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Pipeline detail

FM701

Classification	Description
FM701	4th generation anti-cancer therapy Preclinical R&D in progress
Indication	Non-Small Cell Lung Cancer (NSCLC) with LKB1/KRAS Mutation
Unmet Needs	Cancer patients with LKB1/KRAS Co-Mutation has low survivability and are resistant to Anti-PD-1/PD Among the L1LKB1/KRAS Co-Mutation patients, the higher MDH 1 / 2 expression, the lower the survival rate. No LKB1/KRAS Co-Mutation specific targeting treatment currently available.
Mechanism of Action	Anti-cancer effect mediated by dual inhibition of MDH (Malate Dehydrogenase) 1 / 2 Inducing cancer apoptosis by modulating tumor-specific metabolism LKB1- mutation are sensitive to metabolic stress, enabling the tumor apoptosis Reprogramming of tumor metabolism and microenvironment by controlling HIF-1α and related signaling pathway. Enhancing therapeutic benefit by co-treatment of anti-PD-1/PD-L1
Efficacy	In Vitro: MDH 1/2 dual inhibition assay In Vitro: Inhibiting cellular respiration/ AMPK activation / ATP inhibition In Vitro: Increased intracellular oxygen / facilitated HIF-1 degradation In Vivo: Anti-tumor efficacy in various tumor
Market	연 평균 성장률(CAGR): 12.1 % 전세계 비소세포성폐암 시장 규모: 403억 달러 by 2027

Indication Non-small cell lung cancer

Lung cancer is mainly divided into small cell lung cancer and non-small cell lung cancer according to histological type. Types of non-small cell lung cancer include adenocarcinoma of the lung, squamous cell carcinoma, and large cell carcinoma. Non-small cell lung cancer grows relatively slowly compared to small cell lung cancer and spreads to surrounding tissues before metastasizing throughout the body. In the early stages, it can be cured through surgery. Although surgery is the most effective treatment option, surgery can be performed in less than a quarter of lung cancer patients

Unmet Needs

When a malignant tumor occurs due to a mutation in non-small cell lung cancer, it is refractory to standard treatment. Among mutations that cause low survival rates, a well-known example of refractory to standard treatment is KRAS-mutated carcinoma, and among these mutations, KRAS mutations and LKB1 are simultaneously expressed in about 7-14%.

KRAS/LKB1 co-expressing non-small cell lung cancer patients are basically refractory to standard anti-cancer treatments and do not show significant effects even when administered with immuno-anticancer drugs, so there is a high demand for the development of anti-cancer drugs that can effectively treat them.

Mechanism of Action

- Inhibition of MDH1
- decreased NAD+ synthesis, lower influx rate of NADH into mitochondria
- Inhibition of fatty acid synthesis, influence the glutamine metabolism, and decreased level of NADPH
- Inhibition of MDH2
- Inhibition of NADH and OXPHS to reduce ATP synthesis
- MAS (Malate aspartate shuttle)
- Reduced influx of NADH into mitochondria leads to decreased ATP synthesis
- dual inhibition of MDH1/2 reduces total intracellular ATP and NADPH in tumor

LKB1 mutation and vulnerabilities to metabolic stress

Studies reports that KRAS/LKB1 mutation makes tumor vulnerable to metabolic stress
The expression of MDH1/2 is highly correlated wit the survival rate of patients with NSCLC
FM701 could effectively suppress KRAS/LKB1 mutant tumors by dual inhibition of MDH1/2