BioWorld Today Contributing Writer

A small biotech that has flown under the radar for nearly a decade may be poised to make an impact in the global hepatitis B space. Spring Bank Pharmaceuticals Inc. expects to file an investigational new drug (IND) application with the FDA this year for SB 9200, an orally bioavailable hepatitis B drug based on the company's small molecule nucleic acid hybrid (SMNH) technology.

The molecules designed by Spring Bank, based in Milford, Mass., combine the advantages of nucleic acid-based therapeutics, such as selective targeting and specificity, with conventional pharmaceutical properties such as oral delivery, effective pharmacokinetics, minimal side effects and ease of manufacture, according to Douglas J. Jensen, the company's co-founder, president and CEO.

Jensen and Kris Iyer, Spring Bank's chief scientific officer, were longtime colleagues at Hybridon Inc., of Cambridge, Mass. (now Idera Pharmaceuticals Inc.). In 1999, they left Hybridon to manage its spinout, Origenix Technologies Inc., which was launched with support from several Montreal-based venture capital firms. The company's goal was to develop antisense compounds and other technology that had been sitting on the shelf at Hybridon. (See BioWorld Today, Feb. 18, 1999.)

In 2002, Origenix sold its intellectual property and a portfolio of preclinical candidates to Micrologix Biotech Inc. (See BioWorld Today, Sept. 13, 2002.)

The following year, Jensen and Iyer founded Spring Bank to advance technology based on chemistry developed by Iyer. The company's name refers to a Scottish village frequented by Jensen's lifelong friend and former Hybridon CEO Andy Grinstead, who had succumbed to brain cancer. The fledgling company attracted a five-year, $3 million U01 cooperative research project grant from the National Institutes of Health (NIH) to develop its lead molecule, SB 9200, as an antiviral treatment for hepatitis B.

"That [grant] helped us to launch the company," Jensen told BioWorld Today.

For the next five years, Spring Bank quietly refined the molecule, developing an oral formulation, creating a novel manufacturing process and conducting preclinical studies that provided animal proof-of-concept data. When the U01 grant was completed in 2008, "we started to prepare for pre-IND studies to move this program into the clinic for hepatitis B," Jensen said.

Over the past three years, Spring Bank scientists have further elucidated SB 9200's mechanism of action, demonstrating that the molecule exhibits both direct antiviral activity as well as immune-stimulating properties. The compound "works on a host mechanism as opposed to a viral mechanism," Jensen explained, potentially distinguishing SB 9200 in the antiviral field to target drug-resistant strains and to work in combination with other classes of antivirals. The drug has an excellent safety profile, "and we discovered that it's also active against hepatitis C, so we expanded the application of this program beyond hepatitis B," he said.

Effective hepatitis treatment remains a substantially unmet medical need, with current therapies suffering from incomplete responses or initial responses followed by the development of resistant viral strains, Jensen said. In addition, many patients cannot tolerate common treatment combinations, such as ribavirin and interferon for HCV or interferon and nucleoside or nucleotide analogues for hepatitis B.

HCV protease inhibitors, like Merck & Co. Inc.'s recently approved Victrelis (boceprevir) and Vertex Pharmaceutical Inc.'s Incivek (telaprevir), represent a major advance but still require combination with interferon, he added. (See BioWorld Today, May 17, 2011, and May 24, 2011.)

"The future gold standard is expected to be combination therapy with two or more directly acting antiviral drugs plus an immune system booster that is more easily administered and better tolerated than interferon," Jensen said.

SB 9200 activates retinoic-acid-inducible gene I, a human protein involved in the detection of viral RNA in cells, so it is unlikely to elicit resistance, he added. Since the compound is orally available and well tolerated in IND-enabling toxicology studies, it could potentially replace ribavirin and/or interferon in combination therapy. The company plans to begin Phase I trials of SB 9200 later this year.

Several biotechs represent potential competitors for Spring Bank. Johnson & Johnson subsidiary Tibotec BVBA and Boehringer Ingelheim GmbH both are in Phase III studies with protease inhibitors that are designed to reduce or eliminate the need for interferon. (See BioWorld Today, April 26, 2011.)

However, Spring Bank officials are confident that the unique attributes of their chemistry will set them apart in the hepatitis B space.

"We've been able to demonstrate that we can design molecules that are very selective for targeting nucleic acid binding sites in proteins," Jensen said. "We've got very efficacious molecules that appear to be very safe, can be used in combination with other drugs and, as oral drugs, are easy to use."

In fact, Spring Bank officials are optimistic that SB 9200 will show efficacy against the hepatitis 1A, 1B, 2 and 3 genotypes, noted Don Mitchell, the company's vice president of corporate development. "Our drug is the only mechanism out there that can be combined with multiple direct-acting antivirals to come up with the optimal combination therapy for hepatitis" – the real future of hepatitis treatment, he said.

Spring Bank has been fiscally conservative, garnering most of its funding from nondilutive NIH grants. The original U01 grant was followed in 2009 by a $600,000 Small Business Innovation Research grant. Last month, the company was awarded a five-year, $3.9 million RO1 grant from the National Institute of Allergy and Infectious Diseases. To date, federal funding exceeds $12 million, according to the company.

Spring Bank's next financing step is a planned Series A. Although Jensen declined to disclose a precise timetable or target for the round, the company hopes to provide an 18- to 24-month runway to move SB 9200 through Phase IIa studies in man.

Behind SB 9200 are drug discovery programs for chronic obstructive pulmonary disease, other viral infections and cancer. SMNH compounds can be designed to interact specifically and selectively with a broad range of targets, so they can be applied across an array of therapeutic indications.

Long term, the company hopes to identify partnering opportunities, both on a disease-specific and geographic-specific basis. China, where an estimated 350 million people are infected with hepatitis B, is a huge potential market, for instance.

Spring Bank plans to expand from seven to 14 employees over the next 24 months, but "I don't foresee us moving in the direction of building a sales and marketing team," Jensen said. "We've adopted a very cash-efficient, semi-virtual business model."