On September 7, 2021 Isoprene Pharmaceuticals, Inc., an early-stage small molecule oncology company developing oral therapeutics for triple negative breast cancer (TNBC) and other cancers, reported that the National Institute of Health’s (NIH) NCI has awarded the company a two-year $2 million Small Business Innovation Research (SBIR) Direct-to-Phase II grant (Press release, Isoprene Pharmaceuticals, SEP 7, 2021, View Source [SID1234587365]). This grant will support ongoing advanced pre-clinical studies intended to lead to the filing of an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA), as a prelude to Phase I clinical trials. Vidya P. Ramamurthy, PhD, Isoprene’s chief scientific officer, and Vincent C. O. Njar, PhD, co-founder and chief executive officer of Isoprene and Professor at the University of Maryland School of Medicine (UMSOM), are the principal investigators for the program.
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"Currently, there are no effective therapies for patients with TNBC, an aggressive and highly metastatic disease. Isoprene’s orally dosed novel small molecules function as protein degraders, breaking down protein kinases Mnk1/2," stated Rana Quraishi, PhD, chief business officer of Isoprene and director of UMB’s New Ventures Initiative. "In TNBC xenograft models, the molecules have been shown to result in remarkable dose-dependent anti-tumor activity with no apparent host toxicity."
Isoprene’s orally bioavailable lead molecule exhibits remarkable dose-dependent antitumor (91% to 100% growth inhibition) and antimetastatic (~80% inhibition) activities against cell line and patient-derived TNBC xenograft models. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader is a novel therapeutic strategy that can be developed as monotherapy for the effective treatment of patients with both primary and metastatic TNBC.
"By targeting Mnk1/2 protein degradation, our molecules potently inhibit two critical signaling pathways and strongly regulate downstream factors involved in cell cycle regulation, cell death (apoptosis), pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis," said Dr. Njar. "This plays a critical role in the development, progression and metastasis of TNBC. Mnk1/2 are particularly attractive therapeutic targets because Mnk1/2 activity and the phosphorylation of eIF4E are dispensable for normal development."
Dr. Njar’s laboratory developed Isoprene’s novel small molecule technology at the UMSOM where he is a long-standing faculty member with primary faculty appointments in the Department of Pharmacology and the Center for Biomolecular Therapeutics.
Margaret M. McCarthy, PhD, professor and chair of the Department of Pharmacology, commented, "This is another in a long line of successes for Dr. Njar. His dedication and devotion to the creation and implementation of life-saving cancer therapeutics is beyond measure. We can all celebrate this important affirmation from the NIH of the potential impact of the newly developed retinoic acid metabolism blocking agents (RAMBAs)/Mnk1/2 protein degraders."
David J. Weber, PhD, professor and director of the Center for Biomolecular Therapeutics, added, "Dr. Njar’s research and development involving RAMBAs/Mnk1/2 protein degraders is extremely exciting for treatment of cancer and other diseases, and this recently funded fast-track NIH/NCI Award will significantly accelerate the ‘bench to bedside’ research required to get these novel therapeutic agents to patients."
Isoprene is part of UMB’s New Ventures Initiative (NVI) program, a unique model for select UMB startups with significant commercial promise. The NVI program accelerates research and startup growth, positioning companies for a strategic exit. Managed by an expert team with executive-level experience developing and executing business strategies, raising private and public capital, and taking drugs through Phase II clinical trials, NVI portfolio companies benefit from full management, business formation strategy, office space and a fully equipped laboratory space, along with direct access to early-stage capital. Since the program was established in 2015, the NVI team has fully managed and exited two startups: Living Pharma, which was acquired by Miltenyi, and SurgiGYN, which was acquired by a large medical device company. Isoprene is the third NVI portfolio company.
"We are very impressed with Isoprene’s progress," said Phil Robilotto, DO, MBA, associate vice president of UMB’s Office of Technology Transfer and director of UM Ventures at Baltimore. "The NVI program helps our startups advance faster and is a critical tool for commercializing UMB’s most promising technologies. We continue to be pleased with the program’s track record."