Transcription:
The Business of Cancer Drug Development

John Leonard, MD (Host):  Welcome to Weill Cornell Medicine CancerCast; Conversations About New Developments in Medicine, cancer care and research. I’m your host Dr. John Leonard. And today, we’ll be discussing the business side of cancer drug development

I’m really excited today to have as our guest, Dr. David Schenkein. He’s currently a general partner at GV, formerly known as Google Ventures where he co-leads the life science investment team. Previously, he spent ten years as Chief Executive Officer of Agios Pharmaceuticals where he remains executive chairman. Before Agios, he was a Senior Vice President at Genentech. Dr. Schenkein has been a hematologist and medical oncologist for 30 years. And in that capacity is where I first met him. I think we shared a few patients several decades ago. He also currently serves as an adjunct attending physician in hematology at Tufts Medical Center. So, David, it’s really great to have you here today. I really appreciate you taking the time. I know you are very busy.

David Schenkein, MD (Guest):  John thrilled to be here and it’s great to see you and I’m really looking forward to this.

Host:  Great. So, one of the reasons why we wanted to have you on the program was really, you have a really great perspective I think as someone who has been an academic physician who has treated cancer patients, taught and researched, moved into industry where you’ve obviously been key in the development of a number of new drugs that impact patients and have improved outcomes for patients. And now have moved into your current work with Google Ventures. So, you really span I think, a number of the key areas of how drugs and treatments get developed. Tell us how this kind of evolution happened. I know a number of academic physicians, treating physicians, go in industry. Kind of how did that happen for you or why did that happen for you?

Dr. Schenkein:  Sure as I view it, I’ve had three chapters in my career. At my core, probably very similar to you, I consider myself first and foremost always a physician. To me that’s the driving force between my career. What has really shaped it has really been searching for areas where as a physician I can make bigger and bigger impacts across a large number of patients. And I think what happened to me in the early 2000s is I started getting more and more frustrated that the medicines we had for our patients with a variety of malignancies particularly in the hematologic malignancies where I did most of my work, just weren’t effective enough and had a lot of toxicity.

And through a set of circumstances. I met somebody who was at a relatively small biotech company in Cambridge, Mass called Millennium and they reached out to me if I was interested in a position in industry running their oncology group and I said no. But I started digging in a little more and they had a very interesting drug that was in very early clinical trials which eventually become the drug  Velcade for multiple myeloma.

Host:  I’ve heard of that one.

Dr. Schenkein:  Yeah, and I saw the potential to make a bigger impact if I could bring a new medicine forward. And so I went over there, and within a few years, we got Velcade approved and I realized how quickly I was able to touch with that tens of thousands if not hundreds of thousands of patients and I realized that the impact could be pretty broad. And that’s what kept me in the industry, took me to Genentech where millions of patients have been treated with some of the cancer drugs that I worked on, rituximab, Avastin, Tarceva, Herceptin. 

I left Genentech when Rosch came in because I wanted to try my hand at running a startup, with the concept of could we create cancer medicines in a different way based on the metabolism of the cancer which I have been for the last ten years. And after running a public company for a period of time, it was time to do something that gives me a little bit more flexibility in life. Now in a position, which we’ll come back to; where I can help start many, many companies which therefore can start many, many hopefully new medicines to impact patients. So, I would say the guiding force through all of this is trying to increase a lens of impact in patient care.

Host:  That’s great and as you say, in one way or another, you’ve been able to do that How does this all happen? I mean patients, they get the end results of the work, but there are so many different companies working from small companies with a few employees to huge companies that people have heard of for many, many years. how do drugs bubble up or get developed in a general sense? 

Dr. Schenkein:  Yeah. Absolutely. I mean I think first of all, I think everybody probably recognizes and maybe some don’t that drug development, taking it from an idea to a medicine that actually can be in a patient’s pharmacy or be given in the hospital; is an incredibly challenging endeavor. Because the vast majority of medicines that are in development, never make it. The current stats are that literally for every 100 new medicines that get put into early clinical trials; at most five will ever make it to the other end.

Imagine if you were working in a car factory and only five out of every 100 on the assembly line made it. you wouldn’t last very long. And it’s a delicate ecosystem between academia, the small and large companies and patients of course that’s the ecosystem we live in. so, as you said, not every company is created equal. We have about 20 big companies in our ecosystem but about 1500 small ones. And in general, I would say that the two most important driving factors at virtually all companies that are making new medicines are the first is, is this new medicine or mechanism that we’re trying to make a medicine, likely to make an impact?

And that means, is there a patient population that is at need for a new medicine? Most of us are not particularly interested in making medicines that aren’t any better than what’s out there today or maybe they are slightly different color. Really, it’s how do we change the game? How do we really make a big impact? So, that’s the driver and you really got to ask carefully are there enough patients out there to do a clinical development plan and are they well served with medicines today or do they need something new?

The second most important factor is what we like to call PTS, probability of technical success. What’s the likelihood it’s going to work? And really what that means to me is what’s your confidence in the scientific underpinnings of whatever approach you’re taking to treat that patient? In the current era, most of us a relying pretty heavily particularly in cancer therapy, on is there a genetic handle? Do we understand the genetics of the patient’s tumor and tell us by turning something on or off based on that genetic profile; we are more likely to benefit that patient. It also allows us, which I think is critically important in cancer development; when we go into clinical trials, we’re not trying to treat everybody with that particular disease, but those that have the right genetic background that are more likely to respond and develop the medicine with a companion diagnostic.

So, I think those are the two most important drivers. I think there’s a misconception in general in the lay population that’s not in our ecosystem that we’re focused on how much money can we make or how big is the market size and that was really drug development in the 60s, 70s and 80s. And largely unsuccessfully. And so, what we really want to focus on is what’s the likelihood it’s going to work and what kind of impact. Because particularly on the small company side, we’re pretty confident and there are about 1500 small companies out there today that if we make a big impact in a patient’s life or a group of patients with a certain disease; that all the business side will work itself out.

Host:  So, you alluded to kind of high impact drugs. On the other hand, we have a lot of drugs that are of the same class, but are there some drugs where we do have maybe too many me too drugs 

Dr. Schenkein:  Yeah, in general, again, most of us strive to develop what we call either the first in class or best in class. The challenge we have, is that the average time from the scientist in the lab either here are Cornell or at one of our – at a company has that discovery, to the time we actually get into the clinic let alone approval could be a decade or so. So, you thought you were the only ones working on this when it got started. By the time you get into clinical trials, there are four or five of them. I do think there are probably too many of them and they are hard to distinguish one from another. I think it’s better if we focus on first, and then if you are going to come with the same type of medicine; make it better. Whether it’s given a different way, or it’s more effective, or it’s safer, because we learn obviously together with our patients. We learn as these new medicines are being put into clinical trials and then on the marketplace really how useful they are.

You really don’t understand how good a medicine you’ve made until it’s been in tens of thousands of patients around the world and then you talk about how can we make it better.

Host:  In the general sense, how do companies that have a broad portfolio, at some point you alluded to that; needing to make decisions about likelihood of success and impact. Clearly there’s a winnowing out process of candidate drugs. How do companies do that and how can we make that better so that the pretest likelihood before a drug gets too far down the line is more likely to be successful?

Dr. Schenkein:  Yeah, so every company probably does it a little bit differently. We all do what we call portfolio management and even at Agios where I have been for the past ten years, although it’s a relatively small company, we would have seven or eight programs in clinical trials and have two approved medicines. We do have to manage that portfolio. And so, you set out a strategy. We’re going to be a cancer company or we’re going to focus on breast cancer or we’re going to focus on this cancer. And so that’s your overarching strategy and then as you make portfolio decisions, it really comes down to what’s the likelihood it’s going to work.

And that should be the most important factor and how much you can afford to do. Because clinical trials as you know, are not getting less expensive, they are getting more expensive and for smaller companies; they really have to make tradeoff decisions and so those are usually the most important factors. Or if it turns out someone else has made a medicine ahead of you and therefore the need is just not there anymore; then many companies will say we’ll take that off or we’ll deprioritize that medicine or give it to a smaller company that may be is happy to do that.

Host:  Can you describe some of the basic or early research that’s going on in companies. I know certain drugs are licensed or collaborative with academic centers and basic labs but what some people may or may not know is that some companies have very extensive either basic or translational research labs where they are obviously focused on therapeutics but are pretty extensive in early phase and what they are doing.

Dr. Schenkein:  Yeah, again, not every company is the same. Some companies are more development. Many companies, the companies I’ve worked in Genentech and the company that I worked at for the last ten years at Agios were basically research driven organizations in which the largest number of people working in the company are basic scientists. This is the delicate ecosystem between academia and industry. It turns out, that close to 70% of the new medicines that are FDA approved come from smaller companies. That’s where they are first discovered. They may end up from a commercial perspective ending up in a large company because that company gets bought, but the basic research that drove that medicine was done either in academia or in the small company most likely in the small company.

I’ll give you a good example. So, the first medicine we made at Agios an academic researcher published a paper on a novel mutation in a metabolic enzyme which was our area of interest. But the paper suggested the enzyme was turned off. It was dead. Which is very interesting science and was published in a high profile journal but not something you could think about from a drug development perspective because if it’s already turned off, it’s already turned off.

We looked at that as literally about 20 scientists at the time at Agios, that’s all we had, 20 scientists. And we looked at it and said you know this doesn’t seem right, maybe we should do some experiments here. And uncovered something that was completely different. That the enzyme was actually turned on. And from there, lead a drug discovery process where we understood the biology working in our laboratories and started making chemicals, small molecules that would turn into a pill, doing the clinical trials and now the drugs are approved. And so, in that example, 90+% of all of the research was done at our company.

But there are plenty of medicines where some of the early research was done in academia or the medicine was made there. Most are made in the company small or large. At Genentech, we had several thousand scientists. So, bigger than most cancer centers. Much of that research is actually fundamental basic research. But it is critically important that we do the work in academia and marry that with the work of making new medicines.

In most circumstances; it’s the company that’s actually making the medicine whether it’s an antibody or the pill and doing all the preclinical and clinical testing to get it approved.

Host:  And there are a lot of partnerships with companies and academic institutions. I mean Agios has connection with faculty here at Weill Cornell. What do you see as the trends of those sorts or I don’t want to comment on that one specifically but academic industry either partnerships or researchers starting companies. I mean where do you see the trend going there?  Where do you see that going?

Dr. Schenkein:  It’s going in the right direction. It’s a really positive trend. If you think back John when you and I were in training, which is a long time ago; very few people went into industry and there was basically a wall between academic medicine and industry. And that wall now is porous. And so, not only are people going back and forth, but the ties between, in a good way, with all the conflict of interest, everything being disclosed; the collaboration between academic medicine and the companies that are trying to make new medicines has become more and more robust.

And that is in the best interest of patients because we’re each doing what we are good at and that’s part of that delicate ecosystem that leads to better and better medicines. So, I think that trend is going to continue, hopefully.

Host:  So, one sees, and patients obviously deal with issues around drug prices, around the expensive medicines, I mean people with companies, at pharma companies and biotech companies have cancer themselves, have family members with cancer; care about solving these problems and easing suffering but obviously, there is some duty to shareholders in trying to deal with the revenue and the business aspects. How do individuals and organizations kind of straddle that? 

Dr. Schenkein:  Obviously, a very important issue and it’s a complicated issue. I do think that if we think back to the ecosystem, the part that I find the most challenging is the difficulty that patients are having in many circumstances affording medicines, that and access to new medicines is not equal across our country and across the world. And those have to be addressed. Every company is a little bit different and like every industry, we certainly have some bad actors in our industry that are doing things that are just not in the best interest of patients whether it’s price increases that don’t make sense or making medicines that really aren’t any better than another one but charging more for them.

So, some of those things really need to change. We do need to remember that we have to ask ourselves as a society how much do we want to spend in general on healthcare. And the medicines are a piece of that. They are not the totality of all the money we spend in healthcare. And we just need to make sure we have the right balance. I think industry has to do a much better job of not only explaining what we do but making sure we are not doing things that aren’t in the best interest of patients. And we know that legislation is on it’s way in some form and industry needs to be part of that. I do think we need to really think seriously about whether these price increases that are happening on medicines makes sense above inflation. I think we desperately need to make sure we can find a way to make sure that patients don’t have to pay excessive copays for their medicines.

So, the insurance industry has to be part of that conversation. And then we have to just ask in general, how do we make sure that we control those factors and not go too far that it prevents true innovation happening because we are at, I think a special moment in time where the science particularly in cancer, but other therapeutic areas as well, is really breaking open at a breathtaking pace. And if we go too far making it hard to get investors to be interested in investing in very risky early stage biotech companies; we’ll lose that wave of important innovation for patients.

Host:  What would be the biggest surprise to a patient about kind of what goes on at a either a pharma or biotech company?

Dr. Schenkein:  So, I’ve been in a lot of those meetings myself over the years. I think probably two things. First is how hard drug development is and how few medicines based on the number of ideas we have, actually make it. So, how many failures there are along the way. So, I think that’s one. I think the other one is understanding, and I think patients are often surprised at how expensive it is to take from an idea to make a medicine. For a smaller company, hundreds and hundreds if not billions of dollars to bring a medicine all the way there and that may take a decade before that money is recouped. And remember, investors are saying where’s my return? So, I think those are two areas.

Every once in a while, I’ll meet with a patient group and they are surprised at how patient focused we are. And I find that a little disappointing. Right now I think the word I’ve heard is that the public perception of the pharma industry is slightly below the tobacco industry which is really sad. And I think it's in part, we’ve done on the industry side not a very good job communicating what we do and everyone just sees the bad actors and misses the fact that all these companies are packed full of dedicated scientists and physicians and people in all parts of the organization that truly come to work everyday to make an impact in patients’ lives.

At the companies I’ve been in, we always bring patients in to communicate what they’re going through so that scientists who have never seen a patient understand why every day matters. Every day matters. Every day that our new medicine is not out there, there’s a patient out there who needs it and is not getting it. And that’s important.

Host:  Are there a couple of things you think we should do to kind of make that go better? Any kind of big picture if you could wave your wand and make this whole process work better that you see is high impact?

Dr. Schenkein:  There’s no question I think particularly for serious diseases, cancers and other serious diseases; I think we need to figure out a system so that copays above a trivial amount disappear. There’s no way a patient with a serious disorder in my mind should have to worry about can I afford this medicine or pay for my rent. That has to go away. And I think we need to figure out as a medical community, how to be much more efficient in making sure patients get access to our medicines and to the medical care that they need in hospitals in a way that’s responsible to cost. Because we know there’s a limit to how much money we can spend and make sure people understand all the different components of the ecosystem and what role they play.

I think those are important things. Like in every industry, we’ll always have people who are trying to get around the system. We can’t eliminate them. We have to point them out and make sure we move them out as quickly as we can.

Host:  As far as getting new drugs approved faster or better, assuming of course that they should be approved and are better drugs; one of the big areas that has gotten a lot of attention is various terms, big data, real world evidence things like that. What are your thoughts about that? There are people certainly in my community in academic medicine, some who are very, very positive and seeing big things, others who are more skeptical. Clearly the patients who end up on clinical trials are not necessarily reflective of all patients with a specific condition, on the other hand, the limitations of real world data or broader data also have issues. Any thoughts on where and I’m sure Google has a lot of activity in that area shall we say.

Dr. Schenkein:  Right. So, I am sitting at a data company so, I don’t think there’s any question this is an exciting time as we think about how to responsibly collect large amounts of data whether it’s genomic data or clinical data and use that to make not only better medicines but better decisions. As you and I know, when we sit and see a patient and decide on treatment, we’re thinking about okay the last few patients I saw and the medical report I read; but now we have the ability to aggregate tens of thousands, hundreds of thousands of patients’ worth of data to help physicians and patients make better decisions.

I think we are going to see that on a sharp rise, and I think it’ll help us not only again, make better medicines, I think it will change the way we do clinical trials over time and allow for better outcomes. There’s some overhype in the system. No question about it. We need to make sure we’re doing it with the appropriate levels of privacy, and I think it’s being responsibly done. I think machine learning and AI are coming to play now. Those are also a little bit overhyped. But I do think over the next decade, we’re going to see a big change in how we think about these areas because of the access to large amounts of clinical and research data coming together.

Host:  Yeah. I’m sure many people have concerns about personal privacy. On the other hand, when you have a patient as you know who is sick and wants to get better; if giving up some of their privacy which happens in the course of medical care; can make a difference in them getting better, finding information et cetera; most people are going to say I’ll give a little bit of my privacy if it’s really going to make a difference as long as it’s being done in a respectful way. But there is a sweet spot in there.

Dr. Schenkein:  Absolutely. I think the key is that patients should have the choice. I was very close to a young man, he was a very brave young man who unfortunately recently passed away from a brain tumor and he felt passionate and he was written up in the New York Times and other places, about patients should be able to have the option to share all of their data so that some smart researcher somewhere can aggregate 100,000 patients with that profile and come up with a new medicine. So, patients should have the ability to share that. It is shocking to see how much people willing to share on Facebook and other places, yet their medical data, they are nervous about.

I’d like to be able to have all of my medical data on a chip so that if I show up in an emergency room in a different city, I can just give them a chip and they’ll have access to everything that they know about me. So, we’ll get there.

Host:  So, let’s move to your current activities. Tell me a little bit about GV I guess is the proper name. How is that different than what you’ve been doing in the past? And how do you think that’s going to make another phase of impact in your career?

Dr. Schenkein:  Yeah, so this is my third chapter and so far, it’s been extraordinarily rewarding and exciting. So, GV was started about ten years ago and we’re a fund directly from Alphabet, the parent company of Google and our vision and mission is to create new companies that make an impact in the world both in technology and life science. Obviously, I focus on the life science side. And we have an extraordinary team of physicians and scientists who are trying to start new companies and our vision because of our sole investor which is Alphabet, is not look at me too or incremental ideas but really trying to change the game. And really try and make a big impact and we have a unique lens in that we don’t just look at one part of medicine, but all of medicine.

So, we invest in new companies that are making new medicines, so therapeutic companies. We look at diagnostic companies. We look at big data companies. And we also look at the payor provider space. So, we may start a new medical clinic or a new approach to a certain type of delivery of healthcare along side a new data company or a new therapeutic company. Out goal is to get in there, provide capital for those early companies and then provide our expertise as well.

We’re not a strategic fund. So, we are not looking to invest in things that Google or Alphabet may like, and we can invest in things that are directly competitive with them.  And then because we live within the amazing infrastructure of Google and Alphabet; we can tap into all of the resources there to help our portfolio companies and in the life science side, we already have 90 companies in our portfolio, and we think they are going to make a big impact in healthcare.

Host:  So, is there an example of one you could share around I guess a company that being part of GV, being in that ecosystem as opposed to being just supported by a venture fund or something else where that company is now situated where that’s going to make it much better or more likely to be successful?

Dr. Schenkein:  Yeah, a good example would be a company that came directly out of GV that I think has made an impact for patients and so, I think it’s probably five or six years ago, there were two young computer scientists at Google who were interested in healthcare but weren’t quite sure what to do with that, who met one of my partners at Google Ventures named Krishna Yeshwant and together they brainstormed about maybe we should start a company that would help cancer docs and cancer patients better understand how medicines worked and they thought about it for about a year and started the company known as Flatiron and because of the resources that we had behind us on the computation side; they created this company as I’m sure you know well, called Flatiron which became I think a really important data company for oncology which now is part of the Roche system.

But that’s an example of a company that probably wouldn’t have started as easily without the resources not only financial but other resources that GV can provide. 

Host:  So, before we wrap up, I’ll have you kind of put your crystal ball on and someone whose listening who may either be dealing with a cancer diagnosis in the future or whose managing this; what are some of the key features of how cancer research, cancer care are going to be different let’s say five years from now. Things are changing so quickly. I mean even over the course of a few years; I mean we have so many different categories of drugs and targeted therapies. Some of the AI things that have had an impact. Where are we going to be in really a short term period of time, five years let’s say.

Dr. Schenkein:  I’m an optimist. I’ve always been that. I have never been more optimistic that we’re going to start seeing bigger and bigger impacts in cancer. I’ve never, in the past, because John as you know, we both worked in the area of lymphoma where we do cure some patients and have done so for many years. So, I’ve never been scared of the word cure. But in many of the diseases in cancer, in oncology; that’s just not been a reality. I think that’s going to start changing. Not only for cancer but rare diseases. We’re seeing that with not only more precision targeted therapies, we’re seeing that with the new cellular therapies. We are very involved in some of the new gene editing companies.

So, I think in the next decade, we’re going to see another step function change in outcome for patients hopefully safer medicines, more targeted to the individual patient’s genetics but also more cures. So, I’m an optimist. And I’m really excited about what that next decade is going to look like.

Host:  Great, well I want to thank you so much for joining us today. It’s been great to have you here and get your perspectives, I know they are unique and broad and it’s really great to share with our listeners your insights into this important area and lots of different dimensions of this. So, thank you for being here.

Dr. Schenkein:  John, always a pleasure and I really appreciated it and was thrilled to have the opportunity.

Host:  So, I want o invite our audience to download, subscribe, rate and review CancerCast on Apple Podcasts, Google Play Music or online at www.weillcornell.org. We encourage you to write to us at CancerCast@med.cornell.edu with questions, comments and topics you’d like us to cover more in depth in the future. That’s it for CancerCast; Conversations About New Developments in Medicine, Cancer Care and Research. I’m Dr. John Leonard. Thanks for tuning in.