ES-SCLC: extensive-stage small cell lung cancer; TNBC: triple-negative breast cancer; T-NEPC: treatment-emergent neuroendocrine prostate cancer; mSTS: metastatic soft-tissue sarcoma
HSB-1216, is a novel formulation of salinomycin, a potent compound, which uses the QuatramerTM delivery platform and targets both chemotherapy resistant tumors due to its effects on epithelial-mesenchymal transition (EMT). Recently, research suggests an even more powerful mechanism called ferroptosis is key to how the drug stops tumors – this process which sequesters iron in lysosomes allows HSB-114 to cause lysosomal membrane permeabilization of hard-to-treat cancer cells – causing them to rupture and stop replicating. An area of interest for the development of HSB-1216 could small cell lung cancer or other rare cancers with high unmet need.
Small Cell Lung Cancer (SCLC)
About 10% to 15% of all lung cancers are SCLC and it is sometimes called oat cell cancer, according to the American Cancer Society. This means that in 2020, almost 30,000 new cases will arise of this cancer which tends to grow and spread faster than non-small cell lung cancer (NSCLC). About 70% of people with SCLC will have cancer that has already spread at the time they are diagnosed. Since this cancer grows quickly, it tends to respond well to chemotherapy and radiation therapy. Unfortunately, for most people, the cancer will return at some point. It’s these patients, where the tumor returns, called refractory extensive-stage SCLC (ES-SCLC), where the outcomes the prognosis remains poor and outcomes are severe, including death. New treatments are needed in order to improve the prognosis of ES-SCLC, as median survival with current standards of treatment is still only 9–10 months from diagnosis. The general 5-year survival rate for people with SCLC is 6%, making this one of the deadliest human cancers for which treatments are urgently needed.
HSB-114 is a next generation immunotherapeutic agent of a previously developed predecessor compound. QuatramerTM technology allows a proprietary TNF-a cDNA to be incorporated preferentially into tumor nuclei, hijacking the cancer’s genome and tricking its machinery to make the powerful cytokine and destroy itself. HSB-114 can be injected intratumorally or given systemically for metastatic soft tissue sarcoma (mSTS).
Metastatic Soft Tissue Sarcoma (mSTS)
According to the American Society of Clinical Oncology, in 2020, about 13,300 people will be diagnosed with soft tissue sarcoma (STS) in the United States. An estimated 5,350 adults and children are expected to die of the disease this year. Soft tissue sarcoma is a rare type of cancer that begins in the tissues that connect, support and surround other body structures. This includes muscle, fat, blood vessels, nerves, tendons and the lining of joints. Sarcomas are described as being localized, locally advanced, or metastatic when they are first found. About 15% of sarcomas are found in a metastatic stage, meaning they’ve spread beyond the primary tumor area. The 5-year survival rate for people with metastatic sarcoma is 16%.
HSB-720 is a novel immuno-oncology (IO) agent with QuatramerTM technology delivering a proprietary IL-2 cDNA to be incorporated preferentially into tumor nuclei so the cancer cell can generate IL-2, a key cytokine produced endogenously by activated T-cells. Although highly effective, it is very toxic and associated with treatment-related morbidity making it unsafe for patients in treating a variety of solid tumors. IL-2 toxicity can occur in multiple organ systems including capillary leak syndrome, a hypovolemic state that results in fluid accumulation and is extremely dangerous. HSB-720 would be a revolutionary new strategy to deliver this high effective, yet toxic, cytokine safely and preferentially inside tumors, using the cancer’s own genomic machinery, minimizing toxicity and maximizing effectiveness. Such a strategy could become a backbone of IO-based therapies for cancer treatment in the future.