Dr. Itzchak Angel, CEO of the Israeli stem cell company, Accellta, has more than 30 years of experience guiding the business development efforts of new and established companies across the Israeli pharmaceutical industry. Dr. Angel was formerly Vice President of R&D at Proteologics Ltd. and at D-Pharm Biopharmaceuticals. Before those positions, he served as the head of pharmacology in Synthelabo (now Sanofi) where he launched blockbuster drugs such as Xatral, Ambien and Mizollen into the marketplace.
Holding the position of CEO at Accellta, Dr. Angel now leads a team of executives and researches who are world-renowned experts at growing stem cells in suspension. What impressed me most during my time speaking with Dr. Angel is his ability to explain his company’s novel technology, as well as the potential breadth and depth of its applications within the marketplace. Between his vision and decades of experience, he has a profound ability to identify his company’s strengths and articulate a plan to bring forth its potential within the marketplace.
In this interview with Dr. Angel, we explore a range of fascinating topics, including Accellta’s strategies for penetrating the stem cell marketplace, technical strengths of the company, current licensing deals, new areas of business development, and a financing round that is now underway. We also discuss Accellta’s revolutionary stem cell culture technologies.
Without question, Accellta has introduced a paradigm shift to the stem cell marketplace, by quickly, efficiently, and cost-effectively growing massive quantities of clinical grade cells in xeno-free, feeder-free culture, utilizing methods of growing the cells in suspension.
Specifically, the company can increase a cell population from 1 million cells to 10 billion cells in two weeks with a bi-weekly change of media and an overall cost of about $3,000, by using bioreactors to do it in a very efficient way. Using traditional adherent culture, this would take about 70 liters of medium and an overall cost of $150,000, because it would take 40 to 50 days to do the expansion.
Accellta’s novel stem cell growth technologies are altering the use of stem cells for clinical and regenerative applications by providing large quantities of stem cells for high-throughput drug screening and development, providing source material for the use of stem cells within therapeutic applications, and supporting the exponential growth areas of 3D printing and bio fabrication.
I am also honored to introduce Accellta’s head of business development and intellectual property officer, Eran Cohen, in the second part of this interview.
To learn more about Accellta’s pioneering technologies for rapidly producing mass quantities of high-quality cells, enjoy this rare interview with Accellta’s CEO, Dr. Itzchak Angel (Part 1) and Head of Business Development, Dr. Eran Cohen (Part 2).
Interview with Accellta’s CEO, Dr. Itzchak Angel – Part 1
Cade Hildreth: How you did get involved with the Accellta and what is your background?
Dr. Itzchak Angel: I come from the pharmaceutical world. I am a biochemist by training. I got my PhD from Hamburg University in Germany, but spent many years in Paris as head of pharmacology at the Synthélabo (today Sanofi), where I took part in bringing several drugs to the market, including Ambien, Xatral, and Mizollen.
Initially, back in Israel, I started as VP of R&D at D-Pharm, and later continued as a consultant to several companies, including the Alfred Mann Institute at the Technion, which was within the founding nucleus of Accellta. At first I was a consultant, later a board member, and then I was a chairman. Today, I’m both the chairman and CEO of the company.
As I said, Accellta was established through the support of the Alfred Mann Institute at the Technion. The company was officially established three years ago, in November 2012. The company had its first round of financing (beyond the initial support of the Alfred Mann Institute at the Technion) only a year ago, through a Round A financing headed by Horizons Venture (the venture arm of Lee-Ka-Ching).
Accellta resulted from the fruits of more than 15 years of research carried out at the stem cell laboratories at the Technion. Pioneering work in the field of embryonic stem cells (ESCs) was carried out at the laboratories of Dr. Michal Amit, who is now Accellta’s chief technology officer (CTO). She was able to establish the requirements necessary to keep embryonic stem cells undifferentiated for long periods of time under various experimental and artificial conditions.
Cade Hildreth: What differentiates Accellta in stem cells in the market place?
Dr. Itzchak Angel: Accellta has developed several technologies, mainly aiming at growing stem cells in large quantities in suspension cultures, particularly in unlimited numbers. We have solutions to grow cells in suspension, in feeder-free, carrier-free conditions. This breaks the “glass ceiling” that had limited the expansion of stem cells beyond petri dishes or classic methods of feeder-dependent or support-dependent growth.
Accellta has a range of patents and intellectual property (IP) that enables the growth of stem cells in suspension, but also can differentiate stem cells in suspension. This is done in two different technologies where we can grow the cells either as single cells or as clumps in which the cells adhere to each other. Therefore, we can grow high densities of cells (>20 million cells/ml) in large vessels (bioreactors) that can be as large as 20 liters.
This is enables us to grow very large quantities of homogeneous populations of cells over long periods of time, while maintaining their differentiation status as pluripotent cells. We can also differentiate them into the desired type of cell.
Cade Hildreth: What are your goals in the next 3 to 5 years for penetrating the stem cell market with this new technology?
Dr. Itzchak Angel: Our technology enables large scale growth of cells. Therefore, we can provide cells for pharmaceutical industry research, as well as provide the regenerative medicine field with large quantities of cells. In comparison to traditional culture, we can do the same thing in a much faster and a more cost effective manner.
To give you some numbers, if we want to increase the quantity of cells from one million cells to ten billion cells, using traditional adherent culture it would take about 70 liters of medium and an overall cost of $150,000, because it would take about 40 to 50 days. Accellta can now do the same thing within two weeks with a bi-weekly change of media and an overall cost of about $3,000, because we can do it in bioreactors in a very efficient way.
Our view into the future is to explore and consolidate this technology toward new fields from what we’ve done so far. I didn’t mention it before, but we have already established seven licensing deals with key media distributors and developers that are selling their media based on our intellectual property (IP). This gives Accellta a reliable stream of income.
Now we are moving towards into new areas that involve cutting -edge science, areas that we believe will benefit the most from our technology. For example, this may include the field of bio fabrication, as we are very actively going into the fields of 3D stem cell printing and 3D stem cell weaving. We are already talking to several companies in the marketplace for collaboration. So, this is one direction in which we are going to expand.
Currently, we are in several MOU (“memorandum of understanding”) stage discussions with companies where we can custom make the cells to fit their specific needs by using our technologies and IP.
Cade Hildreth: Very interesting. If you move into the area of 3D stem cell printing, what type of impact do you expect that you could have?
Dr. Itzchak Angel: This is a very active area and we are starting to participate in it. Today, we have published that we can convert embryonic stem cells (ESCs) into beating cardiomyocytes and we can do this in suspension. Our view of the future is that we should be involved in creating a healthy beating heart for transplantation. In order to get there, we are doing different activities internally, as well as discussing potential collaborations.
We are now consolidating our knowledge of growing germ layer cells and progenitor cells into suspension. This is something which has not been achieved so far, but we want to be a key player there, because we believe that germ layer and progenitor cells, by using our suspension technology, could be the ink that could feed 3D printers that are being used to create tissue.
So, we are working to consolidate our technology and deepen our knowledge, understanding, and know-how, in order to support this growing field of 3D printing applications.
Cade Hildreth: Excellent. Can you speak more about the area of bio fabrication and opportunities that you see it presenting for Accellta?
Dr. Itzchak Angel: The field of bio fabrication is growing very quickly and we are seeing several different movements within in this field. I recently came back from a meeting that was held in Utrecht, Holland, where all the major players were present. There were interesting discussions about the field and several new developments.
In my opinion, it is not only the ink which is going to play a major role, but it is also the medium in which the cells are going to be embedded. The matrix and the scaffolding of the tissues will be important. Another issue that is important is the continuous supply of the cells. We believe that by using bioreactors we can offer a continuous supply of large quantities of cells.
We are now in discussions with several companies within the 3D printing area, some which are focused on bio-manufacturing and others that are involved with other 3D printing areas in which we have identified synergy. At this time I cannot speak further about this, but I hope that in the near future I will be able to tell you more.
Cade Hildreth: What types of partnerships or collaborations interest Accellta?
Dr. Itzchak Angel: At the present time, we have three types of collaborations. We have already established several partnerships and licensing agreements with media providers. This is something which gives us a very nice stream of income. This is something that we will aim to consolidate, as we advance and develop novel types of media and more sophisticated types of media. We are also getting into differentiation media. So, one arm is continuing these collaborations and the selling of the media.
Another type of partnership in which we engage are custom made collaborations with companies that wish to use our technologies. For example, we can provide companies with cells for clinical trials, where we eliminate their need for the use of feeder cells and can expand the cells in 3D to manufacture very large quantities of cells. We also equipped with the GMP facility here with cleanrooms, so we can manufacture GMP type materials for companies. Additionally, we are working and talking to companies so that we can provide them cells to create organoids (tissues on a well or on a chip) which they can use for drugs screening campaigns.
A third area in which we are interested in collaboration is 3D printing. Ultimately, we think that we could provide companies with specific custom made, or specific large scale kits, that could be used for a variety of uses, including regenerating medicine applications, as well as drug screening applications, toxicological studies, metabolism studies, and more.
Cade Hildreth: As far as your licensing deals for media providers, you have announced a major deal with Thermo Fisher Scientific, STEMCELL Technologies, and Miltenyi Biotec. Are you able to provide the identity of your other four (4) partnerships or is that confidential?
Dr. Itzchak Angel: Our licensing deals with those three companies have been presented publicly. In addition, we have a licensing deal with Ajinomoto, which has also been publicly announced. Ajinomoto licenses are for media in Japan. In their media packaging, they include a print-out saying, “this media is licensed from technology provided by Accellta.”
STEMCELL Technologies, Thermo Fisher Scientific, Miltenyi Biotec, and Ajinomoto, those are well known agreements.
On our website, you can also find that we have a deal with EMD Millipore and see other partnerships.
Cade Hildreth: To date, how has Accellta been funded? Were there founder funds, investments rounds, or other approaches that were used
Dr. Itzchak Angel: Yes. All together there has been about $3 million dollars invested in the company. The initial investors were the Alfred Mann Institute at the Technion and the Technion itself, and our Round A, that was led by Horizons Ventures which invested $1.9 million dollars. We are currently doing a financing round in order to raise an additional $10 million dollars, to enable further development in the areas that I was mentioning, such as germ layer and progenitor development and applications in the 3D printing area.
Although we are relatively young (3 years in this field is very young) we already have a nice flow off funds from existing licensing deals and we have several ongoing discussions that could markedly increase our resources. So, we think early stage venture funds and ventures funds already in this area will be interested in investing in our company.
Cade Hildreth: Do you see your location in Israel as being an advantage or disadvantage?
Dr. Itzchak Angel: Israel is a great place for innovation, novel developments, great ideas, and also synergies between types of innovation that come from related or unrelated fields. So whenever we want to develop something a little “outside of the box,” I think Israel offers very fertile ground and support to come up with these technologies.
However, having said that, Israel is not a big market by itself, and if we think about a potential exit in within few years like an IPO or an M&A, we would definitely need to expand our activities into Europe, the U.S., and Japan, because Japan has been playing a very important role in the stem cell field. So, we are actively looking at this potential expansion, but we would like to do it at the right stage.
Cade Hildreth: You know the capacity to manufacture stem cells that could be used in clinical trials?
Dr. Itzchak Angel: Yes indeed.
Cade Hildreth: Have you supplied stem cells for clinical trials today or is that an area you plan to move into?
Dr. Itzchak Angel: One of Accellta’s stem cell lines is currently being used in a clinical trial, and we are under negotiation with several companies to expand their cells into clinical type batches for future studies. Cells developed at Accellta will be used in many clinical trials.
Cade Hildreth: To date, Accellta has been relatively quiet to the press. Why have you chosen now to share information publically and do an interview?
Dr. Itzchak Angel: We are coming “on the radar” now because we have already consolidated many of the possibilities within the media field and analysis of our growth of income from the media field shows that this will continue to grow over the next few years. We think that in order for Accellta to be a key player and utilize its full potential, we need to think bigger. This idea brought us to get involved in novel markets, novels areas, and to change our business development approach.
It’s a question of maturity of the company, as well as financial maturity and better financial safety. This type of thinking would not be possible without the investment of licensee a year ago. It would also not be possible without the recent licensing deals that were signed four and six months ago.
Cade Hildreth: Are there any themes or trends in the stem cell market place that you see as benefiting Accellta?
Dr. Itzchak Angel: We are all excited and waiting to see how the induced pluripotent stem cell (iPSC) field is growing. Currently, it is mainly Japan that is playing the clinical part there and many companies are starting to look into it. I believe that consolidating this technology would enable us to markedly expand our technology, because speed would be the essence for the utilization of personalized cells for regenerative medicine.
I think our technology’s ability to grow huge numbers of cells within a very short period of time will provide key advantages. This approach provides a faster, safer, and more effective approach. In the future, we may be able to use this technology to replace sick or missing cells, or even all of a tissue or organ. So, we are looking forward to developments in this arena.
At the same time, as I said, the 3D printing and the whole area of biofabrication is growing exponentially. These advances imply that there will have to be changes from the current growth of stem cells in petri dishes to providing a constant supply of cells to feed those 3D printers. We think that we can provide the solution, which is to grow huge numbers of cells very quickly.
Cade Hildreth: One of the most impressive things that you have mentioned so far is that you can take 1 million cells up to 10 billion cells. For clarity, can you please summarize that cost and timeline again?
Dr. Itzchak Angel: Yes, indeed. We can do that within two weeks with just one liter of medium with bi-weekly changes and a cost of three thousand dollars.
One thing I didn’t mention previously is that we can have a very high density of cells. Usually, in a classic adherent culture, the optimum density of cells is around 1 million cells per milliliter. We can grow cells in density going beyond 40 million cells per milliliter.
So, we have changed from one petri dish, which has only a few milliliters of volume, to growing the cells in a high density which can go up to 20 liters at this time. Therefore, we can supply one single batch of clinical material, which would contain 400 billion cells in one batch. That’s unprecedented.
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