Broad-spectrum preventatives

Target Product Concept

Context

Spirit: The Target Product Concept (TPC) describes the shape of the products that we think should exist, the spirit of which is: safe and tolerable long-acting preventatives that will prevent ≥75% of symptomatic respiratory infections in as few doses as possible, administered as easily as possible, and that have a credible path to ~60% uptake. We will prioritize approaches that are convenient to administer with minimal side effects to support the goals of widespread adoption and uptake.
TPC vs TPP: We are publishing a “target product concept” rather than a target product profile to accommodate the wide spectrum between our defined minimal and optimal attributes for our target product. We aim to prioritize broad-spectrum preventatives (BSPs) that meet our optimal attributes, but recognize that this will be technically challenging and the pathway to advance such candidates through development is unproven. We propose minimum targets that are also aspirational but are more likely to achieve regulatory approval based on current drug development paradigms. Depending on where your candidate fits along this minimal/optimal spectrum, we understand the implications for product development could vary widely.
Anticipated future refinement of the TPC: We expect to refine this over time as we and the field progress. Still, we expect that the spirit/direction of it will stay the same.
How to use this TPC: The TPC is meant as an aspirational guide for developers—those with platforms, candidates, and/or technologies that could lead to the discovery and development of broad-spectrum preventatives (BSPs). We recognize that a multivalent preventative product for respiratory viruses sits at the frontier of product development and that there is real uncertainty about how to advance BSPs with these attributes through clinical development and regulatory approval. Still, the TPC offers a north star for designing such an optimal product.
How we’ll use the TPC: We’ll use this TPC as one of the ways we evaluate potential candidates for funding. We know that most candidates won’t meet our full TPC today. For that reason, we’ll assess proposed candidates on their potential to meet our TPC, ideally on short timelines. To that end, you’ll notice that the application has a section where applicants will assess their candidate’s future ability to hit the TPC.

Attributes

Target Product Concept attributes, with minimal and optimal targets for each
Attribute	Minimal	Optimal
Indication for use ¹Note: Our hypothesis is that a product that protects against severe disease will also lead to protection of mild/moderate symptoms.	Prevention of severe disease due to infection by commonly circulating respiratory viruses.	Prevention of symptomatic infection and viral shedding due to commonly circulating respiratory viruses.
Target population ²Note: The minimal target reflects a strategy where we seek approval for a product based on severe endpoints and follow with label expansion (healthy, age, etc) after approval.	Individuals at higher risk of severe disease due to respiratory infections, such as those who are immunocompromised, adults with one or more underlying comorbidities, newborns/infants, and adults ≥ 65 years old.	Healthy adults aged 18–64 years, adults aged ≥65 years, children (≥ 5 yo) and newborns/infants.
Clinical efficacy ³Note: The target attributes presented here are lower confidence and will require more robust case definition of symptoms across the common respiratory viruses.	At least 75% reduction in severe lower respiratory tract disease, such as individual manifestations or combinations of wheezing, bronchiolitis, pneumonia, hospitalization, ICU/mechanical ventilation, hypoxia, myocarditis, encephalopathy, multi-organ dysfunction, severe exacerbations of COPD/asthma in adults, and ARDS.	At least 75% reduction in mild to moderate symptoms in the upper- and lower-respiratory tracts, such as rhinorrhea, nasal congestion, sneezing, sore throat, fever, sputum production, wheeze, dyspnea, tachypnea.
Virus coverage ⁴Note: The goal is a product that prevents ≥75% of symptomatic infection. This attribute is intended to describe more specifically what this means in practice, but we welcome any virus coverage combinations that can achieve this target.	Protection demonstrated against ≥ 3 respiratory viruses (detailed in this table), one of which must include HRV.	Protection demonstrated against ≥ 6 of the most common respiratory virus families.
Durability of protection	≥ 6 months of protection from a single dose	≥ 12 months of protection from a single dose
Future-proofing ⁵Note: We will upweight candidates based on their potential to cover emerging viruses and/or viruses with pandemic potential.	The platform is easily adaptable to emerging variants of concern for the indicated virus families.	The product will be broadly protective, and not require any updates based on viral evolution.
Delivery route	IM/SC injection, intranasal administration, intradermal patch, oral, or inhaled dry powder	Intranasal delivery, intradermal patch, or oral delivery
Safety and tolerability	Safety and tolerability similar to vaccines and monoclonal antibodies and no AEs associated with repeat dosing.	Safety and tolerability similar to OTC drugs and no AEs associated with repeat dosing.
Drug-drug interactions	No evidence of harmful interaction and/or contraindication with routine immunizations or common drugs.	No evidence of harmful interaction and/or contraindication with routine immunizations or common drugs.
Stability and storage	Stable under freezing (–80°C) for ≥ 12 months.	Room-temperature stable for ≥ 12 months, removing cold-chain dependence and lowering delivered cost.
Manufacturing and scale	A credible path to population scale manufacturing and a cost of goods compatible with mass use.	Scalable manufacturing at a cost low enough for advance market commitment volumes.
Access and affordability	A cost-effectiveness case across the target populations.	Delivered cost per protected person low enough to sustain broad, recurring use and to anchor an advance market commitment with large employers and payers. The product should demonstrate overall cost savings for purchasers and health systems.

Common respiratory viruses under consideration for a broad-spectrum preventative

Common respiratory viruses under consideration for a broad-spectrum preventative
Family	Genus	Virus	Types
Picornaviridae	Enterovirus	HRV-A, HRV-B, HRV-C	>160 types
Picornaviridae	Enterovirus	Enterovirus A-D	>100 types
Coronaviridae	Alphacoronavirus	229E	Variants, clades
Coronaviridae	Alphacoronavirus	NL63	Variants, clades
Coronaviridae	Betacoronavirus	OC43	Variants, genotypes
Coronaviridae	Betacoronavirus	HKU1	Variants, genotypes
Coronaviridae	Betacoronavirus	SARS-CoV-2	Variants, lineages
Pneumoviridae	Metapneumovirus	HMPV (groups A and B)	Clades
Paramyxoviridae	Respirovirus	HPIV1, HPIV3	Clades, genotypes
Paramyxoviridae	Orthorubulavirus	HPIV2, HPIV4	Clades, genotypes
Orthomyxoviridae	Alphainfluenzavirus	Influenza A	18 HA and 11 NA (HxNy) subtypes
Orthomyxoviridae	Betainfluenzavirus	Influenza B	Victoria lineages
Pneumoviridae	Orthopneumovirus	RSV-A, RSV-B	Genotypes, lineages
Adenoviridae	Mastadenovirus	Human Ad B,C,E	Types

If your work could meaningfully contribute to achieving this Target Product Concept, we want to hear from you — see our request for candidates for what we fund and how to apply.