바이오스펙테이터

by Dongyoung.Park

Development of Single Strain Microbiome-based Drugs by Investigating In-depth Molecular Mechanism..On-going Global Clinical Trials of Drug Candidates targeting Inflammatory Disesease such as Psoriasis

Most researches on microbiome have been focusing on correlations between intestinal microbes and diseases. These researches have postulated that intestinal microorganisms are associated with diverse diseases including cancer, metabolic disorders, and inflammatory diseases. Leading pharmaceutical companies in the global market are exploiting the consortium other than a single strain of microorganism or engrafting feces of healthy donor. However, the approach of KoBioLabs Inc. to develop microbiome-based new drugs is different from these approaches.

KoBioLabs Inc. strives for the development of microbiome new drugs based on ‘Single strain of microorganisms or effective substance originated from them’. President Ko Gwang-pyo of KoBioLabs Inc. thinks that scientific approaches to explicate certain mechanism are necessary to find the crucial microbiome involved in developing diseases among a number of microorganisms. The accomplishment of KoBioLabs Inc. including a global clinical trial for the first time among domestic companies in August this year is based on this thinking. The application for a Phase II Clinical Trial of the drug candidate for psoriasis acquired an approval from FDA of USA last August by presenting data obtained from a Phase I Clinical Trial explicating the mode of action.

Most companies that develop new drugs based on microbiome strive for the development of therapeutic agents for intestinal diseases such as ‘Clostridium Difficile Infection (CDI)’ and Inflammatory Bowel Disease (IBD). This can be attributable to the prevalent presence of microbiome in the intestine. Different from them, KoBioLabs Inc. is focusing on the development of therapeutic agents targeting psoriasis, asthma, atopic dermatitis, and so on. This is the one of the differences of KoBioLabs Inc. from other microbiome-based drug developing companies.

What are reasons behind this approach? KoBioLabs Inc. expresses its confidence and will of its scientific approach free from intense competition with leading pharmaceutical companies striving for the development of new drugs for different diseases.

Lead-programs of KoBioLabs Inc. include ▲ ‘KBL697’, a candidate for psoriasis and IBD and ▲ ‘KBL693’, a candidate for asthma and atopic dermatitis. The company acquired an approval for Phase II Clinical Trial for ‘KBL697’ from FDA of USA last August. Simultaneously, the company started a Phase I Clinical Trial for ‘KBL693’ with 18 patients of asthma in Australia. It is scheduled to be terminated at the end of November this year (NCT04307173). Besides, preliminary clinical trials for validation of efficacy for asthma and atopic dermatitis are currently in progress in four domestic institutions. The technological competence of KoBioLabs Inc. in terms of the development of microbiome new drugs has been recognized officially and the company is preparing for being listed in KOSDAQ this November.

KoBioLabs Inc. currently develops microbiome new drugs based on three platforms: ‘BaxData’, ‘BaxBank’, and ‘BaxPlore’. The company secured data of more than 3,000 human genomes, multiomics, epidemics, and clinical records from five major university hospitals and ‘SNU Graduate School of Public Health’ for the development of ‘BaxData’ platform. By exploiting the ‘BaxBank’ platform, the microbiome library, and the ‘BaxPlore’ platform developed for studying mechanisms, the company has selected target candidates and conducted researches for investigating the molecular mechanism.

President Ko Gwang-pyo of KoBioLabs Inc. stated, “‘BaxData’ and ‘BaxBank’ as platforms of KoBioLabs Inc. based on a vast amount of big data exhibit high levels of expandability”, “by exploiting such expandability, studies on diverse kinds of diseases including cancer and alcoholic fatty liver are enabled, thus contributing to the foundation for excavation of pipelines of KoBioLabs Inc.”.

① ‘KBL697’… Approval of Phase II Clinical Trial in USA, Domestic Preliminary Clinical Trial to Determine Efficacy on IBD

‘KBL697’, a therapeutic agent for psoriasis, is currently leading program for the KoBioLabs Inc.. The company has discovered that live bacteria showed superior IL-10 inducing capability against inflammation among identical species by exploiting BaxBank. With an in vivo mouse model of psoriasis, KBL697 exhibited higher therapeutic effects than existing oral therapeutic agent for psoriasis such as ‘Apremilast’ and ‘Dexamethasone’. The mechanism of the therapeutic agent is inhibiting inflammatory ‘Helper T Cell Type 17’ through secretion of IL-10.

Last May, KoBioLabs Inc. reported final results of the Phase I Clinical Trial for KBL697 conducted with 36 patients of psoriasis last year (NCT04056130). Results revealed lower ratio of occurrence of abnormal reactions for patients administered with KBL697 compared to patients in the group of placebo administration (42% vs. 50%). Their symptoms were negligible, belonging to ‘Grade 1’. Pharmacokinetic analysis of KBL697 rendered a dose-dependent KBL697 detected from fecal samples upon administration of KBL697.

President Ko Gwang-pyo stated, “Medical unmet needs are present due to the presence of adverse effects associated with the administration of PDE4 (Phosphodiesterase 4) inhibitor of Amgen, Apremilast”, “I expect that KBL697 will be the ‘best-in-class’ drug replacing Apremilast”.

KBL697 also manifested therapeutic effects on IBD. An in vivo IBD model rendered an improvement of disease from co-administration of KBL697 with a standard therapeutic agent Infliximab, a TNF-α inhibitor. Currently, preliminary clinical trials to determine the efficacy of KBL697 with subjects suffering ‘Ulcerative Colitis’ are in progress in four domestic hospitals.

② ‘KBL693’… Phase I Clinical Trial in Australia with Subjects Suffering Asthma: Domestic Preliminary Clinical Trial to Determine Efficacy on Asthma and Atopic Dermatitis

Another program that leads KoBioLabs Inc. is ‘KBL693’, a therapeutic agent for atopic dermatitis. KoBioLabs Inc. has identified the microbiome present in female vagina is significant in exerting internal immune reaction against human papilloma virus (HPV) through a previous study. Based on the results, the research team has identified the strain obtained from healthy female subjects and analyzed its capabilities for inhibiting secretion of Histamine, IL-4/IL-5 suppression, and IL-10 inducement comprehensively to determine the most suitable live bacteria. KBL-693 exhibits the mechanism of curing auto-immune diseases by inhibiting secretion of inflammatory IL-4 and IL-5 through the aid of ‘Helper T Cell Type 2’. A mouse model of asthma after treatment with KBL693 manifested decreases of secretion of IL-5 and IL-13 and count of ‘Eosinophil’, together with amelioration of hypersensitive airway reaction

KBL693 also demonstrated therapeutic effects on atopic dermatitis. Upon administration of KBL693 to a mouse model of asthma induced by DNCB(2, 4-DiNitroChloroBenzene), the dermatitis score representing atopic severity appeared to be decreasing. KoBioLabs Inc. is going to develop new drugs based on microbiome targeting metabolic diseases such as liver disease, ‘NASH’, autistic spectroscopic disorder, and cancer.