After successfully licensing out its GLP-1 pipeline to the emerging US biotech Hercules using the NewCo model for the first time in May last year, Hengrui Medicine has secured another victory by reaching a new overseas licensing cooperation.

01 NewCo again

Today (September 5), Hengrui Medicine reached an exclusive licensing agreement with Braveheart Bio, a US company, to license Braveheart Bio the exclusive rights to develop, produce and commercialize its independently developed cardiac myosin (Myosin) small molecule inhibitor HRS-1893 project globally, excluding mainland China, the Hong Kong Special Administrative Region, the Macao Special Administrative Region and Taiwan.
Under the agreement, Braveheart Bio will pay Hengrui Medicine an initial payment of US$65 million (consisting of US$32.5 million in cash and an equivalent of US$32.5 million in Braveheart Bio equity) and US$10 million in near-term milestone payments upon completion of technology transfer, for a total of US$75 million. In addition, Hengrui Medicine will receive up to US$1.013 billion in clinical development and sales-related milestone payments, as well as royalties on sales.

The HRS-1893 authorized this time is a Class 1 innovative drug independently developed by Hengrui Medicine. It is a highly selective small molecule inhibitor of cardiac myosin that can specifically inhibit the activity of cardiac myosin ATPase, normalize myocardial contractile performance, reduce left ventricular hypertrophy and improve diastolic compliance.

The drug is currently in Phase III clinical development for the treatment of obstructive hypertrophic cardiomyopathy (oHCM). It has previously been approved for clinical trials for hypertrophic cardiomyopathy, and its application for clinical trials for heart failure with preserved ejection fraction has also been approved. For this indication, no similar drug has been approved for marketing at home or abroad.

From the perspective of transaction model, this authorization continues Hengrui Medicine's NewCo model.

The NewCo model, or New Company model, involves licensing an innovative drug project to a newly established company focused on drug development and commercialization. This model leverages the strengths of both parties. Hengrui Medicine will leverage Braveheart Bio's overseas resources and channels to accelerate the development and commercialization of HRS-1893 overseas, while also generating substantial returns, including down payments, milestone payments, and sales commissions. Braveheart Bio, on the other hand, will acquire a promising innovative drug, enriching its product pipeline and expanding its presence in the cardiovascular field.

This licensing transaction not only generates substantial economic benefits for Hengrui Medicine, but also helps enhance its influence and brand awareness in the international pharmaceutical market, further promoting its innovative drugs globally and providing more treatment options for patients worldwide. It also demonstrates Hengrui Medicine's strong capabilities and international competitiveness in innovative drug research and development, as well as its mature experience in operating the NewCo model.

02 Drug Progress Analysis

Hypertrophic cardiomyopathy (HCM), a primary cardiomyopathy characterized by left ventricular hypertrophy, is the most common inherited heart disease and the leading cause of sudden cardiac death in adolescents and athletes. Epidemiological surveys show that the global prevalence of HCM is approximately 1 in 500, suggesting a significant global prevalence.

Currently, there is an unmet need for the treatment of hypertrophic cardiomyopathy.

Traditional treatments include medication and surgery, but these methods have limitations. Commonly used medications, such as beta-blockers and calcium channel blockers, can only alleviate symptoms to a certain extent and have limited effect on improving cardiac structure. Surgery carries a higher risk, and not all patients are suitable for surgery.

In recent years, with the in-depth understanding of the pathophysiological mechanisms of hypertrophic cardiomyopathy and the continuous advancement of drug development technology, significant progress has been made in the development of drugs for this disease.

Cardiac myosin inhibitors (CMIs) have attracted widespread attention as a new therapeutic drug. These drugs inhibit the activity of cardiac myosin, thereby reducing excessive myocardial contraction and improving diastolic function, bringing new hope for the treatment of hypertrophic cardiomyopathy.

According to Yaozhi data, there is currently only one drug with the same target approved for marketing in the world, namely Bristol-Myers Squibb's Mavacamten. The drug was approved by the FDA in April 2022 and approved for marketing in China in April 2024. It is used to treat adult patients with obstructive hypertrophic cardiomyopathy (oHCM) with NYHA heart function grade II to III. Its sales reached US$602 million in 2024, a year-on-year increase of 161%.

In addition, Aficamten tablets, jointly developed by Cytokinetics and Jixing Pharmaceutical, are also a second-generation cardiac myosin inhibitor. An application for marketing approval has been submitted in China. In December 2024, the FDA accepted Aficamten's marketing application for the treatment of obstructive hypertrophic cardiomyopathy (HCM), and the review progress is expected to be updated in 2025.

Hengrui Medicine's HRS-1893 is of great significance as the first domestically produced cardiac myosin inhibitor to enter Phase III clinical trials.

According to information recently disclosed by Hengrui Medicine at the 2025 European Society of Cardiology (ESC) Congress, the HRS-1893-101 (NCT07033455) study is a multicenter, randomized, double-blind, placebo-controlled Phase I study divided into four parts: Parts 1, 2, and 3 are studies in healthy subjects, and Part 4 is a multiple-dose escalation trial in subjects with oHCM. Part 4 enrolled subjects with oHCM and a left ventricular ejection fraction (LVEF) ≥ 60%, receiving a dose of 60 mg twice daily for 14 consecutive days.

HRS-1893-101 Part 4 Study Design
Image source: Hengrui Medicine official Weibo

A total of 8 subjects with oHCM were included in the study, of whom 6 were in the HRS-1893 group.

Safety: HRS-1893 was well tolerated by all oHCM subjects, with all adverse events in the HRS-1893 group being mild. No subject developed an LVEF <50% during the study.

Pharmacokinetics: After oral administration of 60 mg BID to oHCM subjects, the drug reached steady-state around the 8th day of administration. The peak concentration at steady-state and the accumulation index of the area under the curve within the dosing interval were comparable to those of healthy subjects, at 1.30 and 2.04, respectively.

Efficacy: HRS-1893 60 mg BID significantly reduced left ventricular outflow tract gradient (LVOT-G) levels in subjects with oHCM, reaching a nadir on day 5, with an average resting LVOT-G of 6.0 mmHg. Following the Valsalva maneuver, LVOT-G reached a nadir of 8.0 mmHg on day 5, both values falling below the oHCM treatment target (LVOT-G <30 mmHg) and maintained until the last dose.

Overall, HRS-1893 demonstrated a favorable safety profile in oHCM subjects, effectively reducing LVOT-G at rest and after the Valsalva maneuver, while maintaining LVEF within a safe range. If approved, it would become the first domestically produced cardiac myosin inhibitor.

Conclusion : Hengrui Medicine's overseas licensing of HRS-1893 to Braveheart Bio is another successful example of outsourcing under the NewCo model. This will generate substantial revenue for the company and provide strong support for the overseas development and commercialization of HRS-1893. The market for hypertrophic cardiomyopathy drugs holds broad prospects. With the continued advancement of HRS-1893 and other investigational drugs, we are expected to provide patients with more effective treatment options and address the significant clinical unmet need.

https://news.yaozh.com/archive/46012.html