Harnessing the Innate Immune System By Developing Three Types of iPSC-Derived Natural Killer Cells With Daniel Teper

 

Companies in the biotech space are making contributions to help find a cure for cancer. Today’s guest is no exception. In today’s episode, Ammon Rivera sits down with Daniel Teper, Co-Founder and CEO of Cytovia Therapeutics, to talk about the unique technology they’re using to develop a treatment for cancer. Daniel discusses how they’ve developed three types of iPSC-Derived Natural Killer Cells and are now targeting unmet needs in treating hepatocellular carcinoma (HCC). There is a lot of disruptive innovation coming from the biotech industry. Daniel also discusses how the field is dealing with worsening market conditions amidst recent news of a special purpose acquisition with Isleworth Healthcare Corporation. There’s much to learn from this episode, both in medicine and economics.

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Harnessing the Innate Immune System By Developing Three Types of iPSC-Derived Natural Killer Cells With Daniel Teper

I am personally grateful that you’re here and tuning in to the show. If this is your first time stopping by, thank you for doing so. Please don’t hesitate to go back and read some of the earlier episodes of the show. If you’ve been a time reader of the show and you haven’t reached out to me on LinkedIn yet, I encourage you to do so. You can find me under @AmmonRivera. Shoot me a connection request. You can go on there and like our page, @BioTechIQ on LinkedIn, where we post different types of content, video updates, and short clips of some of the episodes so that you can have some more information out there to consume.

Our guest is Daniel Teper, the Co-Founder, Chairman, and CEO at Cytovia Therapeutics. He brings with him a long history here in the industry, having been a founder, board director, CEO, and chairman of multiple different biotech companies. Going a little further back, he completed a PharmD at the Université Paris-Saclay. He also completed an MBA with INSEAD. He brings with him a long history here in the industry to Cytovia.

Cytovia Therapeutics is a biotech company. They were formed in 2019. They’re building a portfolio of products that harness the power of NK cells. We’ve heard a lot about natural killer cells in the past. They are targeting the treatment of cancer. Daniel will explain to us what it is that they are doing that makes their technology unique.

To give you a quick explanation here, their core technology is a gene-edited allergenic CAR-NK cell produced from iPSCs and NK engager multi-specific antibodies. Their therapeutic pipeline includes both hematological malignancies, such as multiple myeloma, and solid tumors, including hepatocellular carcinoma and glioblastoma. Without further ado, I will let you get to the episode. Thank you so much for stopping by and for being here. Don’t forget to like subscribe, share, or leave us a review. I do my best to go and read every single review that is left on the show. I do value the opinion of the readers of the show. Let’s roll.

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Welcome to the show, Dr. Daniel Teper.

It’s nice to meet you.

It’s nice to meet you as well. There are a lot of exciting things happening with Cytovia Therapeutics. I’m excited to get into discussing those and learn a little bit more about you.

I’ve dedicated my professional life to the biopharmaceutical industry. A good part of that career has been on and around cancer and immunology. I started early in my career at Novartis in Basel and I worked on transplant drugs. In the last years, I work primarily on immunology for autoimmune diseases as well as cancer. The opportunity to start Cytovia in one of the most exciting phases of the development of a cell therapy for cancer has been exciting. It’s only the beginning, but it’s accelerating.

 Before we get into that, let’s talk a little bit about your background. What was it that inspired you to study what you did and to end up where you’re at?

I studied Pharmacy and have a Doctorate of Pharmacy. I had a general interest in Medicine and Pharmacology, but I wanted to have an impact on the industry. I went to business school and then joined Novartis. At the time before it was Novartis, it was Sandoz in Basel and then in the United States. I’ve gone back and forth between drug development and the commercialization of drugs in the United States, as well as internationally. I’ve been on and off and also in entrepreneurial ventures. This new venture, Cytovia, which we formed is probably the most exciting venture adventure that has been involved.

 

 Tell me a little bit about the genesis of Cytovia. Where did this all start? How did you discover what you did?

Being in the field of oncology and immunology, you have a constant dialogue with scientists and clinicians. We saw the emergence of cell therapy over the last several years, particularly with the CAR T-cells, which came to markets around 2017 with companies like Kite and Juno, which were acquired respectively by Gilead and Celgene, two Nobel Prizes. The first one was in 2012 on induced pluripotent stem cells, and then in 2020 on CRISPR gene editing. There’s a lot of activity, but rapid translation from fundamental science into the clinic.

You’re looking for the next trends. The next trend in 2019 was to look at the innate immune system and particularly natural killer cells, and identify what were the technology and products that would be the most appropriate to start a new biotech company. We formed a number of alliances with an academic institution and other biotech to assemble the core technology and built the initial inner product pipeline.

We were a virtual company and now we’re 40 people. The majority are in Natick, Massachusetts. The researchers were headquartered in Aventura, Florida, North of Miami. We have a cell manufacturing facility in Puerto Rico. We are a fully integrated biopharmaceutical company. We’re ready to become a clinical-stage company in early 2023. 

You’re well on track to do that. I’m glad to know you’re leveraging some of what Puerto Rico has to offer. Let’s talk a little bit about some of the data then released here on Cytovia. We talked about the genesis of the company. You’re focused on your lead asset or indication, hypnotic cell carcinoma, hard-to-treat cancer. What makes your technology or approach different than the other companies developing NK killer cells and all that?

First of all, although we’re leveraging cutting-edge technologies, our primary focus is clinical. When you asked me about my background, I can also say the background of the rest of the management team. We have experience in translating science into clinical development and commercialization. Rather than just being focused on the technology and our technologies that are state-of-the-art, our focus was to identify unmet medical needs that we could address with our technology.

Assembling the GPC-3 with our ability to engineer the cells and the antibody is giving us a potential solution to the unmet medical need in HCC. Click To Tweet

If you take liver cancer, hepatocellular carcinoma is 90% of the liver cancer. There are 700,000 patients with HCC worldwide. Half of them are in Asia, particularly in China and Japan. The treatments are not satisfactory. The advances in treatment that use checkpoint inhibitors get only under 30% of partial response and 6.8 months of progression-free survival. It is better than chemotherapy that was used in earlier days, but it’s still not satisfactory.

We identified this as a therapeutic focus and match it with what we had. We have a two-platform technology. One is NK cells derived from induced pluripotent stem cells. Remember, I talked about the Nobel prize from 2012. The other one is multi-specific antibodies that we direct NK cells to kill the tumor cells. The question is, “How do you target the hepatocellular across HTC cells?” There’s a marker called GPC3, which is expressing over 80% of the HCC cells. We license an antibody from the National Cancer Institute here in the United States that specifically targets GPC3. Assembling the GPC3 with our ability to engineer the cells and the antibody is giving us a potential solution to the unmet medical need in HCC.

The differentiation between this and other companies that are maybe focused on pluripotent stem cells and developing those into NK cells. Help us understand a little bit more about what it is that sets your approach technology apart from another company’s technology?

It’s the choice of the indication. We’re the only company among those that have iPSC technology that focused on liver cancer. In the United States, there are only four companies that focus on iPSC technology for cell therapy. Two of them are public, Fate and Century, and the other two are Shoreline and Cytovia. There are only a handful of companies that master the process of development to go from stem cells into immune cells, specifically, NK cells. That’s one thing.

There are plenty of cancer indications that we can go after. We selected some that are different from our competitors. The other difference is that we’re the only company that has both the antibody technology that allows redirecting the NK cells toward the cancer cells and the NK cells. Why is that important? In the rapid progression, autologous CAR T is taking the patient’s cells, sending them to the lab, engineering, sending them back, and re-injecting them to the same patient. The next generation is donor-derived. The third generation, which was one of the few companies, is iPSC.

The cells by themselves have an effect. If you combine them with the antibody, you have more of an effect. Why is that? In patients that have cancer, NK cell is the innate immune system. There are the natural cells that are killing the foreign invaders. In cancer patients, the number of functional NK cells decreases quickly. If you have an antibody that targets the NK cells and the tumor cells, they’re missing the soldiers to kill the cancer cells. By adding the cells to the antibody, you’re maximizing the effect.

 

There are only a couple of companies that I’ve experimented with that in the clinic. At the American Association of Cancer Research, one of those companies showed that combining the antibodies and the cells gave close to 100% response versus only 30% with the antibody alone. It’s a significant advance in cancer treatment because so far, we’re the only company with the two technologies. We have a competitive advantage to evaluate this combination.

You mentioned some of the other companies. You announced that you’re going to be taking the company public through a merger with SPAC.

It’s a merger with a Special Purpose Acquisition Corporation called Isleworth Healthcare Acquisition. Why did we do that? First of all, the majority of our direct competitors are public companies. Even if they’re in the late preclinical stage or early clinical, the reason they’re a public company is that there is more capital available for public companies than from private companies.

That being said, the financial markets in general and the biotech financial market, in particular, have been challenging in the last several months. The index is significantly down and the IPO market is frozen. How do you become a public company? Becoming a public company through a merger with a SPAC is one of the potential avenues to get to our goal.

You would say, “Isn’t that risky to become a public company in the moving waters of the financial markets?” The answer is no because we have a long-term view. We’re not concerned about the markets going up and down on a weekly or monthly basis. We’re concerned about building value over time. We know and have seen that if you have good data and you’re a public company, the market is responding. Even in a bad market, the market is responding to a level that allows you to raise more capital.

What drove us into doing this transaction is the ability now and in the future to raise more capital to accelerate the development of the company. We were lucky to meet partners that are not just financial operators. They’re entrepreneurs and corporate executives. They have a complementary experience to our team. They like to say that they have a high deal IQ. They’re real partners. We all want to build a company that will address the challenges of cancer therapy and toward a cancer cure in a sustainable way. It is not just a financial plan.

There's also a phenomenon where most of the innovation is coming from biotech companies rather than from big pharma. Click To Tweet

I find this market that we’re in interesting because stocks are generally down. You’re talking about the freeze, new IPOs, and how we take a company public in this environment that we’re in. I love how you explained that in the strategy that you’re taking there. I was reading an article on GOBankingRates.com. They were talking about biotechnology, in general, being the second entry with the largest amount of growth projected, at least according to this article.

They talk about how the global biotechnology market forecasting to reach $2.44 trillion by 2028. That was interesting because I understand by financially looking at things. There is a bit of stagnation and freeze going on in some places. Even with that happening, there’s still so much potential for what biotechnology can do. We’re talking about your company here and how it’s so focused on this area that has a massive unmet medical need, 700,000 people worldwide. It’s an exciting time, but also interesting.

There’s also a phenomenon where most of the engine in the innovation is not coming from biotech companies but rather from large pharma. We have a lot of corporate development, merger, and acquisition activity, which drives the value of the innovative biotech companies significantly. You also have a general phenomenon with generic drugs being available for most common conditions. The industry is focusing on disruptive innovation.

That’s why you see transactions between big pharma and relatively early-stage companies at high values. This is what they need to sustain their growth. The big pharma companies are hundreds of billions of dollars in market cap. When they lose 90% of the revenues at patent expiry, they need revenues to replace. That’s coming increasingly from family innovation.

I’ll give you two examples. In the multiple myeloma market, there are 100,000 patients with multiple myeloma. It was relatively sleepy for many years until biologics and cell therapy came. Now it’s over $20 billion in value. The majority of that value is coming from disruptive biologics. We think that a market like hepatocellular carcinoma has the potential to see a similar transformation over the next years with novel treatments becoming available.

In the last few years, there’s been quite a bit of cash that was infused into markets across the board here. We’ve got all these things going on. We’ve got inflation, war, and some uncertainty going on. Do you think that the biotech companies generally are still pretty well-positioned financially? Do you think you’re going to start seeing companies shrinking their force, not really focusing on growth because there’s not enough cash available? Do you think they’re still sitting on that money that they got within the last few years?

 

Unfortunately, a high percentage of biotech companies have less than a year of cash. That’s concerning for any CEO. If they are public, even if it’s challenging, there’s always an option to raise capital. If they’re private, it’s much more challenging. We anticipate that there will be some level of consolidation, not just acquisition by the big pharma company but maybe M&A activity among small and medium-sized biotechs so that you can create companies that have the potential to grow. Clearly for us, becoming a public company is positioning us better to be part of those corporate development M&A activities than as a self-standing private company.

What’s the plan moving forward from here? When I look at the website, robust pipeline, we’ve been talking about your lead indication here of HCC, multiple myeloma. It looks like you’ve got multiple IND applications. You are moving towards the clinic in 2023. Tell us a little bit about your plan, strategy, and where you’re headed from here.

We’re laser-focused beyond executing this transaction. We’ve announced the business combination agreement, but the closing of the transaction is only during the summer. We still have to execute at that level. We’re laser-focused to bring products to the clinic and become a clinical-stage in a company in early 2023. We’re laser-focused on the HCC program where we see the most differentiation and where we have the best competitive position. There are other companies pursuing the same target and indications, but all of them are in late preclinical, early clinical development.

This is where the value is. The second level is that we have validated our two platforms, the cell therapy, and the antibody platform. We validated them from a process development from a manufacturing standpoint, and now in vitro activity. We’re better positioned beyond our internal pipeline to enter into partnership with pharma companies, whereby we could have an external pipeline that leverages our technology. In 2023, being in the clinic, generating clinical data, and at the same time, building partnerships with pharmaceutical companies so that we can leverage our technology.

All the readers know I specialize in recruiting. That’s my professional career. I like to try to ask questions about that and how companies make decisions about hiring. For the readers, it’s Cytoviatx.com. You could do a little more research on the company on what they’ve got going on. There are a few positions here listed. Most biotech companies have about a year of cash in the bank, but they’ve got to build this team that has years of work to do. How are you making hiring decisions? Is that something that you talk about in smaller biotech at the executive level? Do you leave it to the hiring managers? What’s your approach to all of that?

We need to have a strategic plan and different scenarios based on how much capital we can raise. We’ve publicly disclosed that with $100,000 at the closing of the merger, we will be able to fund the company until the second half of 2024 for clinical data. That supports expanding our team. Our team is close to 40 people, including 25 people in Massachusetts.

Learn the business or learn the science. If you want to be a top scientist, a work in the lab, learn to do the experiments. If you want to be in on the business side, learn the business. Click To Tweet

We’re outgrowing our lab space. We’re looking for new lab space in 2023. You’re talking about Puerto Rico. We’re looking to hire people in Puerto Rico because we have our own autonomous cell manufacturing facility. We have a few employees already there locally, but we’ll need more as we scale up. There’s growth to have ahead of us.

Someone was asking me, “How many people do you expect to have in 2023?” I would say, “If we have the appropriate level of financing, we could double our staff.” So far, we’re extremely pleased with the quality of the people that we’ve hired. We had no labs, no scientists other than our Chief Scientific Officer, Dr. Wei Li in the Boston area. Now, we have more than 25. They’re coming from top academic institutions and biotech companies. They embraced the vision that we have, and also the entrepreneurial agility of the company. That has allowed us in a little bit more than two years, that go from the strategic region into being a fully integrated company and ready to move into the clinic in early 2023.

You’re in a great spot. It’s also an awesome thing that you were able to structure this going public through the merger and able to fund yourselves to get in that clinical data. Throughout my career, I’ve talked with a lot of CEOs. I’ve had conversations with some and I call them a recruiter. I’m like, “I’ve got an individual specialized in X, Y, and Z.” They will say, “We’re trying to get funding now.” I’ve got a couple of contacts that are in the early stage that are like, “We’re working towards Series A,” and they’re trying to get started to get off the ground.

The financial is on their mind. “We got to make sure we have the funding to do what we need to do to take things into the clinic and to ultimately get treatments developed that are going to help people.” I would like to shift the discussion to ask these final three questions that I like to ask most guests that come on the show. The first one is if you could go back to the start of your career, what advice would you give yourself?

I was privileged to be given a number of opportunities early in my career. The advice that I would give is to choose not only the company but the person that you’re going to be working with. Having a mentor or series of mentors early in your career is transformational. Do not think that because you have advanced degrees from top schools you should be a CEO in two years. Learn the business or the science. If you want to be a top scientist, work in the lab. Learn to do the experiments. If you want to be in on the business side, learn the business.

I started my career doing portfolio strategy at the headquarters of Novartis, but my next job was to be a sales rep in Florida. That’s probably the most informative experience that I had in my career. A lot of graduates from top schools say, “Why would I do that? I’m a physician or an MBA. I deserve to be at a high level.” Sometimes, I compare it to the hospitality industry. Nobody in the hospitality industry succeeds if they haven’t been working in the kitchen, doing housekeeping, or all of the basics. Don’t jump over that opportunity to learn the basics of the business.

 

The next question is, are there any books or a book that you read that you felt had an impact on your life or your career?

If you’re talking about business books, one that I’m making reference into the investor presentation is Blue Ocean Strategy. It’s a top seller. It’s Harvard Business School Press. It’s a top seller of a business book in the New York Times. A lot of people know it, but the basic concept is that don’t jump into red oceans where all the sharks are killing each other. Open new territories. Go to the blue ocean.

When we are going as a company into hepatocellular carcinoma, we’re going in a space where there are relatively few players, there’s a huge unmet medical need. Essentially, we can satisfy that need and create a substantial market. There are several books on Blue Ocean Strategy, but they’re easy reading. Not for more industry, but a lot of case studies that should help your readers consider opportunities.

I haven’t read that book, but I’ve heard of it. It’s been recommended by other individuals that I’ve talked to, not on the show. You’re the first person to mention it here on the show, which is great. The last question I got for you is, generally, where do you think the biotech industry is headed?

The biotech industry has a bright future. Increasingly, among the top twenty biopharmaceutical companies, you have a large number of companies that were started up years ago. Some of them get integrated into pharma companies. It’s interesting to see that Gilead became a $100 billion market cap company. They had acquired Kite, which was a startup. There’s a great future for biotech companies, not only to do early development and get sold after a few years but also to scale up. We’ll see in the future, in the top twenty, more than half will be companies that have under twenty years of history.

I appreciate you being on the show. Thanks for telling us a little bit more about Cytovia. We’ll be excited to see how things turn out in the next couple of years.

Thank you and see you in Puerto Rico.

 

Important Links

• @AmmonRivera
• @BioTechIQ
• Cytovia Therapeutics
• Blue Ocean Strategy
• Isleworth Healthcare Acquisition
• GOBankingRates.com