BOLD-100 and ATR Inhibitors as a New Avenue for PDAC Targeting at AACR 2024

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Apr 05, 2024, 08:41 ET

VANCOUVER, BC, April 5, 2024 /PRNewswire/ -- Bold Therapeutics, a clinical-stage biopharmaceutical company at the forefront of developing innovative metallotherapeutics, has announced that Dr. Do-Youn Oh's group at Seoul National University College of Medicine, Seoul, South Korea, will be presenting at the AACR Annual Meeting, April 5-10, 2024, in San Diego, California on the use of BOLD-100 in combination with ATR (Ataxia telangiectasia and Rad3-related protein serine/threonine kinase) inhibitors as anticancer therapies for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC).

Bold Therapeutics announced Dr. Do-Youn Oh’s group at Seoul National University College of Medicine, Seoul, South Korea, will present at the AACR Annual Meeting, April 5-10, 2024, in San Diego, California on the use of BOLD-100 in combination with ATR inhibitors as anticancer therapies for the treatment of Pancreatic Ductal Adenocarcinoma (PDAC).

Dr. Do-Youn Oh, MD, PhD, Seoul National University College of Medicine

Bold Therapeutics' BOLD-100, a pioneering ruthenium-based small molecule, uniquely acts by (1) targeting GRP78 to modulate the unfolded protein response (UPR) and (2) generating reactive oxygen species (ROS) leading to DNA damage and cell cycle arrest. This dual action triggers cell death across a spectrum of cancer types, including those resistant to current treatments. As a result, BOLD-100 holds promise for significantly enhancing treatment outcomes in a diverse array of both solid and liquid tumors when used alongside a broad range of anticancer treatments, from conventional chemotherapies to cutting-edge targeted therapies and immuno-oncology agents. Our recent presentation at ASCO GI 2024 showcased positive Phase 2 clinical trial results in the treatment of advanced metastatic colorectal cancer (mCRC) in patients previously treated with FOLFOX / CAPOX. The data, highlighting patients treated with a combination of BOLD-100 and FOLFOX, demonstrated notable safety and clinical improvements, bolstering confidence in the therapeutic value of BOLD-100.

Dr. Do-Youn Oh's group at Seoul National University College of Medicine, South Korea will be presenting a poster entitled, "Co-downregulation of GRP78 and ATR enhances apoptosis in pancreatic ductal adenocarcinoma," (Poster no. 12, Session: Cellular Stress Responses 1). This work underscores the significant impact of BOLD-100 in inducing GRP78 inhibition, which substantially triggers oxidative stress. Furthermore, when combined with ATR inhibition, this synergy effectively promotes cell death.

Key Findings:

BOLD-100 elevates ER stress and ROS, leading to activation of the UPR pathway and CHOP-dependent apoptosis, which inhibits PDAC growth;
ROS accumulation activates the ATR-CHK1 DNA damage repair pathway, which NAC can abrogate; and
The combination of BOLD-100 with the ATR inhibitor AZD6738 exhibits a synergistic effect, suggesting GRP78/ATR dual targeting as a promising therapeutic approach for PDAC.

These findings unveil a compelling strategy for combinational targeting to inhibit PDAC growth.

"DNA repair mechanisms play a crucial role in maintaining genomic integrity, leading to cell cycle arrest and thereby preventing the uncontrolled growth and progression of cancer cells. Our in-vitro and in-vivo findings indicate that combining BOLD-100 with ATR inhibition results in synthetic lethality against highly aggressive Pancreatic Ductal Adenocarcinoma. We are eager to delve deeper into this research path and its potential clinical utility," stated Dr. Oh.

Mark Bazett, Sr Director, Preclinical Development at Bold Therapeutics added, "BOLD-100 has already demonstrated remarkable safety and efficacy in the treatment of metastatic colorectal cancer (mCRC). Diverging from the path of targeted therapies, BOLD-100's unique multi-modal mechanism-of-action opens avenues for potent combination therapies designed to tackle some of the most difficult-to-treat cancers including those resistant to standard treatments. The synergistic combination identified by Dr. Oh's group holds particular promise, and we look forward to further exploring this potential."

Jim Pankovich, EVP, Clinical Development at Bold Therapeutics, and Mark Bazett, Sr Director, Preclinical Development at Bold Therapeutics, will also be attending the 2024 AACR Annual Meeting in San Diego and are available for in-person discussions related to BOLD-100.

For additional details, visit Bold Therapeutics' website at www.bold-therapeutics.com or the AACR conference site at https://www.aacr.org/meeting/aacr-annual-meeting-2024/

Contact:
E. Russell McAllister, CEO
[email protected]
+1 (604) 262-9899

SOURCE Bold Therapeutics Inc.