SUMMARY / ABSTRACT
Preterm birth is the leading cause of infant mortality and morbidity for which efficacious
preventative treatments are essentially absent. Pre-term labor occurring prior to 37 weeks of
gestation is associated with up to 18% of all births and significantly increases the risks for a slew
of health complications, and medical costs associated with pre-term births have exceeded $26B.
Treatments preventing pre-term birth are extremely limited. The only approved prophylactic
treatment is weekly injection with the hormone progesterone beginning around week 16 through
the end of gestation indicated specifically for at-risk mothers which benefits only ideal candidates
who meet the risk criteria and promptly and faithfully receive treatment. Tocolytics are helpful in
delaying delivery for a typically a few days allowing additional treatments to be administered to
minimize risk, but they are not consistently effective nor are they able to postpone delivery until
full term. There is a need for new therapies that halt pre-term labor at its onset and delay delivery
indefinitely until 37 weeks are reached. Force generation by uterine cells, which is a central event
in labor, is a logical and appropriate therapeutic target for preventing pre-term births.
Forcyte Biotechnologies is an early-stage bio-pharmaceutical company in Los Angeles that has
partnered with advanced high-throughput screening and laboratory automation as well as
nanofabrication facilities at UCLA, that is leveraging a microtechnology known as FLECS – a high-
throughput screening (HTS) platform that measures contractility of single-cells in a 384-wellplate
format – to identify and bring to market new compound classes that act on force-generating
pathways within cells. This is the first and only reported assay that obtains functional force
generation data for single cells, at HTS scales. Our existing programs have focused on treatment
resistant asthma and hypertension, and have already had success in discovering novel
phenotypic modulators relating to these indications.
This proposal aims to develop a functional assay for screening and developing novel therapeutics
that are able to halt uterine contraction during pre-term labor and return it to quiescent state to
prevent pre-term births, which are the leading cause of infant mortality and morbidity, and lack
efficacious treatment. Our approach implements a target-agnostic functional screen directly
evaluating cell force generation – a hallmark of labor – with a miniaturized and fully automated
cell-contractility assay implemented in the 384-wellplate format. Such a transformative
improvement will enable us to rapidly screen entire compound libraries and greatly improving the
probability of successful discovery. Furthermore, the proposed assay would offer high-throughput
functional pre-clinical follow-up to other target-based affinity assays that cannot predict
phenotypic activity. Furthermore, the proposed assay would offer high-throughput functional
follow-up to other target-based affinity assays that cannot predict phenotypic activity.
A follow-on Phase II proposal will perform screens of an expanded library in commercially
available and patient-derived cells, as well as cell lines derived from smooth muscle in pregnant
women. Selectivity counter-screens will also be performed in other contractile cell types to
establish a deep safety profile for the discovered hits, to facilitate transitions to later stages of
drug development. The completed assay will also be distributed through our commercial partners.
