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Acrivon Therapeutics Presents Data at AACR Annual Meeting Highlighting the Capabilities of Acrivon Predictive Precision Proteomics (AP3) for the Discovery of ACR-2316, a Novel, Selective WEE1/PKMYT1 Inhibitor, and the Identification of Actionable Resistan - Seite 2
In the second poster titled “Acrivon predictive precision proteomics (AP3) uncovers mechanism of resistance to ACR-368, a clinical-stage CHK1/2 inhibitor, and identifies rational combination treatment,” preclinical studies using five ovarian cancer cell lines that were generated to be durably resistant to ACR-368 were reported. These cell lines were profiled using AP3 mass spectrometry, and comprehensive pathway reconstitution, and kinase activity analysis was performed to identify drug resistance mechanisms to ACR-368 to uncover actionable vulnerabilities. As a result, ULDG was identified as a rational sensitization treatment, and in in vivo CDX and PDX models of ovarian cancer, data confirmed that ULDG sensitizes cancer cells to ACR-368. This corresponded with the subsequent upregulation of ACR-368 OncoSignature biomarkers, indicating that the OncoSignature assay can predict which ULDG sensitized tumors would be responsive to treatment with ACR-368.
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About Acrivon Therapeutics
Acrivon is a clinical stage biopharmaceutical company developing precision oncology medicines that it matches to patients whose tumors are predicted to be sensitive to each specific medicine by
utilizing Acrivon’s proprietary proteomics-based patient responder identification platform, Acrivon Predictive Precision Proteomics, or AP3. The AP3 platform is engineered to measure
compound-specific effects on the entire tumor cell protein signaling network and drug-induced resistance mechanisms in an unbiased manner. These distinctive capabilities enable AP3’s direct
application for drug design optimization for monotherapy activity, the identification of rational drug combinations, and the creation of drug-specific proprietary OncoSignature companion
diagnostics that are used to identify the patients most likely to benefit from Acrivon’s drug candidates. Acrivon is currently advancing its lead candidate, ACR-368, a selective small molecule
inhibitor targeting CHK1 and CHK2 in a potentially registrational Phase 2 trial across multiple tumor types. The company has received Fast Track designation from the Food and Drug Administration,
or FDA, for the investigation of ACR-368 as monotherapy based on OncoSignature-predicted sensitivity in patients with platinum-resistant ovarian or endometrial cancer. Acrivon’s ACR-368
OncoSignature test, which has not yet obtained regulatory approval, has been extensively evaluated in preclinical studies, including in two separate, blinded, prospectively-designed studies on
pretreatment tumor biopsies collected from past third-party Phase 2 trials in patients with ovarian cancer treated with ACR-368. The FDA has granted Breakthrough Device designation for the ACR-368
OncoSignature assay for the identification of ovarian cancer patients who may benefit from ACR-368 treatment. In addition to ACR-368, Acrivon is also leveraging its proprietary AP3 precision
medicine platform for developing its co-crystallography-driven, internally-discovered preclinical stage pipeline programs. These include ACR-2316, a potent, selective WEE1/PKMYT1 inhibitor designed
for superior single-agent activity as demonstrated in preclinical studies against benchmark inhibitors, and a cell cycle program with an undisclosed target.