Emerging Mechanism of Action: Ferroptosis – Strengthens Company’s Oncology Pipeline
Chester, New Jersey, February 10, 2020 – Hillstream BioPharma Inc. (“Hillstream”), a near-clinical stage biotechnology company focused on rare, orphan and unmet need cancers announced today, acquisition of a salinomycin analogue portfolio with related global patents, non-clinical data, other filings and know-how.
Salinomycin, a novel ionophoric small molecule has been shown, via high throughput screening, to be a potent cancer killing agent with high potency and toxicity1. Hillstream’s novel formulation of salinomycin, HSB-1216, is encapsulated in Hillstream’s proprietary QUATRAMERTM system, thereby lowering toxicity to normal tissue while leveraging salinomycin’s beneficial and potent cancer killing effects. HSB-1216’s mechanism of action, ferroptosis, has recently been elucidated by researchers and provides insights into a key weakness of tumor cells.2 Ferroptosis involves the drug triggering a molecular trap of cytoplasmic and mitochondrial iron into the cell’s lysosomes. Research on ferroptosis shows iron sequestered in the lysosomal compartment and displacing a Fenton reaction, which produces specific types of reactive oxygen species (ROS) that puncture lysosomal membranes, oxidizes lipids and ultimately causes an iron-induced cell death. This novel and emerging mechanism of cell death is exploited by HSB-1216 into a targeted approach for high unmet need cancers.
The salinomycin analogs licensed today are various novel molecular constructs with increased efficacy against a sub-group of tumors consisting of breast, pancreatic and prostate cancers. Due to the increased potency of these compounds, these salinomycin analogs are expected to have ferroptotic effects greater than salinomycin at micro-dosage levels, thereby creating an increased therapeutic index. Hillstream expects to develop these advanced compounds as follow-on therapeutics to HSB-1216 to treat a variety of high unmet need, including orphan cancers, which are sensitive to the ferroptotic pathway.
“We are very excited and pleased to add these salinomycin analogs to our portfolio” stated Randy Milby, Hillstream’s Chief Executive Officer. “These assets are an ideal complement to our existing QUATRAMERTM salinomycin (HSB-1216) which recently obtained Orphan Drug Designation for Small Cell Lung Cancer. Furthermore, the acquisition of these novel salinomycin analogs will result in a more focused product portfolio with an emerging novel mechanism of action which is gaining increased attention as fundamental strategy used by cancer cells to highjack the normal cell’s circuitry”. We believe treatment with HSB-1216 and these more potent salinomycin analogs represent a powerful single agent as well as complementary approach to other approved therapies.”
About HSB-1216 (Salinomycin)
HSB-1216 is a novel formulation of salinomycin, a potent anti-ferroptotic compound, encapsulated within the QUATRAMERTM technology. Salinomycin kills cancer cells by ferroptosis, a novel emerging mechanism of action, when iron is sequestered in the lysosomal compartment of the cell unleashing membrane permeabilization and cell death. With highly potent activity, a narrow therapeutic index and short half-life, salinomycin needed to be re-formulated within QUATRAMERTM to create HSB-1216, a powerful drug candidate.
About Hillstream BioPharma Inc.
Hillstream BioPharma Inc. (“Hillstream”) is a development-stage company advancing improved therapies for patients with cancer via a unique QUATRAMERTM nanoparticle platform. This unique technology enables intranuclear and intracellular delivery of small molecules, peptides, genes, other macromolecules and biologics to the tumor cello, while significantly minimizing exposure to normal tissues. Hillstream’s competitive advantage is to enhance the safety and efficacy of oncology therapies by encapsulating them in its proprietary polymeric injectable suspension comprised of FDA-recognized inactive ingredients. Encapsulation ensures delivery within the tumor cells and prevents free drug levels in circulation that can cause toxicity. The slow and sustained release of the therapy may also reduce the frequency of dosing while maintaining its efficacy. The novel formulation allows Hillstream to build a strong patent estate and seek both FDA Orphan Drug Designation and more rapid FDA review in specific indications. For more information, please visit www.hillstreambio.com.
Forward Looking Statements
This press release includes forward-looking statements including, but not limited to, statements related to the development of drug candidates, our operations and business strategy, our expected financial results, and corporate updates. The forward-looking statements contained in this press release are based on management’s current expectations and are subject to substantial risks, uncertainty and changes in circumstances. Actual results may differ materially from those expressed by these expectations due to risks and uncertainties, including, among others, those related to our ability to obtain additional capital on favorable terms to us, or at all, including, without limitation, to fund our current and future preclinical studies and clinical trials and the success, timing and cost of our drug development program and our ongoing or future preclinical studies and clinical trials, including, without limitation, the possibility of unfavorable new clinical and preclinical data and additional analyses of existing data, as well as the risks that prior clinical and preclinical results may not be replicated. Forward-looking statements speak only as of the date of this press release, and we undertake no obligation to review or update any forward-looking statement except as may be required by applicable law.
Hillstream BioPharma Inc.
President & CEO
Hillstream Biopharma Inc.
Tel: +1 302.743.2995
Jennifer K. Zimmons, Ph.D.
Zimmons International Communications
Tel: +1 917.214.3514
- Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009; 138:645–59. DOI: 10.1016/j.cell.2009.06.034
- Mai TT, Hamai A, Hienzsch A, Caneque T, Muller S, Wicinski J, Cabaud O, Leroy C, David A, Acevedo V, et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem. 2017;9:1025–33. DOI: 10.1038/nchem.2778
- Salinomycin derivatives and therapeutic uses thereof. US Patent 10, 364,253 B2 issued Jul 30, 2019