On March 21, 2024 Accent Therapeutics, a biopharmaceutical company pioneering a new class of small molecule precision cancer therapies, reported four upcoming presentations and posters at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 5-10 in San Diego, California (Press release, Accent Therapeutics, MAR 21, 2024, View Source [SID1234641361]).
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The oral symposium presentations will speak to the promise of RNA-modifying enzyme inhibitors as precision cancer therapeutics, and more specifically detail the rationale for DHX9 inhibition as a novel treatment modality for patients with BRCA1/2 loss-of-function across multiple tumor types, including breast cancer, as well as dMMR/MSI-H tumors, including colorectal, gastric and endometrial cancers. Posters will present data supporting inhibition of KIF18A in chromosomally instable tumors and induction of circBRIP1 RNA as a biomarker for DHX9 inhibition.
Details for the presentations and posters are as follows:
Major Symposium Presentation Title: Small molecule inhibitors of RNA modifying enzymes as precision cancer therapeutics
Presentation Number: SY11-02
Session Date and Time: Monday, April 8, 2024, 10:40 AM – 10:55 AM PT
Location: Room 29 – Upper Level
Presenter: Robert Copeland, Ph.D.
Mini Symposium Presentation Title: DHX9 inhibition as a novel therapeutic for cancer with loss-of-function mutations in DNA damage repair genes BRCA1 and BRCA2
Abstract Number: 3908
Session Date and Time: Monday, April 8, 2024, 2:50 PM – 3:05 PM PT
Location: Ballroom 6 DE – Upper Level
Presenter: Jennifer Castro
Poster Title: Inhibition of KIF18A leads to mitotic arrest and robust anti-tumor activity in chromosomally instable tumors
Abstract Number: 3337
Session Date and Time: Monday, April 8, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 28
Poster Board Number: 25
Presenter: Maureen Lynes, Ph.D.
Poster Title: circBRIP1 RNA as a non-invasive target engagement pharmacodynamic biomarker for DHX9 inhibition
Abstract Number: 520
Session Date and Time: Sunday, April 7, 2024, 1:30 PM – 5:00 PM PT
Location: Poster Section 21
Poster Board Number: 17
Presenter: David Brennen
About DHX9
Accent’s lead program is a first-in-class DHX9 inhibitor with the potential to address high unmet need indications not adequately served by existing therapies, including tumors with BRCA loss of function (breast, ovarian), mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) cancers (colorectal, endometrial, gastric) and additional undisclosed cancer types representing large patient populations. DHX9 is a DNA/RNA helicase that has been reported to play important roles in replication, transcription, translation, RNA splicing, RNA processing, and maintenance of genomic stability. Hence, this enzyme represents a compelling novel oncology target as inhibition of DHX9 exploits key tumor vulnerabilities, resulting in cancer-specific death. Accent is currently conducting IND-enabling studies evaluating its DHX9 inhibitor.
About KIF18A
Accent’s second lead program is a potential best-in-class inhibitor for KIF18A which may address a large patient population across several cancer indications, including ovarian and triple negative breast cancer (TNBC). KIF18A is a mitotic kinesin motor protein critical for cell division in select tumors with chromosomal instability. A subset of tumor cells with an abnormal number of chromosomes (aneuploid) are reliant on KIF18A and show rapid cell killing in vitro and in vivo upon KIF18A inhibitor treatment, while cells with normal numbers of chromosomes (euploid) are unaffected. Accent is planning to initiate IND-enabling studies for KIF18A in the first half of 2024.