publication date: Mar. 18, 2016

 Slamming the Door

Part VIII – A Conversation with DePinho

 

By Paul Goldberg

The $18 million never made it from Austin to Houston.

MD Anderson’s initial stance was to deflect all CPRIT-related questions to CPRIT, but this didn’t make the controversy go away. So, the cancer center suggested that the grant undergo scientific review, as well as commercial.

Recently, I asked Dan Fontaine, MD Anderson’s executive chief of staff why the money never changed hands.

At the time that the consternation and the questions were being raised, things seemed to be going about internal workings at CPRIT that we were not a privy to,” he said. “It still became apparent that there was at least one constituency within CPRIT that felt—even though the RFA had specifically said that it was going to go through the commercial review group—that it needed to go through both the commercial review group and the scientific group.

“If the process was going to change to do that, we felt that it was important to be very clear that we were happy to let the process take place a second time and have whatever we had submitted go through both review processes. So we wrote a letter, as you may recall, to CPRIT and we suggested two things: kind of belt-and-suspenders:

“We said that, number one, whatever additional review process you want it to go through, please have it go through. And if there’s questions raised; if there’s more scientific information that is wanted, since this is supposed to be a business plan—if there’s more scientific information that is wanted, we would be happy to supplement that as requested. So we would be happy to do whatever additional review process CPRIT wanted to do at that point in time.

“Secondly, we also suggested that we would even allow CPRIT to hold the money in escrow for a year, to see what kind of milestones we hit with progress on the grant.

“They wrote us back and said we’ll put it through the additional review process, thank you very much, and we’re not going to make you put it in escrow for a year, because once we’ve gone through the award process, we will make the award immediately.

“So at that point in time, we anticipated that there would be some sort of additional review process. As it turned out, I think in looking back, other things and other controversies at CPRIT began to arise. To my knowledge, they never put it through an additional process. We never resubmitted, because there was never an RFA or any communication to us.

“I know there were a couple of instances when we may have contacted them and said is there anything else—but, you’ll recall, shortly after that the controversy grew to the point that the granting was stopped at some point in time. There were directives, etc. And we never got beyond that point. We never resubmitted; they never re-reviewed. And funds never changed hands.”

As all of this was proceeding, Gilman told me that he couldn’t understand how the MD Anderson proposal in its original form could get through scientific review. There was nothing there to review.

On the purely aesthetic level, he was surprised to see the word “prosecute” used in the context of clinical trials and discovery program. If you look at the proposal as submitted, it suggests deep, complex research, but calls it commercialization. This wording struck Gilman as particularly perplexing: “CPRIT funding will also provide the resources necessary to strategically invest in innovative chemistry platforms to tap into previously ‘undruggable’ target classes.”

Indeed, the number of academic researchers and pharma companies seeking to do just that is not small. Why should the MD Anderson group be allowed to get funding for this endeavor based on a 211-word paragraph in a six-and-a-half-page document?

Is the following enough information to support a funding decision?

“CPRIT funding will also provide the resources necessary to strategically invest in innovative chemistry platforms to tap into previously ‘undruggable’ target classes. Current chemotherapeutic agents target a restricted portfolio of protein targets, including kinases and nuclear hormone receptors. The IACS team has developed a work plan to go beyond this limited repertoire of targets by leveraging inhibitors that are outside classical small molecule physicochemical drug space (including as one example, phosphatases) and leveraging proprietary delivery platforms to bring the therapeutics to the site of action. We plan to execute on our work plan by deploying cross-functional teams of medicinal chemists, pharmacologist and drug metabolism scientists to rapidly advance this proprietary chemistry platform through progressively more challenging hurdles from cell lines, to rodent models, and ultimately to canine and/or non-human primate models in a series of well-defined proof of concept studies. Further opportunities exist through collaborations with investigators such as Dr. Venkitaraman at the University of Cambridge around drugging protein-protein interactions known to be essential for tumor maintenance. By opening up a new druggable space, we believe these platform assets will be optimally advanced through the formation of a Texas-based NewCo and this strategic expansion will provide an opportunity to this entrepreneurial exit at an earlier time point than with other programs.”

Most importantly, Gilman wanted to know, how is this not research?

When Fontaine and I spoke recently, he said that as IACS moved forward, it became a commercial success.

“I really think that four years hence, our commitment to bridging that gap between the discoveries in the academic world and products in the commercial world, which is what the [IACS] was designed to do, I think history is on our side on this one,” he said.

“I think it’s being proven out that we are on the right path. And I’m not sure that Dr. Gilman’s resignation had anything to do with that at all, or the resignations of any of the scientific board. We went on without the CPRIT grant, and while I think all of the benefits of the [IACS] are yet to come, certainly there are some early successes in what we have been trying to do, partnered with our strategic industry ventures department, to really put together ways of accelerating discoveries into therapeutics and diagnostics.”

Fontaine’s words prompted me to request documents under the Texas Public Information Act. Based on preliminary responses, it appears that some information will be released.

 

 

During our first conversation, a few days after Gilman submitted his letter of resignation, he wanted to make sure that I understood the nuanced nature of the story.

The politics of CPRIT was one aspect. The politics of MD Anderson was another. Science policy, regulation of conflicts or interest, the structures of drug development and transfer of technology from academia to the private sector also figured in the story as well.

And that’s just for starters.

I assured Gilman that I understood, but made the argument that this is all one massive story. I would jump in and let it develop. Sure, it’s a broad as Texas. I would just have to deal with it.

In the summer of 2012, a few months in, I started to realize that I was trying to describe a Texas landscape by looking through a peephole. It was difficult to imagine that just a few months earlier I had no idea who DePinho was. It was all the more scary that I had no deep understanding of IACS and the manner in which it fit into MD Anderson’s structure.

So, in the summer of 2012, DePinho and I met at a coffee shop off DuPont Circle, in Washington. He was in town for a meeting at Brookings Institution.

My office is a couple miles away, so I rode a bike down Massachusetts Avenue. There was a tape recorder in my pannier. Also, I had a notebook with a few simple questions. To be fair, I sent the questions to DePinho a few days earlier. The deal was, the conversation would be on record.

As we sat down, DePinho told me about his father’s arrival in America as a stowaway, and about his father’s cancer, and about the way his father’s death shaped his career, moving his focus from science for its own sake to science aimed at producing drugs, saving lives. He told me about Lynda’s immigration from China, her adolescence spent above a laundry in New York’s Chinatown.

He told me that he fully realized that my coverage wasn’t self-serving, that I am interested in the public good.

I assured him that this was correct, and that I was finding it a bit unsettling to be in anything but a friendly relationship with MD Anderson. I told him that, like Alvaro DePinho, I am an immigrant, though not a stowaway. I came here from the USSR at age 14, in 1973. During his first year in the US, my father, a writer and poet, pushed a broom.

I don’t hide my immigrant roots. My kids, friends and colleagues are well aware of them, but my immigrant roots were not a part of the story I was supposed to cover at that coffee shop. And it’s certainly not unusual for an immigrant kid to do reasonably well in this country.

Then I went on to disclose something even less relevant. I said that when my mother was diagnosed with ovarian cancer, she received Taxol, then a new drug, in a clinical trial at NCI. After Taxol failed, she went to MD Anderson.

Though my mother died of her disease, going through a thorough evaluation of available options by MD Anderson physicians proved to be an extremely valuable experience for my father. It gave him the assurance that everything that was available was, in fact, tried.

The doctor who treated my mother is a fantastic, compassionate man, Andrzej Kudelka. He is the sort of doc who gave his patients his home phone number and his direct number that bypasses the receptionist. When I run into him, which happens roughly once a year, he asks me how my father is doing.

All of this is, of course, true, but by opening my mouth, I made my mother a part of the story.

It was as though cancer suddenly became a personal attack. It is not. It’s a molecular process devoid of capability to discern whether its host is Alvaro DePinho of Sofia Aronovna Goldberg.

 

 

That morning, DePinho and I didn’t get around to doing the Q&A. There was too much other material he wanted to cover, and the noise from city buses made it impossible to tape. We decided to try again—over the phone.

A few days later, he took my call. I told him that I would have my tape recorder running.

For months, DePinho was receiving a massive amount of attention from The Cancer Letter, far more than Harold Varmus, director of the National Cancer Institute. If I can be forgiven for lapsing into the war metaphor, if DePinho is a general in the war on cancer, Varmus was the field marshal, perhaps even generalissimo.

It was possible that I was unfair in devoting so much attention on DePinho’s every move. He was owed an opportunity to explain himself in a way that was completely unfiltered.

To his credit, DePinho didn’t avoid me. Our on-record conversation clearly lays out the DePinho story as he saw it at the time. Originally published Sept. 7, 2012, it remains an important document.

 

 

Paul Goldberg: In your job interviews, originally with the UT System chancellor and the regents, you were asked, I’m sure, to describe your vision for MD Anderson. In a nutshell, what were the plans you described for them?

Ronald DePinho: The interview process was a very essential and lengthy one, during which I was asked to describe my vision for MD Anderson and for cancer care in the future, which, I’m sure, was asked of all the candidates.

PG: Of course. What was your answer?

RD: If I recall, just to distill it down to the most elemental points, the major emphasis was that we were entering into an era of science-driven cancer care, in which patients would be administered therapies that would be more effective, based on their genetics, and also avoiding toxicities based on their inherent genetic make-up.

That was an important aspect that permeated most of my comments. I also spoke about the need for increased prevention and early detection.

Prevention is one area that really focuses on understanding why we get cancer in the first place, also developing the right educational tools that enable us to, for example, protect children from sun exposure, to reduce childhood obesity as well as to prevent children each and every day from starting smoking; things of that nature.

Also with respect to early detection, this is where I think some of the greatest near-term impact is going to occur, with the revolution ongoing in serum proteomics and imaging. We have a tremendous opportunity to shift our discovery of cancers to much earlier stages, when the chance for cure is greater.

I place a great deal of emphasis on prevention and early detection.

PG: Would this be what you were going to do at MD Anderson—look at prevention and early detection?

RD: I think in general, the field of cancer has focused significantly on understanding the genetic basis of cancer and focusing significantly on treatment, which is continuing to be a major emphasis for us. But I mentioned that we are entering into an era where we can be far more proactive in understanding cancer genesis and using that knowledge to prevent disease—look at the revolution that occurred as a result of the HPV vaccine, the knowledge of hepatitis virus, H. pylori.

These are all opportunities for us to understand what drives cancer and intervene in ways that are most effective. I think that the future, while it will continue to focus heavily upon the treatment of advanced disease, will also focus increasingly on preventive-interventive strategies as well as early detection.

PG: So that’s your vision for MD Anderson?

RD: Actually, this has been part of our mission for some time. I think it’s a matter of emphasis, but it has been central to our mission for many, many years.

PG: Did you get to mention the biotech incubator at that point, or was that not a large enough…

RD: Not yet. But just to finish your first question, the other thing that I also expressed strong interest in, during the interview, was the maintenance of academic excellence.

I talked a lot about mentorship, enhancing our trainee experience, enhancing the ability of our junior faculty to develop sustainable careers, making sure that physician scientists, who wear many hats, are fully supported to achieve the kinds of translational activities that are critically important to drive discoveries into practical endpoints that make a difference for patients.

Your next question?

PG: Was the incubator part of the plans you discussed then?

RD: No, but perhaps you mean the Institute for Applied Cancer Science?

PG: Correct.

RD: If you are talking about the Institute for Applied Cancer Science, Giulio Draetta is the director—he was Merck’s worldwide head of oncology drug discovery, and prior to that vice president of Pharmacia. The IACS is based on the construct of an institute that started 2003 at Dana Farber called the Belfer Institute for Applied Cancer Science, an institute that focuses on trying to drive discoveries to drug-development endpoints.

It’s a new organizational construct that’s designed to rigorously validate targets, develop drugs against those targets, and develop a clinical path hypothesis, so that we can test these novel drugs in the right patient population.

We had some success in Boston, and I was eager to explore similar possibilities on the scale that MD Anderson could provide.

PG: So it’s a way of making it bigger?

RD: Not necessarily bigger, but we added some very exciting components to it that in the area of biotherapeutics, whereas in Boston, we were focused mostly on small molecules, so we’ve expanded into a number of areas.

So the institute supports professional staff that are focused on timelines, deliverables, and milestones, who work in collaboration with the academic investigators, and together move knowledge forward in a very directed way toward drug development endpoints that make a difference for patients.

PG: And so what were the promises that the UT chancellor and the regents made to you, what mandate did they offer?

RD: If you’re talking about CPRIT, there were no promises because CPRIT is an independent state agency over which UT System has no control.

PG: Well, I guess what I’m really wondering about is did the CPRIT funds figure into it in any way at all?

RD: I see what the confusion is, because you are going back between UT System and CPRIT.

PG: Correct. I’m not necessarily confused; I mean, I understand the difference…

RD: Because you don’t know.

PG: I don’t know.

RD: So the Institute for Applied Cancer Science was a construct that we had at Harvard that we wanted to recreate at MD Anderson. That had nothing to do with CPRIT, it was something that was focused on what MD Anderson should do, and that was a discussion that occurred with [UT Executive Vice Chancellor for Health Affairs] Ken Shine and the Board of Regents as a means of bringing individuals down like Giulio Draetta, Lynda Chin [Department of Genomic Medicine chair and IACS scientific director], Phil Jones [head of drug discovery] and others to basically have that same construct be developed at MD Anderson.

So that was a discussion that occurred with the regents, MD Anderson and numerous individuals. I wasn’t involved in the Institute for Applied Cancer Science—that wasn’t one of the things that I was discussing with the regents or with Ken Shine.

PG: You did not? I thought that would be a crucial part of what you would do? Or…?

RD: Lynda Chin, Giulio Draetta—they are independent investigators. And in recruiting them down, that discussion was focused on them: where they would have the opportunity to develop their programs that they had in Boston and transplant their activities to MD Anderson.

PG: So that was occurring subsequently to your being offered the job?

RD: Some conversations were simultaneous and some were subsequent. They were all part of the negotiations to try to bring the entire group of individuals down.

PG: I see. So these were different negotiations within the whole process?

RD: They were the typical negotiations that tend to occur between academic investigators and institutions. There is nothing different that was any different from, let’s say, us recruiting investigators recently like Sam Hanash, who is now leading a very important proteomics early detection program here, or any different from our recruitment of Jim Allison, where we’ve invested significantly into our immunology program, or any different from Raghu Kalluri, who is coming down to head our program of cancer biology, or any different from Andy Futreal [professor of genomic medicine], where we made very significant investments in genomic medicine.

PG: When did Dr. Chin’s incubator proposal emerge?

RD: Now you’re talking about the CPRIT side of the equation.

PG: Right.

RD: Let me put this into a bit of a context. When we came down early on in September, October—Giulio, Lynda, myself, Phil Jones, Eric Devroe [executive director of strategic alliances]—there was great community interest in Houston in trying to understand the Belfer Institute.

There was also great interest in starting biotechnology industry in Houston, and so many individuals asked us to talk about matters of translation, commercialization, and some of these novel constructs.

During the course of those months, there were numerous presentations that were made—I must have made personally at least three or four in which we had many components of the Houston community listening to our presentations.

PG: When was Dr. Chin’s incubator merged with rest of the…

RD: I’m leading to that. At that point, there were individuals who came to us from CPRIT that were extremely interested in what we were talking about and recognized a proposal that had been submitted to CPRIT by Rice as an incubator. Rice had an excellent infrastructure; they had a very good proposal, but they didn’t have content for that incubator—something that we generate through the IACS—the content to incubate assets for ultimate commercialization.

And so, the idea was proposed by CPRIT that we should join forces with Rice. I believe those discussions occurred in late November, early December. We were then alerted to the fact that there was this request for proposals in the incubator commercialization group for a component of CPRIT.

The leadership of the institute—which was Guilio Draetta, Lynda Chin, Eric Devroe and Phil Jones—got together with the Rice colleagues, and, under the guidance of the commercialization team at CPRIT, organized this cohesive entity. And that took about two to three months of planning and back and forth, all under the guidance of CPRIT.

PG: I’ve seen that e-mail from CPRIT, which I got under the Texas freedom of information law, and it appears that that Charles Tate, who’s a member of CPRIT oversight committee and commercialization board, is being mentioned as playing a role in devising the application. What role did he play in this process?

RD: I think that that’s a question you need to ask CPRIT. I don’t know. My understanding is that he is involved on the commercialization side of things, but to my understanding, I do not know of any role that he played, but I would ask that you ask CPRIT or ask Charles Tate himself.

PG: I will, of course. But there were no conversations between you and him?

RD: No one even knew about the institute until we started talking about it after we were here on the ground at Texas and then months after that, this request for consideration that we would merge with Rice emerged. And then we went through the process under the guidance of CPRIT to eventually file the grant.

PG: Does the governor’s office plays a role, or lieutenant governor, or the legislature in what you are trying to accomplish in MD Anderson?

RD: No direct role as it relates to our CPRIT funding, but because MD Anderson is a state institution, we do receive crucial funding from the state of Texas to eliminate cancer, which is what we’re trying to accomplish at MD Anderson. The governor did visit MD Anderson to celebrate the opening of the Institute for Applied Cancer Science early on. There was a major press conference for that, but none of the individuals were involved in any way with the incubator proposal.

The Institute for Applied Cancer Science staff submitted a document that was requested in the Request for Applications, and that is what occurred.

PG: The MD Anderson proposal for the incubator is less than seven pages long, and it was funded to receive $18 million three weeks later. It’s sort of unusual, did that in any way surprise you that it was so quick and so successful?

RD: I wasn’t involved in the detailed aspects of timing and things of that nature.

As the chancellor’s external report reviewed, there was a very specific timeline of activities that occurred.

The grant was submitted, it was reviewed by an external review team from outside the state and then the recommendation went to the oversight committee and it was recommended for funding.

With respect to the length of the proposal, my understanding is that CPRIT gave very clear guidance on the nature of the proposal and what was to be in the proposal. Second, the point about it being a lot of support—as you know, cancer drug development is extremely expensive—you might know that it takes on average between $15 and $40 million dollars in industry for a single Investigational New Drug, on

average, collectively per IND about 140 FTEs [full-time equivalents].

So the drug discovery and development process is very expensive if you are trying to develop lead clinical candidates as opposed to research tool compounds.

PG: Since you have withdrawn this proposal and you are now resubmitting the document, what would it look like, and will you be resubmitting it for scientific review as opposed to just commercialization?

RD: First, I’m sure it’s going to be a very, very strong and compelling proposal—the progress in the institute has been quite impressive.

Although we didn’t withdraw the original document, we did offer to resubmit and will do so. We are waiting for the revised commercialization request for proposals now and I’m confident that the IACS leadership will respond fully and creatively with a proposal that demonstrates the expertise, the intellect and resources that we have at the institute.

PG: So it will be longer than seven pages this time around.

RD: I actually don’t know. I think we’re waiting for the guidance from CPRIT, but I’m not involved at that level.

PG: Will it go through a scientific review as well, or…?

RD: My understanding is that there are going to be commercialization and scientific review. You may want to check with CPRIT.

PG: I will.

RD: I think it would be an extremely welcome and healthy way of reviewing the grant, but I’m not familiar with the guidelines at this point or what the content of the grant would be.

PG: Well, let’s just be done with the incubator, but I guess the more interesting question is, what role does the institute play, within MD Anderson structure? And what role does Dr. Chin’s scientific vision play at MD Anderson now?

RD: First of all, Dr. Chin plays a very important role, just as all of our department chairs do. She is chair of a new department of genomic medicine, and her focus is on genomics at a precise moment when technology and scientific thought, concepts, are coming together to cause major disruptive change in the way that cancer is viewed and treated.

She’ll sink or swim on her own scientific merit and accomplishment here. I have great confidence in her ability to succeed, as evidenced by her track record, her stature in the field and her publications, including her recent Cell paper that just came out.

In the institute, she is the scientific director and she is one of the leadership group under Giulio Draetta, along with Phil Jones, Jannik Andersen [senior associate director of drug discovery], Joe Marszalek [senior associate director of target validation] and others that are in the leadership group that help manage the myriad activities that occur in the institute.

PG: It must be really challenging to work closely with one’s spouse. How is that working out for you?

RD: We have always been bound together by our common interests, not just in our family lives, but in our scientific lives and it’s been a tremendous source of, what’s the right word…Well, it has just been a very gratifying experience to share a common passion.

So, we have always been able to work very effectively together, because while we work in the same area, we emphasize different things. I’m more of a cancer biologist and geneticist, whereas Lynda is more focused on genomics. And I also work on aging and she doesn’t work in that area.

PG: At this point, it’s just a potential for, basically, side conversations—and just the difficulty of managing the potential conflicts and appearances of conflicts.

RD: Anybody that’s in the room for a few minutes with each of us recognizes that we actually spend very little time talking about science.

With three young children, we tend to focus most of our energies on raising our kids whenever we do have time together. We had, over the years, joint lab meetings—that’s where most of the professional interaction is.

Just to give you an example of how little we do communicate on the scientific level, it came as a surprise (to me) that Lynda had a paper published in Cell. And the way I found out about it is that MD Anderson had a press release today and I read the press release and I saw Lynda’s name in it and I’m reading on it, and I thought maybe she was commenting on another group’s paper, and it turns out that it was her paper in Cell.

So we are independent, we are colleagues, and we do have a lot of common interests scientifically—but we don’t spend a lot of free time together on our jobs. In the time that we do spend together, we tend to focus on family, our children and each other.

PG: I understand that you’ve said in the past that you made a financial sacrifice to come to MD Anderson, is that correct?

RD: I have never said that I have made a financial sacrifice. I have said that I’ve made a sacrifice or a personal sacrifice and I feel very honored and privileged to be the leader of MD Anderson, an extraordinary institution that each and every day does amazing things for many, many thousands of patients here and around the world.

PG: What was the sacrifice?

RD: To put it in perspective, Lynda and I spent four years renovating our dream home in Brookline, Massachusetts, and we were a few months away from completion, when the call came to lead this great institution. We felt that the choice, really…that that option took precedent over any personal challenges that we might have.

Also, our three young children were happy in school with their friends, they were thriving, and Lynda’s career was going very well. We had a very large support network of both of our families and relatively near in New York City. Dismantling all of that, particularly uprooting our children, was not easy but leading an institution such as MD Anderson is a tremendous honor and we’re delighted with the career choices we’ve made.

We’ve had the most fulfilling year of our lives, the children are amazingly adaptive, the schools in Houston are extraordinary, the arts wonderful. The quality of life here is spectacular.

It’s a vibrant city with great culture; great personality, and we feel very welcomed in Houston and it’s been a very, very gratifying experience overall. And I feel blessed, and I guess that’s all I have to say about on that matter.

PG: What were some of the business interests which you have that—investments and equity stakes in companies—that you had to give up or sell? How were those decisions made, about what stays and what goes?

RD: Sure. I have made a complete disclosure to the UT System and also to the Texas Ethics Commission, so you are free to look at that public information if there’s anything specific.

But on a high level, I eliminated my role in a number of companies that I was advising them in, due to the limitations of time and the need for intensive focus in the job that I now have the privilege of having.

The only companies that I elected to remain on were companies that I felt I was playing a special role that was essential for the success of the company, and by extension, where my role would help the companies succeed so that they could help patients.

The three companies were AVEO Pharmaceuticals, which is a company that Lynda and I co-founded over ten years ago. It’s focused on the development of drugs using sophisticated genetics and cancer biology as well as mouse model systems. The other one was Metamark Genetics.

Again, we were co-founders of that company and that company is focused on diagnostics to develop diagnostics for individuals with prostate cancer, to identify which men are at risk for the development of lethal disease in that context as well as in other cancers such as melanoma.

The third is another company that I cofounded, Karyopharm Therapeutics, which is focused on targeting nuclear export machinery as a novel therapeutic approach for cancer.

PG: And you got rid of?

RD: Again, the complete list of a few companies should be in the released documents, but to name a few, I eliminated my role as an advisor for GSK, for Epizyme, for Agios, for Enzon, amongst others, although I still have some equity from my service in Agios and Enzyme.

PG: And the reason is that they could do well without you, they didn’t need…

RD: That’s right. I was not a founder of those companies. I was merely playing a role as an advisor, and the question that I ask myself with anything that I eliminate or retain is, would it impact adversely on the ability of those companies to impact human health.

PG: So it was basically your own decisions, I suppose, with no feedback from the UT System?

RD: That’s correct.

PG: You were able to make the proposals—this is how you’re going to deal with the conflicts and they said, fine?

RD: Yes. And they have very strong conflict management procedures that are in place and we could give those procedures to you.

PG: I would love to see them. Recently there was some press coverage of AVEO trial that was proposed for MD Anderson [http://www.chron.com/news/houston-texas/article/M-D-Andersoninvolved-in-trial-of-drug-marketed-3711441.php].

Do you think, in retrospect, that it would have been better not to go forward with that study, which of course required you to seek a waiver for it to continue? Are you still seeking a waiver?

RD: First of all, there has been a recent story in the press and we’ve been successful in correcting some of the misinformation in that story.

We have not gone forward with the proposed AVEO study and it will not go forward until we receive guidance from UT System on the conflict issues.

Also, no waiver has been requested with respect to this specific proposed AVEO study. A general waiver of certain provisions of MD Anderson’s Conflict of Interest Policies as they pertained to a number of companies, including AVEO, was submitted to UT System.

Hand-in-hand with the waiver request was a detailed proposed plan to monitor and manage conflicts of interest if the waivers were granted.

Shortly after we became aware that AVEO issued a news release incorrectly implying that the study was open at MD Anderson and that a member of MD Anderson’s faculty was the lead investigator, we asked AVEO to clarify the release, as it would not be possible for the lead Principal Investigator to be at MD Anderson even if UT System granted the pending waiver, because of other rules that we have that manage conflicts of interest. It’s important to understand that those discussions between AVEO and MD Anderson started, I believe, in 2009.

This was a number of years before the job for MD Anderson president even emerged. But at this point, the trial will not open at MD Anderson unless the waiver is approved by UT System.

PG: So you’re still seeking the waiver?

RD: Yes. Absent a waiver, AVEO is unable to sponsor any research if the principal investigator is at MD Anderson.

PG: Right. With waiver requests, or one single waiver?

RD: One single request has been sent to UT System, but it includes multiple waiver requests and is not exclusive to this trial or to AVEO, and it includes a comprehensive conflict management plan depending on the company and type of trial involved. For instance, there are different rules depending upon whether the trial involves patients or not.

PG: Are you still aiming for the goal you called the moon shot? And does it still mean curing five cancers in five years, and is it sort of clear which of the cancers will be chosen, and when will this be rolled out?

RD: Well, I don’t know where you got the “cure in five years” information from, we are…

PG: I think it was from one of your speeches. If it has changed, that’s fine.

RD: No, no it hasn’t changed ever. I think it would be rather unrealistic that we would be able to cure cancer in five years.

PG: Or five diseases.

RD: So that we are extremely clear on that one point.

What I have said is that we have reached a point where there is a confluence of technological advances and significant conceptual breakthroughs and clinical proof of concept, such has harnessing the power of the immune system, affecting cell cycle, altering apoptotic responses, and a variety of other hallmarks for cancer where we have drugs that target those hallmarks result in clinical responses, some of which are quite dramatic, that puts us in a position to say that if we organize ourselves in a comprehensive way, in an integrated way, from prevention to early detection to prognostication to treatment and survivorship and recurrence, that we can significantly reduce mortality in this decade for certain cancers.

There are some cancers where we’re showing very impressive progress that if we apply what we already know today in a way that is translated and reduced to practice to help patients; in the area of early detection, for example, or in the area of combining very potent drugs with very significant clinical responses, that we will dramatically reduce mortality in those cancers. I can give you a specific example or two, if you’d like.

PG: I’d love to hear which cancers you are targeting.

RD: We’re actually going to have a review process from an internal and external advisory group, in fact, tomorrow and the next day, and that will allow us to prioritize these cancers.

We’ll initially select up to five cancers, inaugural programs, that we feel that we can put a team on the field that the knowledge in that particular area which is positioned for significant progress—diseases where we have great model systems, enough genomic information, drug interventions where we have significant responses in a proportion of patients that we can build on these current successes and make significant advances.

So based on those guiding principles, we will have selected inaugural programs, but the exercise of going through this strategic planning has set the stage for ultimate cure in the decades ahead, that what we are focused on is trying to develop a strategy for all of the major cancers that we’re focused on here, and for those that are not selected, this process will have identified areas for strategic investment at MD Anderson and our collaborators around the country and around the world to work together towards organizing this significant effort that leads to impact on patient survival.

PG: So what’s the target of when this will happen and which cancers…?

RD: We will make an announcement in September around the 50th anniversary of Kennedy’s moon shot speech which occurred here in Houston in 1962 and it’s an aspirational effort that, I think, is quite realistic based on the technological advances and based on the tremendous progress that we’ve made in the field in a number of cancers.

PG: What’s the target date to have these cancers, if not eliminated, controlled?

RD: I think it would be very difficult to answer that question. I think nobody knows the answer.

PG: You do not have that date?

RD: No, of course not, I think it’s just not possible to know that. But I do think, and I’m sure you would agree, that we’ve reached a significant turning point in history of the field. Let’s take melanomas, for example.

In melanoma, if one applies across a broad front, strategies and prevention, detection, and treatment advances, we believe that we can make significant reductions in mortality. In the area of prevention, we now know that excessive sun exposure during childhood leads to a dramatic increase in the incidence of melanoma in your 30s and 40s.

So one effort would be to implement educational programs in our schools in much the same we did for traffic safety with seatbelts, and ensure that children and their parents learn that they need to be protected from the sun at that vulnerable period in their lives.

PG: But that’s something that people knew for a long time, and do you need MD Anderson to tell you that?

RD: The educational programs that exist in this country are highly fragmented and of course, we’ll work with the entire system but what we want to do is inspire our schools to have that as part of their curriculum and to organize the information needed—the public service announcements and the educational materials so that we can move forward on that front.

MD Anderson does happen to be the most significant distributor of educational material to oncologists in the world and we would continue that effort in this particular context.

And here I’m giving you just a very specific example. In the area of prevention you would really focus on ensuring that there’s good sun protection at a very early stage in life.

Secondly, with respect to early detection, we know from a pilot screening program in Germany that a seven-year screening effort resulted in a 50 percent reduction in mortality, because you are catching these cancers at an earlier stage where the chance for survival is much greater simply by surgical excision.

With regard to early detection, there are also major advances in optical imaging, recognition software that is being developed as we speak to enable us to more rapidly identify skin lesions that would allow us to move forward on, and much improve early detection efforts.

There are also major diagnostic advances in early-stage cancer in melanoma that enable stratification of cancers that are hardwired to progress to lethal metastatic disease. Such prognostic determinants are being developed that allow us to stratify patients into aggressive versus more benign treatment paradigms.

And then, lastly, in the area of therapeutics.

The year 2009 brought truly historic advances on the treatment level, and here the discovery of the BRAF mutation in 2002 from Michael Stratton and Andy Futreal, who’s now at MD Anderson, and the development of the drugs squarely directed against that signature mutational lesion has led to a very significant increase in the survival of patients that have that specific event.

In addition, a truly historic event occurred from the work of Jim Allison, also another recent faculty member, who discovered why the immune system is dampened in the context of cancer.

As you know, cancers are not recognized well by the immune system—they appear to be sequestered from the immune response—he discovered a molecule, CTLA-4, that puts the brakes on the immune system, developed the drug against that (anti-CTLA antibody), and now it appears that one in four patients are alive at five years as a result of that treatment.

So let’s say we pick melanoma as an inaugural program—we haven’t made this decision yet—we would organize our efforts across the broad front involving aggressive educational programs with our school systems, new imaging modalities that more accurately identify early-stage lesions and new prognostic determinants to identify which lesions are hardwired for lethal progression and finally build on the tremendous therapeutic successes since 2009, with BRAF inhibitors, with anti-CTLA antibodies, some of the newer immune modulating drugs like PD-1 which are showing very exciting results in early trials.

With all of those integrated efforts—it’s easy to imagine that the now 25 percent survival rates of advanced melanoma and the impact of the mortality that we now have could easily rise to 50 percent within this decade as a result of those comprehensive activities that apply existing knowledge.

PG: Does CPRIT have a role in this?

RD: Well, CPRIT certainly would have a role from the standpoint that part of the way that we’re going to be funding this is through a combination of philanthropy as well as through grants from foundations as well as through a number of other federal grants.

PG: I understand that you have told the clinical department chairs at MD Anderson that they would have to boost revenues by another 10 percent. Is that correct?

RD: Yes. The clinical divisions have been asked, as in recent years, for an activity of volume increase ranging from five to 10 percent.

But this is for a division as a whole. We have more faculty each year to accommodate these volume increases, so the number of new patients seen by any individual faculty will be no higher than what’s achieved in many previous years.

We do target a modest increase of two to three percent in patients seen per provider as we seek to become more efficient over time and enhance, for example, IT capabilities, etc. And we always adjust the number of new patients expected to be seen by the faculty members’ stated clinical commitment.

PG: Will you increase the percentage of salary and grants to basic scientists? I think it was 30 percent and I believe it’s going up to 40?

RD: In 2006, John Mendelsohn [professor of experimental therapeutics and immediate past president of MD Anderson] and Margaret Kripke [professor of immunology emerita and former executive vice president and chief academic officer of MD Anderson] had an external group review of our research. One of their recommendations of the Washington Advisory Group was to increase the salary on grants, which at 30 percent, was significantly lower than comparable institutions.

That was increased to 40 percent in 2011.

Investigators were given about two years advance notice. I wouldn’t rule out further increase, but let’s remember, at many places, it is north of 80 percent, so this is something we’ll evaluate over time.

We also have an incentive plan, and if someone garners more than 40 percent, they get resources back—I believe it is still a very generous arrangement and it helps us both with retention and recruitment.

PG: I hear some of your staff tell me that there’s a great deal of excitement at MD Anderson, but directors of other centers and cancer hospitals are telling me that they are recruiting aggressively on the clinical side at MD Anderson and some are successful. Does this worry you?

RD: I believe that we have the most outstanding clinical staff that has been assembled anywhere. It has not been surprising that we do lose some wonderful people to other fine institutions so that they can lead other great institutions, but the number recruited away is small when you consider the critical mass of expertise assembled here.

We have 19,000 employees. Nonetheless, we fight hard to keep as many who are offered elsewhere.

We do our fair share recruiting as well and this has been an extraordinary year in recruitment. And so that’s more or less what I have to say about that.

PG: I guess you’ve stepped on some toes this year and you have stepped on a few landmines as well. What do you think are your strengths and weaknesses as a manager of such a massive institution?

RD: I’m having the time of my life. I’m new at this job and I believe I’m learning and growing every day and I suspect I’ll continue to learn and grow for the next decade or so.

I think I’m open and direct and I try to be respectful of everyone I work with. I probably try and pack quite a bit into each day—perhaps too much, but I also want to see my children for breakfast when I can.

John Mendelsohn and both his predecessors were all amazingly successful during their tenures as president, and that’s the great strength of MD Anderson.

PG: What about your strengths and weaknesses as a manager?

RD: Well, we now are, once again, ranked number one as the best cancer hospital. We have had our most successful year financially in its history. We have successfully recruited a number of extraordinary faculty and administrators. We are number one in NCI grants; we’re competing very effectively.

The largest number of high-profile papers in the history of the institution—Cell, Science, Nature, New England Journal of Medicine, and other journals of note—I think that we’re doing well as reflected by the progress that we’ve made in the institution.

PG: Was there a humbling moment—I have one every week, on a good week. Was there anything that you wish you had done differently?

RD: I think that a greater level of communication with respect to how the CPRIT episode was handled—would it have been better perhaps if they’d been more proactive to really explain what occurred factually. We attempted to do that again with respect to this recent story on AVEO, but unfortunately the facts were not as, let’s say, incorporated into the story.

So I think finding ways to be more effective in communicating across many different constituents in such a large and complex organization is something that I need to strive and work for each and every day.

PG: Well, thank you very much.

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