Ascentage Pharma Group Internationa...is pleased to announce that the novel Class I drug Olverembatinib (the determined English common name of HQP1351)...has been included in the list of “Priority Review”...for the treatment of adult patients with acquired resistance to tyrosine kinase inhibitor (TKI) and T315I-mutant chronic phase chronic myeloid leukemia (CML) and accelerated phase CML.

Ascentage Pharma...announced that the US Food and Drug Administration (FDA) has granted HQP1351, the Company’s core drug candidate, a Fast Track Designation (FTD) for the treatment of patients with chronic myeloid leukemia (CML) with certain genetic mutations who have failed to respond to treatments with existing tyrosine kinase inhibitors (TKIs).

...After any targeted BCR-ABL1 tyrosine kinase inhibitors (TKI) treatment, CML-AP patients with T315I mutation...

...After any targeted BCR-ABL1 tyrosine kinase inhibitors (TKI) treatment, CML-CP patients with T315I mutation...

At baseline, compound mutations were detected in 12 (11.9%) patients, of whom 8 (66.7%) harbored the BCR-ABL1T315I mutation….Of evaluable patients with the T315I mutations, 100% of those with CML-CP experienced CHR, 83.7% MCyR, and 73.1% MMR and 80.0% with CML-AP had CHR and 54.5% each for MCyR and MMR.

In this multicenter, open-label, randomized trial, olverembatinib is administered orally on alternate days (QOD) in adults with chronic-phase (CP-CML), accelerated-phase (AP-CML), or blast-phase CML (BP-CML) or Ph+ ALL….Even in patients with CML who were ponatinib or asciminib resistant, or who had T315I mutations, olverembatinib showed strong efficacy.

Olverembatinib was efficacious and well tolerated in pts with TKI-resistant CML-CP and CML-AP with the BCR-ABL1 T315I mutation.

The highest response rates were observed in patients with a single T315I mutation. Among 38 patients with CML-AP, the 3-year cumulative incidences of achieving MCyR, CCyR, MMR, MR4.0, and MR4.5 were 47.4%, 47.4%, 44.7%, 39.3%, and 32.1%, respectively. In multivariate analyses, baseline BCR-ABL1 mutation status was significantly associated with cytogenetic and molecular responses...Olverembatinib was well tolerated, with significant antileukemic activity in adults with TKI-resistant CML-CP and CML-AP, especially those with the T315I mutation.

Most evaluable patients with T315I mutations experienced 100% for CHR, 83.7% for MCyR, and 71.2% for MMR among patients in CP-CML, as well as 80.0% for CHR and 54.5% each for MCyR and MMR in AP-CML. At 36 months, the PFS rate (95% CI) was 96.3% (89.1%-98.8%) in patients with CP-CML and 71.4% (40.6%‒88.2%) in those with AP-CML....In patients with TKI-resistant CML-CP or CML-AP and long-term treatment, olverembatinib was efficacious and well tolerated.

HQP1351-CC201 and HQP1351-CC202 are Chinese open, single-arm, multicenter phase 2 trials evaluating the safety and efficacy of olverembatinib in adults with TKI-resistant (BCR-ABL1T351-mutated) CML-CP and CML-CP, respectively…..Study CC201 (CML-CP: At 12 months, the PFS rate was 89.3% (95% CI = 73.9%-95.8%), and the OS was 100% (95% CI = 100%-100%)....Study CC202 (CML-AP: At 12 months, the PFS rate was 74.1% (95% CI = 48.2%-88.4%), and the OS was 91.3% (95% CI = 69.5%-97.8%)....Olverembatinib was efficacious and well tolerated when administered as monotherapy in pts with TKI-resistant CP-CML and AP-CML and the BCR-ABL1T315I mutation.

HQP1351 has been shown highly efficacious in heavily TKI-pretreated patients with T315I-mutated CML-CP or CML-AP and was well tolerated.

HQP1351 was highly active in patients with or without T315I mutation at baseline. The preliminary results of the phase 1 study showed that HQP1351, a novel 3rd-generation TKI, is safe and highly active in treatment of the TKI-resistant patients with CP-CML and AP-CML,with or without T315I mutation.

n vivo efficacy was evaluated using the syngeneic mouse model derived from BaF3 cells with T315I or compound mutations. The cell based antiproliferation studies demonstrated superior activity of olverembatinib toward BCR-ABL single or compound mutations with IC50 values ranging between 6-300 nM.