AnHeart Therapeutics is developing a portfolio of precision oncology therapies. Chief commercial officer and co-founder Lihua Zheng outlined the company’s strategy in response to emailed questions.
Why did you start this company?
Lihua Zheng
Founded in 2018, AnHeart Therapeutics is a New York-based clinical-stage global biopharmaceutical company developing a broad range of novel, next-generation precision oncology therapeutics in areas of significant unmet medical need where patients have few options.
I co-founded AnHeart with Dr. Junyuan (Jerry) Wang, CEO, and Bing Yan, MD, Chief Medical Officer, to address the unmet medical needs of cancer patients.
We want to use our work experience in the biopharmaceutical field to develop medicines that change the lives of patients. Our lead asset, taletrectinib, a next-generation ROS1 inhibitor, is currently in Phase 2 first- and second-line trials in ROS1 fusion-positive non-small cell lung cancer (NSCLC).
Our pipeline also includes AB-218, an mIDH1 inhibitor in Phase 2 trials in low-grade glioma, cholangiocarcinoma, and other tumors, and AB-329, an AXL inhibitor in Phase 1 studies with Checkpoint Inhibitor or chemotherapy combination for non-small cell lung cancer and other solid tumors.
What needs are you seeking to address in healthcare?
Develop drugs for cancer patients who need better options, as well as therapies that can address drug resistance and penetrate the blood-brain barrier. Drug resistance and brain metastases are common in lung cancer, and most drugs have no effect on drug resistance, cannot penetrate the blood-brain barrier, and are therefore ineffective.
That’s why we’re excited about our pipeline of precision oncology treatments, starting with our lead asset, taletrectinib, a first-in-class next-generation ROS1 inhibitor.
What does your lead product do? How does it work?
Taletrectinib is a first-in-class, next-generation ROS1 tyrosine kinase inhibitor (TKI). It is a brain-penetrating, potent and selective ROS1 inhibitor for patients with solid tumors with ROS1 fusion mutations.
ROS1 oncogenic fusions occur in approximately 1-2% or approximately 20,000 NSCLC patients worldwide each year. These rare mutations are also observed in several other cancers, such as cholangiocarcinoma, glioblastoma, ovarian, gastric and colorectal cancers.
After crizotinib treatment, the incidence of CNS metastases at diagnosis in patients with ROS1 fusion-positive NSCLC ranged from about 20% to 30% to 50%.
The first-generation ROS1 tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have received US FDA approval for advanced ROS1 fusion-positive NSCLC.
There are currently no FDA-approved drugs for patients who are unresponsive or resistant to these first-generation ROS1 inhibitors. Unfortunately, resistance to first-generation ROS1 inhibitors will eventually develop on targeted resistance, such as the acquired ROS1 G2032R solvent-front mutation, one of the most common mutations in therapy resistance.
Taletrectinib has demonstrated clinically meaningful efficacy and safety in patients with ROS1+ NSCLC in Phase 1 studies in the United States and Japan and the ongoing Phase 2 TRUST study in China (NCT04395677).
Taletrectinib can overcome crizotinib resistance and cross the blood-brain barrier. It has demonstrated significant clinical activity against the ROS1 G2032R resistance mutation and intracranial central nervous system (CNS) metastases in the ongoing Phase 2 TRUST study in China (NCT04395677).
The compound has been reported to have a strong safety profile in patients with ROS1 fusion-positive NSCLC. Selective inhibition of TRKB by ROS1 by tatratinib (Nature Communications 2019) contributed to a significant reduction in CNS adverse events associated with TRKB.
Is this your first healthcare startup? What is your background in healthcare?
This is my first healthcare startup. I am a trained scientist and lawyer. As a scientist, I studied human genetics first at Baylor College of Medicine and then at Columbia University Medical Center. As a lawyer, I first practiced in a large New York law firm before founding and leading a boutique New York law firm specializing in venture financing and intellectual property transactions. I started my legal career helping biotech companies go public and realized that I really wanted to be involved with biotech companies, not as a consultant.
What is your company’s business model?
We are pursuing outsourcing licensing opportunities for our pipeline and plan to commercialize our lead candidate ourselves.
Is your product clinically proven?
We recently received NMPA Breakthrough Therapy Designation in China based on the results of our Phase 2 TRUST trial in patients with ROS1 fusion-positive NSCLC treated with tatratinib.
Confirmed objective response rate in the crizotinib-naïve patient group (n=21), according to data presented at the Chinese Society of Clinical Oncology (CSCO) 2021 Annual Meeting (cutoff date: June 16, 2021) (ORR) was 90.5% (19/21) and disease control rate (DCR) was 90.5% (19/21). In the crizotinib-pretreated group of patients (n=16), the confirmed ORR was 43.8% (7/16); the DCR was 75.0% (12/16).
In addition, tatratinib showed promising efficacy in crizotinib-resistant G2032R-mutated patients, with intracranial antitumor activity in patients with brain metastases and few neurological adverse events. Taletrectinib was well tolerated, with treatment-related adverse events mainly including gastrointestinal adverse events and reversible aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations.
What stage of development is your lead product at?
Our lead compound is currently in Phase II development. We have other assets in our pipeline in early stages of clinical development.
Any additional comments?
We recently raised $61 million in a Series B round led by new investor Octagon Capital, with participation from Innovent Biologics, Cenova, Laurion Capital and Sage Partners last December. Since our inception in December 2018, we have raised a total of $100 million in gross proceeds through private financing.
Contact the company, email: lzheng@anhearttherapeutics.com
Photo: Peshkova, Getty Images
