ANALYTICAL & LABORATORY EQUIPMENT
signalling pathways for antiviral defence. Inarigivir is orally bioavailable and has the potential to be part of a simple, safe and selective combinatorial treatment modality that can significantly enhance the functional cure rates for patients with chronic HBV during a finite duration of therapy. Inarigivir is currently in global Phase II clinical trials against HBV. Cancer. Current cancer treatments include a variety of modalities, including surgery, radiation, chemotherapy with cytotoxic drugs and targeted agents. Each modality is associated with significant risk of relapse due to resistance development and metastasis upon treatment cessation, as well as, considerable side effects and tolerability issues. Recently, therapies designed to activate the host immune system using a class of drugs called “check- point inhibitors” have shown much promise by providing durable cancer cure in a subset of cancer patients. Indeed, immunotherapy is revolutionising the treatment of cancer – patients who have failed all available therapeutic options are now being cured. Spring Bank has developed SMNH compounds as a powerful new class of immunotherapeutic agents for cancer treatment that can be combined with other agents such as checkpoint inhibitors to enhance cancer cure rates. STimulator of INterferon Genes (STING) is an integral component of the body’s innate immune system that senses cytosolic DNA and produces interferon, which is necessary for fighting cancer and viral infections. Targeting this protein potentially enables modulation of the body’s immune response to eliminate cancer. For example, Spring Bank has designed a platform of SMNH compounds that form nanostructures that enable them to enter cells readily, bind to STING to activate the interferon pathway, recruit immune cells for tumour killing and also make cold tumours hot. Tese attributes make them potent immunotherapeutic agents. Te lead compound SB 11285 has recently entered clinical trials. Some other water-soluble STING agonist drugs developed by other companies do not enter cells readily and therefore lack the same efficacy. In addition, several existing STING agonists currently in clinical trials for solid tumours are administered exclusively by direct injection into tumours, which is an inefficient and often painful process that requires considerable resources only available through specialised treatment
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Inarigivir was developed to treat the hepatitis B virus infection
facilities and hospital care. Effective engagement of the immune system to attack a tumour requires key specialised immune cells to traffic from the periphery to the tumour site. With drugs injected directly into tumours, the critical tumour- attacking immune cells might not exist in adequate numbers at a tumour site. To ensure that an immunotherapeutic agent can safely and effectively harness the immune system through the activation of the STING pathway, compounds may need to be administered by systemic routes, for example, intravenous (IV) or subcutaneous. Tis could also enable treatment of many cancers that are not accessible by intratumoral injection.
IV administration of cancer drugs is a commonly accepted modality in current cancer treatment, which often requires a combination of drugs. Furthermore, IV administration of a STING agonist would enable combination therapy in a typical hospital setting. For example, SB 11285, a potent STING agonist developed by Spring Bank that can be administered by multiple routes, including IV and IT, has just entered clinical trials for treatment of cancers, Looking ahead, to achieve targeted delivery to the site of the tumour, these STING agonists are also being conjugated with antibodies to form antibody-drug conjugates (ADCs).
THE SMNH CHEMISTRY OUTLOOK
SMNH compounds are relatively easy to manufacture and offer multiple potential administration routes, including oral and intravenous. Endowed with a novel mechanism of action, they demonstrate the potential to treat large populations facing deadly diseases such as chronic HBV infection and cancer. In addition to viral and oncological applications, SMNH compounds are being designed as immunomodulatory agents for the treatment of numerous common and rare inflammatory diseases, including Lupus, Sjogren’s syndrome, Aicardi’s Goutières syndrome, Parkinson’s disease and multiple sclerosis. As this novel drug development platform evolves, the experience gained in discovering drugs designed to treat HBV, cancer and inflammatory diseases can be applied broadly to other diseases, including cardiovascular, metabolic and central nervous system disorders.
R.P. “Kris” Iyer, is chief scientific officer at Spring Bank Pharmaceuticals.
www.springbankpharm.com
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