Pipeline Focused on Rare & Pediatric Cancers

HSB-1216: Novel Ferroptosis Inducer

HSB-1216, is a novel and potent inducer of a powerful mechanism called ferroptosis.  This process which sequesters iron in lysosomes allows HSB-1216 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 is small cell lung cancer and 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-888: HSB-1216 + Novel Low Dose Anthracycline

Sarcomas tumors are mesenchymal in nature and capable of forming in connective tissue, blood, lymphatic and vessels, believed to also effect bone and soft tissue. Sarcomas are rare and account for 1% of cancers – yet encompass about 13% of cases under the age of 20. Most common in bone are osteosarcoma and Ewing’s sarcoma, while those arising from soft tissue are commonly rhabdomyosarcomas. Other sarcomas, such as desmoplastic small round cell and synovial sarcoma are more common into adolescence and young adulthood.

The components of HSB-888 are two anticancer drugs with distinct and complementary mechanisms of actions (ferroptosis and DNA intercalation) which together constitute an active combination for treating sarcomas. Hillstream investigated whether the efficacy of this combination could be improved by controlling drug ratios following in vitro and vivo administration. The combinations were evaluated systematically for drug ratio-dependent synergy in vitro using multiple tumor cell lines. In vitro screening informatics on drug ratio-dependent cytotoxicity identified a consistently antagonistic region between payloads at various molar ratios, which also showed multiple synergistic ratios, dependent on the chemical characteristics of either DNA intercalating payload combined with a ferroptosis inducer.

Co-formulations of these two agents were developed that maintained a fixed drug ratio for stability and release profiling over broad timelines. Drug ratio-dependent antitumor activity was demonstrated in vitro and in vivo for these ratios and improved antitumor activity was observed for a specific molar ratio of DNA intercalator:ferroptosis inducer (designated HSB-888) compared to drug cocktails in models tested. HSB-888, is a fixed-ratio formulation of DNA intercalator and ferroptosis inducer, and a lead near-clinical candidate for development which we intend to develop in multiple sarcomas.

HSB-1218: Novel Ferroptosis Inducer for SARS-CoV-2

HSB-1218 has been shown to interfere with SARS-CoV-2 virus infection of tissue culture cells.  Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic. Despite a safe and effective vaccines to prevent infection it is unknown how long the pandemic will last and in the absence of safe and effective therapeutics to treat those who are infected it is expected that many more may become infected. To address anti-SARS-CoV-2 therapeutics, multiple different drugs which are currently approved by the FDA have been evaluated and shown to interfere with SARS-CoV-2 infection in the laboratory but have had limited success in the clinic. There remains an urgent need for antiviral therapies to treat those afflicted with COVID-19 and improve patient outcomes. We plan to further study HSB-1218 as a therapeutic for to treat Covid-19.

HSB-114: TNF-alpha DNA 

HSB-114 is a next generation immunotherapeutic agent of a previously developed predecessor compound. Quatramer technology allows a proprietary TNF-alpha 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%.