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今日生物世界(BioWorld Today)报道圣诺在中国递交首个小核酸新药申报
来源: | 作者:Sirnaomics | 发布时间: 2016-01-20 | 147 次浏览 | 分享到:

《今日生物世界》(BioWorld Today)报道圣诺在中国递交首个小核酸新药申报

Sirnaomics files first China IND for siRNA trial; U.S. filing next

By Shannon Ellis, Staff Writer

SHANGHAI – Sirnaomics Inc. is a biopharma straddling the pacific. While one half is in China, with facilities in Suzhou and Guangzhou, it calls Gaithersburg, Maryland., its headquarters, where the company first got its start seven years ago.

But it is the Chinese side, with two years under its belt, that is out of the start gate first, filing an investigational new drug application (IND) with the CFDA for STP705, a potentially first-in-class treatment for hypertrophic skin scars.

STP705 is the first siRNA (short interfering RNA) therapy submitted in China under the innovative drug classification referred to as 1.1. It targets two genes essential to fibrogenesis; fibrogenic diseases such as liver, lung, kidney fibrosis and hypertrophic scars are especially lacking in therapeutic options.

“In China, we are the first to file siRNA therapeutics with our own intellectual property and technology platform,” Alan Lu, executive vice president of Sirnaomics, told BioWorld Today. The strategy, however, is to go after both the China and U.S. trials at the same time.

Lu said the U.S. team was in the company “war room,” preparing documentation for an imminent pre-IND meeting with the FDA.

Although China’s regulatory requirements have nudged closer to the U.S., there is still a difference between the two systems that can cost a company precious time. Sirnaomics has determined that it is best to conduct parallel development, given that data prepared in one location may be not be easily accepted by the other country’s regulator.

IT’S ALL IN THE DELIVERY

With the ability to interfere on the RNA pathway, siRNA technology can silence or turn down the expression of specific genes with complementary nucleotide sequences. Known as a gene knockdown tool, siRNA holds promise as a therapy for many hard-to-treat diseases characterized by highly expressed genes by attacking disease early in the molecular progression.

Discovered 16 years ago, the last couple of years have seen a resurgence of industry interest. Canadian Tekmira Pharmaceuticals Corp.’s Ebola drug was approved for emergency use and has started testing in healthy volunteers, while Cambridge-based Alynlam Pharmaceutical Inc.’s model has had success in phase II studies, to name a few examples.

The major hurdle for siRNA therapies has been figuring out the delivery mechanism into the cell and that is where the greatest progress has been made. While companies like Tekmira have found success with a liposomal-based carrier, Sirnaomics is going another route, using an infrared-activated system that the company believes will work well for local and topical administration of siRNA therapeutics.

“We use a polypeptide of histidine-lysine polymer (HKP), a positively charged polypeptide. It can transform stable nanoparticles with negatively charged siRNA and this complex can get into the cells easily. We have proved it can work and we have proved it can work in nine different disease models in vivo animals studies,” explained Lu.

LOW-HANGING FRUIT

Sirnaomics clearly has an ambitious agenda, with 11 siRNA candidates in the pipeline for indications such as cancer of the lung, breast and liver and for human papillomavirus. But practicality is also a driver; the company said it is going after the “low-hanging fruit” first, betting it will be easier to get siRNA through trials with a topical treatment such as STP705.

At the request of the CFDA, Sirnaomics organized a workshop in China last autumn with leading experts from the U.S. to update the authorities about the latest developments covering manufacturing, CMC, clinical trials and other pressing topics.

“Basically, it was an education class for the CFDA, so they will know what the U.S. FDA is dealing with in the RNAI therapeutic areas,” explained Lu. “At least right now, the CFDA and CDE are very enthusiastic regarding RNAI technology.”

So much so that Sirnaomics has been allowed to import raw material from the US. Since China does not yet have production facilities for clinical stage siRNA, the authorities waived the rule regarding manufacturing that forces many other biotech companies to establish their own pilot facilities. (See BioWorld Asia, Sept. 30, 2014.) That buys time while the company builds its own GMP manufacturing facility in Guangzhou with the promise to the CFDA that it will be online in time for the new drug application filing and before the product is ready for market.

There is the potential that the treatment could be granted green channel status given its first-in-class potential. Lu said the firm is optimistic that it can finish all three phases of trials for STP705 in a timely three to five years.

Lu added that he even picked up on a sense of friendly professional competition with the Chinese regulators intending to stay ahead of the U.S., which could lead to approval being granted in China first.

FUNDING FROM GOVERNMENT, PHARMA, BUT NOT VC

Sirnaomics partnered STP705 with a local company, Guangzhou Xiangxue Pharmaceutical, back in 2011. The Xiangxue partnership will support the project to phase II.

“Since Xiangxue is a public pharma company [in Shenzhen],” Lu said, “they are very experienced with, for example, how to deal with the CFDA, how to deal with the regulations, how to deal with the market. The collaboration is very helpful.”

Sirnaomics has another partnership with Guangdong Zhongsheng Pharmaceutical Co. Ltd. for the development of siRNA therapeutics to treat diabetic retinopathy and agerelated macular degeneration. Having local partnerships is useful for a company that got its start in the U.S.

Patrick Lu, co-founder of Sirnaomics, is a returnee that has not entirely returned to China. Born in China, he went to the U.S. to do post-doctorate work and spent time in the industry working for companies such as Novartis AG as well as having co-founded a company prior Sirnaomics, Intradigm Corp., of Rockville, MD. Although first founded in the U.S., Sirnaomics, through it’s Suzhou affiliate, Suzhou Sirnaomics Pharmaceutics Co. Ltd., has been very successful applying and receiving grants from the numerous Chinese government programs established to support innovation in the biotech industry, including key programs from national to the provincial level programs as well as supports from high-tech development zones.

For Lu, the greater hurdle in China is not getting the technology approved, but rather getting the backing of the wider financial community. “The market is the most difficult for us to face,” he said. “The Chinese market still needs some time for people, like the VCs, to understand the potential of this technology.”