- Disease/Indication – Primary disease focus of the agreement, including named indications
- Technology/Sub-technology – Primary technology focus of the agreement, including any sub-technology
- Compound Name – The most advanced compound included in the agreement
- Mechanism of Action – Basis of compound activity (e.g. mRNA, protein subunit, viral vector)
- Molecular Target – Specific antiviral target
- Deal Source – The primary public source of data utilized for each agreement, including press releases (PR), SEC-filed contracts (Redacted or Full), and Freedom of Information Act (FOIA) versions of unredacted contracts.
The deal press releases, financial notes disclosures and/or full contract(s) are accessible via the “Deal” links to BiosciDB subscribers.
Notice: All “Deal” links found within the attached spreadsheets are only accessible by BiosciDB subscribers.
Coronavirus Is the Dominant Disease Focus of Recent Antiviral Alliances.
With 102 coronavirus-associated alliances to date, of which 64 have been announced since February, COVID-19 has quickly become the largest category of disease indications for antiviral alliances. As shown in Figure 1, coronavirus deals have surpassed all other antiviral indications pursued over the past decade, and have done so over a two month period. For antiviral alliances in aggregate, deals targeting HIV have been second most common, followed by Hepatitis C, Hepatitis B and Influenza. Given the urgent nature of these endeavors, most coronavirus collaborations have been launched with minimal attention to provisions dealing with ownership, control and economics.
Coronavirus Alliances are Early Stage.
Figure 2 shows the stage at signing of announced coronavirus deals to date. All five of the Phase I/II alliances involve repurposing of compounds that have been in humans for other indications (e.g. MERS or Ebola), so essentially all coronavirus deals are early stage. Several antiviral alliances that were initiated for other indications have been expanded to include coronavirus – for example, the 2017 Alnylam/Vir Biotechnology alliance for RNAi compounds to treat Hepatitis B was expanded in March to include coronavirus. A Deal Snapshot of the expanded Alnylam/Vir alliance is available here. For antiviral alliances in aggregate, of approximately 300 compounds in development, one-third were in the clinic, a third were preclinical stage, and the balance were discovery or lead molecule stage at signing.
Most Coronavirus Alliances are Vaccine-Oriented.
Figure 3 shows the technologies that form the basis of coronavirus deals to date. 51 coronavirus alliances are attempting to develop vaccines – of these, 11 are doing so in conjunction with other technologies. There are 21 monoclonals in development plus nine synthetics, several of which are associated with screening of repurposed drugs. Other approaches include cell therapy, oligonucleotides (e.g. mRNA) and recombinant proteins or peptides. For antiviral alliances in aggregate, of approximately 400 antiviral alliances having one or more of these six approaches, 45% were vaccines, 28% were synthetics, 18% were monoclonals, and the balance were fairly evenly divided between oligos, peptides and cell therapy.
Mechanism of Action of Coronavirus Vaccine Compounds/Programs.
As noted above, vaccines form the primary mechanism of action (MOA) for the majority of coronavirus compounds currently in development. Top 5 categories for coronavirus vaccines include protein-based subunit vaccines (31%), DNA vaccines (17%), mRNA vaccines (14%), live attenuated vaccines (11%) and non-replicating viral vector vaccines (11%). Within each of the top vaccine MOA categories, most compounds were in the pre-clinical stage of development at the time of alliance signing, as shown in Figure 4. Other vaccine MOA categories include live modified, peptide, gene-encoded antibody, RNA, replicating viral vector, and DNA-encoded monoclonal antibody (dMAb) vaccines.
BioSci will continue to track coronavirus alliance formation as we do all biopharma alliances. To see the latest data, please go to BiosciDB.com and sign up for a two week free trial.