Tumor that represents an approach to the immunity. Fred hutchins focus is just a few notes before i turn the floor over to our first speaker, dr. Gilliland. Turn your cell phone to mute or off any other noise making devices. Once dr. Maloney made his remarks, we will open it up to questions. When you are called on to pose a question, identify yourself by name and organization. Dr. Gilliland . Thank you very much david for that fantastic introduction. I think you covered most of my talking points. I am gary gilliland, the president and director of the fred hutch. My colleague, dr. David maloney and i are excited to be here for an important announcement. Ill start with what david alluded to, which is the fred hutch has been in existence for about 41 years. Its the place where bone marrow transplantation was invented by dr. Don thomas. He went on to win the nobel prize for that work where patients with leukemias are treated with chemotherapy and radiation. Such high doses they would die from that treatment meant to rad kate the leukemia. What we didnt appreciate at the time but came to an understanding of is that it was the donors immune system that was so critical and the cure for potential of bone marrow transplantation. We didnt understand how that worked at the time, this was decades ago. Over the years, we and others have a deep and broad understanding of how our immune system works around the mechanisms that activate the immune system and turn the immune system off. Tumors have a way of turning the immune system down and that by understanding those mechanisms, we can develop novel approaches that harness the extraordinary power of our immune system to fight cancer. Based on the insights, dr. Maloney and his colleagues have developed approaches for treating cancer where we remove immune cells, tcells from a persons body that has cancer. They are genetically reprogrammed use zing technologies to seek and destroy cancer cells. They are expanded and then given back to patients as a single dose, one dose of a medicine. The dose of tcells we give is about the size of a grain of rice. Its a very small dose. And for patients who have acute leukemia, who have not responded to any treatments, in some cases have not responded even to bone marrow transplantation with the worst of the worst diseases with weeks or months to live will be injected with these tcells. In 90 of cases, we see complete responses that are durable. Thats another way of saying, from a clinical perspective, they may be cured of their disease. They have complete responses where we cant detect disease. Thats astonishing. When you see that type of result, its not like anything i have ever seen in the years and decades i have been working in this field of Cancer Research and treatment. You need to act on it and move with it because we can see curative potential ahead. To facilitate this effort, we have completed the building of a new imknow therapy clinic at the hutch, brandnew construction. A formal opening on december 12 with Scientific Symposium i invite you all to attend. This is named the baso family imewe know therapy program. This is in recognition to the extraordinary contributions the family made to the effort. Back in 2009 when imknow therapy was hardly a household word, they believed in investigators at the hutch who thought they could engineer the tcells. At the time, it was thought to be nearly impossible. They believed in us. As you know, the family is not adverse to risk, they are not adverse to failure. Through their support, we enjoyed extraordinary success in bringing the treatments to patients the certain type of blood form cancers. We are excited about this. You will hear more about it from my colleague dr. Maloney, the medical director of the unit. Its a first of its kind, state of the art, 15bed unit, patient centric where we bring everything to the patient, including the new therapies that require intensive monitoring. Much as for stem cell transplantation in the early days of those programs. We are sure it will propagate across the country as the bone marrow programs did. We are very excited to be on the leading edge of innovation in this space, to be able to treat patients with these approaches. We are especially grateful for the family for believing in us. They dont provide resources to name something. They are providing resources to shine a spotlight on the science, on the patients, on the investigators and we are delighted to be able to continue to Work Together with them towards developing curative approaches to cancer. What about that cure word . Its a bold and provocative statement to say we are on the cusp. We are on an Inflection Point where we can anticipate seeing more and more cure to therapy through cancer evolve. We are curing people already. Thats not the point. We know how to cure certain types of cancers. We may have more. Our challenge is to execute in the space. We need to expand the treatments so every patient responds. 90 of patients respond with a. L. L. , 10 dont. Who are the 10 . Why dont they respond . How durable are the responses . How do we mitigate the side effects . So, theres a lot we need to learn. How do we expand this into all types of tumors in addition to malignancies . They are the challenges we are working on. They are trackable. They are things we believe we can achieve and we have put a stake in the ground that said if we dont develop cures to all cancers in the next ten years, shame on us. We do have the capacity to move this field forward rapidly. Thats what this is going to help us do. The other challenge we face, of course, is how do we enable these technologies to move forward. It is one small part of that. We have many other issues to address. David alluded to the moon shot effort, which we participated in and met with Vice President bidens staff with greg simon yesterday. We have been activelyprocess. Its fantastic for supporting awareness and enhancing collaboration between the various Cancer Centers both here in the United States and worldwide. We are appreciative of the support that the moon shot brings. There are other enablers that the moon shot highlights like how do all patients have access to the treatments if they cant come to seattle . We need to make sure theres access and ensure they are trackable from a Health Care Cost effective stand. They can be expensive. Are they worth the value . If you are curing people, yes, they are Cost Effective. We need to solve for those challenges in a context where oncology costs are spiraling upwards. There are a number of policy issues to address. We are grateful to the fda for their support of development of the treatments where you can move drugs forward through a mechanism they developed called breakthrough status. You have a drug that has a dramatic effect. They help facilitate the development of those drugs. I had that experience when i was senior Vice President at merck. This is another therapy thats used to treat president jimmy carter. That drug was approved not on a random trial but an expansion study because the fda was supportive. We are excited about ricks leadership in bringing together in oncology the device in the fda that is responsible for Biomarker Tests and diagnostics and Drug Development and putting them together under one oversight responsibility. So, thats another fantastic enabler. We also need resources to support the development of these treatments. The nih budget is something we are affected in treating and grateful to our senator for providing support in the nih budget. But, we still rely on resource that is will come from other sources including philanthropy. I will conclude my comments there and pass the baton to my colleague to tell about the inner workers of the unit. David . Thanks, gary. Its my pleasure to be here and be named the medical director of the clinic. This is really a unique effort that we have taken in seattle based on the encouraging activity we have seen with this therapy. As you know, there are many things in immunotherapy. There are three we are conducting in the clinic. The first received the most press. Thats the gene modified or socalled receptor of modified tcells, car tcells. This is where we take normal tcells from a patient with cancer, insert a receptor, modify the gene to make a receptor to attack or attach to a target thats on the tumor cell. These cells can be grown outside the patients body and given back and track and attack the cancer. So, unlike any other cancer therapy, this is a living therapy. As dr. Gilliland said, we can give minute number of cells that multiply, track and destroy the cancer cells. They will go wherever the cancer cells can go. This form of therapy has yielded unprecedented responses, as you heard. About 90 of patients with instage leukemia can go back into remission. Early on after this treatment. Now, theres still a lot to be done. We are seeing a phenomenal signal that the power of the immune system of these tcells and their ability to get rid of a large volume of tumor especially in leukemia are impressive. We are seeing results, not quite as good, but encouraging in other diseases including nonhodgkins s lymphoma. The key of further development of the technology is to figure out why they work so well in some cases and why they dont work. We have seen relapses in some patients. When they relapse, we need to understand that. Another form of therapy is tilt therapy. In that case, you elect those trying to attack the tumor. The third subset is tcell recepto receptors. That is another approach we are seeing activity now in another form of leukemia called aml. What is unique about our center is that we believe the types of tcells you use to modify to attack the cancer is important. So, we actually will select a type of tcell, a helper tcell and a killer tcell modify each of them and give them back to attack the cancer. In Laboratory Studies in the lab we found that giving equal mixtures is way better than random mixtures which you get if you are unselecting the patient population. Why is that important . Its important because for the first time, we have been able to identify a dose end response relationship as well as a dose and toxicity relationship. What does that mean . We can tailor the dose of tcells but maintain theeth ka si. Thats one of the examples of how the approach is different in our series. Now, the clinic will enable us to translate research from the physician scientist to the clinic in a more rapid pace. Itis important to treat more patients and important that we can get new Clinical Trials on board. Right now, the focus in all the buzz has been in the malignancies. Obviously, those are not the most common types of cancers. The more common are Breast Cancer and lung cancer. We are beginning to develop tcells in the clinic now in those diseases as well. The future is extremely bright and hopefully translate the results we are seeing in the lymphoma into the more common cell cancers. Now, the again, the purpose of the clinic is to be able to translate the Clinical Trials from the Research Labs into patient Clinical Trials, obtain samples from the patients, blood test, analyze them and make advances and go back and forth. Because we are making them, we have the opportunity to modify those procedures and come up with advances. What does this mean for patients . I think it means well be able to treat more patients in clinics and have more trials open. Personally, for me, i have been involved in many Cancer Therapies over the years. I was involved in an antibody over lymphoma. But to actually see patients now with literally pounds of tumor have it melt away within three to four weeks and patients go into remission is extremely gratifying. But, we have a long way to go. We need to learn. We need to learn why it works in some patients, why it doesnt in some. Why the cancer can come back in some cases and be able to make this more deliverable to patients. Again, thats the purpose of the center. We start off small. We start off as one center. Thats the way bone marrow transplants start and are available in most countries throughout the world thanks to dr. Thomas leadership. I think i will stop there. Well take some questions. Okay, we are going to take questions from the press first, then anybody else who has information they want to pass. We have a microphone for you, please. Thank you. Im allen with science and enterprise. I know a spin off company from your Medical Center juneau therapeutics has licensed the Car T Technology and has been conducting some of the Clinical Trials. Are there other are there other Licensing Activities planned and will this help speed up the Development Process . Thank you. Thats a terrific question. The commercialization of these novel medicines is one of the most important aspects of what we are trying to do because, to the point i made earlier, thats how we are going to get it out to the general population. So, we are delighted to be able to license to partners like juneau that are experts in xherlization. Having industry experience is something we are not capable of doing in the academic environment. We look for opportunities to license technology and enable most importantly, enable access to patients. Patients are at the top of the list for us. The companies that we do partner with and license to are capable of executing in that space. Do you have anything to add [ inaudible ] any other licensing in the works or juneau the only one . Well, we have spun out about 42 companies in the history of the hutch. We have minnesota licensee ease. There are always licensing deals discussed and going on. We are actively engaged in that space. Lauren with the associated press. Why did this start with the blood cancers . Is there something unique that the tcells work better with those that will be a better challenge for the tumors . Ill take a crack at that one. Its a great question. I think it started, basically, because thats where we had the antibodies were the most effective. If you go back through the development of immunotherapy, in the 80s and 90s, we developed the antibodies. That took a long time to take off. The reason it finally took off is the targets on the leukemias and lymphomas were well defined and we could develop antibodies against the targets. What a car tcell is is the recognition part of the car. Its an antibody. A portion of the antibody can bind to the target. Its natural they will follow the trail of what antibodies have been developed, at least thats been in the malignancies. There may be an access phenomenon meaning in leukemias and lymphomas, they are blood cancers, the tcells could quickly get to the tumor. They are injected intravenously. They can get to the tumor quickly. Its not the case with a solid tumor. There are challenges ahead to translate into solid cancers because we have to worry more about the microenvironment of the cancers and the tcells to get there and do their duty. Good question. Sarah with the Hill Extra Health care. You mentioned the fdas breakthrough approval process and how helpful that was. Are there other things you need from the agency from the fda to keep this Therapy Development going . As i said, i think that the fda has been quite proactive of late in approving oncology drugs using breakthrough status. A number have been approved in a fairly short order. In fact, light speed compared to the typical time from enrollment of a first patient in to registration path for the drugs. One example, the median is 8 1 2 years to fda registration. Keep in mind, 90 of drugs that go first in humans fail to register. Itis a small fraction that get through the fda has chosen those designated with a high degree offeth ka si. The path of it is more rapid. That has an important impact for patients waiting to get access to the medications. As i mentioned, because we now know that we can stratify oncology patients for response to drugs, we need to have a test or diagnostic test. Having that process synchronize under the leadership is going to add further value. So, from my perspective, they are doing a terrific job. Theres another oncological form of cancer i know of that i havent heard of. I wonder if its inclued or applicab applicable. Thats multiple milo ma. Yeah. Thats a great question. So, we are actively developing Clinical Trials in multiple milo ma including tcell that is would be active in this arena. There are trial that is have been done at the nci and other centers that are beginning to show some activity in that regard. So, its a matter of identifying the target molecules on the tumor that you want not to be on any other normal tissues so when the car tcell or the tcell attacks it doesnt cause too much damage. The best way to think about it. We are actively working on targets and hope to have a program open in the next six months or so with testing of car tcells and that malignancy. Great question. Im carol james, member of the club and independent. Looking at how you seek to grow your model. How will you extend your collective cooperative to other Academic Centers of immunology across the country. Well, i think thats first of all, every center is trying to get into this space and calling it whether its antibodies or check point inhibitors or eventually krar tcells. Everybody is developing programs. I think what it will require is that these products are commercialized and theres several Companies Involved in trying to commercialize car tcells for leukemia and lymphoma and slowly advancing. Once those are commercialized, centers of excellence or centers that have the monitoring capacity to treat and monitor patients receiving this therapy will spring up across the country very widely. Is the process predominantly competitive rather than collaborative . Well, i dont think its completely competitive. It is collaborative. We are learning from all the trials. Theres clearly the groups involved, the major groups involved are comparing notes and obviously trying to figure out which process is the most effective and most active. Yeah. Those are very important questions and we wont be successful unless we are highly collaborative. We need to go across centers. Theres an emphasis on making sure we collaborate. I dont think its lack of good intention, we have complicated data sets and differing medical electronic systems. How do we work torgt . The main point is the competition is cancer, not the other Medical Centers. Thats our focus. My name is jerry. Im a Founding Editor of the bar journal and pat enattorney here in town for the last 30 years and retired from government in 1986 after arguing diamond versus before the Appellate Courts in washington and helping the solicitor general argue the case in the u. S. Supreme court. That was called the birth of biotechnology by some. It may have been. 1980. Today, you are, i think both of you are referring to your collaborations with other organizations which you are a part nccn, the National Cancer center network, i believe its an abbreviation for. It might come close. Anyway instant collaboration and telecommunication of knowledge back and forth from the various Clinical Trials that each of them is now being involved with. Theres about 26 centers. You are one in seattle. But there are others. Memorial in kettering, md anderson, kimmel, up here in baltimore, massachusetts general, all over the place. You are going to be communicating with an awful lot of fellow scientists in the future. You make a good point. We already have active and ongoing collaborations. As you know, the 42 designated centers the much is one, are highly collaborative and interactive. Thats part of the mandate from the support of the national institute. Point well taken. Can you tell us about where the tills stand . Well, as you know, till therapy has shown remarkable effectiveness in some melanomas and we are investigating them in other cancers. They are not quite as potent in general as car tcells. But, we are very excited about moving that forward. They were, as you know, developed largely at the nci and we have seen dramatic impact in some of these cancers. So theres not really a new focus then . Is it still melanoma focused . We are continuing with those disease s and trying to use mor tcells and find what the tills are attacking. The tills are cells that are in there and attacking the cancer. If we can figure out the targets, we can modify them to attack that cancer. I had including the incredible work thats been done in hiv infected patients thats led to some fantastic new therapies for hiv. We have the coordinating center for the worldwide Hiv Vaccine Trials Network where were trying to develop a trial vaccine for hiv. Theres a lot of cross talk that is in our approach to diseases. But the point i would like it make emphatically is that a very significant portion of cancers are caused by viruss in humans. About 25 of cancers in the United States that includes for example Cervical Cancer caused by human pap loama virus. Head and neck cancers caused by human pap loama virus. The opportunity when you realize that cancers are dependent upon the virus is that you can use the same techniques we use to treat infectious disease. So we can vaccinate and hutch was a very active participant in the development of human pap loama vaccine known as guardsill of merck. Which can eradicate the cancer worldwide. We just have to get it out. It works against 90 of Cervical Cancer. If we vaccinate girls and boys, we can eradicate Cervical Cancer. Thats from the immediate pathogen sis of disease. The other point i would make is that we have a center we just opened as part of our understanding that we have an understanding of the International Community in uganda. 60 of cancers in africa are caused by viruss. We believe there is a tremendous opportunity there to intervene with preventive approach answers some immune theyre pettic approaches are triggered and activated by viruss. That gives us an opportunity for therapeutic intervention as well. I was on a cruise this summer and met a pair of geneticists who i think are affiliated with the university of california San Francisco probably in their fresno shop. Ill use the first names. Bjorn and cindy. Bjorn travels to africa extensively to work with hiv patients. In africa. I suspect some of the work you just described is work he is now doing. I do not know that. But trying to develop vaccines for hiv or for any cancers caused by hiv virus, i dont know if thats yeah. Hiv does contribute to the development of cancers including cancers like sarcoma and cancers now the leading cause of death in patients with hiv which is something we need to work on. But its a sign of progress that hiv infected individuals are no longer dying from infectious complications. But to your point, this is a worldwide effort and were very excited to be a part of that and there is a direct interface between treating diseases he and treating cancer. Okay. Anyone else . I have a lot of questions. We would be happy to talk with you after the conference if youd like. Sorry . We would be happy to talk with you after the conference too. That would be fine. I think you gentlemen are closer to that than weve ever come, can you comment on what were going to be expectinging in the next five or ten years . Well, were putting the burden on our shoulders and saying we expect to have spectacular progress in the next five to ten years. I applaud the Vice President s goals of moving progress forward in five years what would have taken ten. Thats a difficult thing to measure. Were targeting cures for cancer in the foreseeable future. I also i would say that we dont want to overpromise and underdeliver, but compared to the other promises that have been made in the past, and the Vice President made this comment in the speeches, that when nixon declared war on cancer in 1971, he had good intent. But we had a knowledge about the underpinnings of cancer. And as Vice President said, he didnt have an army for that war. We now have an army. And we know where we need to go and we understand the mechanisms. So again, i would not want it overpromise and underdeliver but i believe we can put the stake in the ground and say this is the time we need to move on this. Okay. Anyone else . We have a question up here . Hi. I was just reading your literature about the Womens Health initiative and kind of the advances youve had in dealing with Breast Cancer. I was wondering if you could comment on the work you were doing there, how you can leverage what youre trying to do with immuno therapy and bring down instances of Breast Cancer. Thank you for that question, ryan. The Womens Health initiative is a fantastic study and it is another example of how we at the hutch are focussing not just on how do we treat kearns but how do we prevent cancer. It is much better to prevent cancer than it is to treat it. And the human pap loama vaccine is one outstanding cam many of that. The Womens Health study was funded by the government. Funded 160,000 people who have been followed more than a decade and led to remarkable vapss adv in understanding Womens Health at large and how we can understand cancer. For example, the study demonstrated we were using too high a dose of estrogen in symptomatic post menopausal women and that increased risk of Breast Cancer. That had an enormous impact of course on the patients lives and also on the cost of health care and productivity, families, all of the personal things that go along with Breast Cancer diagnosis. Its been estimated that although that study cost upwards of 200 million, that in terms of lives saved, that theres been a 37 billion savings in the cost to our health care system. So just emphasizes the importance of prevention. That if we can get out in front of this and prevent it from ever happening, thats always the most Cost Effective approach. We also have very active Smoking Cessation programs because that could have an enormous impact on lung cancer. We are focused on both ends of that. We are looking at Early Detection methods to pick cancers up before they spread. We hope to come to a time when we dont need therapies from cancer. But we are planning against both ends. We have a question in the back. Thank you. Speaking of estrogen compounds, are they still allowed in the foods that we eat in cows, milk, a lot of the farm animals . I know they had been pretty bad many years ago, and i know that they are very good promotors of Breast Cancer and prostate cancer. My name is doris margolis, member of the press club and president of editorial associates. Thank you. I must tell you that im not an expert in that arena, so i wouldnt be able to provide a definitive answer for you here. But i can find out for you. I can look into that. I dont know the answer to that. Okay. If there are no more questions, we can conclude this news maker. Thank you, gentlemen, for all the work youre doing. And we look forward to more developments to be announced. Thank you. [ applause will bring you three recent u. S. Supreme court cases, first case is solomon versus the u. S. , examining the governments power to prosecute people who profit from trading stocks on insider information. Then a case on how u. S. Citizenship is passed down to children from parents who are not married. Of that a case on whether a disabled girl who was prevented from using her service dog in school can sue the School District for emotional damages. Later attorney general Loretta Lynch talks about Community Policing on college campuses