melts in your tumor, not in your blood

[Rich66]

Nano Takes Aim At Cancer Cells
Josh Wolfe, Forbes/Wolfe Emerging Tech Report 08.12.09, 1:45 PM ET



Oliver Fetzer is president and CEO of Cerulean Pharma, a Cambridge, Mass.-based nanopharmaceuticals company [Full disclosure: my firm Lux Capital is an equity investor]. Before Cerulean, he was senior vice president, corporate development and research and development at Cubist Pharmaceuticals(CBST). Prior to joining Cubist, Dr. Fetzer served as a Managing Director and Partner at the Boston Consulting Group in the firm's health care practice where he was responsible for projects in strategy, operational effectiveness, and mergers and integration. Oliver worked at Bayer AG early in his career and as a director of Auxilium Pharmaceuticals. He holds a Ph.D. in pharmaceutical sciences from the Medical University of South Carolina, an MBA from Carnegie Mellon University, and a BS in biochemistry from the College of Charleston.
Josh Wolfe: Your experience within life sciences is spread over a spectrum of development stages. What attracted you to join Cerulean Pharma given its early stage?
Oliver Fetzer: One of the things I realized while working with BCG is that very large life science companies are often monolithic and it takes a long time before ideas can really gain traction and get implemented. So, the first step was going to a smaller company like Cubist, where I felt that there was really a chance to help build a company, to bring a much-needed drug to the marketplace, and to apply a lot of the things I can with larger companies in a smaller context.
That journey is now continuing at Cerulean where I'm taking a step into an even smaller place. When I joined Cubist, it was already a public entity, and I helped grow it from $200 million to over $1 billion in market cap during my time there. But at Cerulean, I have the opportunity to get in very early on to shape the technology, come up with the product candidates, and grow a team--in other words, to really build a company.
What was it about Cerulean that prompted you to drop everything else and join the company?
After I left Cubist, I decided that I wanted to take a big break and do something that may very well have been a once in a lifetime opportunity--my wife and I took our kids out of school, packed up and traveled all over the world for a year.
Click here to get valuable investment insights where science, commerce and politics intersect in the Forbes Wolfe Emerging Tech Report.

When I left Cubist, I was pretty clear that I wanted to be a CEO of a small company with very exciting science, and the trip confirmed that that was what I wanted to do.
From a strategic perspective, it was important to have sufficiently diverse risk, such that you have an opportunity to get to a commercial stage product rather than just rolling the dice. I've seen too many drug candidates die in the pipeline for all kinds of unforeseen reasons.
Another thing important to me was a strong team, and by that I mean the management team as well as the investors and board members because we were going to be spending a lot of time together and I wanted to make sure that they were strong, but also just fun to be around. In a small company in particular, you need to be able to go through thick and thin together.
So when I looked at a whole selection of companies coming back from our year away, what really struck me about Cerulean was that it was the perfect set of all of these--exciting technology, a commercializable platform and a great team. The technology itself was uniquely compelling to me, and the team was not only impressive in terms of their background but also their personalities. Polaris and Venrock as lead investors made for a very strong, committed syndicate, and the board is very accomplished. So you take all of that and you can see that it's a very unique company. I'm very excited about it.
Explain to our readers exactly what the company is attempting to do.
Many drugs that are out there, despite the fact that they're successful, actually have pretty significant liabilities where the drug metabolism isn't optimal. The drug may not get to the right parts in the body or may be excreted too quickly. Those liabilities, taken together, can result in unwanted safety and toxicity issues, as well as impaired efficacy.
Using nanoparticles of about 100nm in size, you can encapsulate these drugs and engineer how they move through the body. Let's say you have a cancer chemotherapeutic--ultimately, you want that compound to end up in the cancer tumor, not all over the body. The blood vessels in the tumors have slightly larger holes and are a little bit more leaky than normal blood vessels, so the small size of the nanoparticles allows you to preferentially target the tumors.
Cerulean engineers these particles to be just the right size so that they stay in the bloodstream until they are borne into the tumor tissue and leak into the tumor cells. If you think of it like an M&M, the chocolate on the inside is the drug, and the candy coating on the outside is material that you can use to form the nanoparticles with different structural stability.
So like an M&M, it "melts in your tumor, not in your blood?"
Yes! It only melts in the tumor. Effectively, with that coating, you can profoundly change the release characteristics of the drug. Rather than getting a short spike after you infuse a drug into the bloodstream, and then rapidly getting eliminated through the kidney or the liver, by coating it you can keep the drug in the body, target it into the tumor, and release it over a prolonged period of time. Ultimately, you hit the tumor much more effectively than you otherwise could ever do.
Now let me come back to risk. I mentioned before that it was very important to me that I join a company that is somewhat diverse. The beauty of that concept is that you can enhance drugs that are already clinically validated, where you understand the mechanism of how they work.
The technology allows us to optimize on that existing clinical foundation by getting the drug into the right place at the right time for the right duration, thereby significantly increasing efficacy and reducing toxicity, but without the technology risk that plagues so many drugs, particularly in oncology, where the animal models don't translate because human and animal biology are so different. What we can do is take drugs that are already known to work in humans, and we make them work much better.
That sounds very promising. How far along is this technology today?
The lead compound in clinical development, called IT-101, is based on technology that we have in-licensed from Calando Pharmaceuticals, who has made nanoparticles using a sugar backbone. What's exciting about it is that their nanoparticles, just like the ones that we're developing now, are made exclusively from generally regarded as safe (GRAS) substances that are already known to be non-toxic.
By taking the building blocks for the nanoparticles from the GRAS list, you ensure that you are not introducing new toxicities that weren't there before.
In pre-clinical experiments, IT-101 has performed much better than many commercial drugs that are currently out there and is currently in Phase I clinical trials. It is not done with clinical testing, but it has the promise that it could very significantly improve cancer chemotherapy. It is just our first compound but we are working on other compounds that harness the same technology that would target different mechanisms in oncology. Going forward, the technology can also be applied in inflammation, where you have similar drug metabolism and pharmacokinetics (DMPK) issues, as well as different potential indications that we haven't even touched at this point.
In the coming years, what role do you see nanoenabled therapeutics playing in oncology?
I would shy away from saying that nanoparticles are going to cure cancer, because I think that we still haven't fully discovered the underlying mechanism of what makes cancer cells become cancer cells, and how can we target them, but I would liken the potential of nanotherapeutics within oncology to what has happened in HIV/AIDS. While we have yet to cure AIDS, we have learned to manage it quite well.
These days, if you get put on the right combination of drugs, you can live for a very long time symptom-free with nearly undetectable levels of the virus and never get to full blown AIDS.
Why is that relevant for oncology and nanoparticles?
My vision and my dream is that cancer will become a similarly manageable disease. But standing in the way from that happening is mostly the combination of having highly toxic drugs, so we can't dose many of these drugs at a high enough level and for long enough periods of time. What we currently do is give somebody an infusion every two to three weeks, where not all of the cancer cells get wiped out. The cells that survive have an opportunity to mutate and become the next-generation cancer cells. So in two to three weeks, when you get the next course of therapy, you have a fitter pool of cancer cells floating around.
Now, if you had a combination therapy with nanoparticles, the drugs would slowly release into the tumor cells and you would have high, sustained levels of drug in the tumor. In that situation, it is much harder to imagine that cancer cells would become resistant to chemotherapy as quickly as nowadays.
Furthermore, the side effect profiles should be much more beneficial for the patient because smaller, more targeted doses are administered. So that would be my hope: that with the nano-therapeutic approach you could actually be able to manage cancer. Within 20-30 years, I don't think it's reasonable to expect a cure for cancer, but it is reasonable to expect that we can manage the disease much, much better and keep people symptom-free without burdening them with the horrible toxicities they endure nowadays with chemotherapy.
Are there any particular management styles or lessons learned that you bring to the table at Cerulean?
I think one that I just touched on is the ability to really integrate a company. I've often found it unfortunate in companies that you would find an "us vs. them" mentality. I try to look at myself as a bridge builder; somebody who can teach scientists why it is perfectly reasonable for investors to expect a return on capital, and who explains to investors why science isn't always exactly a predictable path that goes from step A to step B on a pre-determined timeline with clearly defined outcomes.
The other one is that I try to have a clearly articulated vision and strategy of where I want to take the company. I hope that vision will be compelling for everybody, but at the same time I encourage people to question my ideas. I really love nothing more than being challenged. I do it a lot with my own team, but I also expect it in return. I want my investors, my board and my team to really challenge me because I think that gets you to a more comprehensive discussion, a deeper understanding and a better-informed decision in the end.
Where do you hope to see Cerulean in five years?
From an investor's point of view, I hope to have been able to provide for a strong exit. Now how does that happen in the current environment? I think it's unreasonable to expect an IPO in this market. I think the legacy I'd like to build for the team is that the technology is so strong, so compelling that whoever goes after us would be excited about keeping Cerulean intact. I think more and more pharmaceutical companies are starting to realize that their best acquisitions are those where they really keep the team and the technology intact; where they buy something because it can compliment what they're doing without trying to force-fit it into their organizations.
From a business perspective, how big of a market is there for cancer therapeutics?
Unfortunately, cancer is quickly becoming the number one cause of death in the United States, even ahead of cardiovascular disease, which we've become better at treating with new drugs and surgical procedures. So in the U.S. and other Western nations, often where life expectancy continues to increase, cancer is becoming more dominant. It's an enormous market that continues to grow in the Western world.
If you can actually make a meaningful difference in patients' lives, you have hit on an enormous opportunity. If you combine that with the potential that this may become a manageable disease, rather than an acute episode of the few cycles of cancer chemotherapy, I think you start to see an outline of a very, very attractive investment proposition in the kind of technology that we have.
What are some of the other interesting technologies or promising new areas that you are seeing in the life sciences?
One of the areas that I'm excited and fascinated by is vaccines. The gratifying thing about infectious disease is that we have many drugs nowadays that can truly cure diseases--this is one of the very few disease areas where that's the case. Vaccines are even more exciting in that you prevent people from getting sick in the first place.
Unfortunately, over the last 20 years, it hasn't been as glamorous or as profitable for pharmaceutical companies as other areas, and subsequently the space has seen very little investment. I think that is starting to change. The science has come a long way and we're starting to see the real benefits of vaccination. There are still significant public health issues, and a lot of unresolved problems out there, so vaccines are a space where both scientifically and from a societal perspective, there are big unmet medical needs.
In addition, we are continuing to find some unexpected connections between diseases. Who would have thought that cervical cancer could essentially be curtailed by vaccinating women against HPV? I think in some instances we haven't even fully recognized how many of the diseases are interconnected. So I find that pretty fascinating as well.
Excerpted from the July issue of the Forbes/Wolfe Emerging Tech Report. Click here to learn more about Forbes/Wolfe Emerging Tech Report and to become a subscriber.