part0025

I chose to spend my life in the biotechnology industry trying to bring medicines to people who need them. The reasons have never been clearer. We are now on the front lines fighting a virus that has killed so many people already, with the potential to kill millions more, and has shut down society and crippled economies around the world. Absent drugs and vaccines, it will take years for sufficient herd immunity to develop so that society can resume. In that case, we would be forced to compromise between continued isolation and the consequent social, emotional, and economic devastation, or relaxing our isolation at the expense of increasing deaths. It is not being overly dramatic to say that the nature of our society over the next decade will depend on our success and how quickly we can achieve it.

VIR was founded to take on major global infectious diseases, including potential pandemics. We did not expect to be confronted with such a serious pandemic so soon, but here we are. For the employees at Vir, many of whom have devoted their lives to preventing and treating infectious diseases,this is our moment: this is why we exist . Since early January, we have been working long hours, seven days a week. We have prioritized COVID-19 activities above all others. We have accelerated timelines, worked with current and potential collaborators, interacted with regulators, and condensed a process that normally takes eighteen months into four months. We plan to begin clinical trials this summer and to complete them in the fall. If successful, we have planned for a drug supply of millions of doses by the end of the year.

We are taking multiple approaches to bring forward potential therapies for prevention and treatment of COVID. Our first clinical programs are likely to be antibodies. Our scientists have repeatedly demonstrated the ability to isolate therapeutically relevant antibodies from patients who have recovered from infections. Two examples are mAb114, which is one of the two treatments that showed some efficacy in the recent Ebola trial conducted in the Congo by NIH, and a pan-influenza-A antibody that recognizes every strain of Flu A that has arisen since the 1918 pandemic and will start Phase 2 trials for flu prophylaxis later this year. A number of years ago, we had isolated antibodies from survivors of the SARS-1 epidemic. When SARS-CoV-2 emerged, we went back to those SARS-1 antibodies to assess whether any of them were capable of cross-reacting with SARS-CoV-2. And of course we also screened antibodies from patients who recovered from CoV-2 infection.

We believe that antibodies that cross-react with an entire viral family, and therefore recognize an epitope that is highly conserved, are likely to have advantages as therapeutic agents because resistant mutants are less likely to arise. Cross-reacting antibodies that also are potently neutralizing do exist—but they are rare and it takes skill to find them. Our lead antibodies are examples and we are moving them rapidly toward the clinic while simultaneously characterizing additional antibodies that could pair with them. Preliminary data as of this writing indicate that we have additional antibodies that act synergistically with our lead and could reduce the dose, and thus increase the number of treatable patients manyfold.

Our second approach comes from our siRNA collaboration with Alnylam. We have been moving forward an siRNA targeting hepatitis B, which has generated good data in a Phase 2 trial. VIR and Alnylam rapidly recognized the potential of siRNAs to inhibit coronaviruses and quickly expanded our collaboration to include CoV-2 as a target. Working rapidly, Alnylam generated a large number of siRNAs. Working together, the companies have tested the siRNAs in a series of assays and have identified a lead candidate that reduces the level of CoV-2 replication by several orders of magnitude. This siRNA is being moved rapidly toward clinical development for direct administration to the respiratory tract. Our goal is to begin file an IND by the end of the year.

Our third approach is to identify cellular genes whose inhibition prevents infection with CoV-2. The approach uses CRISPR constructs to either inactivate or activate every gene in the human genome in a way that leads to any single cell having a single gene alteration. The collection of cells, which among them have every gene altered, can be infected with SARS-CoV-2. Those cells that are refractory to viral replication or that lead to reduced viral replication can be characterized, and the cellular genes responsible for the virus resistance can be identified rapidly. Using sophisticated machine learning algorithms, the genes can be placed into pathways, networks, and cellular processes. We have done this repeatedly with other pathogens including flu, RSV, rhinovirus, and HBV, and have identified the majority of genes that interfere with viral replication when altered. If we are lucky, we will identify some genes that already have been targeted with compounds. That has happened with some of our other screens, and when those compounds were tested, they have potent antiviral activity. We will know within the next weeks or months whether we are able to identify anti-CoV-2 compounds in time to break this pandemic.

Three significant programs using industry-leading approaches is a lot for a company the size of VIR to take on. Fortunately, we have the help of capable and committed partners with each approach. It has been truly heartwarming to see the amazing response to COVID-19 throughout the industry. In a very short time we have established new relationships with GSK, Samsung, Wuxi Biologics, Generation Bio, and others, and have amended our preexisting relationship with Alnylam. We are close to finalizing a relationship with Biogen as well. We are able to do this because of the commitment of each of those companies to put the rapid development of therapies ahead of normal business concerns. People across the industry obviously recognize the seriousness of the situation and have mobilized to do all that they can, and to do so as quickly as possible. We have a major collaboration with GSK that covers our antibodies, our CRISPR approach, and eventually a vaccine. We have begun working together based on a binding preliminary agreement because both companies recognize the urgency and will complete the definitive contract while the work is going on. Similarly, our manufacturing agreement with Samsung is based on a binding letter of intent, and Biogen has begun working on our antibodies based on a letter of intent while we negotiate the final agreement. We amended our agreement with Alnylam in a matter of days.

These interactions, which in my experience are highly unusual, are a sign of how seriously people around the industry are taking this situation. Our industry obviously suffers from a negative public perception, some of which is self-inflicted and deserved, but much of which is incorrect and based on faulty assumptions. Our response to COVID-19 gives us a chance to demonstrate our true motivations. Many companies, including Vir, began aggressively working on COVID-19 at a time when the economic returns were unclear. To a large extent, the economics of a COVID -19 therapy or prophylactic are still unknown. We can only guess the shape of the epidemic in the future, we don’t know to what extent the therapies that arise from our investments will be covered, and of course we don’t yet know if they will even work. Despite those risks, our industry has mobilized to do what we can.

We are at a defining moment for our industry. What we are doing, if successful, will not only affect the millions of people who otherwise would have been sickened or died, but will change life for virtually everyone on the planet. This is a once-in-a-lifetime event: years in the future, we will be asking ourselves what we did to bring the epidemic to an end. Our younger colleagues will tell stories to their children and grandchildren. I, for one, do not want any regrets that I left anything on the table—that I could have done more. So many people around the industry have responded in this manner. I have never been prouder of our industry and the people in it. It is time for all who can to step up and act. We have the capability to do something meaningful, and with that capability comes the responsibility to actually do it—and to keep doing it until a solution is found. Working together, we will bring this to an end.

George Scangos has been CEO of three biotechnology companies: VIR since January 2017, Biogen from 2010 through 2016, and Exelixis from 1996 to 2010. From 1986 to 1996, he worked at Bayer, where he had several positions including SVP of R&D and president of Bayer Biotechnology. He serves on the boards of Agilent, UCSF, Cornell University, and the Fondation Santé. He appreciates the amazing colleagues he has known over the years, many of whom contributed to this book.

VIR combines immunologic insights with cutting-edge technologies to treat and prevent serious infectious diseases. VIR has clinical programs focused on hepatitis B and flu and plans to initiate several additional clinical trials for those diseases as well as COVID and HIV in 2020. VIR’s reason for being is to combat serious diseases like COVID.