Why this matters
Today, we treat respiratory infections like the cold and influenza as a minor nuisance. The evidence increasingly suggests otherwise.
- Healthy people spend roughly 15–25 days each year—about 5% of their lives 1—sick with respiratory infections like the common cold and flu.
- Infections from common respiratory viruses can lead to severe outcomes. In 2021 alone, there were 12.8 billion infections globally. Annually, over 65 million of these progress to serious lower respiratory disease and account for ~7% of deaths from major causes in the U.S. 2
- Respiratory infections raise our risk of serious illness, often years later. While researchers are still early in establishing these connections, it seems plausible that society has meaningfully underestimated the significance of seemingly benign infections on short and long-term health.
9.8x asthma risk by age 6 if infected with rhinovirus between birth and age 3 36.1x heart attack risk for 7 days after flu infection 44.5-5x dementia risk after severe influenza and pneumonia 5
2.6-4.1x Alzheimer’s risk after severe influenza and pneumonia 52.2-3x schizophrenia risk for infant if mother is infected by influenza during pregnancy 61.3x dementia risk after lower respiratory tract infection 7
- Routine respiratory illness imposes a massive, persistent economic burden, driving 1–1.5% annual productivity losses—roughly $600B globally, or ~0.6% of global GDP 8—in non-pandemic years.
- Early converging evidence from population-based administrative data studies suggests that severe prenatal and early postnatal respiratory infections might lead to reduced adult earnings and educational attainment later in life. 9
- Achieving broad protection against respiratory pathogens would meaningfully reduce pandemic risk, 10 serving as a critical first line of defense—alongside air disinfection—against both natural outbreaks and increasingly accessible engineered biological threats.
Why now
Building on platforms from COVID and beyond
The COVID-19 pandemic triggered a wave of investment in vaccines and antivirals. A number of these platforms showed early promise, then stalled when funding dried up as effective vaccines were deployed and COVID waves began to moderate. A second opportunity sits in nearby fields, where modalities developed for other disease areas may point to new categories of broad-spectrum preventatives.
New modality approvals in infectious disease vs other areas
Note: New technologies included: Monoclonal antibodies, Bispecifics, Antibody-drug conjugates, Therapeutic proteins & enzymes, Fusion proteins, Cell therapies (CAR-T), Gene therapies, Oligonucleotides (siRNA, ASOs), mRNA therapeutics
Source: Internally compiled data; spreadsheet available on request
New AI-enabled tools and datasets
New biological datasets and protein design tools may allow us to design new drugs commensurate with the complexity of viral antigenic diversity, as well as explore entirely new antiviral strategies.
Growth of biological datasets and key milestones
Single-cell transcriptomics
Infectious disease genomic surveillance
(GISAID / COVID portals)
Immunology
(ImmPort, AIRR, immune repertoire)
Protein structure
(PDB + AlphaFold DB)
Note: All five lines should be treated as illustrative of the trend and scale rather than audited figures. Single-cell, infectious disease, and immunology data points are order-of-magnitude estimates derived from sequence counts x typical file sizes. Values were normalized to a 0-100 scale.
Source: Katz KS et al. (2022). Nucleic Acids Research 50(D1):D387–D390; ncbi.nlm.nih.gov/sra/stats; GZ CELLxGENE Census; Human Cell Atlas Data Portal; Tabula Sapiens Consortium; GISAID; COVID-19 data portal; ImmPort; AIRR; RCSB PDB; AlphaFold Protein Structure Database
Increasing pandemic risks
The COVID-19 pandemic killed millions and cost trillions, despite years of warning from the public health and biosecurity communities. The key drivers of pandemics — land use change, climate change, and intensive animal agriculture — continue to rise, while rapidly accelerating AI capabilities may dramatically increase risks from man-made biological weapons.
Days to make a virus
Gene synthesis / ordering
Note: The time to generate poliovirus was derived from reports (Jennifer Couzin-Frankel, Science, 2002) and the primary publication. The time to generate synthetic horsepox was also from reports (Saskia v. Popescu, ContagionLive, 2017) and the primary publication. The time to generate synthetic SARS-CoV-2 was derived from the primary publication with estimated turnaround times for synthesis of gene fragments.
Source: Noyce et al, PLoS One, 2018; Cello et al, Science, 2002; Thao et al, Nature, 2020.
Two technologies, working in concert
Two types of technologies working together are likely needed due to the sheer number of different common respiratory viruses and their rapid evolution. The first type protects individuals from infection. The second type cleans indoor air to reduce transmissions.
Broad-spectrum preventatives (BSPs)
These are products — a shot, a nasal spray, a pill — that defend against rhinoviruses, flu, coronaviruses, and other respiratory viruses simultaneously. Our goal is to catalyze the development of preventative drugs that will prevent +75% of symptomatic infections in as few doses as possible, via easy-to-administer modalities.
Approved countermeasures for respiratory viral infections have primarily consisted of vaccines, small-molecule antivirals, and, more recently, monoclonal antibodies. 11 Given recent breakthroughs and emerging data, these technologies now represent a small subset of plausible approaches.
Approaches with numerous approvals
Antibody-centric, strain-specific protection
Investigational approaches worth exploring
Potential to be broad-spectrum technologies
Physical barrier formulations
Despite this increased tractability, developing preventatives for respiratory viruses is far from inevitable. Today, the combination of technical, clinical, and demand uncertainty make this less attractive to work on than other commercial opportunities. Our belief is that a focused, near-term philanthropic intervention can change that.
Air cleaning technologies (ACTs)
Air cleaning technologies improve indoor air quality by removing or inactivating airborne viruses, just like municipal water infrastructure removes or inactivates pathogens from our drinking water supply. Our goal is to catalyze the uptake of air cleaning technologies that safely reduce infectious aerosols by >75% and have a path to >50% uptake in transmission-relevant indoor spaces at low cost. In practice, we’ll initially focus on three technologies that we think could together achieve these targets by layering on top of building ventilation systems: air filtration, antimicrobial light, and antimicrobial vapors.
Luckily, most of these technologies we need already exist: far-UVC antimicrobial lights have a growing body of safety and efficacy evidence from the last decade, and air filtration works, but needs to be trialed and scaled to high-transmission spaces. 12 Antimicrobial vapors have been most commonly used in emergency situations, and we need more research to validate whether they could be deployed productively on a continuous basis. Adoption has been held back by the need for rigorous real-world clinical evidence, a clear regulatory endorsement, and a demand signal large enough to bring costs down to levels required for global deployment. These problems are solvable with capital and focus.
Why both are needed
In short, the uptake required for broad-spectrum preventatives or for air cleaning technologies to each be effective by themselves is extremely high. When deployed together, the uptake needed to achieve our goal is still ambitious but much more realistic.
Seasonal infections based on uptake of broad-spectrum preventatives (BSPs) and air cleaning technologies (ACTs)
BaselineACTs aloneBSPs aloneBSPs + ACTs togetherBSP adoptionACT adoption
Stylized SEIR epidemiological model of influenza demonstrating seasonal infection variance and the impact of combining BSPs and ACTs with increasing uptake.
Intercept is a philanthropic initiative with the goal of developing the technologies needed to radically reduce the global burden of respiratory infections and ultimately eliminate them altogether.
$500M in grants and investments
Make sure the portfolio of technologies needed exist and that they are effective and safe. With broad-spectrum preventatives, our goal is to advance 2+ products that meet our target product profile through Phase 2, after which we expect traditional capital markets to take them the rest of the way. With air cleaning technologies, the goal is to get products that meet the target product profile on a path to widespread adoption. We’ll make both grants and investments, using the most capital-efficient tool to advance our target product profile.
A network of prospective customers
Chart a credible path to the uptake required to achieve our goal, in part by convening a customer advisory board of interested buyers who will provide important customer input to ensure the products being developed are the right ones. Their involvement helps de-risk the market signal problem that has historically stopped this work from happening, and provides iterative feedback as development progresses.
Clinical and regulatory engagement
Improve the probability of success by reducing clinical costs and timelines, and garnering regulatory approvals and recommendations to spur market demand.
A century ago, waterborne diseases posed similar threats until new pharmaceuticals and clean water infrastructure made them rare. The same transformation is possible for respiratory viruses. We believe we will look back in 20 years and think it’s crazy that civilization didn’t address this problem sooner.