PlatBio, Develops new Drugs based on Translational Research, “Open Assist”
입력 2018-12-14 10:10 수정 2018-12-19 16:50
바이오스펙테이터 Sungmin Kim 기자
There have been many cases of candidate materials developed by pharmaceutical companies for new drugs but failed due to trifling differences. Approximately, 60% of the development of new drugs has failed not because of developed materials but because of the ignorance of how to exploit such materials. Apparently, there were cases of new drugs which manifested high toxicity and low efficacy in clinics. PlatBio develops the “First-in-Class” new drugs by conducting translational research using the PTIINT platform.
Sun Jin Kim, the Chairman of the board of PlatBio Inc., said in the meeting with reporters from Biospectator as follows: “PlatBio Inc. was founded in October this year under the slogan, ‘Making Bio-History’.” The position of PlatBio resides in the translational research platform technology from which its domain of spontaneous R&D extends broadly to the extent of the license in/out of new drugs (BD/eRD) and even of CRO.
Founders of PlatBio comprise the team that played key roles in the foundation of the company together with Chairman Kim Seon-jin, who led the leading translational researches of the team since the time he was working as a vice-president of Hanmi Pharm. Co., Ltd. President Cha Mi-yeong was the director-in-charge of the research center and overseas business development (BD) in Hanmi Pharm. Co., Ltd. Director Lee Ho-jeong and Director Ryu Hyeon-gyeong worked in association with Chairman Kim since the time they were working in the MD Anderson Cancer Center and conducted translational researches in the center of research of Hanmi Pharm. Co., Ltd. Ha Yeong-eun, the Chief of the team, was also working in the translational research team in Hanmi Pharm. Co., Ltd., and joined the members of the PlatBio.
PlatBio is differentiated from other start-ups based on the exploitation of the orthotopic model. Chairman Kim Seon-jin explained, “... the orthotopic model can represent over 75~80% of patients’ tumors rendering higher probability of translation...”, “... the environment of the orthotopic model is similar to that of clinics. The process of intrusions of target and cancer into tissues and of the subsequent metastasis by an adaptation thereof is similar to that of an actual patient.”
The orthotopic model reflects the interaction between cancer cells and the microenvironment of tumors in organs. Advantages of the orthotopic model are summarized as follows. First, it has a pattern of target manifestation similar to tumors of the patient. Based on the comparison of the orthotopic model with the model of subcutaneous infusion of cancer cells, the pattern of target manifestation was observed to be different from that of the tumor. In the case of subcutaneous infusion of cell strain of tumors, the cell strain does not manifest correctly in the target organ. Second, the pattern of metastasis of tumors into bones or brain in the orthotopic model is similar to that expressed by the patients. This is the feature that differentiates the orthotopic model from the heterotopic model. Third, the study on the combined administration of anticancer agent can be carried out simultaneously with translational research in the orthotopic model.
The research team used the technique of cross-species hybridization of microarrays (CHME) that can distinguish gene expression in tissues of mouse and cancer cells of humans to examine metastasis of cancer in the orthotopic model.
Interestingly, the cancer cells were observed to have genetic signatures of patterns different from each other according to sites of metastasis. The research team observed the gene expressions of skin (0), lung (1), bone (8), and brain (173) according to organs of metastasis. Chairman Kim added, “... for the metastasis of tumor cells, they have to undergo a process of adaptation and selection in tissue... “, “... here, each organ would manifest respective featured pressure thus, the metastasis would be realized by tumor cells which are able to pass these gates.”
President Cha Mi-yeong explained, “... the vast amount of data on genetic information of metastatic cancers to be manifested in a micro-environment of specified organs have been established. Now, the list of tumor-specific gene signatures of melanoma, colon cancer, breast cancer, lung cancer, prostate cancer, kidney cancer etc. has been secured.”
PlatBio currently develops the primary tumor/metastasis models for 13 kinds of orthotopic graft. For the orthotopic model, cancer cells grow in the target organ and exhibit metastasis phenomena with time. PlatBio selects the target by aiming at the target capable of curing metastatic lesions together with the primary tumors.
PlatBio discovers the therapeutic and diagnostic targets promptly through the PRIINT™ (Platform for Revolutionary Identification & Isolation of Novel Targets). The platform PRIINT finds out the cancer target using sophisticated orthotopic model, specimens from patients, and information on genetics and bioinformatics. It is a tool, which enables the clinical application of the target found from the orthotopic model.
First, a sophisticated orthotopic model is developed. Subsequently, the genes, expressed over twice through RNA analysis (CHME) in the organ of the orthotopic model are screened. Next, the manifestation of the corresponding protein, in the organ of the orthotopic model, in tissues of 150~200 patients, and in blood serum are cross-validated.
The test on pancreatic tumor revealed enhancement in the expression of 56 genes as it was a pancreatic cancer-specific gene signature. Among them, the secretion of 17 proteins was identified; the 14 proteins among them were identified as cancers targetable with antibodies. Chairman Kim explained, “... the targets screened were all the real “first-in-class’ ones unavailable in normal tissues but available in cancer tissues.”
The cancer target, found from PRIINT platform, can be the therapeutic target, and simultaneously, it can be used as a screening marker for early diagnosis as well as the monitoring marker enabling identification of therapeutic efficacy and prognostic consequences.
PlatBio currently scheduled the IND filling of two candidate materials for new drugs aiming at malignant solid cancers including blood cancer until the end of 2021, with the four (4) candidate materials to be employed in pre-clinical trials.
Above all, PlatBio aims at pancreatic cancer and ovarian cancer as they demonstrate the great potential for unmet medical needs. Small molecule compounds targeting pancreatic cancer, are being developed through the fastest pipeline; the application for a clinical trial will be filed in Korea and in the United States of America in 2021. The diagnostic kit for pancreatic cancer is also being developed contemporaneously. In the pipeline for ovarian cancer, the study on an antibody-drug conjugate (ADC) is in progress; a new candidate material for a new drug is scheduled to be released next year.
Chairman Kim stated on the upcoming development of candidate materials for new drugs as follows, “... Some of them might be licensed out, or otherwise, PlatBio may undertake them. Collaboration for clinical development based on 50:50 sharing has also been taken into account.”