Keiichi Fukuda, CEO, Heartseed

As the 21st Century unfolds, heart failure is increasingly affecting people on a global level and becoming a pandemic problem as well. Despite the advances in cardiovascular treatment, cardiac disease has long been a leading cause of deaths worldwide with a higher death rate than most of the cancers. Though several treatment options including drugs and PCI are used to give certain relief to mild/moderate stage of symptoms,severe heart failure is still difficult to be addressed with these approaches.Heart transplants and ventricular assistive devices (VADs) are used to give significant improvement for severe heart failure. However, in this case, recipients are very limited and the cost of the operation and maintenance are quite expensive. This is when cardiac regenerative medicine has emerged as a ray of hope with its extraordinary potential to repair irreversibly damaged heart tissue.

Prof. Keiichi Fukuda, CEO, and Founder of Heartseed and Professor and Chair of Department of Cardiology, Keio University School of Medicine, has been the global leader of research on cardiac regeneration since the 1990s. One of Fukuda’s earliest achievements was the successful differentiation of cardiomyocytes from bone marrow stem cells in 1999 that made him the world’s first inventor of this method. This achievement stimulated researchers and opened the competition of cardiac research all over the world.

The Beginning of Heartseed

Prof. Fukuda realized that the biggest challenge of cardiac regeneration would be both efficiencies to differentiate into functional cardiomyocytes and purity of cardiomyocytes which influences therapeutic safety and efficacy. Thus, he started to develop the most rational method to manufacture cardiomyocytes applicable to a large scale. For its commercialization, Heartseed Inc. was established in November 2015 with the hope that cardiomyocytes will become the seeds of the heart, thereby saving patients with severe heart failure.

“Until now, by raising US $40Mil (record-breaking amount as a Japanese pre-clinical stage biotech) and attracting top-class talents, we have accumulated all the necessary preparation towards the starting of clinical trials in 2021,” asserts Fukuda.

Ground Breaking Products

Heartseed brings an innovative and unique portfolio of products. Its core asset, HS-001 is an transepicardial injection of allogeneic induced pluripotent stem cells (iPSC)-derived ventricular-specific highly purified cardiomyocytes. It could also be a therapy for severe heart failure with the mechanism that the transplanted cardiomyocytes engraft to the patient’s heart and are retained over a substantial period.

The pioneering company’s unique treatment mechanism is called ‘Remuscularization’, a treatment method that transplants and replenishes regenerated cardiomyocytes when the cells that the heart pumping have been weakened or lost due to diseases such as myocardial infarction. As the cardiomyocytes do not have a self-reproductive function and will continue to decrease after birth, Heartseed’s cells help to replace such cardiomyocytes and contribute to re-boot heart pumping function.

In the existent therapeutic approach such as the paracrine effect by mesenchymal stem cells, the transplanted cells survive for only 1-2 months after transplantation. Also, the cell sheet products are doubtful to achieve improvement as the thick lipid layer on the heart where the product is put on and the sheet does not electrically couple with the patient’s myocardium.    

However, Heartseed’s transplanted cardiomyocytes are expected to remain viable for a long period. The company’s special form of cardiomyocyte tissues (spheroids) can stay long and provides direct improvement to ejection fraction benefits.

Fukuda and his team, attempted a huge metabolic analysis to each of iPSCs and cardiomyocytes to find out the difference of energy metabolism. Glucose and glutamine are two key energy sources and both iPSCs and cardiomyocytes cannot survive without them. To their surprise, only cardiomyocytes can survive in without glutamine and glucose when lactate is suppremented. Based on this finding, they developed an innovative medium to only grow cardiomyocytes by adding lactate, but to only terminate iPSCs by removing glutamine and glucose from the medium. This technology achieved both below 0.001% detection of residual iPSCs and 99%+ purity of ventricle-specific cardiomyocytes.

“This level of purification has not been achieved by any other parties and we patented series of our technologies there internationally. Even the world’s top laboratories started to adopt our technologies to their cardiac regeneration research,” elucidates Fukuda.

This innovation gave Heartseed global competitiveness with Remuscularization MoA, the future goal of severe heart failure cell therapy.

He further adds, “Thanks to this technology, in August 2020, our research partner, Keio University successfully received Japan governmental approval to kick off to clinical trial targeting heart failure with dilated cardiomyopathy (DCM). It was firm evidence for our cells to expect both high standards of safety and potential efficacy.”

Creating a Niche in the MedTech Space

Under Fukuda’s indomitable leadership, today, Heartseed is the front runner in the global race in the clinical developments in Remuscularization MoA. In 2014, the Japanese government introduced special approval regulation to allow for conditional and time-limited approval of regenerative medicine if such products can prove safety and presumed efficacy without large- scale phase 3 trials. Furthermore, Japanese nations are homogenous and their HLA types can be easily matched. The success rate of the clinical trial can be raised by matching patients HLA and cardiomyocytes HLA for transplant.

Keeping this in mind, the company aims to secure real-world data in Japan. It also aspires to enlarge market presence globally by future pipelines such as HLA knockout type cell therapy and less-invasive infusion approach like a catheter. This strategy enables the earliest clinical development of marketing in major markets all over the world.   

Futuristic Strides

Heartseed’s mission statement is ‘open the door to the treatment of heart disease’, the world’s leading cause of death, with regenerative medicine. “We are taking on the challenge of clinical development and commercialization of a treatment method that has been considered technically difficult to develop even worldwide,” affirms Prof Fukuda.

As a researcher, the leader’s motto is ‘Never run away or take shortcuts’. His motivation to draw his own spool on fresh snow comes from his 25yr+ career as being a leading cardiac cell researcher. As a clinician in cardiology, he had seen lots of patients suffering from severe heart failure and dying from worsening symptoms for many years at Keio University Hospital. For this reason, he has kept engaging in the development of cardiac regenerative medicine technology with a desire to bring an innovative treatment for heart failure and the belief that ‘regenerative medicine is the only way to treat patients with heart failure’.

The ultimate vision of Heartseed is ‘Change the world via regenerative medicine’ and its first challenge is to establish Remuscularization therapy. As near term milestones, the company is expecting conditional approval in Japan until 2024 and US IND approval.  

In the long run, Heartseed aims to enlarge unique cell therapy pipelines more. “With this evolution ourselves, we hope we could contribute to the regenerative medicine industry to grow US$ multi-billions scale and also want the company to be located at the center in the future. We believe the power of regenerative medicine,” concludes Fukuda.