 With that, we'll now step into one of our standing panels that we have every year. It's a panel on easily the most fast-moving area of drug discovery and drug development, still with immense challenges, but now also immense opportunities. This year, we add a wrinkle, as we do in every panel, which is COVID-19 and the effects that the pandemic is having on oncology drug development. And it's a great pleasure to introduce our panel moderator, Raju Kokhrilapati. Please, Raju. Andy, thank you very much. It's my great pleasure to be a part of this annual event, which is great, and the program has been going tremendously well. We have a great panel for our discussion today, and we have Alice Reisen from Tech Clinic, and we have Laurie Glimcher. And just as an aside, it turns out that Laurie's son, Jake Archencloss, was declared to be the winner of the Democratic primary for the first district of Massachusetts, and so therefore is most likely going to become the new congressman from Massachusetts. And Laurie, congratulations. And then we have Phil Archen from Bayer, and Rehan Bershey from Serono, and Tony Hall from CRISPR therapeutics. So as Andy pointed out at the beginning, there's an explosion in the knowledge about the human disease, and cancer has been leading this knowledge explosion, and so the last 15 years has seen a tremendous amount of change in the way that we've been able to treat cancer patients, and the outcomes for these cancer patients has changed tremendously. But as many people pointed out, the pandemic has an effect on this. We'll stop the discussion, and I would ask Laurie to make a comment. Laurie, how did COVID affect treatment of patients, and did the pandemic affect the overall survival outcomes for patients in treatment? Well, thanks, and I'll let it to be on this panel. Thanks for inviting me to join, and thanks for the kind words about my son, Jake Archencloss. Dana-Farber has certainly, as all hospitals have, seen the impact of the pandemic, and cancer patients, of course, are more susceptible to developing COVID-19 because they're immunosuppressed. But I will say that I've been just overwhelmed and inspired by the way that Dana-Farber and other cancer centers have stood up to make our patients feel safe and welcome. We certainly did the best we could to reduce the risk to patients coming in using a number of methods to do that, including trying to put patients who could be switched from intravenous chemotherapy or infusions to oral medications without affecting the course of their cancer. But I do think that, as Ned Sharpless said, who's the director of the NCI, that we are going to see an increase in cancer mortality over the next year or so because there was a 96% decrease in the number of screenings for colonoscopies, mammograms, pap smears. And so we clearly have seen a decrease in the number of new patients that come in who have been diagnosed with cancer. That's obviously not good for cancer because if we can catch cancer when it's at stage one, we can pretty much cure it. But if it is already metastasized, then we have a more difficult journey ahead for those patients. Dana-Farber did not cease their clinical trials for cancer. As we all know, cancer clinical trials were allowed to proceed. Some cancer centers were not able to do that. But Dana-Farber did continue enrolling patients because 20% of our patients, their best option is to be part of a clinical trial. So a tough time for all of us, but I think that cancer centers around the world have done their very best to provide a safe environment and to continue treating our cancer patients who need us. Laurie, thank you. Thank you very much. And so that actually leads to the next question for all of the panel members. How is this in a COVID pandemic affecting new development of new cancer drugs and therapies? And is this, first of all, is this having an impact on overall clinical trials? And is it also having an effect on R&D? Is it going to change the timing of approval of drugs and the development of new drugs that everybody's anticipating? So maybe we could start with Phil. Yeah. Thank you very much. And I would like to also express my gratitude for being part of the panel. I think it's fair to say that throughout the world, clinical trials in oncology are recruiting at a slow pace for the exact reasons Laurie just mentioned. It's difficult to get the patients to show up at clinical centers, but it's also pretty clear that the diagnosis of cancers are happening at a slow pace because our medical professionals are busy treating patients with COVID-19 and for that reason have less attention to also tracking and discovering early cancers. There is one area in particular where I see a lot of increased activity and that's in the field of repurposing drugs as antivirals and actually quite a lot of the drugs acting on metabolism, cell proliferation, cell division are drugs that come out of cancer screening programs and some of them have shown both based on digital and in silico tools, promising effects on viral metabolism and viral replication. And I'm pretty sure that some of the new antivirals we'll see could come out of repurposed cancer screening programs and I think we'll see that there is a joint effort here that's unprecedented. Many different companies come together in public-private partnerships and try to find fast-track opportunities to really bring forward new antivirals. So maybe just to frame it because we've looked pretty broadly at basically what have been the patterns I think in terms of clinical trial disruptions in oncology and the data is actually quite interesting. What it suggests is during that critical phase about two percent of all oncology clinical trials were impacted by COVID. Some of those which has sort of impacted suspended and some of those have been permanently discontinued and to put that let's say into context it's about 300 clinical trials it's sort of the estimate at this stage and so that's in terms of volume of activity. It's almost like the entire volume of clinical trial activity for a major enterprise, something like Roche, which basically has a portfolio of around 300 clinical trials that they're going to be running at any given time. So that gives you a sense of I think one aspect of the magnitude. I think what's been encouraging is that 60% of those trials have resumed and so I think that's positive and generally speaking I think the common refrain is that more than anything it's really just a case of delays in about four to six months I think in the conduct of those trials. I think what that analysis doesn't sort of tell you is what are the trials that were going to be initiated that weren't initiated. There were estimates there that basically about 60% of those trials potentially was sort of impacted and what it also doesn't tell you is the research activity and how that was impacted. I think Cancer Research UK had some very interesting data and I think when you look at charities that raise a lot of money and basically put that money into cancer research I think they've been particularly impacted and Cancer Research UK is a good example. I think they said that in about they estimate that they put in about 400 million every year and around 150 million I think there's a reduction that they're sort of anticipating. So I think if you put that all in context I think what it says is that there's definitively an impact. It's not catastrophic but definitely I think there's an impact and I think what's been interesting though for sure is the adaptations and I think a lot of the adaptations that have been made both on the provider side the side side and I think on the company side are arguably going to be sort of here to stay and they range from what can you do in terms of remote site initiation, remote visits, remote monitoring, ensuring that you get investigational product direct to patients, administration of investigational medication outside of the actual center and a lot of these things are moving and so I genuinely believe that while there has been an impact it's been an important learning and arguably an important pivot point for the way that we actually do clinical research and I think that not only will that potentially make things more efficient in the future based on the learnings but certainly I think it buffers against a similar sort of impact if COVID comes back as a second wave. Thank you very much Alice. Yeah just a couple things to add to that. On the last point I think it will potentially because of sort of trials at home which I hope will continue it could increase the number of patients who get access to trials and therefore make hopefully enrolling trials in the future easier. There were I think just anecdotally I think depending on what was being studied in the clinical trial some studies were impacted more than others I think some of the CAR T studies in particular probably were impacted because of the type of care that's needed for those patients in the short term as well as the amount of immunosuppression that's being given to those patients and concern around that and I think some of that is starting to get back on so I think it was probably a little bit uneven as well similar to what Laurie was saying that even in just regular care physicians were changing how they might treat patients I think you got the same sort of thing depending on what clinical trials they might want to put patients into. Tony? Yeah so I can just tell you sort of our company's experience we were running for CAR T a trial when the COVID hit and you know it sound our side we're temporary on home where it's a prohibit side business so we we actually had to really quickly adopt to sort of the situation shifting enrollment from the site that's open and also learn how to do site activation remotely also how to teach people how to infuse these cells and manage these cell remotely so I think some of the good came out of these adaptations that make us actually much more efficient and at the end we actually look at our timeline didn't slow us down despite all the challenges but it really teaches us a lesson that you know how to overcome these hurdles I think this will like at least saying you know eventually bring benefit to bring clinical trial to more people and and and broaden the reach of class thank you Tony everybody is thinking that as a result of this pandemic that there is going to be a new normal do you think that Laurie the way that you take care of all of the cancer patients at Dana Farber and other places are going to change is there for example significant amount of online consulting or what has been talked about earlier the role of personalized medicine precision medicine going to play an important role in getting for patients oh I think there's any lining to the pandemic it is the lessons we've learned from COVID-19 and amongst those is that uh telemedicine can be very helpful uh Dana Farber was doing about 10 to 15 telemedicine visits a week before the pandemic started and we talked about oh we should really increase these but when the pandemic came within two weeks we were up to 3 000 telemedicine visits a week for our patients now you know people who have cancer need to be seen in person when they initially present the first time a new patient comes that patient needs to be seen in-house because we assemble a family around that person it's not just the medical oncologist it's the radiation oncologist the nutritionist the nurses the physician assistants the the surgical oncologist we like to surround each patient in this in a time that is so fearful for them and they're so anxious with a team of people who are their new family but when you're coming back for return visits many times that can be done very well virtually and we have found actually in our experience that our patients are very happy with telemedicine um for follow-up visits it saves them time and travel and we're able to assemble that team that family virtually as well as we could in person so my guess is that telemedicine is going to be with us for a long time it needs to be reimbursed at the same rates that an in-house visit will be reimbursed otherwise it's going to be very difficult for providers to basically to afford this because telemedicine is is is a financially losing proposition we lose money on telemedicine so i just want to put in a plug for for all providers and for all payers that we do need to be reimbursed at an adequate level in order to keep on doing this but it is good for our patients i think the second thing is that we've learned the second lesson is that you know a lot of people can work remotely we have 5000 employees at Dana Farber 3000 of them are working remotely um obviously our healthcare workers are are in but but financial administrative tasks can be done remotely and i would guess that of those 3000 people now working remotely probably about 1500 will remain working remotely because it helps in a work-life balance if you don't have to spend time getting to work and leaving work so this can be very good for our workforce as well and i think it's also cost-saving we don't need as much space we don't need people writing the tea etc etc so i think we've learned some really important lessons and if i could just say one further thing i just wanted to follow up on philips comment about repurposing drugs cancer drugs and a good example of that is a brutinib which as you know is used for lymphoma for thousands and thousands of people it's safe it's FDA approved and one of our faculty members at Dana Farber saw that the molecular pathways that activate COVID-19 are similar to the pathways that are activated or inhibited by a brutinib and so doing a clinical trial at Dana Farber which looks very promising that in patients who are on ventilators or are in threat of being on ventilators um you can really help prevent that by treating them with a brutinib which is pretty exciting thank you lori alisa do you think that this pandemic is going to have an impact on drug development and uh or there's going to be a new strategies and approaches um well you know one thing i hope is that there's um in the general public they start to more understand the importance of clinical trials and potentially enrolling in clinical trials and as i said before more you can make a clinical trial where it can be done remotely and you don't need patients to be in the clinic the more access you have to patients who live 50 or more miles away from the nearest clinical trial so i am hopeful that it will have an impact in that way and i think as has been discussed you know on other panels i certainly hope there is a greater understanding of the need for investment in r&d and i'll i'll give a pitch it was you know for antibiotic research for resistant antibiotics and and other things i have an id background originally so um something near and dear to my heart because i really think it is something that we will be dealing with in the future and unless we invest in it now we won't be ready for it and and it impacts cancer patients in particular because when you get resistance or organisms you tend to see them earliest infections or immunocompromised bill do you have a comment yeah there there's one thing i i uh wanted to um you know that's essentially um sort of a plea to uh the clinical research community because uh today we have a very large proportion of uh cancer patients being exposed to um uh covid or to the coronavirus and with you know a positive test it should be possible in a real-world setting to understand you know which of the patients on what medicines fare worse which are you know actually you know having a lighter because i don't think it necessarily goes that every patient on um you know cytostatic therapy or more personalized cancer medicines would actually have a worse outcome it might be that the cytokine storms we see in conjunction with covid 19 or actually um you know uh flattened uh and to some extent there could be some benefits there to the case just heard we just heard about in brudenib there might be some of the kinase inhibitors we put patients on that are actually also antivirals and since there are now thousands if not hundreds of thousands of uh patients who've you know been tested positive uh there should be sufficient data material to really understand if um we can you know get some insights from simply just mining the databases rehan well i i would agree and i i would say to maybe just add to Bill's point is i do think that the community has come together in order to to create i think the registries and i think we've started to see some really interesting and informative data start to come from it and and absolutely i think it'll be interesting to see what else we can glean from it um and i would just echo what lori said i think this has been a huge experiment you know we were all forced by the same pressure at the same time to completely you know jump into the future you know a future that we have all been discussing and pontificating about but always resisting because we didn't think it was quite possible to operate in that environment and all of a sudden we've had to do it you know for us we've had to jump into that relationship with physicians with patients and you've had to do the same i think what's what's helped is that it's just been this giant two-sided experiments and everybody's had to adapt at the same time so i believe 100 percent um that we are completely now in a realm of new opportunity um and i think you know it definitely has the prospect of um improving i think patient care and i would also argue back to Elise's point that from a company perspective i think we see tremendous opportunities i think to support um i think access to medicines through the commercial side now in a far more efficient way and i honestly genuinely believe that that could lead to significantly improved investment in r&d across the board and i think that's the challenge that we have to give ourselves 100 percent thank you thank you very much so as we pointed out at the beginning of this conversation that the last 15 years has seen a tremendous revolution in the both the types and the number of cancer drugs and therapies that have become available and these include targeted therapies, immunotherapies, cell-based therapies so what is the perception of all of you in terms of where you know this drug development is going and what are the directions that are taking maybe we'll start with Tony sure i think certainly um you know oncology has progressed uh quite a bit it's very exciting nowadays but i just want to point out you know editing technology like CRISPR help us program cell to gain super ability beyond normal TNK cells for example we can program these cells make them resistant to exhaustion to microenvironment even make them to modulate to microenvironment and endogenous immune response so i think we're just starting to learn how to build these super ability onto these cells and but you know even just a short period of time where we learn quite a bit from them CRISPR really allow us to rapidly prototyping these cells and make multiple versions of these so quickly this the knowledge we gain from these cells in the clinic then can be feedback and refine our design so i think in the future we will be operating more like a technology company rapidly prototyping these cells and learning from them until we achieve pure uh impatience this really uh i think uh as a group transform no CRISPR for example is not a tool company by knowledge driven company in that uh you know knowledge gain will allow us to know what bills and ways that we need to build into the cell for particular tumor type and particular patients and and really the game is eventually gained to cure uh stage thank you uh lori uh you know much of the cancer drug development and therapeutic development really stems from my basic research and are there uh trends at your institution or around the world uh about toward the directions in which cancer therapy is going and what do you think are the prospects for uh developing real cures for cancer but let me say first that this truly the last two decades have been revolutionary for cancer but we really can't be complacent because while the mortality rate from cancer has declined over the last 25 years the incidence of cancer is increasing and alarmingly so in young people an example would be colorectal cancer i i i've seen so many patients come into dana farber who are in their 30s and 40s and who have metastatic colorectal cancer so we have a long ways to go some key priorities i think one of them is an immunotherapy because right now there's only five immunotherapy drugs that are being marketed and they help about 20 to 25 percent of all of our patients and only about 10 or 11 tumors so we have a long ways to go for immunotherapy we need to attack the innate immune system as well as the adaptive immune system we need to control and reprogram the immunosuppressive tumor microenvironment that surrounds that tumor it's full of immune cells and other cells that are immunosuppressive gotta figure out how to make them immunoactive we also need to detect cancer earlier because we all know that if you get stage one cancer you can cure it but the 75 percent of people who prevent who present with metastatic disease much harder to give them a good outcome and early detection is a very big priority for dana farber for example you know 10 percent of cancers are inherited we should be able to identify those individuals and protect them with frequent screenings braca one is an example of that and at dana farber we are testing all women who have an ashkenazi jewish background because one out of 40 of them is going to be braca mutant and we can prevent breast and ovarian cancer and now we know that 10 to 15 percent of patients with pancreatic cancer and with prostate cancer also have dna repair mutations so dna repair understanding how to harness our knowledge about dna repair is going to be very important epigenetics this is the future as well it's the it's figuring out how to take a cancer cell and turn it back into a normal cell and that's just the beginning of this field we need more epigenetic drugs and and there's more but i want to emphasize how important it is to continue to fund basic fundamental science because without basic science there is nothing to translate and i think bill kaylan from dana farber is a great example of that he asked a very simple question how does cells sense oxygen and of our 20 to 30 year career he figured out how that happened and now there are drugs that target the pathway that he discovered and he uh just a few months ago received the nobel prize for that work along with peter ratcliffe and greg semenza so we must continue to fund fundamental science there's so much more to do in cancer glory thank you rehan what's the industry perspective yeah well so i think if you you know if you really want to improve survival then the biggest thing that you have to focus on is the early detection and diagnosis so i agree that i think if you if you want to drive up cure rates then you've got to have an immune therapy in the mix um and so from our perspective you know we're we're genuinely really excited obviously about what's happening platform and the opportunity to learn i think from the tremendous efforts uh and successes i think in the field of immune therapy and i fully agree with with with what lori's saying and so um you know what are we most excited about is the prospect of i think building on the platform i think of pd1 pdl1 success with some very rational well-thought out combinations potentially like addressing the tumor suppressive microenvironments at the same time um and i think the other field honestly that i think is is really exciting and i think we're going to see so much more from it um and it has the prospect of just being able to combine so well with immune therapy and drive up response rates and cure rates uh is is the field of adc's antibody drug conjugates uh i think just the prospect of being able to deliver you know cytotoxic with precision um and basically you know drive up the potential to be able to amp up the immune response i think we've seen some really good experiments that are basically showing the promise of that and i do think in the next two to five years that's going to play a pretty big role that's great i'll see your perspective um maybe i'll just mention a few things with a little bit more detail uh first of all the innate immune system i agree with lori that is definitely i think one of the next new hot areas of the immunotherapy and i think there's some emerging data on um changing the balance between um immunosuppressive macrophages and um immunoactive macrophages that's starting to look promising nk cells are really looking promising both nk car cells which look like they've got good efficacy and maybe a better safety profile as well as the ability to give them allogeneically and as well as um nk engagers that look like they activate and then downstream b and t cells i think the idea you know um liquid biopsies i think is going to change um early detection but i think it's also going to change cancer care as it becomes easier to monitor the mutations that a patient's cancer might get over time so you can really on a per patient basis decide what the next best therapy for that patient is i think the next place that needs to open up and i i think we're in the early stages is what the biomarkers are to determine what the best immunotherapy combinations are per patient we've been talking about that for many years i don't think we've seen quite enough advancement there and i'm hoping we'll see that in the near future thank you and we have a question from one of our participants and i invite tim claxon to ask a question of the panel tim thanks garon um i'm not sure whether i can be seen but it's a pleasure to enjoy this this discussion my question is really pivoting back to to the covert discussion earlier and in particular thinking about the challenges about clinical trials i wonder whether the panel thinks that we could or maybe that we should see some elements of regulatory flexibility as the current wave of clinical trials moves forward i'm wondering for example for highly promising experimental therapies whether that could be a greater leaning on single patient ind data at least for accelerated approval and then for drugs that are already on the market maybe a greater leaning on real world evidence so what does the panel think about opportunities to make lemonade out of lemons from the start with phil phil phil do you want to start yeah and yeah especially the the last point you bring up i think there is a chance to actually um uh you know based on real world evidence to qualify that certain therapeutics will be effective and whether you could get an emergency sort of approval through that or whether you would still be needed to run an rct prospectively is obviously off discussion but i think we've seen a lot of flexibility among the regulatory agencies in the u.s. as well as in europe to provide both you know fast approvals of trial protocols as well as um uh exempt approval for a certain therapy so so that's pretty clear i'm not so sure about you know the ability to get i would say uh approval or a go forward signal based on just a single patient or i i don't think we are quite there yet so i personally i don't think we've in bayer had any experience with that but i would also be hesitant to move that forward because at the end of the day it's also the industry's credibility it's at large which is really um you know at stake here and if we push it too aggressively and we end up with too many i would say uh is it a modest or murky data uh without being able to conclude that and i think we're doing ourselves at this service i agree with philip um we do need to be very careful here we need to make sure that we are administering drugs to patients that are safe for sure and also have clinical efficacy and i think we've seen what's happened at least in the united states in that regard we really we really must listen to to people like tony fouchi dr fouchi and be very careful what we do and not approve drugs that don't have very rigorous and uh well-defined efficacy and safety i i actually i actually think there's a risk for the industry right now that if there is lack of confidence in the fda that could negatively impact us and so really the next few months i think are going to be critical we've been in that position before where the fda got much more strict we've recently we've seen it in the opposite direction especially in oncology and we'd hate to go back someone asked about real-world data there is an example of the fda approving a new indication for therapy using real-world data i think um visor's cdk which was approved for women with breast cancer i think their indication in men with breast cancer was based on real-world data i'll ask tony go ahead go ahead i would just like say that as we have seen covet is very important to have strong and validated clinical data many of the supposed therapy that was initially touted you know just uh you know entire six for example turn out to be negative in randomized trials so so i think we we had to be a little bit rigorous here if you approve a drug that turn out to be ineffective in fact you're actually blocking the more effective drug from coming because you know in oncology you always say you have to fail this drug after failed that drug but you fail a a drug that's not very good actually uh slow down the progress in effect so so i do agree i think the other thing we've learned from covet is that there are ways you know sort of um retroagency can sort of demonstrate leadership and flexibility and certainly i always think oncology you know is always a great example where they they show a lot of flexibility and partnership with the industry i think that should be encouraged especially after this lesson on covet and this will help us progress the drug develop much faster tony thank you very much and i want to thank the panel for this great discussion about the exciting things that are happening and it's now time for a five minute break and i want to remind everyone to participate in our online polling uh below this video window you can scroll down to find the panel two questions and please submit your answers and uh well and then we open for one minute thank you very much