Study Update

Jun 4, 2021

Hello. Welcome to the Cullinan Pearl Clinical Update Webinar hosted by Cullinan Oncology. Please be aware that this call is being recorded. I'm Juliet Labrador with Investor Relations here at Cullinan, and I'm pleased to introduce today's call, which will focus on the ongoing Phase IIIa clinical trial evaluating CLN-eighty 1 in non small cell lung cancer patients EGFR or epidermal growth factor receptor exon 20 insertion mutation. The datasets presented are available at the poster presentation in the 2021 American Society of Clinical Oncology's Annual Meeting. Before we proceed, we may be making certain forward looking statements during this program. This may include statements regarding our preclinical and clinical development plans, clinical trial design, the strategy of our product candidates among other topics. We encourage you to review our forward looking statements in this slide deck, which will be accessible on our website to sequence the call. Providing prepared remarks on the call today will be Owen Hughes, Cullinan's Chief Executive Officer John Wigginton, Senior Advisor to Cullinan and Chairman of the Scientific Advisory Board and Lee Dowell, Chief Scientific Officer of Small Molecules. Cullinan's CFO, Jeff Giglio, will be available during the Q and A. Following the remarks, there will be a live Zoom Q and A session moderated by our CEO. To indicate that you'd like to ask a question, you must click raise hand. When it's your turn, I will introduce you and then unmute your line. Once the call has concluded, an archived recording of the webinar along with all materials presented will be available on our website, colononcology.com. I will now hand the call over to Conant's CEO, Owen Hughes. Thank you, Juliet. On behalf of my colleagues here at Conan and our partners overseas, namely Tylo Pharmaceuticals in Japan and Zai Lab in China, I'm pleased to share with you our latest data set for Conan Pearl's CLN-eighty 1, a selective EGFR kinase inhibitor seeking to address exon20 insertion mutations. Overall, we are very pleased with the emerging profile, both in terms of safety and efficacy. We recognize there is much work ahead. I will be remiss, however, in not thanking our patients first and foremost, the Exon 20 Foundation, as well as our investigators and various collaborators across the world. As you will see, many patients are benefiting from OITE-one. It is our goal to make sure that continues to transpire. So with that, allow me to turn it over to Lee Zhao, our CSO of Small Molecules to provide a bit of background on 81 before we jump into the clinical data. Lee? Thanks, Owen, and good morning, everyone. Let me just take a couple of minutes to set the table for John's clinical update. EGFR is an extremely well validated oncogenic driver in non small cell lung cancer. But the effectiveness of TKIs deployed in the exon 20 insertion mutant population has been limited by challenges in establishing the requisite mutant to wild type selectivity index. It is critical in this space to have a drug that's very potent against exon 20 insertion variants, whilst also sparing wild type EGFR. And a failure to have that requisite selectivity index results in wild type EGFR toxicities like skin rash and diarrhea. CRN-eighty 1, the structure of which is shown in the upper right corner of Slide 5, is based on a unique parolopyrimidine scaffold. The preclinical data package that we were first exposed to indicated to us that 81 had the potential to meet the challenges in the exon 20 insertion space. I want to walk you through 2 pieces of preclinical data, 1st focusing on the lower right hand corner. What you're looking at in the dash oval is a representation of 81's IC50 in cell lines bearing wild type EGFR divided by the IC50 in cell lines bearing 6 different exon 20 insertion mutants. And what you can appreciate is that regardless of the color shape, I. E, which mutant you focus on, the selectivity index is greater than 1, indicating a sufficient delta between mutant and wild type EGFR. We also see that 81 compares quite favorably to a field of EGFR TKIs regardless of which variant you focus on. In addition to having this differentiating wild type to mutant selectivity index, OIT-one is also differentiated in that it is sparing of wild type HER2. It also doesn't have activity against exon 20 HER2. Finally, in preclinical models of exon 20 insertion non small cell lung cancer, as exemplified in the lower left, where we're looking at an ASV variant model, we see potent single agent activity and durable tumor regressions, and this was seen in multiple variants, multiple different models representing different variants of exon 20 insertion mutant lung cancer. So with this profile, we're quite excited to test the compound in the clinic. And with that, I'll turn things over to John to walk you through the clinical update. Thank you, Lee, and good morning to everyone. As Lee highlighted, the features of the molecule suggested based on its selectivity that it could have a more favorable risk benefit profile in the clinic. And as I'll walk you through in the next few slides, we're encouraged by the data that's accumulating on that front to date. Before going any further, let me just highlight that both the data shown and the statements made relate to an April 1, 2021 data cut. There are additional details regarding both the safety and efficacy in our ASCO poster and the presentation by Doctor. Zosia Petrovska and I refer you to that as well. So this first slide here highlights for you the architecture of the trial. We have tested of this in this Phase IIIa trial, we've tested doses ranging from a starting dose of 30 milligrams given orally twice daily on up to 150 milligrams orally twice daily, the highest dose tested to date. Dose escalation began with a single patient accelerated titration design that transitioned to a conventional 3 plus 3 design upon the first occurrence of the Grade 2 or greater drug related adverse event that occurred at 100 milligrams. In addition, the protocol includes a number of nice features that allow us guided by pre specified safety and efficacy criteria to further expand our cohorts to as high as 6, then 13, and 36 patients gated by those criteria. And you'll see here that we've expanded at dose levels including 30, 65 and 100 in particular. And we've noted recently that we're expanding our 100 milligram cohort on all the way out to 36 total patients in our Phase II cohort expansion. The trial is being executed across the geographic footprint in the U. S, EU and Asia Pac. We also hope to begin enrollment in partnership with Zai Labs in China as well. So, this slide highlights some key demographic characteristics for the population to date. Key things that I'd like to call out indicated in the upper green box are that over 70% of patients had at least 2 prior lines of therapy. Also 40% of the patients had prior EGFR TKI, including Pozio or moblosertinib and also 56% of the patients had prior checkpoint inhibitor therapy. So all in all, a very heavily pretreated patient population with 70% of them being 3rd line or greater. As I mentioned, there are more details in the poster regarding the safety profile of CLN-eighty 1. I'm going to focus on some key high level characteristics of the molecule here. Let me orient you. The columns indicate dose levels from left to right starting at 30, the beginning dose, on over to 150 milligrams, the top dose tested to date. In total, we have 45 patients evaluable for safety and their enrollment and the respective dose levels is annotated there for you. So let's turn now to some key eGFR related toxicities, in particular, rash and diarrhea. 76% of patients have some form of rash, although as you will see here, it's grade 1 and grade 2. No grade 3 events have been seen. And it's mostly grade 1 at lower doses. And then as you get into higher dose, as you can see grade 1 or grade 2 manageable with conventional supportive care. Diarrhea, as you know, has been and can be a particularly challenging toxicity for patients being treated with EGFR TKI. Importantly, we've only seen 22% of the patients that have seen diarrhea of any grade and only 1 case of Grade 3 diarrhea at our top dose tested 150 milligrams. So, that contrast quite significantly, as you're probably aware, with some other molecules in the class that have seen rates of all grade diarrhea and grade 3 diarrhea that are several fold higher than those numbers, something that we think may help us to differentiate in this space. Importantly, also it's worth noting as you can see annotated here that we've begun to see some laboratory abnormalities, including transaminase elevations and anemia. We're continuing to follow those. In a few of the patients they have been Grade 3 or greater. I also would highlight for you another issue with molecules in this space have been very high rates of treatment related dose reduction or discontinuation. Down below in the bottom row, we've annotated those by dose level. As you can see so far the modest relatively moderate rate of dose reduction or discontinuations. And importantly, I should mention also only 1 dose limiting toxicity that case of BREED 3 diarrhea that I mentioned to you at our top dose tested of 150 milligram. I'll turn things over to Lee who's going to walk you through encouraging PK data that has been accumulated to date. Thanks, John. So the safety data suggests that we've been able to avoid significant wild type EGFR toxicities so far and this squares well with the PTA profile. So, just a couple of features that I want to point out on Slide 9. So, you're looking at a plot of the unbound plasma exposures of 81 from 30 minutes out to 8 hours. And each curve summarizes that relationship for the 30 mg cohort in blue all the way through to the 150 mg cohort shown in yellow. So, first point to make is we're seeing a nice dose proportional increases in exposure as we increase the dose, suggesting that the PK is well behaved so far. With regard to safety, I want to point your attention to the horizontal red line, which indicates the GI50 for wild type EGFR. So importantly, for much of the dose cohort, we're below or just at the red line for wild type EGFR inhibition. And it's really only at the 150 mg cohort that we creep above that line for a few hours, potentially explaining the safety profile that we're seeing so far. And then finally, the last point is with regard to the potential for efficacy. So, the gray bar and the green bars, the horizontal lines rather at the bottom indicate the GI50 for inhibition of exon 20 mutant cell lines for ASV in gray and SVD in green. And we were quite pleased to see that right out of the gate, even at the 30 mg BID cohort, our plasma exposures were above the GI50 for the entire 8 hour period here required for inhibition of those mutant EGFR cell lines, suggesting broad potential for efficacy. With that, I'll turn things back to John. Thank you. So, I'm going to walk you through now several slides summarizing our efficacy data. Again, I'd refer you to the excellent presentation by Doctor. Zosia Petrousta, poster presentation at ASCO, Doctor. Petroska from the Massachusetts General Hospital. So shown here, we have our swimmer spot and there's a lot going on in this slide. So let me orient you before we dive into the data. Annotated over on the left by patient is the dose level at which they were treated. Low doses at the top, high doses at the bottom. Annotated over on the right are the specific exon 20 mutational subtypes. As you can see in the swimmer's plot, as indicated by the dark green bars, a number of patients achieved confirmed partial responses. The light green bars indicating patients with unconfirmed response partial responses, several of which are quite durable and continuing to build in durability. In addition, I'd highlight the dark blue bars indicating patients with stable disease, again, several of which are highly durable and building. Also highlight for you the gray bars indicating patients that are not yet evaluable, 2 of whom have just not yet reached their 1st on treatment scan. And then the red bar indicating a single patient that had progressive disease as their best response. The red squares that you'll see in the bars indicate points of progression for the treated patients. So what you should take away from this slide in our view is that we see activity, high rates of activity, durable activity that extends across the spectrum of doses tested to date, that extends across a variety of different exon 20 mutational subtypes and is a building durability in this maturing data set. I'd also like to call out a couple of anecdotes. 2 patients at the very top treated at 30. They had 7 prior and 5 prior regimens respectively. Both received prior poziotinib both and responded, but later progressed, both received subsequent moblosertinib, best responses of stable disease but later progressed and came on to this trial and responded to CLN081. So with this, encouraging what appears to be differentiated safety profile and the spectrum of activity that we're seeing here, including the ability of patients to respond after progressing on prior exon 20 EGFR inhibitors, we're very encouraged by this clinical profile and the opportunity to develop this molecule further. So this spider plot here gives you a sense of the kinetics of response. And I think the key takeaway here is that in most patients this drug appears to work pretty rapidly. The first scan that patients go through on treatment is at day 42 or 6 weeks and subsequent scans are every 9 weeks thereafter. And what you can see, each line indicates an individual patient. If you rolled all these up, 76% of the patients have tumor regression at their first post baseline scan. So the drug looks to work quite rapidly in many of the patients, something that could be important in patients that have ulcerative disease in particular. So in this waterfall plot here, we're looking at the percent change in the dimensions of the target lesions from baseline. And what you can see as indicated by the green bars indicating high proportion of patients that achieved partial responses. You also see the blue bars indicating patients with stable disease and a single patient indicated in the gray bar that had progressive disease. So in totality, out of 42 responsive valuable patients, 98% of them achieved either a partial response or stable disease as their best response, several of whom, as you'll see as annotated by the E's, had prior EGFR TKI. And I'd just like to call your attention to even the stable disease patients. You'll see that a number of those folks had substantive disease progression. So this slide here rolls up some of the important numbers looking at the populations. Again, we're looking at dose levels in the columns ranging from the starting dose of 30 on the left over to 150. And then the far right column, rolling up all patients, all 42 response evaluable patients across all of those levels. I'd like to focus in particular at the 100 milligram dose level where we've enrolled 13 patients as of the data cutoff. I mentioned to you and I think you're aware that we've announced that we're expanding that cohort on up with another 23 patients to take us out to the full 36 patients per protocol, encouraged by both the safety and efficacy data that we're seeing to date. What we have seen is 7 out of the 13 patients had a partial response, yielding an objective response rate of 54%. Of those 7, 6 of the responses were confirmed. For a 46% confirmed objective response rate, 1 of the patients will remain unconfirmed. Importantly, we've seen good disease control. Out of the 13 patients, 9 achieved disease control as indicated by either a partial response or stable disease lasting for 6 months or more, yielding a disease control rate of 69. It's important to note that out of those 13 patients, there's another 3 that have ongoing stable disease and had not yet reached a 6 month cutoff point. I'd also like to turn very briefly over to the total population. I mentioned this when we were looking at swimmers. But again, in the 42 response evaluable patients across the totality of dose levels, 21 of those patients achieved an objective response. Of those, 13 were confirmed, yielding a confirmed objective response rate of 31%. Of the 8 that are unconfirmed, 5 are pending a confirmatory scan and 3 will remain unconfirmed. In addition, you'll see a substantive disease control rate as indicated in the lower right hand corner. So once again, the drug showing activity across the dose range tested and we think particularly important activity at 100 milligrams as well. You'll note that we've seen activity at 150 milligrams and we will consider evaluating that dose level further in the future. So I'd like to pause there and turn things back over to Liizhou, who's going to talk a little bit further about some of the other characteristics of CLN-eighty 1 and how those may serve up other opportunities for the molecule. Great. Thanks, Jon. So, obviously, we've been laser focused on the post chemo exon 20 setting. But, yes, just wanted to highlight some 80 1 attributes that speak to the potential to get outside of the exon 20 space. So, in the first slide, I presented a wild type mutant selectivity index that was specific to half a dozen exon 20 variants. And we saw there that the index ranged from 5 fold to over 100 fold depending on the variant in question. What you're looking at is a similar sort of output here comparing OIT-one in green to osamertinib in blue, but here we're focused on the traditional sensitizing mutations, LA58 and exon 19 either with or without the 279 DM. Actually, the wild type mutant selectivity indexes in this population are even greater than in the exon 20 population and compare very favorably to osamertinib, particularly as you can appreciate in the exon-nineteen alone setting. I'd also point out that we've identified a couple of Tagrisso resistance variants where Tagrisso obviously doesn't work, but 81 does. So, again, we're very pleased with the safety profile. We're pleased with the activity in the exon 20 population and this data suggests potential utility in the sensitizing population either early in treatment or post Tagrisso. So, with that, I'll turn things over to Owen for concluding remarks. Thank you, Lee. So based on the data to date, we are very encouraged with 81's emerging profile. There are 2 topics that I'd like to discuss in more detail now. 1, with respect to EXOND-twenty, we will continue to prosecute the existing Phase 2a trial and we'll look to collect additional data that will enable us to initiate a regulatory discussion with the agency sometime in the coming months. In addition, upon confirmation of the recommended Phase 2 dose, which could very well be the 100 mg BID dose that we're studying now in the expansion cohort, we'll look to initiate a first line pivotal study in exon 20 patients. We believe 81 is well poised to address this indication given the need to maintain dose intensity over a prolonged period of time. Secondly, given the safety profile to date and the preclinical data that Lee just touched on, we believe there's an opportunity to extend 81 beyond XL20 non small lung cancer, either as a monotherapy or in combination. And for that matter, the combination hypothesis may very well bear fruit in exon 20 as well. Hence, we are working diligently to bring 81 to as many patients as appropriate and we'll look to update folks as our plans progress. So I just want to touch on 3 things, safety, efficacy and next steps overall. So from a safety perspective, we hope we've been able to show you the data that is very encouraging to us. From a safety profile, we believe that the reduced frequency and severity of GI events has the potential differentiate OA1 relative to other molecules. All AEs to date have been manageable and reversible. From a PK perspective, 81 has been well behaved with no proportional increases in Cmax and AUC and no evidence of accumulation. While preliminary, the initial efficacy data remains encouraging showing anti tumor activity in a heavily pretreated patient population, including efficacy across a range of dose levels, across the spectrum of EGFR insertion 20 variants, after progression on prior TKIs including small molecules addressed specifically for exon 20 variance, after progression on checkpoint inhibitors with high rates of response with solid disease control in a maturing data set. As it relates to next steps, we've experienced a very nice enrollment cadence in the expansion cohort and look forward to updating folks as we progress throughout the year, likely at a major medical meeting in the fall. In addition, assuming the data continues to unfold in a similar fashion, we anticipate initiating a development plan discussion with the agency in the second half of this year. So with that, I want to thank you all for your time today and we'll revert back to Juliet for questions. Thank you, Owen, John and Lee. It's now time for the live Q and A portion of the program. Okay. So the first question is from Andrew Berens at Leerink. Can you hear me? We can indeed. Thanks. I guess I just wanted to get some clarity on the potential development in exon19 given what you just showed us. Would it be a combination strategy with a drug like a MET inhibitor or some other agent? And then also, any idea what type of resistance mechanism you would expect to see in exon 20? Yes. So we're evaluating a number of possibilities. Certainly, the importance of MET in resistance Tagrisso has not lost on us. So a MET inhibitor is certainly 1 combination that we're keen to explore among others. In terms of the resistance, the Tagrisso resistance mutations, I'm going to present some data on that at the non small cell lung cancer summit next month. And we'll talk specifically about which of those resistance mutations 81 works on. But that's also part of our development plans going forward. Okay. And then in terms of Dexon 20, what do you think the resistance mechanism would be there? So we anticipate MET being important. We anticipate C797 alteration being important. But for 81, it's early days and we're keen to track the duration of the response and also what the mechanisms of resistance will be. The next question is from Jeff Hung at Morgan Stanley. Jeff, are you there? Sorry about that. We'll go to Josh Schimmer now. Actually, we'll go to Ed Weiss at H. C. Wainwright. Hi, can you hear me now? We can. Great. Thanks. Congratulations on the data. Just wanted to ask a question about the 100 percent tumor reduction best responses and why those aren't considered to be CRs? Sure. John? Sure. Yes. The waterfall plot that you're looking at reflects the change in the dimensions of the target lesions, right? And so those are patients that may not have had complete resolution of non target lesions, which means there wouldn't be a complete response. Okay. And do you have any data on where these non target lesions were or how relevant they are? Well, I mean across the population, I mean they would represent the diversity of different places that people can have non target issues, I mean, liver, bone, brain, those sorts of things. Okay. Thanks. And just a question for Owen and on the next steps that you're going to take. If you have a discussion with the FDA in the second half of this year, how are you thinking about running a pivotal trial? Is there if you can give us any thoughts on timing or how you think about the size of the trial? Sure. So I think there are some predicates that have been outlined by our competitors in terms of the size of the trials, the duration and the endpoints. Our assumption at this point in time is that although some of those agents will be approved is that we can follow in their footsteps. I think the most important thing for us is to continue to collect the data and achieve what we believe is necessary in order to actually initiate that discussion. And at this point in time, durability is just the 1 thing that we will require and that's simply just additional follow-up on the patients that are on therapy. So our hope is that we can initiate those discussions fairly soon being in the coming months and be in a position to do what many other companies have done in a similar position, which is make or attempt to amend the existing protocol, so that the 36 patients that we have in the 100 mg cohort by the time that we go to the agency can act as the basis for the initiation of the pivotal study, I. E, those patients would serve as the 1st patients in. And let's assume that we would need 100 to 125 patients, plus or minus just based on predicate. We simply need to enroll another 70 patients. And the other thing I would just say there, Ed, as it relates to the accrual, obviously, Exxon 20 is a competitive space. We're certainly aware of that. I think 1 of the benefits of doing the deals that we've done thus far, a, keeping Taiho involved with the Japanese rights and bringing on Zai with the Chinese rights is that you will now have 3 companies actively enrolling all at the same time across the globe, all working on the same protocol. So our hope is that if that can be affected seamlessly is that we would be able to enroll the pivotal study fairly quickly. I don't know what that time frame is exactly. But I know that we're working quite well with our partners in Japan and China. And I know that Tsai is very anxious to get started as are we. Great. Well, thanks for the update, Owen, and again, congratulations. I appreciate it. But fortunately, it's the drug that's doing the work, not us. So thanks to the folks at Tayo for developing a fine drug. Thanks, Ed. Next question is from Jeff Hung at Morgan Stanley who's having some IT difficulties. I'll just read it for you. Can you provide additional details on the 100 mg patient that will remain unconfirmed? And a follow-up question, some it appears that there were some patients in the November data cut, particularly in the 30 mg cohort who had previously seen progression and now they're recorded as responses. So can you please give some details on what changed over time? Sure. John, you want to touch on those? Yes, sure. So the patient at 100 that I believe you're referring to, you said that is an unconfirmed partial response that is not confirmed. That's your question? That's right. Yes, that's right. So that patient had a non drug related adverse event worsening of dyspnea and that PML study possibly complicated by aspiration in PML study before it come from a confirmatory scan. Okay. And then the second question was color on the patients at 30 mg that were previously required as progressors who now have a partial response. Yes, I guess maybe could you be more specific about which patients you're printing? I mean, I think there's I guess more, John, just in terms of given what we experienced from a COVID perspective, given what we've seen with the lack of CRAs being able to get into sites to do site monitoring, just some of the changes that happened in the database. Yes. That happens sometimes where the coding will change and things get adjusted during monitoring. But again, seems we don't see anything that changes the story here. Thanks. Perfect. Now going to Josh Schimmer at Evercore. Thanks for taking the question. You've talked about registration paths and plans both in exon 20 insertion settings and beyond. Are you prepared to be a little bit more granular in terms of what kind of studies, particularly combination studies you think are going to be critical to move into earlier line settings? In exon 20, Josh or outside exon 20? Both really. Sure. I think in the exon 20 space, we're intrigued with the data from those that are developing bispecific antibodies that are targeting EGF and c Met. As Lee mentioned earlier in response to a question, it is very likely 1 of the resistance mechanisms that emerges over time. And I think given the safety profile that we have to date and the efficacy that we've shown across the dose range, I think an interesting combination approach would be taking the antibody and 81 and combining those and really trying to extend durability in the second line. As it relates to areas outside of Exon 20, once again Lee mentioned the Cysteine 797, CMET, those are 2 areas that we're looking at diligently from a business development perspective. We do think that they are of interest with 81 as the backbone. And once again, I think it's a function of what we're seeing from a safety perspective and what we're seeing from a preclinical perspective. And then even beyond that, certainly 1 of our competitors has shown us very intriguing data in the earlier lines of the traditional sensitizing mutations as a combination approach. Obviously, Trogarzo is a phenomenal drug and has established a very large beachhead. I'm not quite sure we would go there just yet. But in certain progressive failures, as well as in second and third line, I think there are opportunities combined with both small molecules and BiSIP antibodies in order to address essentially unmet medical needs for the patients. Lee, anything else you'd talk about? No, I think you covered everything well, Owen, nothing to add. And what about first line exon 20, is that on the table? Yes, I should have mentioned that as well. But yes, by all means, I think the premise holds that if you can extend durability in the second line through a combination approach, by all means, you'd want to do in the frontline as well. I do think that if you can combine 2 small molecules and have a efficacy and safety profile that's commensurate with a single molecule that would be potentially a gold standard. But obviously that's conjecture at this point in time. But rest assured, we're thinking about it and we recognize that we have a very good start here, but we're certainly not resting on our laurels. We do think that there are opportunities to combine various agents in order to improve the outcomes for patients. Next, we'll hear from Chad Messer with Needham. Great. Thanks. Can you hear me okay? We can. Awesome. Great. Never 100% sure, so I guess, yes, the affirmative. I understand. Let me add my congratulations on the great data. Maybe we could just talk about dose a little bit more. I think I get and agree with your rationale for going forward at 100 with this next study, safety tolerability very paramount here. But that said, I think it's really hard to rule out based on what you know about 150, whether might not be perfectly safe or safe enough to merit what might be more efficacy, I guess, would be the conclusion there. So you had mentioned it might be of interest to explore that dose in the future. I was wondering if you could maybe talk a little bit more about what an appropriate setting for that might be? Sure. John, do you want to touch on that? Yes. I mean, I think, as you've seen from the data and we've talked about before, we'll make a decision in terms of a final dose designation based on a matrix of things, including the safety profile, of course, also the response rate, response duration, PK profile, etcetera. And on that front, 100 looks very good, very encouraging based on what we've shown you. Your point is well taken about 150. That is not off the table at this point to take a look at some point. It does have some step up in the safety signal there that we're mindful of, Whereas, as we've shown you, there's no Grade 3 diarrhea at 100 and the safety profile otherwise looks favorable. So that's why we've started emphasizing 100 and we'll reconsider 150 over time. Thank you all for joining. Any other questions? I think at this time, there's no other questions. So just so everyone is aware, a recording of this webinar will be posted to our website and will be available for 30 days after the webinar is complete. And all materials presented will also be available on the website, coloninoncology.com. And then the last thing is just that in July, Lee will be presenting at a non small lung conference. It will be much of the data that you've seen here as well as some additional new preclinical data that we have not shared to date on some atypical EGFR mutations as well as some of the traditional sensitizing mutations. We'll make sure that we get that into your hands as well. With that, thank you very much for your time today and enjoy the long actually not a long weekend, but enjoy the weekend. Thanks. Bye bye.