NextCure and LCB Present Preclinical Data on B7-H4 Antibody Drug Conjugate at AACR 2024
08 Aprile 2024 - 1:00PM
NextCure, Inc. (Nasdaq: NXTC), a clinical-stage
biopharmaceutical company committed to discovering and developing
novel, first-in-class and best-in-class therapies to treat cancer,
today announced the presentation of new preclinical data on LNCB74,
a B7-H4-targeting antibody drug conjugate (ADC) developed in
partnership with LigaChem Biosciences (LCB), formerly LegoChem
Biosciences, (KOSDAQ: 141080), at the 2024 American Association for
Cancer Research (AACR) Annual Meeting in San Diego, CA. The poster
presentation highlights LNBC74’s promising preclinical safety and
anti-tumor activity.
LNCB74 is an ADC utilizing LigaChem Biosciences’ proprietary
site-specific conjugation and plasma-stable, cancer selectively
activating linker technology to link monomethyl auristatin E (MMAE)
to a B7-H4 targeting antibody in a drug-to-antibody ratio of 4
(DAR4). The presentation includes data demonstrating LNCB74’s high
affinity and specificity for human B7-H4, a protein highly
expressed on a range of solid tumors including breast, ovarian and
endometrial cancers. LNCB74 was shown to specifically bind to B7-H4
expressing tumor cells and was rapidly internalized in a
target-dependent manner. In addition, data showed that LNCB74
mediated potent cytotoxicity in B7-H4-positive cancer cells in
vitro and demonstrated serum stability with a favorable
pharmacokinetic (PK) activity in rodents. LNCB74 demonstrated
significant tolerability in cynomolgus monkeys and showed strong
anti-tumor activity in multiple cell-line derived (CDX) and
patient-derived xenograft (PDX) tumor models in vivo. The increase
in tolerability and strong efficacy is expected to translate into
clinical activity of LNCB74.
“LNCB74 was developed through NextCure’s expertise in B7-H4
tumor biology and LCB’s ConjuAllTM technology, resulting in a
potent ADC with initial data demonstrating excellent tolerability
and pharmacokinetics,” said Solomon Langermann, Ph.D., NextCure’s
chief scientific officer. “These data underscore that LNCB74 is a
promising candidate for the treatment of a variety of solid tumor
indications. We look forward to continuing our work building a
robust preclinical dataset to further support advancing this ADC to
the clinic.”
Key Findings:
- LNCB74 was engineered for an improved safety profile and
therapeutic index with increased stability in circulation, tumor
selective payload release, and a reduction in off-target release of
active payload, mitigating toxicity compared to traditional vedotin
ADCs.
- A single 3 mg/kg dose of LNCB74 resulted in durable tumor
regression in multiple CDX and PDX tumor models, suggesting
activity comparable or superior to competitor B7-H4 targeting
ADCs.
- LNCB74 was well tolerated in cynomolgus monkeys following 2
doses of up to 10 mg/kg, showing a superior safety profile compared
to traditional MMAE bearing ADCs.
- LNCB74 demonstrates favorable pharmacokinetics and stability in
rodents, consistent with the molecule’s preclinical safety
profile.
- LNCB74 mediates potent cytotoxicity, with sub-nanomolar to low
nanomolar EC50 values on multiple B7-H4-positive cancer cell
lines.
Details of the presentation are as follows:
Title: LNCB74 is a potent and safe
next-generation antibody-drug-conjugate utilizing a cancer
selective linker for the treatment of B7-H4 expressing
cancersDate and Time: April 8, 2024,
9:00am-12:30pm PTSession: Antibody-Drug Conjugates
and Bispecific AntibodiesAbstract Number: 1898
About NextCure, Inc.
NextCure is a clinical-stage biopharmaceutical company that is
focused on advancing innovative medicines that treat cancer
patients that do not respond to, or have disease progression on,
current therapies, through the use of differentiated mechanisms of
actions including antibody-drug conjugates, antibodies and
proteins. We focus on advancing therapies that leverage our core
strengths in understanding biological pathways and biomarkers, the
interactions of cells, including in the tumor microenvironment, and
the role each interaction plays in a biologic response.
www.nextcure.com
About LigaChem Biosciences, Inc.
LigaChem Biosciences (formerly LegoChem Biosciences, Inc.) is a
clinical stage biopharmaceutical company dedicated to the discovery
and development of innovative medicines by leveraging our medicinal
chemistry expertise to make conventional biologics more targeted
and potent for the benefit of patients with diseases of highly
unmet medical needs. We are advancing sustainable pipelines in
therapeutic areas within antibiotics, anti-fibrotics, oncology, and
antibody-drug conjugate platform technology.
www.legochembio.com
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and uncertainties include, among others: our limited operating
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that pre-clinical research may not be confirmed in clinical trials;
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including NextCure’s most recent Form 10-K and subsequent Form
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Investor InquiriesTimothy Mayer, Ph.D.NextCure,
Inc.Chief Operating Officer(240) 762-6486IR@nextcure.com
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