초록 ▼

S1P 수용체 효능제를 개발하기 위하여 본 연구진에 의해 기 구축된 면역질환 인프라를 효율적으로 활용하여 모델링, 디자인/합성, SAR연구, 약효/약리연구(in-vitro Ca++ Mobilization Assay, in-vitro β -arrestin GPCR assay, in-vitro internalization assay, Rat, Dog, Monkey 모델에서 혈액내 Lymphocyte 억제 시험, Rat, Mouse EAE 모델에서 14일 반복 시험 등), 약동력/대사/물성, Rat, Dog, Monkey 2주 독성 시험

S1P 수용체 효능제를 개발하기 위하여 본 연구진에 의해 기 구축된 면역질환 인프라를 효율적으로 활용하여 모델링, 디자인/합성, SAR연구, 약효/약리연구(in-vitro Ca++ Mobilization Assay, in-vitro β -arrestin GPCR assay, in-vitro internalization assay, Rat, Dog, Monkey 모델에서 혈액내 Lymphocyte 억제 시험, Rat, Mouse EAE 모델에서 14일 반복 시험 등), 약동력/대사/물성, Rat, Dog, Monkey 2주 독성 시험 등의 최적화 연구를 수행, 경쟁물질보다 특장점이 있어서 국제경쟁력이 있는 희귀의 약품으로서 다발성경화증 치료제 전임상 후보물질인 LC51-0255의 도출을 완료하고 전임상 시험 진행함.
시험 결과, 시판중인 약물과 현재 임상개발 중인 약물과 비교시 동등 이상의 우수한 약효를 가짐. 임상에서의 효능을 예측하는 phamacodynamic marker 인 말초혈액에서의 lymphocyte 감소에서 매우 우수한 효능을 가지고 있음. S1P1 기능적 antagonist의 기전적 부작용인 서맥부작용은 경미하거나 충분한 치료지수를 가질 수 있을 것으로 예측됨. 약리/PK 결과 1일 1회 복용이 가능한 profile을 보여 복용 편의성이 우수함. Rat, Dog, Monkey 14일 반복 투여 독성시험 결과 충분한 안전역 확보 가능할 것으로 판단됨.

Abstract ▼

Ⅰ. Purpose
S1P receptor agonist, LC51-0255 was investigated for the treatment of multiple sclerosis. Our goal is to derive pre-clinical candidates as a promising and global competitive agent for multiple sclerosis and to complete preclinical and Phase I IND submission, and approval

II. Con

Ⅰ. Purpose
S1P receptor agonist, LC51-0255 was investigated for the treatment of multiple sclerosis. Our goal is to derive pre-clinical candidates as a promising and global competitive agent for multiple sclerosis and to complete preclinical and Phase I IND submission, and approval

II. Content
S1P receptor agonist was developed by utilizing immune disease infrastructure efficiently. Through optimization studies, derivation of preclinical candidate was completed. Preclinical studies were successfully performed including pharmacology, DMPK, genotoxicity, and 2-weeks toxicology. With various outstanding profiles, LC51-0255 showed high potential of globally agent for multiple sclerosis.

III. Result
1. LC51-0255 shows excellent potency for lymphopenia and experimental multiple sclerosis models.
2. LC51-0255 shows improved safety profiles based on selectivity, β -arrestin-biased signaling and novel chemotype.
3. LC51-0255 shows low risks for lung and/or liver toxicities compared to competitors which showed pulmonary toxicity and/or liver enzyme elevation.
4. LC51-0255 shows only transient heart rate reduction compared to competitor which showed prolonged heart rate reduction.
5. LC51-0255 shows favorable DMPK profiles for once-a-day oral dosing.

IV. Plan
The know-how of preclinical toxicity, preclinical pharmacology, sample production, analytical skills, CRO and project management is to be used for human resources and to be transferred to the industry.
While the domestic orphan drug development as the primary goal, actively seeking licensing-out during Phase 1 or Phase 2 process.