AnHeart Therapeutics' Investigational Medicine Taletrectinib Shrank Tumors in More Than 90 Percent of People With ROS1-Positive Non-Small Cell Lung Cancer Who Were ROS1 TKI Naïve in Global Pivotal TRUST-II Trial

AnHeart Therapeutics ("AnHeart"), a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer, today announced positive interim results from its global pivotal Phase 2 clinical trial, TRUST-II. Interim data from the trial showed taletrectinib, AnHeart's investigational next-generation ROS1 inhibitor, shrank tumors (confirmed objective response rate, cORR, as assessed by an independent review committee, IRC) in 92% of patients with advanced ROS1-positive non-small cell lung cancer (NSCLC) who had not previously been treated with a ROS1 tyrosine kinase inhibitor (TKI naïve). Taletrectinib shrank tumors in 57% of patients who had previously been treated with a ROS1 TKI (TKI pre-treated). Taletrectinib also showed robust intracranial activity in the subgroup of patients with disease that had spread to the brain.

Median progression-free survival (IRC-assessed) was not reached for TKI naïve patients and was 11.7 months for TKI pre-treated patients, respectively. Taletrectinib was generally well tolerated, and its safety profile was consistent with previous trials. The most common treatment emergent adverse events (TEAEs) were increased liver enzymes and gastrointestinal-related adverse events, the majority of which were Grade 1 or Grade 2. Incidence of neurological TEAEs were low; the most common was dizziness (13%), most of which was Grade 1.

"While people with other types of lung cancer have seen great advances, there has been limited progress for people with ROS1-positive NSCLC, which presents significant treatment challenges," said Maurice Pérol, M.D., TRUST-II trial investigator and Head of Thoracic Oncology at Léon Bérard Cancer Center, Lyon, France. "These interim TRUST-II data represent a significant step forward in the pursuit of better treatment options. Taletrectinib's overall profile suggests it has the potential to be the medicine people with ROS1-positive NSCLC have been waiting for."

"We now have consistent results from two Phase 2 trials with taletrectinib. In both trials, taletrectinib shrank tumors in almost every ROS1 TKI naïve person and more than half of people previously treated with a ROS1 TKI, and the responses were durable. Taletrectinib was well tolerated, which is extremely important as we work to extend the time people with advanced ROS1-positive NSCLC live without their disease getting worse," said Jerry Wang, PhD, Chief Executive Officer of AnHeart. "We anticipate reporting final data from TRUST-II next year, and look forward to making continued progress in our efforts to positively impact the lives of people living with lung cancer."

Results will be presented at the European Society of Medical Oncology Congress 2023 by Maurice Pérol, M.D., TRUST-II trial investigator and Head of Thoracic Oncology at Léon Bérard Cancer Center, Lyon, France on October 23, 2023 (abstract #1373P).

Taletrectinib has been granted Breakthrough Therapy Designations for the treatment of advanced or metastatic ROS1-positive NSCLC by both the U.S. Food and Drug Administration and the China National Medical Products Administration (NMPA).

About the TRUST-II Trial

TRUST-II (NCT04919811) is a global pivotal, multicenter, single-arm, open-label, Phase 2 clinical trial evaluating taletrectinib as a monotherapy in approximately 154 patients with ROS1-positive NSCLC and other solid tumors. Patients received 600 mg of taletrectinib once-a-day. Cohorts 1 and 2 of the trial are intended to be registrational and are evaluating taletrectinib in ROS1-positive NSCLC patients who have either not previously been treated with a ROS1 TKI (TKI naïve, n=53), or who have previously been treated with one approved ROS1 TKI (crizotinib or entrectinib, n=46), respectively. Cohorts 3 and 4 are exploratory and are evaluating taletrectinib in ROS1-positive NSCLC patients who have previously been treated with two or more ROS1 TKIs (n=35), or patients with ROS1-positive NSCLC or other ROS1-positive solid tumors who are ineligible for Cohorts 1 to 3 (n=20), respectively. Patients are being enrolled at sites in the United States, Canada, Europe and Asia.

Interim efficacy data for Cohorts 1 and 2 were reported from 46 patients who had approximately six months of follow-up at the data cut-off date of July 12, 2023.

• In ROS1 TKI naïve patients (n=25), 16% of whom had also previously received chemotherapy:
  • 92.0% of patients' tumors shrank in response to taletrectinib treatment (cORR as assessed by IRC)
  • Median duration of response and median progression-free survival were not reached
  • At 12 months, 89.5% of patients who responded to taletrectinib treatment were still responding
  • Taletrectinib shrank brain tumors in 80.0% of people whose cancer had spread to the brain (n=5; intracranial cORR as assessed by IRC)
• In patients previously treated with one ROS1 TKI (n=21), 52% of whom had also previously received chemotherapy:
  • 57.1% of patients' tumors shrank in response to taletrectinib treatment (cORR as assessed by IRC)
  • Median duration of response was not reached
  • At 12 months, 81.5% of patients who responded to taletrectinib were still responding
  • Median progression-free survival was 11.7 months
  • Taletrectinib shrank brain tumors in 62.5% of people whose cancer had spread to the brain (n=8; intracranial cORR as assessed by IRC)

Interim safety data from TRUST-II (n=107) showed the majority of TEAEs were Grade 1 or Grade 2. The most common TEAEs were increased liver enzymes (increased alanine aminotransferase: 64%; increased aspartate aminotransferase: 63%), diarrhea (43%), and nausea (43%), the majority of which were Grade 1 or Grade 2. Incidence of neurological TEAEs were low; the most common was dizziness (13%), most of which was Grade 1. Dose reductions and treatment discontinuations due to TEAEs were 34% and 2%, respectively. There were no treatment-related deaths.

More detailed results from today's presentation can be found on AnHeart's website at https://www.anhearttherapeutics.com/publications/.

For additional information about TRUST-II visit https://www.trust2study.com/.

About Taletrectinib

Taletrectinib is an oral, potent, brain penetrant, selective, next-generation potential best-in-class ROS1 inhibitor being evaluated for the treatment of ROS1-positive NSCLC.

AnHeart previously reported data from the Phase 2 TRUST-I trial (NCT04395677) evaluating taletrectinib in ROS1-positive NSCLC patients in China, which showed a cORR of 92.5% in ROS1 TKI naïve patients (n=67) and 52.6% in crizotinib pre-treated patients (n=38), respectively, as assessed by IRC. The majority of TEAEs were Grade 1 or Grade 2. A pooled analysis of TRUST-I and Phase 1 trials with taletrectinib showed median progression-free survival of 33.2 months and 11.8 months in ROS1 TKI naïve and crizotinib pre-treated patients, respectively.

About ROS1-positive NSCLC

More than one million people are anticipated to be diagnosed with NSCLC, the most common form of lung cancer, in the United States, Europe, China and Japan in 2023. It is estimated that approximately 1-2% of people with NSCLC in western countries and approximately 3% in China are ROS1-positive, meaning more than 22,000 people will be diagnosed with ROS1-positive NSCLC in these regions in 2023. There are two FDA approved first-generation TKIs for people with newly diagnosed advanced or metastatic ROS1-positive NSCLC and no FDA approved therapies for people whose ROS1-positive NSCLC has progressed following treatment with these medicines. Up to 35% of people newly diagnosed with metastatic ROS1-positive NSCLC have tumors that have spread to their brain (brain metastases), increasing up to 55% for those whose cancer has progressed following initial treatment.

About AnHeart Therapeutics

AnHeart Therapeutics ("AnHeart") is a global clinical-stage biopharmaceutical company developing novel precision therapies for people with cancer. Our lead investigational therapy, taletrectinib, is a next-generation ROS1-inhibitor currently in pivotal Phase 2 trials for ROS1-positive non-small cell lung cancer (NSCLC). Taletrectinib has been granted Breakthrough Therapy Designations by both the U.S. Food and Drug Administration and the China National Medical Products Administration. AnHeart's second investigational therapy, safusidenib, is a mIDH1-inhibitor being evaluated in a Phase 2 trial for IDH1-mutant glioma.

Our mission is to improve the lives of people with cancer. We are supported by leading life sciences investors and have built an organization with deep oncology drug discovery and development expertise, with offices in New York and Shanghai. For more information, visit https://www.anhearttherapeutics.com/ or follow us on LinkedIn at https://www.linkedin.com/company/anheart-therapeutics-official/.