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Development of low-cost, field-ready nanobodies against snake venom

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41GM146314-01A1
Agency Tracking Number: R41GM146314
Amount: $255,869.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: 400
Solicitation Number: PA20-265
Solicitation Year: 2020
Award Year: 2021
Award Start Date (Proposal Award Date): 2021-09-15
Award End Date (Contract End Date): 2022-09-14
Small Business Information
San Diego, CA 92110-4124
United States
DUNS: 079811299
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (858) 531-8336
Business Contact
Phone: (858) 531-8336
Research Institution
LA JOLLA, CA 92093-0621
United States

 Nonprofit College or University

Snakebite constitutes one of the largest and most tenacious public health issues on a global scale. Every year,
up to 5 million people will suffer snakebite envenomation, causing approximately 125,000 deaths and 400,000
left with permanent physical disability. Nearly 8,000 snakebites occur in the United States each year. The regions
most affected are in Asia, Africa, Latin America, and Oceania where snakebite has a high socioeconomic impact
on both the local and global economies. As of 2017, the WHO has labeled snakebite as a Category A Neglected
Tropical Disease. Therapies for snakebite victims are animal-based antivenoms, which for over a century have
consisted of the whole sera or purified antibodies of large mammals (horses and sheep) that have been
hyperimmunized with snake venoms. These antivenoms contain a relatively small fraction of effective venom-
specific antibodies, requiring multiple doses that can cause adverse immunogenic effects in patients. Antivenom
also has relatively high batch-to-batch variation and its efficacies are largely species-specific, requiring a match
between the species used in immunization and the venom in need of neutralization. The economics of antivenom
manufacture are challenging to scale to profitability, leading to scarce and unreliable supplies. Further
complicating the issue is the reliance on cold chain storage and distribution and consequential lack of availability
to snakebite victims in remote locations where the bulk of envenomations occur. Despite these issues, antivenom
is one of the few biological therapies that has yet to enter the modern era of mainstream biologics, despite the
presence of an overwhelmingly large patient population.
In order to address the complex medical and economic requirements of snakebite, we propose the use of an
oligoclonal mixture of single-domain antibodies, also known as nanobodies (Nbs). These antibody fragments (15
kDa in molecular weight) are the variable heavy chain regions (VHH) of camelid or shark antibodies with several
attractive properties for the space, including low immunogenicity, high biodistribution and tissue penetration, low
cost of scaled production, and tunable pharmacokinetics. Nbs are also often highly thermostable, allowing for
accessibility in much-needed developing countries. Nbs have long, flexible complementarity-determining regions
(CDRs) which can increase the likelihood of binding conserved or cryptic epitopes on these toxins, allowing for
broad species coverage critical to pan-specificities. Towards this end, Venomyx Therapeutics, Inc. is working in
collaboration with the Chang lab at UCSD to exploit a powerful platform to discover Synthetically Evolved Nbs
(SENs) for high affinity and efficacy against venom targets of interest. Together with the snake venom expertise
at Venomyx, we will generate low-cost, thermostable, broadly-effective Nbs against snake venom toxin as leads
for future development, preclinical testing, and eventual human trials to neutralize venom from snakebite.PROJECT NARRATIVE
Snakebite is a global neglected tropical disease that affects millions of people per year and constitutes one of
the world’s largest public health issues. Treatment currently relies on antiquated animal-based antivenoms that
present significant safety, efficacy, and availability drawbacks. We propose the use of drug discovery techniques
and a particularly well-suited antibody discovery platform to address these issues to discover and produce
modern recombinant antivenoms.

* Information listed above is at the time of submission. *

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