Cheryl Dean:
Thank you everybody for coming. We’d hoped that we would be in person by now, but of course COVID still is persisting. And with the new Omicron variant, we are airing on the side of caution to keep everyone safe. So wanted to let everybody know that, let me, see the next slide, Zoom has a new option for closed caption, which you’ll see at the bottom of the screen, and that’s indicated by the yellow arrow. So if you’d like to use closed captioning, please go ahead and hit that.
And by now, most people have participated in quite a few Zoom webinars during the course of the pandemic, but for those of you who hadn’t, on the next slide, you’ll see where to be able to type in questions at the Q&A icon, and that’s syndicated by this yellow arrow. So please click on that, and then type in whatever questions, we’ve already had a few submitted ahead of time, and then we will hold those at the end. If we don’t get to all of yours at this webinar itself, we’ll be happy to get back to you in person. But, obviously, we can only do that, if you let us know who you are. If you have an anonymous question, we’ll try to answer that during today’s presentation.
So the next slide shows a web webpage where you can go to learn a little, little bit more about Salk’s research on COVID. While that’s not the topic of today’s presentation, just in light of the new Omicron variant, I thought I would mention a little bit of what we’re doing in light of that.
So one of the Salk scientists, Sue Kaech, told me about her newest experiment to see whether generating long lived memory T-cells in the lung will be sufficient to protect against variants that have mutated to evade antibody response. The antibody response that somebody would’ve had through the vaccine that we’ve all been receiving over the past year.
So part of her work will involve testing to see if the mRNA vaccines that would be the Moderna and the Pfizer vaccines, those were the mRNA vaccines, she’ll be seeing if they can generate memory T-cells that offer protection to those variants in the receptor binding domains. Because those are brand new technologies that were used for those vaccines. So here’s the link where you can learn a little bit more about Salk’s research onto COVID. There’s many scientists who have been doing related type work. But again, that’s not part of today’s talk.
Today’s talk is a very broad topic, which is nothing less than the Impact of Salk Science on Humanity, and how could somebody not be interested in that? I’m thrilled that we have today, Dr. Ha Nguyen, Senior Director of the Office of Technology and Development. Dr. Nguyen received her PhD in chemistry and chemical biology from UC San Francisco, after completing her BS in chemistry at UC Irvine. She’s also a registered patent agent with the US patent and trademark office.
Dr. Nguyen has extensive experience working with technology transfer, licensing, and business development, having worked in both academia and industry to manage intellectual property portfolios and commercialized life science technologies. She joined Salk as senior director in 2018. And when Ha isn’t at work, she’s on park fields, cheering on her two children in competitive science, enjoying family walks, now with a one year adorable Labrador puppy in tow, and watching The Great British Bake off for inspiration to bake. Please, welcome Ha Nguyen, and enjoy today’s presentation.
Ha Nguyen:
Well, thank you for having me here today to speak about Salk Innovations and the impact that it’s had on humanity. While I don’t spend my time in the lab anymore, I am a scientist at heart. And I am excited to be here at the Salk Institute and be able to engage with leading scientists around the world and hear about and converse with them about their science, and their innovations and learn about what they’re doing.
But as a tech transfer professional, it’s equally exciting for me to then play an active role in the scientists journey in helping them translate their discoveries into practical applications that will benefit the world. And I think one of the things that drew me to the Salk Institute originally is Jonas’ vision to establish an institute where cures begin. And it’s also encouraged at the Saul Institute for scientists to really not only be at the cutting edge of science and research, but to also push the boundaries and define what that cutting edge is.
And that is embodied in the multidisciplinary research areas at Salk that fosters collaboration and cross-disciplinary research. It’s also embodied in Salk’s undertaking of bold initiatives to help improve and address some of society’s greatest challenges today. As an example, we’ve got the Conquering Cancer Initiative, which tries to tackle the five deadliest cancers today. We have the Harnessing Plant Initiative, which tries to address carbon emissions and effect climate change through use of plants to sequester carbon. We’ve also got redesigning biology of understanding and designing our biological systems for effective use as therapies, which becomes really important for personalized medicine. And then we also have healthy aging and improving the understanding some of the processes of aging, and how we can improve disease as we age.
So with this, this really serves as the backdrop and the foundation from which innovations are born, and the ability for someone like myself to play a role in helping to translate those innovations into products and services that help humanity. And that is really what inspires me and gets me up in the morning every day, to be able to come to the Institute and be a part of it.
So for purposes of today’s talk, I’m going to focus on some of the advances and impact that Salk science has had, historically as well as present time, and also share with you some of the things that we’re doing now to enhance and elevate some of that research to have greater impact.
So let’s start with a historical perspective. So if we look at the approved drugs that have been based on Salk science, there’s been 15 to date. And while each of them will have their own development story, which I won’t go into today, I did want to highlight some of the examples where Salk discoveries have led to therapies that have made a difference.
So in the first one are two drugs, both of which are a histrelin acetate, their hormone therapies, Vantas and Supprelin, that was based on research by Professor Emeritus Roger Guillemin, who won the Nobel Prize in 1977, in physiology and medicine, for his research in neuroendocrinology and discovery of hypothalamic hormones. So you can see these two drugs are now being used for not only cancer, but also in children for central precocious puberty.
We have Targretin and Panretin, both of which are retinoid drugs, based on research from Professor Ron Evans and with his research. These are now compounds that are being used to treat a certain type of skin cancer in one case, and in another case to treat skin lesions that are caused by AIDS related Kaposi’s sarcoma. And in fact, some recent research from the Evans lab identified a new role for or one of these drugs, the Targretin, in neuroprotection, and now these compounds are being studied as potential treatments for Huntington’s disease.
And a third example is Prialt, which is a compound that was based on the work of late Professors Jean Rivier, where in his studies of neurotoxic peptides, and now Prialt is used to treat severe chronic pain.
So these are just a handful of examples to show approved drugs that have been based on Salk science. But I did want to mention that there are many, many more drugs or products and services that are not regulated by the FDA that have been very seminal in advancing scientific knowledge, and enabling new discoveries.
To give you a couple quick examples, antibodies, small molecules, these are compounds that have been used and sold as products by companies for research use. And then we also have nutraceuticals that are sold over the counter.
So now fast forward to present day, we have 15 drugs that are in development right now based on Salk science. And if you look at the examples, which I’ve highlighted here, these are drugs that are at various stages of development, some of which are being pursued for multiple indications, and we’re working with partners to advance these compounds into the market.
And so for purposes of this slide, I really wanted to highlight two main, one, is, just the diversity of therapeutic areas that are being pursued for therapies. So anything ranging from blood disorders like beta-thalassemia to inflammation, to muscle disease, to Alzheimer’s and then to cancer. And so there’s really, again, resonating with the research at Salk, just a breath of areas where Salk is making an impact.
The other point to highlight also is that these are drugs that are in development in partnership, whether it be with existing companies, biotech or pharma, as well as com companies that are founded on some of the Salk science that have been startup and spun out of Salk. And in fact, the four that I’ve listed here, the top four here on this list are startup companies that have spun out from Salk.
And so if I take a step back in thinking about the drug development timeline and process, it’s a really lengthy process that takes a lot of resources to go in. And if you take a step back and think about the number of products that have been approved or that are in the pipeline now coming from Salk science, I am completely awestruck by that number because of the attrition rate, when you go into a development program. And so to see this, it’s just really inspiring. And I really want to take a bit of a deeper dive a bit and let’s break down what the drug development process looks like to really emphasize this and appreciate the amount of effort that goes into getting a drug to market.
So many of you may already be familiar with the drug development process, but as I highlight here, just to kind of break down the phases, it’s fundamental research that goes onto a translational path of drug discovery, preclinical testing, to identify potential lead compounds that have drug-like proper, and then moving those into human clinical trials at different phases for safety and efficacy, before you get to, hopefully, an approved drug.
And I think one of the things that I hope strikes you when you look at this slide is, really, this is a numbers game. And for every drug that makes it to the market, on average the number of compounds that are in the drug discovery phase that are being developed and tested can range from 15,000 to 20,000 compounds. And only two percent of those compounds, on average, will make it to the pre-clinical stage, where you have compounds that look like drugs, but then to test them and get them into human trials, only about two percent of that number then will make it through that stage gate.
And you think about the timeline that it takes, which I’ve represented here, from the time of drug discovery to a time of approval, it can span anywhere, on average, about 15 years. And so it’s an incredible amount of time and resources that go in, and an incredible rate of attrition as you can see. So it really does come down to a numbers game of improving the odds and shots on goal, when you’re at the drug discovery stage, to, hopefully, one day get a product to market.
And I think, the other, I mean, I may be a little bit biased, but I think one of the things that has lent to success at Salk in getting drugs to the market, in partnership, I think, is a caliber of the research and the science that is done here. And I think it speaks volumes to the understanding that our scientists have of the mechanism and how our systems work in understanding how we can intervene and get to effective therapies.
And I think the other thing that I wanted to, and some of you may also be wondering, where does the patent timeline fit in some of this, because a lot of times compounds and drugs are patent protected. And so if we think about the life of a patent, oftentimes, the initial discoveries and innovations patents are filed early on, during the fundamental research stage. And once that patent application is filed, it’s 20 years from that filing date. So your 20 year clock really starts at that point. And so there’s that sense of urgency that once you’ve made that initial discovery protected it with patents, that you really try to partner and work with collaborators to try and move that compound into the translational pathway as soon as possible.
And I think the other thing to note is, because of the early stage and the early nature of the drug development process at the time when we file the patents, the strategy is to, hopefully, cover as broadly as possible. And that will, hopefully, cover the approved drug coming out on the market.
So I wanted to take an example from our pipeline and just to further highlight the drug development process. So let’s look at Rebozyl, which is a drug that was approved in late 2019 based on the work of Professor Wiley Vale’s research. So the original discovery that Dr. Vale and his team made was originally in 1991. And that’s when he identified the activin molecule and its receptor, and noted that it was part of the TGF-beta Superfamily for signaling that affects a broad variety of biological system and activities. But I think then he went on to discover and develop fusion proteins based on the activin receptor and developed molecules that could then dampen or block the activin signaling that could lead to disease. And based on that development, that’s where Rebozyl was inspired from, it’s a ligand trap that will block the activin signaling.
And so following the initial discovery, we had filed patent protection on the molecule, and then partnered it with a company named Acceleron in 2003, and Acceleron was actually a salt startup company that was co-founded by Dr. Vale. And Acceleron then took it from the drug discovery stage and pushed it forward. And in partnership with Celgene in 2011, for a co-development program of Rebozyl, also known as ACE-536, move that molecule into the clinic through phase one, two, and three trials, until it was approved in 2019.
So if you look back in the timeline, this drug took nearly 16 years to develop. And so I think this really underscores how much time and effort it takes from the initial discovery and getting something to market.
As a second example, I wanted to highlight a peroxi proliferating receptor-delta drugs that are based on Professor Ron Evans’ research. And these are also known as PPARdelta compounds. The original discovery made by Dr. Evan and his team was in 2003, where PPARdelta is recognized to be involved in energy consumption and balance as well as muscle fiber. And so with that discovery, the Evans lab began developing PPARdelta agonists that were specific to the delta isoform and none of the other isoforms. And so these were selective compounds, and they made about a 1,000 compounds as part of that drug discovery process.
And in 2013, we partnered the technology with Dr. Evans’ startup company at the time known as Mitokyne, and later changed its name to Mitobridge. But Mitobridge then in collaboration with Salk moved the molecules into further testing and preclinical development. And Mitobridge, then later partnered with Astellas in 2013 to move the lead compounds into clinical trials. And now we’re at the stage of phase two and phase three trials for indications like mitochondrial myopathies and acute kidney function.
And Mitobridge, and Astellas also were able to receive the FDA Fast Track designation for these indications, particularly because they’re either rare disease or very lethal indications that have high unmet needs. And so with the Fast Track designation, these compounds could, potentially, be developed in less than 15 years. So we’re hoping to be able to keep watch and see when something can get through approval.
So as I’ve highlighted from the last few examples, funding and partnership are very key success factors to achieving impact and making a difference for patient lives. And oftentimes, the early funding for the fundamental research and the initial discovery is supported through federal and private granting agencies, as well as philanthropy. And then as we move towards the product development and commercialization, it is heavily supported by the industry partners and investors of potentially new startup companies, as you saw. And technology transfer really plays a heavy role during that translational phase of moving technologies from academia, and partnering them into the hands of industry.
So we’ve had successes, that’s great. And I think in, in the spirit of Jonas Salk and pushing boundaries, we ask ourselves, what can we do more and enhance the impact that we can have? And if you look at this schematic here, you can see that there’s really a great opportunity when we think about the translation gap. And really that’s that gap of funding to support the translational research that oftentimes federal grants or philanthropy and industry aren’t focused in. Their goals and objectives are focused in other areas. And so where can we have greater impact? And that’s really in looking at how to fill that translation gap, also known as the Valley of Death, because that’s where the high attrition rate also happens.
So if we can address this by having a translation fund that will then bridge the fundamental research to the applied research, we can also amplify the translational research culture that is already at Salk, and really help to further accelerate the innovations that are happening here.
And then the co-benefit of being able to do this and fill that translation gap is increasing the value of the Salk technologies prior to the time that we partner it with industry. And that leads to value that goes back to Salk and value that goes back to the Salk innovators for the research that they’ve done.
And as a case in point, I wanted to highlight a very recent story of development around Professor Reuben Shaw’s work for Autophagy ULK1 inhibitors for cancer treatment. And so this story actually began in 2010, when Dr. Reuben Shaw, who is a well known cancer metabolism researcher, he and his team started collaborating with researchers at the Sanford Burnham Prebys Medical Institute, just down the road from us. And they were looking to understand the roles that autophagy has in cancer. And autophagy is the cells recycling system, program, if you will, where it basically takes cellular components, breaks it down for fuel, and as building the locks for new proteins and cellular components.
And what’s the role of autophagy in cancer? Well, cancer, oftentimes, are in very nutrient deprived environments, and they are also hit with chemotherapy agents and put under stress. And so cancer cells will really leverage the autophagy pathway to get the fuel that it needs to grow and proliferate. And so blocking autophagy has been a strategy that has been looked at for many years.
And so with the collaboration between Dr. Shaw’s lab and the researchers at Sanford Burnham, they had developed over 600 compounds and molecules that would inhibit a particular enzyme at the very beginning stage of the autophagy pathway known as the ULK1 protein. And so this is a drugable target that they were going after, and we filed patent applications to protect it. And then we went on to try and find partners for it.
But I think the challenge that we had was really twofold, due to market dynamics. One is the fact that there were actually a lot of research groups working at different angles and approaches to target autophagy, and they were targeting different places, different enzymes within the entire pathway. And in fact, there were already molecules in clinical trials that were being tested at the late stage of the autophagy pathway in combination with other chemotherapeutic agents. So there were already compounds in clinical trials. So it did make for a very congested marketplace in trying to push for new therapies.
The other market dynamic is that, in 2014, big pharma publicly announced that they were dropping their autophagy inhibitor program. And so that left, I think, a lot of skepticism in the minds of partners as to whether or not targeting autophagy and even a target that is upstream, that is a master regulator for autophagy, is that really a good idea as a target?
And so we had a lot of questions that were asked by our potential partners, is ULK1 a good target? Can you show that it has efficacy and will work in disease models that are clinically relevant, oh, and correlated with patient outcomes? And are there any negative side effects from targeting a molecule enzyme that is such high upstream in the autophagy pathway?
And so, in order to address these concerns, we really needed to do some studies that mimicked what a clinical trial would look like. And that these are the types of research that, again, funding from of federal agencies and granting agencies aren’t the type of research that those agencies will support. And we weren’t able to get the industry buy-in yet to get them to support some of these studies.
And so we really needed to identify resources and help with that translation, and we did. So Salk and Sanford Burnham used internal funds to then do a very seminal study that I think propelled us forward. And here I’m showing a data slide to emphasize, this was the key data that that partners were looking for and answered all three of their top questions. So what you’re seeing here is you, the ULK1 inhibitor treated in clinically relevant models that correlated with patient outcomes. So this was something that we were able to access through the translational research with collaborators.
And each of these bars that you see represent a genetically distinct profile that matched up with a patient that had lung cancer and the various mutations within lung cancer. And so what you can see here is that the ULK1 drug was effective, and is effective, in reducing the amount of tumor growth in many of these patients. And this is a percentage of reduction. So the higher the bar, the more tumor reduction that was observed, and you can see that there was clear differentiation across different genetic profiles, which suggests that you can stratify patients based on their mutations for lung cancer.
And so this really answered the question, yes, it’s efficacious. Yes, there is the possibility of using it to stratify the patient population. And in fact, as a result of this data, we were able to identify biomarkers that can be used as a companion diagnostic for patient stratification. And with the models that with were treated for daily dosing for several months, there were no adverse effects that we could see visibly. So I think that was extremely encouraging data. And once our partners saw that, we had multiple, multiple suitors for this technology. And so we really had the opportunity of… then the problem became identifying partners that we could work with and would be a good partner moving forward.
Ultimately, I think we had a lot of partners who were interested, but, ultimately, the happy ending is we were able to announce a partnership with Endeavor Biomedicines last September, which is a local biotech company in San Diego, to work with us and collaborate us to get this molecule now into the clinic in 2022.
And so this is, I think, a beautiful story to highlight the impact that translational funding can have in answering some of these key questions, de-risking the technology, and really increasing then the value of the technology where now partners were extremely excited about it. And so what we would like to be able to do is replicate this and have translational support that could fund other research areas and projects here at the Institute.
And what does success look like? I mean, if we could have the funding to fund the translation gap, if we had the support network that can enable and enhance the translational research here, I think that then lends to partnering, where we’re advancing products closer to the market, we’re able to attract licensing interest at a higher value return for the Institute. And then we’re also able to attract additional funding from other sponsors, whether it be to the program him itself, or just the fact that we’ve got fantastic science and research at Salk that, I think, lends to other successes, and interest of supporters to help the innovations here.
And so I’m actually very pleased to be able to announce that we had launched our inaugural translation fund earlier this year, catalyzed by a generous gift from Jay and Sarah Flatley through the Conquering Cancer Initiative. And with their generous gift, we had launched an inaugural award competition last month, and we are now in the process of accepting applications and proposals. And we’ll make a decision and selection for a proposal to fund first thing of the new year.
Additionally, to the translation fund and the award, Salk will be providing support, network support, of product development experts and project managers who can help then work with the researchers here at Salk and provide additional resources for them to do and perform their translational research.
And so, again, we are thrilled to be able to have this in initial award, and we’re hoping to be able to get additional funding, with a goal of three million dollars a year, to a translation fund that will be able to support across other research areas at Salk, in addition to cancer.
And so with that, I thank you for joining me today and giving me the opportunity to share the wonderful work and the innovations here at Salk and the impact that it’s had. And I leave you with another quote from Dr. Jonas Salk challenging all of us to be good ancestors. Thank you.
Cheryl Dean:
Thank you very much, Ha, that was fantastic. Lots of information sharing about all of the different work that you’re helping all of our scientists do, and to get the science from Salk out to the rest of the world and help humanity. So thank you very much for that.
Ha Nguyen:
Thank you.
Cheryl Dean:
You’re most welcome. To remind everybody, please, use the Q&A below to type any questions that you might have. And there were a few questions that were submitted ahead of time. So Ha if you don’t mind, here’s the first one. How is the money for intellectual property allocated back to the research and the scientists that have made the discoveries?
Ha Nguyen:
I’m sorry, can you repeat the question again? Just so I can make sure… I didn’t catch all of it.
Cheryl Dean:
Absolutely. Absolutely. How is the money for intellectual property allocated back to the research and the scientists that have made the discoveries?
Ha Nguyen:
Ah, thank you. Yeah. Sorry. So under Salk’s policies as innovations are partnered and Salk generates revenues through that partnering relationship, in the form of licensing of the intellectual property, it is shared 40% with the inventors and the research labs. And then the other goes to Salk, that goes back into the research fund in support of the research at Salk.
Cheryl Dean:
Great. Great, thank you. So another nice stream of income to help support future discoveries like this.
Ha Nguyen:
Yes, absolutely.
Cheryl Dean:
Great. Another one that was submitted is Dawn Benson, and she asks, what advancements are being worked on for autoimmune diseases, such as rheumatoid arthritis? And what activities relate to slowing down the aging process and enhancing the mind to reduce Alzheimer’s disease and dementia? So that’s an awful lot there, you can handle one part of it at a time if you like.
Ha Nguyen:
Great. Thank you. Thank you for the question. So maybe I’ll start with the Alzheimer’s disease and age related research, and maybe highlight some of the work that is being done now. I think you may have seen work from Dr. Dave Schubert, the late Dr. Dave Schubert, and Pam Maher, in develop being a compound called CMS121 that they have recently received funding for through the NIH Small Business Research grants to move that compound into clinical trials. And that is compound that is being advanced for the treatment of Alzheimer’s disease.
The other program that we have is in partnership with Abrexa pharmaceuticals, they’ve also licensed a different molecule J147. That was also resulting from the work of Dr. Schubert and Dr. Maher, that is also in a different trial for Alzheimer’s as well. And so these on molecules that are being pushed into the clinic now for the Alzheimer’s and age related disease.
On the rheumatoid arthritis and kind of autoimmunity, there’s work from Dr. Ye Zheng and Dr. Diana Hargreaves who are collaborating in understanding some of the T-regulatory cells that modulate the types of reactions to the immune, and also are exploring potential therapies against some of the targets that are involved in that process. Dr. Susan Kaech and Dr. Ye Zheng are also collaborating on a separate project, looking at rheumatoid arthritis and potential treatments and identification of compounds that could treat that.
So there is certainly active research collaborations going on as well in those areas. I think these are really great examples of projects that are going down the translational path, that would be great candidates for support through a translation fund.
Cheryl Dean:
Thank you for highlighting that. That’s really fantastic. And both of the compounds that are currently in the clinic for Alzheimer’s that were developed by Dave Schubert and Pam Maher that’s really exciting, since there’s so little that’s out there, that’s effective. And thank you for letting everybody know about that as well. Is there anything in particular that you are working on that you’re most excited about or that you would hope to be working on in the future?
Ha Nguyen:
Wow, that’s a really… I thank you for the question. I would say there are so many great technologies at Salk, I can’t pick just one. But I think that with areas of research, I mean, the Harnessing Plants Initiative is certainly one that has received a lot of attention recently in the work that it’s doing in using plant sequester carbon. But I think with the cancer center and the great research and the programs that are happening there in addressing some of the five deadliest cancers, pancreatic cancer, in particular, I think where there’s this high unmet need. There’s the work from Dr. Dannie Engel’s lab, for example, it is really inspiring to be able to be a part of that and support the research there.
Cheryl Dean:
Oh, that’s great. That’s great. And can you tell us a little bit about your colleagues within the Office of Technology Development, because you, personally, can’t possibly be doing all of this, how many people does it take internally for you to be able to address all of the needs that our scientists have?
Ha Nguyen:
We’ve got a fantastic team, so including myself, we’re a team of nine. Some are focused on the initial stages of establishing collaborations and identifying research support in areas for our scientists here, whether it’s academic collaborations or industry collaborations. And then we also have team members who are focused around supporting the intellectual property protection and partnering, marketing of those technologies, business development, and trying to identify companies to partner innovations moving forward. So we really do span the entire spectrum of supporting the research here.
Cheryl Dean:
Great. And is there any chance that you can give us a sneak peek or some additional information about the candidates that you’re looking to be the first recipient of the translational fund that you talked about? Which is really an amazing opportunity to be able to save something from the Valley of Death and funding to actually get some of the research through that part of development so that it can be licensed out or partnered with another company?
Ha Nguyen:
Well, it’s important-
Cheryl Dean:
Are you able to tell us that or not?
Ha Nguyen:
Well, that’s a great question, but since we’re still in the application process and accepting applications, I’d hate to put out any spoilers at this stage. Like I said, I think by January, we’re hoping to be able to announce our first awardee, and we’ll be thrilled to share. So if you can hold out for one more month, we’ll have wonderful news to share then.
Cheryl Dean:
Wonderful. That’s great. But you have received plenty of submissions that you’re able to find something, you think?
Ha Nguyen:
Yes, we have received submissions, and we’re very excited about them.
Cheryl Dean:
Great. Okay, well then we’ll just have to be patient and we’ll get some good news in the new year. I think that is all of the questions that are showing up on my screen right now. So if anybody else has a last minute question that they’re thinking of, please feel free to type it in, but in the meantime, thank you so much for joining us. I apologize for the technical difficulties earlier in the talk with the audio. So glad that that all got fixed up. And this is the last public webinar that we are having at Salk this year. It’s hard to believe we are already in December. But going forward, we obviously hope to be able to transition back to doing some in-person, not in-person webinars, well, actually they will be, in-person events in our auditorium where you can hear directly from our scientists.
But for those of you who are not based here in the La Jolla area, I will be making sure that there is a hybrid component, so that you can join via the internet. We do record them, but it’s not the same, in case you do have a question and want to be able to get that asked in real time. So we will try to be doing those hybrid once we’re back in-person. And you’ll receive information about that from us in the not too distant future. But Dr. Nguyen, thank you very much for your time. And I wish everybody healthy and happy holidays. Thank you for joining us.