Good morning, everyone, and thank you for joining us for the second day of our 2024 Oncology Innovation Summit. We are here to kick off the morning with the team from G1 Therapeutics. We have Andrew Perry, the Chief Commercial Officer, and Dr. Raj Malik, the Chief Medical Officer. Thank you both for joining us today. So maybe just to kick things off, a broad overview. The team is gearing up for two data updates this quarter. We saw the first one through a press release yesterday that you're going to present the data at ASCO. But maybe just to kick things off, a broad overview of the company's recent progress, and maybe what should investors be expecting for the duration of this quarter, but maybe even broadly in 2024? Yeah, thanks, Joe. Yeah. This is an incredibly exciting time for G1 Therapeutics, actually, and the data announcement that we just made this week is really the first step of that, and we were very proud to announce those data. Right now, of course, we're currently focused on commercializing Cosela, trilaciclib, and its initial indication, which is to decrease chemotherapy-induced myelosuppression in extensive-stage small cell lung cancer. And at our first quarter earnings call, we reiterated our guidance for this year in the range of $60 million-$70 million. We also recently announced some out-license agreements for lerociclib, another one of our assets, excluding Asia Pacific, to Pepper Bio and also to Demos Biosciences. But perhaps most exciting are these data readouts, these two data readouts we just announced, the updated survival results from our phase II study of trilaciclib in combination with sacituzumab govitecan or Trodelvy. We're going to be presenting those at ASCO in a couple of days, and we're excited to dig into that more with you this morning. Then we're looking forward to our pivotal phase III study, PRESERVE 2, of trilaciclib in combination with chemotherapy in first-line metastatic triple-negative breast cancer. Those results could be among the most clinically significant data that we've seen generated in this setting, and we anticipate announcing those later this quarter. So very good time to be chatting with you today. Perfect. Maybe we'll start on the commercial side and then dive into some of the data readouts. But, maybe just overall, the launch in the SCLC space, maybe how has the breadth and depth of Cosela uptake evolved, maybe over the past year? I know that the company indicated on the last quarterly call some initiatives to support sales efforts in certain regional soft spots. If you could just dive into that, a little bit, that'd be helpful. Yeah, in terms of breadth and depth, you know, we quite often talk about the top 100 customers who see about 50% of patients in this market. We added three during Q1, brought us to almost 80, actually, of those top 100 customers that have trialed Cosela. Encouragingly, 63 of those top customers that we have with trial usage, 63 actually ordered within the quarter, so are regularly ordering, and that's actually the highest we've seen by some margin. Depth-wise, our latest data, which really are around December, January claims data, they show we've got about 13% penetration in the market, so really a significant opportunity for growth. You mentioned some of the regional variation we saw in Q1. So Q1, our sales volume grew 4%, and that number disguised quite a bit of regional variance, actually. So, in the West region that we have, we grew almost 30%. But the Southeast region, which is one of our larger regions, had a slower start with some of our larger customers, and we actually were able to address that during the quarter. Happy to go into that in more detail. But those customers coming out of the quarter were actually growing in double-digit growth. So we were able to stem that to address any issues that they had, which were really just operational considerations, and get back on track. And as I think we said on the earnings call, April was actually our highest month launch to date. We feel confident, going forward, and we reiterated that guide. Perfect. And maybe just in the SCLC indication in general, how big can this be for Cosela, do you think, at peak? And maybe what remains in the launch to unlock the full value of the asset, specifically in this indication? Obviously, making some solid progress, but are there any inflection points that we should be looking for or just continued growth? How should we think about that? Yeah, so there's around 20,000 patients in the U.S. receiving eligible chemotherapies for small cell. We don't see that changing. There's movement in the market, but we do not see that number changing. So there's still a critical need for chemotherapy, and where there's a critical need for chemotherapy, there will be a critical need for, for Cosela. That overall market for us is worth in the, in excess of $700 million, and as I said, we estimate our share of that right now at around 13%. So there's significant running room there. We have no competition on the horizon. There's no one else entering this market, so it's a very attractive market for us. And again, I look at those... You know, every time we see an example of a large customer adopting Cosela more systematically, that gives us confidence that we're still really just scratching the surface of that 13%. Some of those large customers that can really propel a quarter for us, they're adopting now at 30%, 40%, 50% share within their network and are growing. So there's really nothing to make us think that we should be, you know, topping off anytime soon. Our focus, therefore, remains really in systematizing that adoption within large networks. That's the most efficient way for us to grow sales quarter over quarter. Perfect. Great. Maybe we'll circle back on the commercial franchise later, but we definitely want to dig into some of the data readouts. Maybe we'll start with the data that you announced earlier this week that you presented at ASCO, the Cosela plus Trodelvy data in breast cancer. So you will present the mature OS data at ASCO. The press release yesterday showed about a 15.9-month benefit with the combination. This compares to about 12.1 months that we saw with the ASCENT study with Trodelvy. Maybe just overall, can you talk a little bit about the overall population? What's the significance of this almost four month improvement here for patients? And then I know we'll dive into some of the subset analyses that you, you went into on the press release. ... Yeah, thanks, Joe. I'm happy to. So we're actually quite excited about the data. So we, you know, we set out to do this study to really do two things: to see if we could improve the safety of the combination, as well as improve efficacy. So we've shown pretty convincingly in the mature data that we can improve myelosuppression, we can improve diarrhea, and I think this is very important as we think about future development. But what's very exciting really is the improvement in survival that we're now seeing. And that approximately four month improvement that you mentioned is actually in line or a little bit better than what we were thinking. So our going-in assumption was, okay, if we see an approximately three month or better improvement, it would be a good signal to us to take this forward into Phase III study design. So that's actually where we are, but I'll get back to that. So first of all, high level, we're very encouraged by the approximately four month improvement in median OS. The second point is that if one looks at the landscape that has evolved from the time that ASCENT was conducted and when our trial was conducted, and one of the big differences is that Enhertu is now approved for HER2-low disease, and is therefore now being used in this setting. In the ASCENT trial, we don't anticipate there was, if any, any Enhertu used at all as a subsequent therapy, whereas we had nine patients in our trial who received subsequent Enhertu. And there's actually evolving data looking at how patients do if they receive Enhertu after sacituzumab, where maybe that PFS2 is not quite as robust if patients receive Enhertu in that sort of order. So what we, what we sought to do was a more, if you will, apples-to-apples comparison, to say that, what if we took the patients who received Enhertu as a subsequent therapy and actually censored the data from the time that they started receiving Enhertu? So when we do that, the median OS actually looks even better, so 17.9 months. So, so to us, all of that really provides sort of a robust signal towards improvement in OS. You had mentioned the subset. So there were a few that we thought were, you know, relevant. So one, how did patients do if they'd received prior checkpoint inhibitor therapy? And that subgroup actually looked quite a bit better than those who did not, and could speak also to the immune based mechanism of action. The second was patients who had a primary diagnosis of TNBC versus not, and those who had a primary diagnosis of TNBC also did quite a bit better than those who did not. And finally, if patients had not received a prior CDK4/6 inhibitor, they also did... Their survival was quite a bit longer than if they had. Now, some of these, particularly the primary diagnosis of TNBC or not in prior 4/6, are sort of interrelated, because if a patient initially had ER-positive disease, it's quite likely that they would have received a 4/6. So I think all of these subsets are, you know, important and helping us really design our phase III study, you know, which we would plan to conduct with a partner. So happy to dive into any other data. Yeah. Maybe specifically on the immune-based mechanism of action of Cosela- Yeah ... that you mentioned. Maybe if you could just dive into that a little bit, because I know Cosela, you know, seemingly works a little bit different in different indications and with different partners. So, it'll be great to kinda dive in on what you're seeing there and how you think the drug is playing with prior therapies. Yeah. So, you know, we think that. So particularly, this is really a couple of points I would make. The first is just in vitro work and in vivo work that we had done in animal models showing that trilaciclib can increase immune infiltration in tumors, increase memory T cell differentiation, which could result in better long-term immune surveillance. The second is actually looking at our clinical data. So when we went back to our Phase II trial in TNBC, where we showed the improvement in overall survival, if we looked at patients who had received subsequent anticancer therapy after they had finished receiving trilaciclib plus gemcarbo, those patients did quite a bit better, median OS of 33 months, compared to about 12 months to those patients who had previously received chemo alone and then received chemo. So, our thinking here is that patients really can benefit while they're receiving chemo plus trilaciclib or a cytotoxic, in the case of Trodelvy, by protecting the bone marrow and the immune system. But also, this improvement in memory T cell differentiation and better long-term immune surveillance could result in patients doing better with subsequent therapies as well, resulting in an eventual overall improvement in survival. And, you know, I think the fact that patients who had received prior checkpoint inhibitors as a proxy for patients who have maybe a more immune-sensitive tumor would also sort of fit with that immune-based mechanism of action of trilaciclib in our Trodelvy study. Obviously, in addition to the efficacy benefits that we're seeing, you are also seeing some tolerability benefits as well across neutropenia, diarrhea, anemia, thrombocytopenia. Maybe can you just dive in a little bit, how big of a concern are some of these AEs with ADCs or Trodelvy specifically? And I guess, you know, going forward, even if you don't see an efficacy benefit, do you think there's a role for Cosela solely in improving sort of the AEs in combination with ADCs? How are you thinking about the importance of the efficacy and safety kind of balance? Yeah. So, you know, what we're hearing certainly from physicians that the safety profile of Trodelvy is, you know, a potential issue because patients do have dose reductions, dose delays. Actually, what we're hearing also is a lot of skipping of day eight because it's given as a day one, eight every three weeks. And oftentimes, those cycles become a day one, 15 because the day eight dose can't be administered. So really, that safety and tolerability is a concern, and we feel there is definitely a role for trilaciclib in improving that, not only with Trodelvy, but potentially other Trop-2 ADCs as well. I mean, there was some data reported with the Merck ADC, Trop-2 ADC, where again, you know, myelosuppression is, is a, was the major adverse event profile. So, so we think that that is a potential issue, and we feel there's a role there for trilaciclib. You know, we have shown an improvement, at least a trend towards improvement in survival, and, and we think we can do actually both. We can, we can improve safety as well as improve efficacy. And, and where this really becomes important is in earlier stage disease. So, you know, these ADCs are moving really more towards earlier stage development, even out into the neoadjuvant adjuvant study. In fact, Merck announced a study in that setting. Other companies are evaluating moving into that setting. And here, we think that the role for Trila becomes even more important, you know, not only from a safety, but also, you know, from an efficacy side. So we think there's a lot of potential here for Trila in combination with Trop-2 ADCs. And also not only in TNBC, but also, you know, some other tumors. There's some, certainly some mixed data in non-small cell, as you've seen lately. But, you know, as these ADCs move on to to other settings, you know, we feel that Trila would be a good companion to for both of those reasons. Perfect. And just a reminder to the investor audience, if you do have questions, please feel free to email me at Joseph.Thoma@tdsecurities.com, or put your question into the Wall Street Webcasting chat box. We do actually have one investor question, and more around sort of p-values or stat sig for the combination. Obviously, it was an open-label- Yeah ... study, but you know, in the presentation, did you do any sort of comparisons to historical data, or can you talk any at all about the variants, I guess, that you're seeing between patients? Anything around that, I think maybe is what they're looking for. Yeah. Yeah, it was a single-arm trial, so, you know, there are no p-values. But we presented the confidence intervals. So, you know, so that really provides an idea of the strength of the data. And so those data will be in the poster. Perfect. Excellent. We'll look forward to that. And then, I know you mentioned a partner going forward. Maybe first, what would a Phase III here look like, especially given sort of the changing dynamic with the HER2 in the setting? And second, maybe if you could talk a little bit about the progress on a partnership, and maybe what that would look like for you as a company. Yeah. So, you know, so there are actually, given the data, there are a lot of interesting opportunities, I think. I think I mentioned the neoadjuvant adjuvant setting could be one where, particularly, for example, in neoadjuvant failures, if you will, for patients who do not achieve a path CR, that's a patient population that's high risk, where ADCs are moving. So that could be sort of one setting, you know, in a relatively large patient population. Certainly, in the second, third line setting, could be, you know, could be another approach. But then, of course, there could be some types of, you know, selection. So for example, you know, no prior, no prior 4-6 inhibitor treatment based on kind of the data that we've seen, which would help in a, in a variety of different ways. So, so those are types of the ideas that we're, that we're kicking around, but there are lots of different opportunities, from a, from a trial design, perspective. In terms of partnership, you know, as we've said before, we have a very experienced, chief business officer, 17+ years at Pfizer, many, many deals. And he's at- and including the more recent ones with, with lerociclib that Andrew just mentioned. You know, he's in, and we are, as a company, in contact really with all of the major players there and, you know, looking forward to our data presentation at ASCO and, you know, and further discussions there as well. Perfect. Is there anything else that you wanted to mention that we didn't cover on the combination study? Otherwise, we're gonna jump into the first-line TNBC study, but I didn't know if there is anything else that is left hanging there. No, I think we covered all the points. Just to say that we're excited about the data, and we think that it really provides a strong signal in terms of the survival data, and that, you know, we're taking the data forward and designing phase IIIs. ... Perfect. Great. Well, maybe we'll move on to the phase III PRESERVE 2 study that is gonna be reading out later this quarter. I guess, first of all, can you just remind us what sort of information do you expect to include in the top-line data announcement later this quarter? And maybe just a high-level overview of, you know, kind of the, what patient population is being studied here to level set investors a little bit. Yeah, we will, you know, it's always what you put out in a release is always a balance between, you know, putting out enough information for investors to have a sense of what the data show, and that's certainly where we're leaning, right? To provide, you know, obviously, what the primary, OS, results are. Some important subsets, like the PD-L1, I think is important. So we'll put out enough, enough of a full, fulsome data set for investors to have a sense of what the data are, but keeping enough back that we could, of course, we'll wanna present the data more fully at a medical meeting. But, but it won't be just that the study met the primary endpoint. It'll be much, it'll be more than that, for, you know, for investors to have a sense of the data. In terms of the, Sorry, Joe, your, your other question was the differences from the Phase II, was that your question? Yeah, a little bit. Yeah. Obviously, this is the first-line study versus- Yeah ... you know, the Phase II with later-line, yeah. That's right. So in terms of major design differences, this is a first line only versus first, second, and third line for the phase II. But they're both with gemcarbo. So from that perspective, you know, identical chemo backbone. About three times the size compared, you know, if you look at it on a per arm basis in the phase III, rather, compared to the phase II. So those are some of the differences. Perfect. And obviously, we got the interim update earlier this year. Yeah. The study, you know, was not stopped there. Can you just remind us the, I guess, the level for the hazard ratio that would've stopped the study, I guess, at the interim versus the final analysis, and maybe what gives the company confidence that success on the final analysis could still be possible here? Yeah, so a few considerations there. So the first is just when one looks at the enrollment. It occurred between June 2021 and October 2022, with the majority of patients enrolling just in the few months prior to the end of enrollment. Our interim analysis, when we conducted that, was approximately 15 months from that end of enrollment. And the reason why that's important is, if you look at our Phase II data, in the PDL-1 negative patient population, that's sort of when the curves really started to separate. So the additional follow-up between the interim and the final, we think, you know, could be important for continued separation. The other points are, of course, the final is being conducted with all, the full complement of events, as opposed to, you know, just 80% at the time of the interim. We, of course, have the full complement of alpha as well, as opposed to a much smaller alpha at the interim. But in terms of the hazard ratio boundaries, at the interim, that boundary was approximately 0.61 and is now approximately 0.67 at the final. So we're able to pick up a smaller effect size, if you will, at the final compared to the interim. So you know, we feel confident for all of those reasons, in the Phase III. Okay, perfect. And maybe just in terms of the level of benefit, either from a hazard ratio perspective or a months of OS benefit, what, what do you think is sort of considered practice-changing for this patient population? And is there a good comparator arm, for the non-Cosela arm? Maybe Keynote-355 seems to be the closest. What are you guiding investors towards there? Yeah, so in terms of the improvement, I mean, if the study is positive, it would be the most meaningful improvement in OS in first-line metastatic TNBC. And the reason for that is, if you look at Keynote-355 in the ITT population, the hazard ratio was 0.89, and in the FDA-approved PD-L1 positive population, it was 0.73. So if we hit 0.67 or less in the overall ITT population, it would be quite a bit better than Keynote-355. We'll have to see what the subsets show, but based on prior experience, where the PD-L1 positive did better than PD-L1 negative, it's quite likely that the hazard ratio in PD-L1 positive would be even better, and quite a bit better than the Keynote-355. So that's the way we're thinking about it, and if the study is positive, it will be practice-changing for that reason. In terms of comparator, we still think that Keynote-355 gemcarbo arm is the appropriate comparator. There hasn't been anything more contemporary than that, and that gave a median of around 14.5, 14.7 months. You know, if the data are successful here at the end of the quarter, can you just let us know what would need, or what will be remaining, I guess, to file an sNDA for Cosela for this indication? Is everything else pretty much ready to go, and we just need the data here, or how are you thinking about a potential label expansion? It really is that. So it's a supplemental filing. So there's nothing to do with, like, manufacturing or anything else, right? This is just the clinical data. And so as soon as we have the data, and it's positive, you know, we'll be, you know, meeting with the agency as quickly as possible and filing as quickly as possible as well. And so internally, we're actually gearing up to do that. So, you know, all of the prep work for putting, you know, putting together the documents and what they would look like for an NDA. All of that work is underway. So it's really just the clinical data that we're waiting on. Perfect. And maybe just in the last minute here, talking a little bit about commercial expansion, maybe, Andrew, back to you. Well, I guess what will be needed in terms of a commercial expansion for a TNBC versus what you have currently kind of on the ground for small cell? ... how big would that be, or what are the synergies that you already have? Yeah, significant synergies. I mean, we already have the commercial infrastructure in place. The majority of triple-negative is treated in the community just like small cell. We would add to our field teams just to ensure our regional coverage reflected the demographics of TNBC. We have already allocated for that, actually, in our cash runway that we talked about at Q1. And, you know, I'm sure you're gonna ask that question, but we ended Q1 with cash equivalents of $65.2 million, and that is sufficient to get us into Q3 2025, and does include anticipated expenses for that TNBC launch. Perfect. Great. Well, you did definitely address the last question that we were gonna end on, so that's perfect. So we are at time. Thank you both for taking the time to be with us this morning, and best of luck for the upcoming readouts and data presentations. We'll talk to you soon.