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Vision of 'GenoFocus', Microbiome Engineering for New Drug

입력 2018-05-24 15:53 수정 2018-05-24 15:53

by Euna Lee

GenoFocus, an industrial and pharmaceutical enzyme development company, has recently been making a full-fledged effort to develop a new concept of microbiome drugs potentiated with enzyme combination.

Eui-Joong Kim, CEO of GenoFocus, introduced the specialty of the company, saying, “We have developed a system to identify therapeutic candidates from GRAS (generally recognized as safe) bacterial strains, and deliver them to the gastrointestinal (GI) tract. This is Spore Biologics using Bacillus spores. Spores are used as vehicles to deliver enzyme or protein drugs displayed on the spore surface.

More interestingly, spores reach the intestine safely and then produce therapeutic proteins or enzymes in situ.” Being transient passengers of the GI tract, but adapted to carry out their entire sporulation cycle within this environment. Bacillus spores are to germinate and release therapeutic proteins into the GI tract.

GenoFocus has been listed in the KOSDAQ market in 2015 as a new technology company, and has the platform technologies of ‘microbial display’ and ‘secretion expression’. Based on these core technologies, they have developed customized enzymes in various fields, such as food, medical and industrial enzymes. Among them, Lactase, Catalase, and Lipase are the representatives.

Last year, sales totaled 11.5 billion won, an increase of 63 % from 2016. GenoFocus, which expects full-fledged sales this year, secured a production capacity of 150 tons, including the Daejeon bioprocess plant, by acquiring GF Fermentech (formerly Sungwun Bio) last year. In 2012, it has also established a Chinese subsidiary, Genofocus Biotechnology China, which operates a Chinese factory and infrastructure.

GenoFocus’ leading pipeline for new drug development is the superoxide dismutase (SOD) ‘GF-101’. SOD is a representative antioxidant enzyme scavenging reactive oxygen species (ROS), and its first indication is inflammatory bowel disease (IBD). After testing for its effectiveness in ulcerative colitis mouse model, experiments on IBD dogs are being successfully conducted. Kim confidently said, “Our goal is to submit the clinical trial approval (IND) next year. We plan to expand indications for age-related macular degeneration (AMD) and other diseases caused by ROS surge.

◇ Strength of GenoFocus: Microbial display, protein secretion expression technology

Based on its core technologies of ‘microbial display’ and ‘protein secretion’, GenoFocus plans to develop a new concept of microbiome therapy that enables intestinal microorganisms to be modulated, and produce therapeutic proteins in the GI tract.

Firstly, ‘Microbial display’ is a technology to display the target proteins on the surface of bacterial cells or on the spores. By displaying mutant enzyme library or genomic library, it will facilitate high-throughput screening of improved enzymes or candidate proteins.

The second core technology is ‘protein secretion expression’. The target proteins can be over-expressed and secreted, enabling an economical production. GenoFocus has the protein expression and secretion platform technology both in Bacillus and in fungi.

◇ 'Spore Biologics', producing therapeutic proteins in the intestine

GenoFocus has developed ‘Spore Biologics’, a system that delivers therapeutic proteins to the intestinal mucosa. ‘Spore Biologics’ can deliver or produce large quantities of therapeutic proteins. First, microbial display technology may be used to coat the spores with therapeutic proteins or enzymes. The primary effects are realized with spore-displayed proteins or enzymes. Then, spores germinate in the intestines, and secrete proteins in situ, eliciting secondary effects.

Bacilllus can be further modified to produce other therapeutic proteins in the intestine, providing the additional effects. Metabolic enzymes breaking down harmful substances in the intestine can also be expressed.

GenoFocus also seeks to develop life-style medicines that treat diseases and improve the quality of life of patients by manipulating intestinal microbiota. In particular, it has a focus on enzymes derived from GRAS microbes to meet the safety, delivery, and efficacy issues of drugs.

President Kim emphasized, “We are screening candidates from microbes classified as ‘generally regarded as safe’ (GRAS) by the US FDA or drug-proven microorganisms. This means that the safety problem, which is a major risk factor in the development of new drugs, will be fundamentally solved from the initial screening step of candidates.

◇ Treating inflammatory bowel disease with ‘SOD enzyme’… “IND submission planned next year”

The primary target disease of GenoFocus is Inflammatory Bowel Disease (IBD). Protein candidates have been identified in microorganisms that have been approved for acute diarrhea and enteritis treatment. One of them is superoxide dismutase (Mn-SOD), an antioxidant enzyme that removes reactive oxygen species. This is derived from Bacillus amyloliquefaciens, a safety-proven GRAS probiotic microorganism.

Reactive oxygen species (ROS) are generated in all living organisms. When overproduced, they cause various chronic diseases such as gastrointestinal diseases, cardiovascular diseases, neurological disorders, sensory impairments, autoimmune diseases, infectious diseases, fibrotic diseases and eventually cancers. “We have developed the Bacillus strain suitable for SOD overproduction. It is possible to produce a large quantity of SOD with high purity. We have secured patent and economic competitiveness for Bacillus SOD”, Kim explained.

He continued, “We have already confirmed the therapeutic effect of GF-101 in mouse animal model. Oral administration of enteric coated SOD enzyme and SOD-producing Bacillus spores ameliorated ulcerative colitis in mouse.”

Kim added, “Interestingly, SOD in the blood also increased with oral administration of SOD. In addition, activity of the typical antioxidant enzymes, such as catalase and glutathione peroxidase, also increased. Its first effect is in the intestine, and then boosts SOD activity in the blood, enhancing the overall antioxidant effect.”

He also said, “We are currently undergoing further assessment through animal experiments, and are planning to submit an IND at the end of next year. We are developing a therapeutic agent in three forms: a purified SOD enzyme, SODs coated on the surface of Bacillus spores, and Bacillus spores overproducing SODs. In particular, SOD enzyme alone is effective, but since it has a mechanism to remove reactive oxygen species, it may be also effective as combination therapy with existing therapeutic agents.”

SOD-based pipeline GF-101 has the potential to expand its indication into treatments for diseases such as AMD and other diseases that are induced by excessive free radicals.

◇ “Planning to establish a spin-off drug development company”… “JV through strategic investment is also under review”

GenoFocus plans to expand its portfolio and external network through strategic investments. President Kim added, “The company acquired a 15 % stake in Probionic, a company specializing in lactic acid bacteria with allergy indication. We are also investing in the Microbiome specialized company with metagenome analysis technology. Further, we are considering establishing a joint venture (JV) for the development of microbiome treatment drugs for the specific diseases.”

To facilitate drug development efforts, GenoFocus decided to spin-off the new drug development company soon. And they are hiring experienced management level scientists. ‘We are pleased to announce that Dr. Won-Bae Kim, former Dong-A S&T CEO with more than 40+ years of drug development business, is joining us as our senior board member”, Kim added.

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