Pipeline

AnHeart’s pipeline consists of three clinical stage assets: Taletrectinib, a next generation ROS1 and NTRK inhibitor currently in Phase 2; an mIDH1 inhibitor entering Phase 2 for low grade glioma, cholangiocarcinoma, AML and other tumors; and an AXL inhibitor in Phase 1 for overcoming checkpoint inhibitor or EGFRi resistance in various tumors.

TALETRECTINIB (ROS1/NTRK inhibitor)

ROS1 oncogenic fusions are observed in ~1-2% NSCLC (Non-Small Cell Lung Cancer) patients. There are more than 20,000 patients newly diagnosed with ROS1 fusion-positive NSCLC each year. ROS1 fusions are also observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers.

Two ROS1 tyrosine kinase inhibitors (TKIS), crizotinib and entrectnib, have been approved in the U.S. and Japan for advanced ROS1 fusion-positive NSCLC. However, resistance to ROS1 TKIs invariably occurs with on-target resistance such as the acquired ROS1 G2032R solvent front mutation (one of the most common resistance mechanisms).

  • Taletrectinib is a potent, novel, highly selective, next-generation ROS1/NTRK inhibitor for solid tumors with ROS1 fusion or NTRK fusion mutations. It can overcome crizotinib resistance and cross the blood-brain barrier.
  • There is no approved drug targeting crizotinib resistance mutations.
  • Phase 1 clinical trials show promising efficacy and saefty signals in 22 ROS1 NSCLC patients.
    • mPFS 29.1 months and 14.2 months in TKI-naive patients and 1 Prior-TKI patients, respectively.
    • ORR 6/9 (66.7%) and 2/6(33.3%) in TKI-naive patients and 1 Prior-TKI patients, respectively.
    • Generally favorable safety profile (n=61).
  • Currently in Phase 2 trials for first line and second line ROS1 NSCLC patients in China and ex-China first line and second line ROS1 NSCLC patients global Phase 2 trials to start in early 2021.
Early Generation Next generation Taletrectinib Crizotinib Entrectinib Ros1 Fusion Ros1 Fusion with resistance mutations F NH N N N H2N OH O O O HO HN N N NH 2 O F N Cl Cl O HN O HN-N N H F F N N Ros1 Fusion Ros1 Fusion with resistance mutations
Anheart pipeline consulting

AB-218 (mIDH1 inhibitor)

Glioma is a type of cancer that develops in the glial cells of the brain. Glial cells support the brain’s nerve cells and keep them healthy. Gliomas are classified into grades I, II, III or IV. Mutations in IDH1 are present in the majority of adults grades II and III tumors (categorized as lower-grade glioma, or LrGG). There are approximately 30,000 patients diagnosed with IDH1+ LrGG in US, Europe and China each year.

  • AB-218 is a mIDH1 inhibitor with good brain penetration for multiple solid tumors and hematological cancers with mIDH1 mutations.
  • IDH1 mutations are seen in about 75% of lower-grade gliomas which lacks any targeted therapy.
  • Phase 1 clinical trials of AB-218 in glioma patients demonstrated promising efficacy and safety profiles in 12 non-enhancing and 35 enhancing glioma patients.
    • ORR 33% and 17.1% in non-enhancing and enhancing patients, respectively

AB-329 (AXL inhibitor)

Immune checkpoint inhibitors have revolutionized the treatment of cancer over the last decade, allowing a subset of patients to see sustained treatment responses, and some advanced cancers were even made “curable”.

Despite the increasing success, a substantial number of patients do not benefit from checkpoint inhibitor immunotherapy. Their tumors are either resistant in the beginning or develop resistance after initial response. Resistance to checkpoint inhibitors may occur due to various factors within the tumor cells or the tumor microenvironment (TME).

Emerging evidence indicates that myeloid cells with regulatory activity in TME are key players in limiting host antitumor immunity and reducing the efficacy of immunotherapies.

AXL, a member of the TAM receptor kinase family, is expressed in both tumor cells and immune cells (e.g. myeloid cells) in the tumor microenvironment. Due to its pro-oncogenic and immune-inhibitory features, AXL is a promising target for cancer treatment and its inhibition may enhance checkpoint inhibitor therapy.

  • AB-329 is a potent and selective AXL inhibitor potentially to be used in combination with other therapeutic agents in overcoming resistance in multiple solid tumors and hematological cancers.
  • Resistance to therapeutic agents such as checkpoint inhibitors or EGFRi remain to be addressed.
  • AB-329 has demonstrated a favorable safety profile in Phase 1 studies.
  • We plan to test in combination with checkpoint inhibitors for NSCLC.
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