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Subject BMT Takes ‘Shorter’ Approach to Develop RNAi-Based Drugs
Writer 관리자 Date 2018.05.30 See 1120
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BMT Takes ‘Shorter’ Approach to Develop RNAi-Based Drugs

By Jennifer Boggs

Assistant Managing Editor

(BioWorld Today, October 28. 2010)


South Korean start-up BioMolecular Therapeutics Inc. became the latest fi rm to start playing in the RNAi sandbox – and it’s brought its own toys.

“As far as I know, we’re the only Asia-based company with freedom to operate” in the RNAi space, said Dong-ki Lee, an associate professor of chemistry at Sungkyunkwan University in Suwon, Korea, and inventor of BMT’s technology.


RNAi has been heavily touted as one the more promising drug development approaches – the silencing of genes to treat disease – but trying to move into the space without infringing on intellectual property held by a handful of RNAi heavyweights such as Alnylam Pharmaceuticals Inc. and Silence Therapeutics plc is tricky business.


Most companies working on siRNA compounds aim to improve the molecules via chemical modifi cations “but without touching the backbone structure,” Dong-ki Lee to BioWorld Today. “We’re able to change that backbone structure” in way so that the IP does not infringe the Tuschl patent, he added, referring to the patent series relating to siRNAs.

Specifi cally, BMT reduced the number of base pairs. The Tuschl patents call for duplex regions with 19 base pairs. “It was suggested that that length was critical for optimal gene silencing,” Dong-ki Lee said.

“But we reduced [the base pairs] to 16 and then to 15 and were able to achieve comparable silencing,” he said.


The shortened siRNAs – called asymmetric shorterduplex siRNA, or asiRNA – also could have a leg up over traditional siRNAs in diseases in which treatment can be hampered by innate immune stimulation such as agerelated macular degeneration.

A duplex of 19 base pairs or longer can trigger an innate immune receptor, namely Toll-like receptor 3, a discovery made by BMT advisor Jayakrishna Ambati, an ophthalmologist and professor at the University of Kentucky Medical School, and apparently born out in two AMD studies. In the past two years, Opko Health Inc. cut short a Phase III AMD trial of siRNA bevasiranib after a data monitoring committee determined the study was unlikely to meet its primary endpoint, and Allergan Inc. dropped work on AGN211745 in AMD after disappointing Phase II data. (See BioWorld Today, March 9, 2009.)

BMT found that the shorter duplexes do not trigger TLR3.

The fi rm is going after AMD as its fi rst indication, hoping to fi le an investigational new drug application in late 2011 or early 2012. Beyond that, asiRNAs could have applications in both infectious diseases, including herpes-simplex virus, and cancer.


Dong-ki Lee said a locally delivered asiRNA for vaginal HSV could be next in line for the small biotech. The larger cancer indication likely will need a partner.

“We’ve been acquiring data on the activity on [asiRNAs] in cancer but we have no internal programs,” he said, but added that “we do have a midsize pharmaceutical company interested” in the technology.

To date, BMT has operated on money from its founders, but the fi rm, which recently was selected as venture company by the Korean government and picked up some government funding, is planning a Series A fi nancing, probably next year, with plans to seek funding globally, including from U.S. venture capitalists.

“That’s one of the reasons we recruited Johannes Freuhauf,” a biotech veteran with experience in RNAi and an offi ce in Boston to “help the company develop in the U.S.,” Dong-ki Lee said.


The fi rm also plans to seek funding in Korea, but that might be challenging.

In Korea, “there’s a lot of money around waiting to invest in biotech,” he said, but most is going toward the less risky biosimilars business. “My opinion is that they’re afraid of investing in novel technologies.”


In the coming months, BMT plans to work on strengthening its IP portfolio and scouting out possible early collaborations and licensing deals.