AnHeart Therapeutics is developing a pipeline of precision oncology therapeutics. Chief Business Officer and Co-founder Lihua Zheng provided an overview of company’s strategy in response to emailed questions.
Why did you start this company?
Lihua Zheng
AnHeart Therapeutics was founded in 2018, and is a New York-based clinical-stage global biopharmaceutical company developing a broad pipeline of novel, next-generation precision oncology therapeutics in areas of significant unmet medical need, where patients have little to no options.
I co-founded this company with AnHeart CEO Junyuan (Jerry) Wang, Ph.D., and Chief Medical Officer, Bing Yan, M.D., to address an unmet medical need for cancer patients.
We wanted to leverage our work experience in biopharma and develop drugs to make a difference in patients’ lives. Our lead asset, taletrectinib, is a next-generation ROS1 inhibitor currently in Phase 2 trials for the first-line and second-line ROS1 fusion positive non-small cell lung cancer (NSCLC).
Our pipeline also includes AB-218, a mIDH1 inhibitor in Phase 2 trials for lower grade glioma, cholangiocarcinoma, and other tumors, and AB-329, an AXL inhibitor in Phase 1 studies to be used in combination with checkpoint inhibitors or chemotherapy in NSCLC and other solid tumors.
What need are you seeking to address in healthcare?
To develop drugs for cancer patients who need better options, and also therapies that can address drug resistance and penetrate the blood-brain barrier. Drug resistance and brain metastasis are common occurrences in lung cancer, and most of the drugs aren’t effective since they are not active against drug resistance and can’t penetrate the blood-brain barrier.
That’s why we’re excited about our pipeline of precision oncology therapeutics, beginning with our lead asset, taletrectinib, a best-in-class next-generation ROS1 inhibitor.
What does your lead product do? How does it work?
Taletrectinib is a best-in-class next-generation ROS1 tyrosine kinase inhibitor (TKI). It is a brain-penetrant, highly potent and selective ROS1 inhibitor for patients with solid tumors that have ROS1 fusion mutations.
ROS1 oncogenic fusions occur in ~1-2% of or about 20,000 NSCLC patients each year worldwide. These rare mutations are also observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers.
The incidence of CNS metastasis in ROS1 fusion-positive NSCLC patients at the time of diagnosis range from 20% to mid-30% to as high as mid-50% range, post-crizotinib treatment.
First generation ROS1 tyrosine kinase inhibitors (TKIs), crizotinib and entrectinib, have received U.S. FDA approval for advanced ROS1 fusion-positive NSCLC.
There are currently no FDA approved drugs for patients who do not respond to these first generation ROS1 inhibitors or have treatment resistance. Resistance to first-generation ROS1 inhibitors unfortunately will ultimately occur with on-target resistance such as with acquired ROS1 G2032R solvent front mutations, one of the most common treatment-resistant mutations.
Taletrectinib has shown clinically meaningful efficacy and safety profiles in ROS1+ NSCLC patients in phase 1 studies in the U.S. and Japan as well as in the ongoing Phase 2 TRUST study (NCT04395677) in China.
Taletrectinib can overcome crizotinib resistance and cross the blood-brain barrier. It has notably demonstrated clinical activity against ROS1 G2032R resistance mutation and intracranial activity against central nervous system (CNS) metastases in the ongoing Phase 2 TRUST study (NCT04395677) in China.
The compound has reported a strong safety profile in ROS1 fusion-positive NSCLC patients. The selective inhibition of ROS1 over TRKB by taletrectinib (Nature Communications 2019) helps significantly reduce TRKB-related CNS adverse events.
Is this your first healthcare startup? What’s your background in healthcare?
This is my first healthcare startup. I’m a scientist and an attorney by training. As a scientist, I studied human genetics first at Baylor College of Medicine and then at Columbia University Medical Center. As an attorney, I first practiced at a big law firm in New York, and then founded and led a boutique New York law firm specializing in venture financing and intellectual property transactions. I started my law career helping biotech companies go public, and realized I really wanted to be involved at a biotech company, instead of acting as an advisor.
What is your company’s business model?
We are pursuing both out-licensing opportunities for our pipeline, and also plan to commercialize our lead candidate ourselves as well.
Do you have clinical validation for your product?
We recently received NMPA Breakthrough Therapy Designation in China, which was based on results from our Phase 2 TRUST trial of ROS1 fusion-positive NSCLC patients treated with taletrectinib.
According to the data presented (cut-off date: June 16, 2021) at the Chinese Society of Clinical Oncology (CSCO) 2021 Annual Meeting, in the crizotinib treatment-naïve patient group (n=21), the confirmed objective response rate (ORR) was 90.5% (19/21) and the disease control rate (DCR) was 90.5% (19/21). In the crizotinib pre-treated patient group (n=16), the confirmed ORR was 43.8% (7/16); and the DCR was 75.0% (12/16).
In addition, taletrectinib showed promising efficacy in patients with crizotinib-resistant G2032R mutation, intracranial antitumor activity in brain metastatic patients with few neurological adverse events. Taletrectinib was well-tolerated and treatment-related adverse events primarily included gastrointestinal adverse events and reversible aspartate aminotransferase (AST) and alanine aminotransferase (ALT) increased.
At what stage of development is your lead product?
Our lead compound is in Phase 2 development right now. We have other assets in our pipeline which are earlier-stage in clinical development.
Any additional comments?
We recently raised $61 million in Series B financing round led by new investor Octagon Capital, with participation from Innovent Biologics, Cenova, Laurion Capital, and Sage Partners last December. We’ve raised a total of $100 million in gross proceeds in private financings since inception in December 2018.
To contact the company, email: lzheng@anhearttherapeutics.com
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