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Novel small molecule drug for cancer cachexia

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  • Project profile
    Project name: Novel small molecule drug for cancer cachexia
    Indications: Cancer cachexia
    Research phase: Preclinical candidate compound identified
    Cooperation demands: License-out or co-development.
  • Highlights
    1.Huge unmet clinical needs.

    The first drug for cancer cachexia, anamorelin, is approved only in Japan. However, anamorelin has not demonstrated any effect on enhancing muscle strength measured by handgrip strength or muscle endurance evaluation, i.e. 6-minute walking test. Furthermore, anamorelin could not improve the survival time of patients with cancer cachexia. Therefore, treatment of cancer cachexia still have huge room of improvement and unmet need.

    2.Large market size.

    a)The incidence of cancer cachexia is high. Evidence shows about 60%-80% of progressive tumors are complicated with cancer cachexia, of which more than 20% of patients with malignant tumors die due to cachexia, while 50% of cancer patients still carry cachexia postmortem.

    b)The global cancer cachexia market is valued at USD 2.25 billion in 2020 and is expected to reach USD 3.0 billion by 2026, growing at a CAGR of 4.47%.

    3.Clear mechanism of action.

    a)Inhibition of TNF-α and IL-6 secretion by macrophages and tumor cells.

    b)Modulation of myotubular cell-related signaling pathways to reduce muscle protein degradation and to promote protein synthesis.

    c)Modulation of adipocyte-related signaling pathways to reduce fat mobilization and fat browning.

    4.Significant clinical efficacy with less toxic side effects.

    a)The head-to-head study comparing anamorelin and Z526 in vivo show similiar efficacy, significantly alleviating weight loss in C26 tumor-bearing mice. On the otherhand, Z526shows far better data than anamorelin in enhancing muscle strength.

    Fig. 1 Change in body weight of tumor-bearing mice

    b)Z526 combined with oxaliplation doesn’t affect the therapeutic efficacy of oxaliplatin , treating cancer cachexia induced by chemotherapeutics.

    Fig. 2 Change in body weight of tumor-bearing mice

    5.Preliminary toxicological studies in vivo show there is no obvious toxicity and side effect .
  • Project Introduction

    1. Drug type: Novel small molecule

    2. Indications: Cancer cachexia

    3. Administration route : Oral administration

    4. Mechanism of action: This compound significantly inhibits the production and secretion of inflammatory factors and alleviates myasthenia and lipolysis by promoting protein synthesis and inhibiting lipid degradation, improving tumor cachexia.

    5. Indications: Cancer cachexia

    6. Research progress:

    a) The studies in C26 tumor-bearing mice,

    i. Significantly inhibit the elevation of TNF-α and IL-6 levels in serum and tumor of C26-bearing mice.

    ii. Promote protein synthesis, inhibit lipid degradation and other signaling pathways to alleviate myasthenia and lipolysis and improve tumor cachexia.

    b) The studies by head-to-head with anamorelin in vivo show better efficacy in enhancing muscle strength.

    c) Preliminary toxicology studies were completed, and the hERG IC50 is 34.1uM, and the therapeutic window is 20 folds

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