HOPKINTON, MA, USA I October 20, 2016 I Spring Bank Pharmaceuticals, Inc. (SBPH), a clinical-stage biopharmaceutical company developing novel therapeutics for the treatment of viral infections, cancer, and inflammatory diseases today announced the presentation of scientific data relating to its novel, proprietary STING (STimulator of INterferon Genes) agonist compound, SB 11285, at the American Association for Cancer Research (AACR) Special Conference on Tumor Immunology and Immunotherapy taking place on October 20-23, 2016 at the Boston Marriott Copley Place in Boston, MA.

“The data presented at this year’s AACR Special Conference on Tumor Immunology and Immunotherapy are important because they provide compelling early scientific evidence supporting the further development of SB 11285 as a potential novel immunotherapeutic agent in the treatment of various cancers,” stated Radhakrishnan (Kris) Iyer, PhD, Chief Scientific Officer of Spring Bank. “Among the key pre-clinical findings were that SB 11285 is a highly potent STING agonist that causes the induction of Interferons (IFN), NF-KB, Interferon-stimulating genes (ISGs), cytokines, and pattern recognition receptors (PRRs). SB 11285 was also shown to cause apoptosis of multiple tumor-derived cell lines.”

Dr. Iyer continued, “Immunotherapy has emerged as a transformative approach for the treatment of cancer; nevertheless, many patients remain unresponsive to treatment. It is being recognized that induction of type I interferons (IFN) and interferon-stimulated genes (ISGs) in tumor cells and within the tumor microenvironment (TME) is essential for modulating the host-immune response for amplifying anti-tumor response. We plan to continue the development of SB 11285 in an effort to potentially demonstrate that this novel agent could be an important addition to current standard of care in the treatment of various cancers and hope to increase the treatment responses in patients.“

A summary of the data presented by Spring Bank’s scientists Dr. Shenghua Zhou and Dr. Rupa Challa at the AACR Special Conference on Tumor Immunology and Immunotherapy is described below:

Poster Presentations

Poster Title: Novel dinucleotides that activate STING signaling for Immuno-oncology
Date and Time: Saturday, October 22, 2016, 6:15 – 8:45 pm
Poster Session: Poster Session B
Board Number: B39
Session Location: Back Bay

Results: Through in vitro assays in conjunction with Structure Activity Relationship studies, we have identified potent compounds that activate cGAS-STING signaling pathway for induction of IRF, IFN, and NF-KB. These compounds also cause induction of expression of PRRs, including RIG-I, MDA-5, LGP2, as well as, ISG54 and OAS-1.

Conclusion: We have discovered potent, first-in-class agents that cause induction of IFN, NF-KB, ISGs, and PRRs. Further optimization and preclinical evaluation of the compounds for application in immuno-oncology is underway.  

Poster Title: Nucleotide analogs as Novel STING agonists for Immuno-oncology
Date and Time: Saturday, October 22, 2016, 6:00 – 8:45 pm
Poster Session: Poster Session B
Board Number: B40
Session Location:  Back Bay

Results: Through in vitro assays in conjunction with Structure Activity Relationship (SAR) studies, we have identified several highly potent and selective first-in-class STING agonists. A promising lead nucleotide compound SB 11285 caused STING-dependent induction of: (a) IRF with an EC50 of 2 nM that is 1000-fold more potent than the natural STING agonist 2’,3’-cGAMP, (b) NF-KB with an EC50 of 200 nM that is >200-fold more potent than 2’,3’-cGAMP, (c) selective apoptosis of human monocyte leukemic cell lines (CC50, 500 nM) as compared to normal PBMCs through induction of IFN, and NF-KB signaling, and (d) expression of various PRRs and ISGs including RIG-I, MDA-5, LGP2, ISG54 and OAS-1, as well as, PDL1 and PDL2. Finally, SB 11285 showed potent in vitro anti-tumor activity in multiple tumor cell lines.

Conclusion: We have discovered highly potent first-in-class STING agonists that show excellent selectivity in induction of IFN, NF-KB, ISGs, and PRRs, and apoptosis of tumor-derived cell lines. The lead STING agonist SB 11285 has potent immune-modulating, as well as, anti-tumor activities and is being advanced for additional preclinical studies for application in immuno-oncology.  

About Spring Bank Pharmaceuticals

Spring Bank Pharmaceuticals is a clinical-stage biopharmaceutical company engaged in the discovery and development of a novel class of therapeutics using its proprietary small molecule nucleic acid hybrid, or SMNH, chemistry platform. SMNH compounds are small segments of nucleic acids that the company designs to selectively target and modulate the activity of specific proteins implicated in various disease states. The company is developing its most advanced SMNH product candidate, SB 9200, for the treatment of viral diseases, including hepatitis B virus. SB 9200 has been designed to selectively activate within infected cells the cellular proteins, retinoic acid-inducible gene 1, or RIG-I, and nucleotide-binding oligomerization domain-containing protein 2, or NOD2, which have been implicated in the body’s immune response to viral infections. Spring Bank believes that SB 9200 may play an important role in antiviral therapy by modulating the body’s immune response through its mechanisms of action to fight viral infections such as HBV. For more information please visit: www.springbankpharm.com.

SOURCE: Spring Bank Pharmaceuticals