Video Feature

Vol.19, November 2020

Takahiro Iwamiya and Kenichi Nogami

Co-Founders & CEOs
Metcela Inc.

Revolutionizing the Way We Treat Heart Failure

Developing a novel cell therapy for heart failure patients

Background and goals of the Company

Metcela is a venture company developing new regenerative medicine products for patients with heart failure. Once afflicted with heart failure, the disease gets increasingly worse and it is difficult to treat it with current medical procedures.

Therefore, we aim to cure patients with heart failure using special cells based on special heart fibroblasts. I discovered them when I was at Tokyo Women's Medical University between 2010-2014. These cells cannot only protect and proliferate heart muscle cells but also develop lymphatic vessels of the heart. This will improve the systolic function of the heart with restored mechanical properties of ventricular walls due to heart failure.

As a university researcher, I was initially thinking of providing these cells to patients with heart failure, but at the time I was a young researcher, so it was very difficult to get such huge research funding.

It was a big wall to overcome. In Japan, it is difficult for young researchers to obtain large funding to develop cell pharmaceuticals. I thought about starting up Metcela to attract funding from investors to develop our technology for treating heart failure. We worked together on this research in 2014 and since the beginning of 2014 thought about how to commercialize it. After about two years of preparation we launched the company. During those two years I talked with many investors, and of course applied for funding and was finally awarded 70 million yen before the establishment of the company.
We were able to launch the company to ease risk taking with the participation of investors in March 2016. At that time King SkyFront, including this Life Innovation Center was being developed and we also had an introduction from Kanagawa Prefecture, and decided to move at the same time as the company was established. This is how we came to King SkyFront and founded the company.

Features of the Research

First of all, I think it is important to ensure that the VCF we are developing can be delivered to patients with heart failure and to pass clinical trials. Next, heart failure is a disease that cannot be cured at present, but I have a dream of making it a general medical treatment and providing it to various patients as a matter of course.

Regarding Metcela itself. In the past, academia drive science, while companies drive business and seek economic rationality in their products. Of course Metcela is a company, but I would like to establish science and develop the company as a research and development venture, a hybrid of both. The biggest turning point in our vision is whether we can start clinical trials. Until now, it has been difficult for bio-ventures to enter clinical trials with only our company's patents and without a license from academia.

Metcela has a very deep basic research base and has accumulated enough scientific evidence to start clinical trials only using its own research and development. I wonder if this is a manifestation of our very big vision. The other is how to differentiate our business. We think that it will be necessary to launch four major business pillars underscoring our core competence. One is to firmly support the scientific basis of VCF technology. We want everyone in the world, pharmaceutical companies, and patients to understand why this is working.

Secondly, Metcela is also looking into regenerative medicine. We want to administer cells to patients that are taken from the patients themselves. Up until now, some people have thought that direct treatment in regenerative medicine is difficult due to the cost and differences in cells of individual patients. Metcela is taking on challenges from both a scientific and business perspective. We hope that people will understand that direct regenerative medicine is a very attractive approach, so as Metcela because we confront it seriously.

The third is that our company taking up the challenge of using of catheters. Since the heart is a moving organ it has been difficult to administer cells properly. In many cases, patients undergo thoracotomy to administer cells. Metcela has formed a very strong partnership with a company called Japan Lifeline to develop new types of catheters in collaboration with Tsukuba University. In that sense, Metcela not only develops cells but also formulates comprehensive approaches on administer them to patients. The third challenge is how to translate catheter development into clinical applications.

The final remaining challenge is how to accurately administer cells, and in our partnership, we are able to accurately observe the heart in real time and it is possible to administer cells to precise points where failure is occurring. There are few companies in the world that can achieve this, and this is a unique cell therapy that can be achieved only by our partnership with Japan Lifeline, with cells and application methods and resulting cell therapy. I think that it will be one of the strengths of Metcela. In order to achieve this Metcela is now establishing a subsidiary in the United States to expand overseas, so with the help of King SkyFront, we will firmly establish a global presence in Japan and overseas. I would like to proceed with the strategy.

Challenges

We have shown the medicinal effects of our cells to treat heart failure, but whether they can be manufactured at low cost is another problem. Regenerative medicine is generally expensive. Although our products use a raw material called fibroblasts, they are inevitably expensive because we must go through the process of culturing live cells and delivering them to patients.

In order to overcome this, it is necessary to automate the culture process and consider carefully using raw materials such as proteins to reduce costs. Although the effectiveness of our treatment was reported in September 2020 in PLOS ONE we also have other unreleased scientific results that we will report in high impact journals as well as patents. I also think that it is important to report such results at conferences. What I want most as a Metcela right now are talented people who find a solution on their own while conducting the research and development.

Solution discovery is important in the fundamental research as there is more flexibility. We already have people of many nationalities working at Metcela. We will continue to hire talented people globally to pursue the goals of our research and development. It is big theme for us to discover such human resources. Another issue is governance, especially for companies that start from basic research where if speed is prioritized then governance may be sacrificed.

The reliability of data submitted to the FDA and PMDA must be guaranteed, so the governance of the company must be enhanced. Metcela is about to undergo a major change; from a start-up to the company with social status. To say to patients that, "This cell is okay. It is safe. Please rest assured", it is extremely important to have strong governance in-house. I would like to focus on this point as a theme for the next three years.

Why I started the research

Regenerative medicine is a discipline that can provide new treatment methods for a variety of intractable organ diseases. The reason why I focused on heart disease was that my first impression of cardiomyocytes under the microscope is that they are cute because they contract by themselves. Heart related disease is the number 1 cause of death worldwide. The cells of the heart muscle do not divide after birth, so once you have heart failure, there is no cure. Being able to cure this with regenerative medicine and saving lives is socially important.

Current medical care for heart failure is very expensive, so developing this technology contribute to the reduction of social medical expenses. The first thing I learned during research and development of VCF was that our heart muscles can also re-undergo cell division. As I mentioned earlier, the heart muscles are cells that cannot divide after birth, but if we could regenerate such cells then it would be possible to treat infarcts of failure heart.

So I decided to start research on the development of VCFs for heart failure. The fibroblasts of the heart are said to be the cells that cause the onset of a disease called the heart fibrosis. The general scientific image of cardiac fibroblasts is that they are treated like villains such as cancer cells. However, we found that there are various types of cardiac fibroblasts, some of which are bad cells that cause fibrosis, but we found VCAM 1-positive cardiac fibroblasts that are special fibroblast and have a very important function in maintaining the homeostasis of the heart. The point of view is that their good functions had been overlooked for a long time, so I think this is unique and interesting.

How we met

Research at the start was difficult with only the funding available at the time. Especially in 2014 for in-vivo animal experiments to test effectiveness when administered to rat. There was a gap in the Kaken grant at that time, and it was difficult to do. While he was consulting with friends from his junior high and high school days, my name came up, and at that time I had been working in a major investment company that gave advice on investment and acquisitions for 6 and half years. We talked about the really innovative technology and its potential and eventually decided to work together as partners in the quest to treat heart failure.

Expectations for King SkyFront

We moved to King SkyFront in early 2016. It's an incredibly attractive place. At first, I rarely met people because there were not many people here. It was difficult to find a place to eat lunch, it was far from the station, and we encountered several problems. But now I have no problems. In many ways, the appeal of the location has increased dramatically, such as the shuttle bus connection to Haneda Airport in the near future.

That is why, as a start-up launched here, I'm really looking forward to more and more startups. I don't think it's necessary to be here from scratch, but I'd really like to see startups at various stages of development, some are about to get listed, or are already listed, for example. A community where you can exchange experimental equipment or learn from each other’s experiences. I think this will give rise to new synergies. We could introduce investors to each other, and procure funding at King SkyFront. I want it to be an ecosystem where startups can come and procure funding.

We hope that King SkyFront will be a major hub for bio-startups. In order to write patents, papers, and push the frontiers of science, I think we need a place to interact and concentrate. For example, a cafe where we can interact and concentrate on our work, it would lead to advancements in science of all companies at King SkyFront, and the development of King SkyFront as a whole.

I think that King SkyFront could be become an even more inspiring hub by strategic fusion of the infrastructure that already exists such as the fashionable hotel, park and greenery, and river nearby, with environments for scientists to think alone as well as relaxing spaces enabling scientists to interact and discuss their research and related ideas.