Inno Biopharma's Innovative Discovery in the 'Final Battlefield of Heart Disease' Offers New Hope for Heart Failure Patients

Heart failure remains an unmet medical challenge worldwide, often referred to as “the final battlefield of heart disease.” It is characterized by high incidence and mortality rates, as well as poor prognosis. Statistics show that the prevalence of heart failure reaches 20% among individuals aged 70–80 years, and 50% of patients die within five years after diagnosis. As China joins the ranks of aging societies, the number of patients with heart failure is expected to rise further.

However, there is currently a lack of truly effective treatments for heart failure. For end-stage heart failure, the most effective treatment is heart transplantation, but donor organs are often severely scarce, imposing a heavy burden on society and the healthcare system. Statistics show that heart failure patients are hospitalized an average of 2.4 times per year. Globally, annual spending on heart failure amounts to $108 billion, with hospitalization costs accounting for 60%–70% of total treatment expenses. In the United States, heart failure ranks as the leading contributor to overall healthcare expenditures.

Currently, the latest pharmacological treatments for heart failure primarily target downstream pathways following cardiac decompensation. These interventions, such as diuresis, inotropic support, and vasodilation, can alleviate heart failure symptoms to a certain extent and reduce the workload on the diseased heart. However, these therapeutic strategies have very limited efficacy in repairing damaged myocardium or reversing cardiac remodeling; they merely salvage myocardial cells that are not yet necrotic. For patients, the eventual progression to complete heart failure, accompanied by multi-organ failure and death, remains inevitable. This raises the question: Is it possible to achieve repair of ischemically injured cardiac tissue?

In an accidental experiment in the early 1990s, Professor Kang Yujian, Fellow of the American College of Toxicology, made a discovery that opened a new frontier in the treatment of heart failure patients. This groundbreaking research, spanning three decades, laid the foundation for the establishment of Innolife.

Innolife, established in 2014, is a company that hasTargeted Regulation of Gene Expression to Mobilize Cardiac Self-Repair and Reverse Pathological Myocardial Hypertrophy and Fibrosis for the Treatment of Heart Diseasea novel drug development company. The company’s core technology lies in promoting HIF-1-mediated angiogenesis in the injured area, remodeling the tissue microenvironment and releasing injury signals, thereby mobilizing autologous stem cells to home to the damaged myocardial tissue and induce myocardial regeneration, ultimately improving the structure and function of the failing heart. By “reconstructing the tissue injury signaling system and mobilizing the body’s intrinsic repair capacity,” it aims to achieve the therapeutic goal of autonomous regenerative repair of ischemically injured tissues by the body itself.

Professor Kang Yujian’s team has discovered that the correlation between copper ions and cardiomyocyte repair is associated with hypoxia-inducible factor-1 (HIF-1). HIF-1 serves as an upstream regulatory element in the body’s response to ischemia and hypoxia, a discovery for which its researchers were awarded the 2019 Nobel Prize in Physiology or Medicine. HIF-1 effectively improves blood supply and facilitates the repair of damaged myocardium through multiple mechanisms, including promoting angiogenesis, stimulating erythropoietin (EPO) production, mitigating ischemic and hypoxic injury, and recruiting stem cells.

Innolife utilizes low-dose INL1 (trientine hydrochloride) as a copper ion carrier to deliver targeted copper supplementation to the myocardium, thereby promoting HIF-1 expression (a novel mechanism of action). Previously, INL1 was approved for binding with copper to facilitate the excretion of excess copper ions from the blood caused by metabolic disorders. If the efficacy of INL1 in heart failure patients is confirmed, this discovery by Professor Kang’s team will be revolutionary.

Given the immense therapeutic potential,INL 1 has successively obtained the U.S. FDA Investigational New Drug (IND) approval and the clinical trial approval from China’s National Medical Products Administration (NMPA). It is currently being evaluated in the TRACER-HF study, a global multicenter Phase IIa clinical trial conducted simultaneously in China and the United States across 24 leading heart failure centers.

The Global Principal Investigator of this study is Professor James Louis Januzzi from Harvard University in the United States. The Principal Investigators in China are: Professor Zhang Jian, Director of the Key Laboratory of Clinical Research on Cardiovascular Drugs under the National Health Commission, Chairman of the Heart Failure Professional Committee of the Chinese Medical Doctor Association, and affiliated with Fuwai Hospital, Chinese Academy of Medical Sciences; Professor Zhang Yuhui, Secretary-General of the Heart Failure Professional Committee of the National Center for Cardiovascular Diseases Expert Committee, Director-General of the Heart Failure Professional Committee of the Chinese Medical Doctor Association, and affiliated with Fuwai Hospital, Chinese Academy of Medical Sciences; and Professor Yu Jing, Standing Committee Member of the Heart Failure Professional Committee of the Chinese Medical Doctor Association, Vice Chairman of the National Cardiovascular Disease Center Hypertension Specialized Medical Consortium and Director of its Gansu Center, and affiliated with the Second Hospital of Lanzhou University.

In late July this year, Innolife announced that the randomized, double-blind, placebo-controlled, global multicenter Phase IIa registration clinical trial evaluating the efficacy of INL1 in patients with heart failure and reduced ejection fraction (the TRACER-HF study) has been fully launched in both China and the United States. Following patient enrollment at multiple research centers in the United States, the first Chinese patient was successfully enrolled at the Second Hospital of Lanzhou University in recent days and completed the initial dosing without incident. Chen Xiaozhong, Founder and COO of Innolife, revealed to VCBeat that preliminary Phase II clinical data in humans have shownSignificant Efficacy Results Meeting Expectations, suggesting that INL1 may demonstrate superior efficacy compared to all existing standard heart failure therapies, positioning it as a revolutionary, breakthrough therapeutic agent with a novel mechanism of action.

Next, in China, the TRACER-HF study will be implemented at 11 leading clinical research centers for heart failure, including Fuwai Hospital of the Chinese Academy of Medical Sciences, West China Hospital of Sichuan University, and Peking University First Hospital.

In addition to conducting clinical trials of INL 1 for the indication of heart failure with reduced ejection fraction (HFrEF), Innolife has also received FDA approval to conduct exploratory clinical trials for all cardiac-related diseases, aiming to explore the broader potential of INL 1 in addressing currently intractable and fatal cardiac conditions, including myocardial fibrosis and pathological cardiac hypertrophy.

In addition, Innolife is also developing a drug for acute myocardial infarction and conducting research on a biomarker product, creating synergies with its existing development pipeline.

Dr. Kang Yujian, Founder & CEO of InnolifeHe wields considerable influence in academia. He is not only a Fellow of the Academy of Toxicological Sciences (USA) and Chairman of the Regenerative Medicine Research and Application Consortium (RMRACC), but also a recipient of the Albert Nelson Marquis Lifetime Achievement Award in the United States, as well as a Tenured Professor and Distinguished Scholar at the University of Louisville, USA. Professor Kang has undertaken numerous projects under China’s National Key Basic Research Program (973 Program) and National High-Tech R&D Program (863 Program), as well as key projects and major programs funded by the National Natural Science Foundation of China. He has been recognized by Elsevier as one of the “Highly Cited Chinese Researchers.”

Professor Kang’s team has made a groundbreaking discovery in the field of heart failure: an innovative mechanism that targets gene regulation to mobilize the heart’s self-repair capabilities, thereby reversing pathological cardiac hypertrophy and myocardial fibrosis. The foundation of Innolife lies in the accumulation and translation of Professor Kang’s team’s outstanding scientific achievements over more than three decades.

Chen Xiaozhong, Founder & COO of InnolifeWith a medical background, he previously served as a spine surgeon. His early frontline clinical experience has given him a profound understanding of patients’ clinical needs. Meanwhile, having navigated the industry for many years, he possesses keen business acumen in market assessment and extensive experience in mergers and acquisitions, new drug R&D and manufacturing, regulatory submissions, and new product certification.

Chen Xiaozhong has held multiple senior management positions, including General Manager of Woerwag Pharma GmbH & Co. KG’s China region and Investment Director of China Resources Pharmaceutical Group Limited. He is highly adept at building and effectively managing high-performing teams.

Dr. Li Gang, Vice President of InnolifeHe is a Doctor of Public Health (DrPH) candidate at Johns Hopkins University and holds an MBA from Renmin University of China. He has previously worked at renowned multinational pharmaceutical companies such as Johnson & Johnson, Pfizer, and Novartis, as well as at Yili Group, a major publicly listed company in China. Throughout his career, he has held senior leadership positions across multiple departments, including sales, marketing, medical affairs, market access and government affairs, and R&D. He has led and participated in the successful launch of several blockbuster drugs and their inclusion in the National Reimbursement Drug List. He possesses extensive experience in nutritional ingredient research, new product development, and conducting randomized controlled clinical trials.

During his tenure at Yili, Dr. Li Gang led the establishment of the “Yili Maternal and Infant Nutrition Research Institute.” During his time at Novartis, he spearheaded the strategic transformation of Novartis’s cardiovascular team and was a key member responsible for driving the launch in China of Entresto® (sacubitril/valsartan sodium tablets), the blockbuster heart failure medication.

Innolife’s global multicenter clinical research advisory team also boasts a stellar lineup of experts, including Dr. John Cleland, former Chairman of the Heart Failure Association of the UK; Dr. Gary Michael Felker, Director of the Duke University Heart Center; Dr. Javed Butler, a renowned U.S. expert in heart failure and diabetic cardiomyopathy; and Dr. Jian Zhang, Deputy Director of the National Clinical Research Center for Cardiovascular Diseases and Chairman of the Heart Failure Professional Committee of the Chinese Medical Doctor Association.

At the 2021 European Society of Cardiology (ESC) Annual Congress held on August 27, 2021, the results of the EMPEROR-Preserved trial were announced, ending the era in which no medication had been shown to clearly improve outcomes for heart failure with preserved ejection fraction (HFpEF) in randomized controlled trials (RCTs). The study was simultaneously published in the prestigious medical journal The New England Journal of Medicine, in which it was co-firstProfessor Javed Butter, first author, as well as Professor James L. Januzzi and Professor Zhang JianAll are members of the Innolife advisory team.

Following the release of the landmark results from the EMPEROR-Reduced trial, an article published in the European Journal of Heart Failure outlined the rationale behind the study design, noting:“The role of SGLT2 inhibitors in the long-term prognosis of patients with heart failure cannot be explained by their traditional diuretic and glucose-lowering mechanisms.”Shruti S Joshi, in a review published in the prestigious journal The BMJ in 2021, argued that:“Non-traditional mechanisms of SGLT2 inhibitors, such as upregulating the expression of hypoxia-inducible factor HIF-1, may be the true reason for improving heart failure prognosis.”This is precisely the core mechanism of action by which Innolife’s INL1 treats heart failure. Compared with SGLT2 inhibitors, INL1 exerts more direct and potent pharmacological effects, suggesting the potential for superior clinical outcomes.

Unbeknownst to us, Innolife has already grown through seven “spring, summer, autumn, and winter” cycles.

As the team continues to expand, the company keeps growing, and the pipeline advances steadily, the one constant remains the core team’s original commitment to making tangible contributions to the heart failure field, where there is a significant unmet clinical need. With the smooth progress of the INL 1 clinical trial and the acquisition of encouraging clinical data, the Innolife team is moving closer to its initial vision.

Every day may bring countless difficulties and trials. It is hardly surprising that many people find the high pressure of entrepreneurship unbearable, often remarking that “starting a business is arduous.” Chen Xiaozhong, however, holds a different view. He prefers to regard entrepreneurship as a journey of spiritual refinement, with the ultimate goal of developing drugs that truly address clinical needs for patients.

“Therefore, I am not overly concerned about clinical outcomes. In drug development, I believe that as long as we identify the right direction and work diligently, other factors are less critical. If a drug possesses substantial intrinsic value, I am confident it will ultimately succeed in reaching the market,” said Chen Xiaozhong.

As an investor behind Innolife,Wang Haining, Founding Partner of Longmen CapitalHe expressed his recognition of the therapeutic area in which Innolife operates, as well as his hopes for the company’s future development: “Heart failure is a chronic disease that modern medicine has yet to effectively conquer. Innolife is one of the few small-molecule novel drug developers we have invested in. When participating in Innolife’s Series A financing, we were impressed by its in-depth mechanistic studies and outstanding animal data. Although we recognize that there is still a long road ahead before achieving clinical efficacy and regulatory approval, we are willing to take certain risks in the heart failure field given the exciting new pathway involving HIF-1. We look forward to INL1’s clinical trials delivering pleasant surprises.”

Longmen Capital is a specialized venture capital firm in the pharmaceutical industry, focusing on early-stage and growth-stage investments in innovative pharmaceuticals and biotechnology. The team members possess interdisciplinary educational backgrounds in medicine, pharmacy, biology, and finance, along with extensive experience in pharmaceutical venture capital and industry operations. Since its establishment in 2017, Longmen Capital has invested in more than 30 innovative pharmaceutical companies, with assets under management nearing RMB 3 billion.