By Stephen Towers, PhD

The program for this year’s Biotech Showcase Digital – the leading investor and networking conference for mostly small- and mid-cap biotechnology companies – highlighted several important advances in healthcare that have been greatly accelerated by the COVID-19 pandemic (to put a modern spin on the old adage, necessity is the mother of innovation), including the embrace of digital health and advancement of novel vaccine technologies. In other areas of the industry (such as cell and genetic medicine development) progress continued at an impressively brisk pace despite the pandemic. Here, we provide some insights on 3 key topics based on panel discussions with industry leaders at this year’s event.

 #1. A vision for how the biopharmaceutical industry will shape the world’s ongoing response to COVID-19 – during the pandemic and beyond – is emerging

As part of a series of compelling conversations with COVID-19 leaders, outgoing Operation Warp Speed (OWS) chief scientific adviser Moncef Slaoui reflected on his 8 months working at the intersection of government, industry, and academia, articulating his pride in what the industry has managed to achieve in a relatively short space of time:

 “I’m very proud of the industry, I have to say…of having the capabilities, the will, the commitment, the generosity to do what the industry has done. And I don’t shy away from saying the industry is saving the world, the pharmaceutical and biotech industry.” – Moncef Slaoui

Regarding OWS’s support for vaccine development, Dr Slaoui noted that 5 of the 6 vaccines selected (from a total of 94 programs) are currently in phase 3 development or approved. In his opinion, the pandemic is proving to be a valuable opportunity to validate platforms and technologies, such as mRNA vaccines, that otherwise would have taken 3 or 4 years. The response to this crisis has “transformed the vaccine industry.”

While the bulk of media attention has, understandably, gone to those mRNA vaccines from Pfizer/BioNTech and Moderna, both their uncertain duration of protection and the need to vaccinate almost 8 billion individuals worldwide makes it clear that additional vaccines will be needed to end the pandemic and for use after the pandemic. Biotech Showcase Digital provided a useful opportunity to understand how the value propositions of some earlier-stage vaccine candidates might shape the global response to the disease. Arcturus Therapeutics has a mRNA vaccine candidate – LUNAR-COV19 – that is differentiated from other mRNA vaccines by its self-amplifying mRNA payload, which prolongs expression of the SARS-CoV-2 spike glycoprotein relative to conventional mRNA. Joseph Payne (President and CEO, Arcturus Therapeutics) explained how this may equip it to be a single-shot vaccine that can be dosed at a lower level, thus increasing the number of individuals who can be vaccinated and avoiding the logistical challenges of two-dose regimens. It’s widely acknowledged that optimal vaccine immunity results from engaging both humoral and cellular responses, but less attention has been given to the role of mucosal immunity in protecting against COVID-19, which is surprising considering SARS-CoV-2 enters the human body primarily through the mucosal surfaces of the upper respiratory tract. Perhaps this omission is because the systemically administered vaccines are unable to stimulate robust immune responses in the mucosae, despite generating systemic neutralizing antibody (and possibly T cell) responses. Scot Roberts (Chief Scientific Officer, Altimmune) explained how Altimmune’s single-dose intranasal COVID-19 vaccine AdCOVID, in addition to providing systemic humoral immunity, was also effective at eliciting mucosal immunity in the nasal cavity in preclinical studies. Achieving local mucosal immunity is particularly valuable because it may be needed to provide “sterilizing immunity” to SARS-CoV-2, in which individuals are protected not only against the disease, but also against infection and the ability to transmit the virus to others. Assuming these findings are replicated in clinical trials, this vaccine, with its more-appealing route of administration and convenient (refrigerator) storage requirements could make an important contribution to containing the disease.

Recommendations and predictions for how the COVID-19 therapeutics landscape will evolve in 2021 emerged from several sessions. Because COVID-19 can progress rapidly from a respiratory disease to a multisystemic inflammatory and coagulopathic disorder, there is a need to develop not only antiviral therapies, but also drugs that block complement activation, coagulation, and cytokines, according to Prabhavathi Fernandes (Chair, National Biodefense Science Board). To reduce the risk of progression from mild to severe disease, the goal would be to develop therapies that arrest those pathogenic processes for treatment of early or presymptomatic patients in the outpatient setting. Identifying biomarkers that are reliably predictive of disease progression will also be required to enable risk stratification of patients and, eventually, individualization of treatment. Michael Kurilla (Director of Division of Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health) described the work of the National COVID Cohort Collaborative (N3C) which has established perhaps the largest single repository of clinical data on COVID-19 (from >400,000 COVID-19 patients). Analyses of this large dataset should help to identify prognostic biomarkers and support therapeutic development. Regarding the use of direct-acting anti-SARS-CoV-2 therapeutics (such as nucleoside analogs, protease inhibitors, and monoclonal antibodies), the panel stressed the need for constant surveillance to track changes in the viral genome that might result from their use. Developing therapeutics for treatment of the complex array of symptoms that persist in COVID-19 “long hauler” patients is another 2021 imperative articulated by Drs Fernandes and Kurilla. This effort will require us to obtain a greater understanding of the clinical phenotypes of these patients, the underlying etiologies, and the extent to which COVID-19 is exacerbating underlying comorbidities.

While the extent of the industry’s commitment to COVID-19 therapeutic development is impressive, it has also brought challenges. The first of these is the large number of clinical trials, many with a small enrollment and observational design. Moncef Slaoui reiterated the importance of conducting controlled trials that are large enough to come to a conclusion, and he argued for more central organization of clinical trials in situations of global crisis. The second clear challenge, articulated by Dr Kurilla, is understanding how to educate practitioners and keep them up to date with current recommendations:

“Communication is something that the academic community in general, and the medical community needs to play some catch-up. We rely almost exclusively on published literature. We need to have a serious examination of 21st century communication methods (it’s not Twitter or Facebook) that can rapidly disseminate information from trusted voices and partners.” – Michael Kurilla

#2. The evolution and increased acceptance of digital health products will continue beyond the pandemic

Compared with 2019, global investment in digital health innovation grew by 56% in 2020, according to Logan Plaster, director of Startup Health. Last year’s merger of Teladoc and Livongo, which was the largest digital health deal in history, was cited by several panelists as an indicator of the vibrancy of the sector. All panelists agreed that 2020 is a year that will define how healthcare is delivered for many years to come. The forced embrace of telemedicine by consumers and providers because of the pandemic is likely a trend that will continue to a great extent even after the pandemic. Douglas Lee of Bayer Pharmaceuticals described this change as a major shift in how patients access healthcare and “a change in the mindset that you need to see the doctor for everything.” Though these changes were borne out of necessity, most panelists believe that consumers largely appreciate the convenience of virtual healthcare. Last year’s expansion in reimbursement of telehealth, so that many services are reimbursed at a comparable rate to in-person visits, has also broadened access to these services for traditionally underserved groups. According to Bill Evans of Rock Health, the ongoing adoption of digital health products, such as telehealth, will depend on the degree to which CMS and state regulators retain relaxed rules that allow physicians to cross state lines and enable reimbursement for digital services.

Several future trends were identified:

  • Fulfilling the promise of digital health will require that new technologies empower patients to take greater control of their health by providing them full access to their data and educating them so as to increase their medical literacy.
  • In the future, digital health technologies will transform care from the current reactive approach to a proactive one. With the current reactive approach, patients seek health services when they feel ill, sort through the options, and only sufficient data to confirm the diagnosis is captured. In the future, data will be captured through medical grade wearables. Based on their algorithms, care organizations will contact the patient in the event of an anomaly. When the patient is referred, a large historical data set (including biomarker and genetic data) will be available to the provider.
  • Self-care technologies, including mobile apps, will not only collect data about the patient, but they will also increasingly deliver recommendations, and this feedback loop will help the patient to become more of a steward of their own healthcare.

#3. The field of genetic medicine is continuing to make great advances, despite the challenges of the pandemic

Despite the operational and clinical disruptions wrought by COVID-19, 2020 was a groundbreaking year in the development of novel genetic medicines. In their annual Cell & Gene Therapy State of the Industry Briefing, the Alliance for Regenerative Medicine identified as many as 1085 gene and cell therapy companies worldwide. Notable scientific and clinical successes in 2020 include promising data from the first-ever induced pluripotent stem cell (iPSC) treatment for Parkinson’s disease, initiation of first-in-human trials of both ex vivo and in vivo CRISPR-based gene-editing therapies, and the continuing maturation of canonical gene therapy as an established modality with commercial-stage products and deep pipelines. From a policy perspective, progress included improved Medicare reimbursement for chimeric antigen receptor T-cell (CAR-T) therapies and a new rule from the Centers for Medicare & Medicaid Services (CMS) designed to facilitate innovative payment models in Medicaid which should ultimately benefit the increasing number of costly genetic medicines.