Circle Pharma files first Investigational New Drug application for first-in-class oral cyclin A/B RxL inhibitor for treatment of advanced solid tumors
July 01 2024 - 6:05AM
Business Wire
Circle Pharma, a leader in macrocycle drug discovery and
development, announced the submission of its first Investigational
New Drug (IND) application to the U.S. Food and Drug Administration
(FDA) for CID-078, a first-and-only-in-class cyclin A/B RxL
inhibitor. This milestone marks a significant advancement in the
development of novel drug candidates generated by Circle’s
proprietary MXMO™ platform for difficult-to-drug targets in
oncology and other serious illnesses.
CID-078 is an orally bioavailable macrocycle that has shown
preclinical efficacy across multiple tumor types characterized by
high E2F expression, including small cell lung cancer, triple
negative breast cancer, ER-low breast cancer, and HR-positive
breast cancer following a CDK 4/6-inhibitor. The IND submission
includes comprehensive data from preclinical studies which have
demonstrated a safety, efficacy, and pharmacokinetic profile of
CID-078 to support the proposed phase 1 trial.
CID-078 is designed to selectively inhibit key
protein-to-protein interactions involving cyclins A and B, which
are implicated in the proliferation and survival of cancer cells.
Cyclins are a family of proteins that function as master regulators
of the cell cycle. Early work in the laboratory of Nobel Laureate
and Circle Pharma’s Scientific Advisory Board Chair William G.
Kaelin Jr., MD, showed that disrupting the function of cyclins in
certain types of cancer cells that had dysregulated cell cycle
control was synthetic lethal – meaning that these cancer cells were
selectively killed while the viability of normal cells was
unaffected.1 The mechanism of action of CID-078 offers a novel
therapeutic approach to potentially address unmet medical needs in
patients with advanced solid tumors who currently have limited
therapeutic choices.
“I am proud that we have reached this critical milestone in the
development of CID-078,” said David J. Earp, CEO of Circle Pharma.
“Our team has worked diligently to advance this promising candidate
from discovery through preclinical development. The IND filing
represents a major step forward in our mission to harness the power
of macrocycle therapies to create effective treatments for cancer
and other serious illnesses.”
“We believe, based on our preclinical data package, that CID-078
has the potential to provide a transformative therapeutic option
for patients with cancer,” said Michael Cox, PharmD, MHSc, BCOP,
head of Early Development and senior vice president. “We are
excited to advance CID-078 into clinical studies. This step
underscores our commitment to develop innovative therapeutics that
target challenging and previously undruggable proteins.”
Pending regulatory approval, Circle Pharma plans to initiate a
phase 1 clinical trial of CID-078 in patients with advanced solid
tumor malignancies. The dose escalation and dose expansion portions
of the trial will evaluate safety, tolerability, and
pharmacokinetics, as well as anti-tumor activity as assessed by
objective response rate and duration of response.
About CID-078, Circle Pharma’s Cyclin A/B RxL Inhibitor
Program
CID-078 is an orally bioavailable macrocycle with dual cyclin A
and B RxL inhibitory activity that selectively targets tumor cells
with oncogenic alterations that cause cell cycle dysregulation. In
biochemical and cellular studies, Circle’s cyclin A/B RxL
inhibitors have been shown to potently and selectively disrupt the
protein-to-protein interaction between cyclins A and B and their
key substrates and modulators, including E2F (a substrate of cyclin
A) and Myt1 (a modulator of cyclin B). Preclinical studies have
demonstrated the ability of these cyclin A/B RxL inhibitors to
cause single-agent tumor regressions in multiple xenograft
models.
About Circle Pharma, Inc.
South San Francisco-based Circle Pharma is advancing the
discovery and development of intrinsically cell-permeable
macrocycles that can be delivered by multiple routes, including
oral administration. Circle Pharma’s MXMO™ platform combines
structure-based rational drug design and advanced synthetic
chemistry to develop a new generation of macrocycle therapies for
challenging targets to address unmet clinical needs. Circle Pharma
is focusing its development efforts on cyclins, which are master
regulators of the machinery that controls the progression of cells
through the cell cycle and are key drivers in many cancers.
To learn more about Circle Pharma, please visit
www.circlepharma.com.
1 Chen et al., PNAS 96, 4235 (1999)
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Roslyn Patterson 650.825.4099
roslyn.patterson@circlepharma.com