Good morning, everyone. I'm Will Roberts, Vice President of Corporate Communications and Investor Relations here at G1. On behalf of the entire team, I'm very excited to welcome you to our virtual 2022 R&D Day, Innovations in Oncology: The Science of Trilaciclib. We have a packed agenda this morning, which would run about an hour and a half or so, and I'll review it momentarily. Before I do, I want to remind you that today's webcast does contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements represent management judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from those expressed in or implied by those forward-looking statements. For more information on those forward-looking statements, please refer to our filings with the Securities and Exchange Commission. Any forward-looking statements represent our views as of today, September 15th, 2022. I'll remind you that although we're commercializing our first product, that's not what today is about. Today is focused on our investigational therapy, trilaciclib, its mechanism of action as a transient CDK4/6 inhibitor, its synergistic potential, current and future clinical evaluations, and our strategy for development in multiple treatment combinations with drug classes expected to be foundational in future standards of care. After my introduction, I'll turn the call over to Jack Bailey, our Chief Executive Officer, to introduce G1, to describe our history, and provide an overview of the trilaciclib development program. Jack will then pass the call off to Dr. Raj Malik, our Chief Medical Officer, for his section called Trilaciclib: From Premise to Promise, in which he'll walk you through the history of trilaciclib, provide an overview of its mechanism effects, highlight the importance of some key clinical data from our earlier extensive stage small cell lung cancer and triple-negative breast cancer trials, and introduce our development strategy. We'll then hear from our first guest speaker, Dr. Shom Goel from Peter MacCallum Cancer Centre at the University of Melbourne. Dr. Goel is a leading authority on CDK4/6 inhibition and its potential to induce antitumor effects, and he'll discuss it at length, including the importance of transient CDK4/6 inhibition with trilaciclib. Dr. Goel will then turn the call over to Dr. John Yi, our Senior Director of Translational Medicine, who'll describe in great detail the mechanism of action of trilaciclib, including its potential to enhance the cancer immunity cycle and provide, for the first time, new preclinical data showing its potential synergistic benefit in combination with a variety of current and future therapeutic interventions in oncology. John Yi will be followed by Dr. Samantha Melamed, our Vice President of Clinical Development, will discuss our ongoing phase two and phase three clinical trials, what to expect from those data and why, and importantly, the strategies behind our ongoing trials to expand the opportunity for trilaciclib. Up next is Norm Nagl, G1's Vice President of Medical Affairs, will moderate a discussion with our second guest speaker, Dr. Richard Goldberg, Professor Emeritus and former director of the West Virginia University Cancer Institute, about the colorectal cancer landscape and the need for better therapeutic options for these patients. After this, Mark Avagliano, our Chief Business Officer, will discuss where we're heading with trilaciclib, the market opportunities, and the importance of the data that we're generating today to guide tomorrow's developmental decisions. Jack will then be back to make a few concluding comments to close the prepared portion of the call. At that point, we'll gather the team for some Q&A with our listeners. Now, I've been accepting questions for some time, but I'll remind you that you can still ask questions. If you're listening through the R&D Day, Q&A panel, as most of you are, you can certainly do so there. If email is easier for a remote listener, you can send one to questions@g1therapeutics.com, so Q-U-E-S-T-I-O-N-S @g1therapeutics.com. I'll get them either way. Now, we won't get to them all, as I have quite a number in queue already, but we'll do the best we can. Once again, thank you for joining us today for our 2022 R&D Day. If you're listening to the replay, thanks for joining us there as well. I look forward to speaking with most of you over the coming days and weeks. With that, I'll turn the call over to Jack Bailey, our Chief Executive Officer. Jack. Thank you, Will, and thank you all for joining us today as we provide a scientific and development update on trilaciclib, brand name COSELA. My goal in this brief opening section is to set the stage for the emerging data and exciting development opportunities we have for trilaciclib, which will be reviewed in today's session. Now let me start with a quick reminder about the origins of G1 Therapeutics, which was founded by Doctors Ned Sharpless and Kwok Wong in 2008 to focus on cell cycle modulation and its potential to safeguard patients from the damages of chemotherapy by protecting both the myeloid and the lymphoid lineages in the bone marrow. The team determined that intermittent administration of an intelligently designed CDK4/6 inhibitor named trilaciclib was the key. We first tested trilaciclib in extensive-stage small cell lung cancer across three phase II studies, and trilaciclib showed impressive and consistent myeloprotection that would ultimately lead to an FDA Breakthrough Therapy designation, a Priority Review, and become our first on-market indication that was launched in 2021. Even back then, we had no intention of stopping at small cell lung cancer with the development of trilaciclib. Logically deducing that there were many other tumors which could benefit from trilaciclib. We went on to also test trilaciclib in triple-negative breast cancer and saw incredible survival benefits in this tough-to-treat tumor. That has led to a series of clinical studies we have underway, which we will discuss today, that seek to further leverage the benefits of trilaciclib can provide in terms of improving overall survival for patients across an array of tumor types. Now, moving on, these benefits derived from trilaciclib can best be seen on slide six, which reflects the myeloprotection benefit that was seen in extensive-stage small cell lung cancer and will be denoted in blue throughout today's presentation. Also the focus on survival that is our direction going forward derive both from myeloprotection that enables greater exposure to cytotoxic therapy while also protecting the immune system, which will be colored in orange throughout today's presentation and/or also improving survival via trilaciclib's immunomodulatory effects denoted throughout today's presentation in green and of course, the natural interplay between those two respective effects. Our clinical readouts surrounding these expected benefits, as seen on slide seven, begin to unfold in Q4 this year and extend throughout 2023. Each of these studies will be overviewed today by our Head of Clinical Development, along with our thoughts on the next chapter of clinical studies in other expansion areas that pending these near-term readouts, we will look to pursue as part of our tumor-agnostic vision for trilaciclib, and which will be discussed by our Head of Corporate Strategy. It's clear we are entering a very exciting time for trilaciclib and its potential to benefit a growing number of patients. Now, before we dive into the science of trilaciclib, let me summarize on slide eight what we hope you will take away from these next few presentations. First, that trilaciclib's unique effect on the bone marrow is directly attributable to the transient, potent, and selective CDK4/6 inhibition and the fact that it directly targets the host. Second, that trilaciclib enhances multiple immunological processes within the cancer immunity cycle, as will be overviewed by our Head of Translational Science today. Third, that trilaciclib has the potential for improved survival via both improved immune response and increased cytotoxic exposure, while also protecting the immune system. Fourth, we will share new preclinical data that shows consistent synergistic potential with multiple combination treatments. Fifth, we have meaningful clinical readouts starting in the next three months and continuing throughout next year. Finally, that trilaciclib represents a true pipeline-in-a-molecule opportunity with significant expansion opportunities in future standards of care. Now, I'll be back at the end of today's session, but for now, let me turn things over to Dr. Raj Malik, G1 Therapeutics Chief Medical Officer, who will dive a bit deeper into the science of trilaciclib. Raj? Thanks, Jack. I am Raj Malik, and I've been the Chief Medical Officer at G1 since 2014. I'm excited to discuss the evolution of G1 and the future ahead as we anticipate upcoming trilaciclib data readouts. The original premise for forming G1 was to use transient CDK4/6 inhibition to protect hematopoietic stem and progenitor cells in the bone marrow from the cytotoxic effects of chemotherapy. We rationally designed and optimized trilaciclib for this purpose. The initial indication for COSELA as a first-in-class myeloprotection therapy was obtained based on three randomized, placebo-controlled phase II trials in extensive stage small cell lung cancer. Our fourth phase II trial in triple-negative breast cancer demonstrated a robust improvement in overall survival with 60%-70% reductions in the risk of death in the two trilaciclib arms, consistent with an immune modulatory mechanism of action. We believe that trilaciclib has the potential to improve overall survival through dual benefits of myeloprotection, allowing increased cytotoxic exposure while protecting the immune system, and secondly, by enhancing antitumor immunity and both of these could also happen together. We have an aggressive development plan underway to evaluate these effects that Samantha Melamed will be discussing a little later. Trilaciclib's mechanism of action directly affects the host, specifically the patient's bone marrow, leading to myeloprotection of hematopoietic stem and progenitor cells and myeloid and lymphoid lineages and the tumor immune microenvironment, resulting in enhancement of antitumor immunity. It is important to note that trilaciclib administered intermittently does not directly inhibit the proliferation of tumor cells, which makes it distinct from the oral CDK4/6 inhibitors that are approved in ER-positive breast cancer. When trilaciclib is administered intermittently, it induces a transient G1 cell cycle arrest in cells in the host that are susceptible to CDK4/6 inhibition. These include hematopoietic stem and progenitor cells and cells in the tumor immune microenvironment. As shown on the left-hand side of the slide, myeloprotection of hematopoietic stem and progenitor cells, in addition to myeloid and lymphoid lineages, reduces hematologic adverse events across multiple lineages with resulting decrease in supportive care interventions and hospitalizations, and improvement in quality of life as measured by improvement in patient-reported outcomes and protection of immune system function from cytotoxic therapy. These factors could contribute to patients being able to tolerate a greater exposure to cytotoxic therapy. As shown on the right side of the slide, enhancing T-cell activation, favorably altering the tumor immune microenvironment, and improving long-term immune surveillance are hypothesized to improve the antitumor immune response and potentially increase antitumor efficacy for tumors that are sensitive to immune modulation. John Yi will be discussing this in greater detail a little later. We designed trilaciclib to have unique attributes in order to take advantage of these dual benefits, and these include a rapid onset of effect following IV administration with immediate target engagement, a short half-life so that the duration of G1 cell cycle arrest is transient and controlled. An arrest that is too short or too long could result in greater myelotoxicity and potent and selective CDK4/6 inhibition to achieve a clean G1 arrest. We want to avoid CDK2 inhibition, which would result in an S-phase arrest and potentially cause greater toxicity when combined with cytotoxic therapy. Turning now to clinical data that resulted in the FDA approval of trilaciclib, which is marketed as COSELA and indicated for use in combination with etoposide platinum and topotecan-containing regimens for extensive-stage small cell lung cancer. We observed robust multi-lineage myeloprotection benefits in three randomized placebo-controlled phase II trials in extensive-stage small cell lung cancer. Data on the left-hand side of the slide are from the pivotal first-line combination with etoposide, carboplatin, and atezolizumab, which is the most commonly used regimen in the first-line setting. This trial showed multi-lineage myeloprotection with improvement in severe neutropenia, grade 3/4 anemia, red cell transfusions, and chemotherapy dose reductions. The data on the right is from a pooled analysis from all three small cell lung cancer studies showing reductions in grade 3/4 hematologic adverse events across all lineages for patients who received COSELA. We also conducted a randomized open-label phase II study with three arms in approximately 100 patients with triple-negative breast cancer in combination with gemcitabine and carboplatin. This trial showed robust statistically significant overall survival improvement in both trilaciclib arms, with hazard ratios of 0.31 and 0.4. This improvement in overall survival was seen regardless of tumor PD-L1 expression. To remind you, pembrolizumab is only approved in patients with PD-L1 positive tumors. Looking at the overall survival curve, there is a greater improvement over time in both trilaciclib arms, which has also been seen with checkpoint inhibitors and is consistent with an immunomodulatory effect. Digging down deeper into the efficacy data from this triple negative breast cancer phase II study, as shown on the left, the most robust result was an improvement in overall survival with a highly statistically significant effect. In the middle of the slide are data from progression-free survival, which was also improved with a hazard ratio of approximately 0.6 and more than a three-month improvement in the median, but this did not meet statistical significance in this small study. The least effect was observed on response rate, as shown on the right. This greater effect on longer event-driven endpoints, like overall survival and progression-free survival, has been seen with immune checkpoint inhibitors and is consistent with an immune modulatory mechanism of action. As we look forward to the data readouts from our phase II and phase III studies, it is important to note that we are more likely to see improvements in overall survival and progression-free survival compared to response rate. Based on the trilaciclib mechanism of action, we are pursuing a broad clinical development program across some key areas. We have an approval in extensive-stage small cell lung cancer for myeloprotection based on reduction of hematologic adverse events, as shown on the left. For future indications, we are focusing on trying to improve survival when trilaciclib is combined with leading and emerging agents. We believe that improved survival could occur by myeloprotection, enabling increased cytotoxic exposure while protecting the immune system, by improving the antitumor immune response to trilaciclib, or by a combination of both. This is a busy slide, but I want to take you all through this carefully because as we anticipate data readouts from our studies, it is important to note that the benefits of trilaciclib will depend on a few factors. First, whether there is myeloprotection with cytotoxic therapy or the ADC payload. Second, whether the standard of care for treatment of a tumor is to continue therapy until disease progression, and whether myeloprotection allows the administration of extended cycles of cytotoxic therapy. Third, whether the tumor is known to be immunogenic, and fourth, whether we're combining trilaciclib with an immunotherapy. As previously discussed, there are two potential ways by which antitumor efficacy could be improved by trilaciclib. The first is myeloprotection, enabling increased cytotoxic exposure while protecting the immune system, and the second is immunomodulation, improving the overall immune response. Both occurring together could also play a role in improving efficacy. Thinking about our indications in this context, we believe that improved efficacy in first-line colorectal cancer is most likely to be driven by myeloprotection, enabling increased cytotoxic exposure since chemotherapy's treatment is given until progressive disease. This is also gonna be important for the second, third-line triple-negative breast cancer study in combination with sacituzumab govitecan, given the myelosuppressive toxicities of this agent and the close correlation between the greater exposure of sacituzumab and improvement in efficacy. In addition, triple-negative breast cancer is a known immunogenic tumor, and immunomodulation by trilaciclib could also play a role in improving efficacy. For the remaining indications, we believe the immune modulatory aspect of trilaciclib's mechanism is likely going to be more important for improving efficacy. In the case of the first-line triple-negative breast cancer in combination with gemcitabine carboplatin, this is based on our prior phase II data showing an improvement in overall survival, which I showed you previously, and for the bladder and neoadjuvant triple-negative breast cancer studies where trilaciclib is combined with chemotherapy and immune checkpoint inhibitors. As you may recall, we did not see myeloprotection with gemcitabine and carboplatin in our phase II triple-negative breast cancer study. Therefore, we do not expect to see it in the phase III triple-negative breast cancer and bladder studies since they both use gemcitabine-containing chemotherapy. We believe this could be due to gemcitabine and its effects on the cell cycle. Finally, in extensive-stage small cell lung cancer, a setting where chemotherapy is given for a limited duration of time and the tumor is not known to be very immunogenic, the benefits of trilaciclib were limited to myeloprotection only without an increase in overall survival. To summarize, this is a very exciting time for the development of trilaciclib. The dual benefits of myeloprotection, allowing greater exposure of cytotoxic therapy while protecting the immune system and enhanced immune function, could result in improving survival outcomes. These effects are driven by the unique attributes of trilaciclib as a transient, potent, and selective intravenous CDK 4/6 inhibitor. The robust antitumor efficacy outcomes are expected to be event-driven endpoints like survival with the least impact on response rate. We are expecting meaningful data readouts starting in the next three months, and we look forward to sharing these data with you in the near term. Thank you for your attention. With that, next, I'd like to introduce Dr. Shom Goel, who will discuss trilaciclib as an immunomodulatory therapy for cancer. Well, thanks very much, Raj, and hello, everyone. My name is Shom Goel, and I'm a medical oncologist and laboratory head at the Peter MacCallum Cancer Centre and the University of Melbourne in Australia. I'm really pleased to have this opportunity to be with you today to discuss the way I think about trilaciclib and in particular the concept that trilaciclib could be used as an immunomodulatory drug to improve outcomes for a wide range of cancer patients. We all know that trilaciclib is an inhibitor of cyclin-dependent kinases 4 and 6, or CDK 4/6, and that these enzymes are very important drivers of cell division. When the CDK 4/6 inhibitors were developed as a class of drug, the main goal was to find agents that would inhibit cell proliferation and in particular inhibit the proliferation of cancer cells. Indeed, as we know, sustained proliferation is indeed a hallmark of many cancers. With that goal in mind, three CDK 4/6 inhibitors have been successfully developed on that very premise and have shown significant activity in hormone receptor-positive breast cancer. Indeed, we now have those three inhibitors approved for that disease, and their effects there are largely manifest through their ability to stop cancer cells from dividing. Now, my team in the lab has been studying the CDK 4/6 pathway and CDK 4/6 inhibitors for several years. Through our work, we have come to appreciate that the effects of CDK 4/6 inhibitors are much broader, and I guess much more profound than simply that of stopping cancer cell division. Indeed, we recently published this review article in which we synthesized the vast literature on CDK4/6 inhibitors, and we proposed this conceptual framework which describes the many different ways in which CDK4/6 inhibitors can impact upon a tumor. As you can see, proliferative arrest in tumor cells is just one of the many mechanisms that these drugs can co-opt. There are, in fact, many other important consequences of treatment with CDK4/6 inhibitors, including the induction of tumor cell senescence, for example, and also an array of effects that these drugs have on cells other than cancer cells, most notably immune populations within tumors. My team's work specifically has been heavily focused on one of these unanticipated effects of CDK4/6 inhibitors, and it's one that I think is very important, and that is the capacity for these drugs to boost antitumor immune responses. We first presented this concept in this paper published in Nature in 2017. Our discovery at this time began with work in animal models, and at the time was not one that we necessarily anticipated. Since publishing this paper, our preclinical work has been confirmed by a number of groups, and there is a growing consensus in the field now that this important effect of CDK4/6 inhibitors is indeed a real phenomenon. In retrospect, perhaps we shouldn't have been so surprised when we made that discovery as we were, because if one performs a careful review of the scientific literature, you do in fact uncover a number of studies in which the CDK 4/6 pathway has been implicated as a very important regulator of immune cell function. Now, the studies on this slide were all done before the pharmacologic CDK 4/6 inhibitors were on the scene, but they all clearly suggest that if one were to inhibit CDK 4 and 6, it could modify immune cell function, and in particular T cell function, in a way that would indeed enhance antitumor immune cell responses in diseases such as cancer. Furthermore, since our work was published, quite a large number of studies now have been presented which all converge upon this notion. Here I'm showing you a list of papers which have all demonstrated enhancement of antitumor immunity with CDK4/6 inhibition. As you can see on this slide, a variety of different mechanisms have been implicated. To some extent, the precise details of why this happens are still being worked out at the cellular level. Indeed, that's something that my laboratory is still very heavily engaged in studying. That said, one very striking and very consistent observation has been that CDK4/6 inhibitors enhance the immune-mediated clearance of tumors, which are already being treated with immune checkpoint inhibitors. As you can see here listed in red, all of those studies and others have indeed found marked synergy when CDK4/6 inhibitors are combined with a variety of different immunotherapies, including, immune checkpoint inhibitors, also stimulators of activatory immune checkpoints, and also in combination with cancer vaccines and even with CAR T-cell therapy. Indeed, the most striking experiment that I've ever done with my own hands in the lab was the one where we showed for the first time that combined CDK4/6 inhibition and immune checkpoint inhibition could result in dramatic clearance of tumors in mice, which neither agent came close to doing, when given alone. It's also worth mentioning that a number of the studies on this page have also confirmed, this observation in human samples. We've shown in human breast cancer that CDK4/6 inhibitors can enhance gene expression profiles, consistent with immune activation, and other investigators have found similar results in other cancer types. With all of this in mind, I think the question then becomes. How do we proceed from here? How do we take this very striking and reproducible observation and turn it into a clinical strategy to improve outcomes for cancer patients? This is indeed where I believe trilaciclib, as a drug, has immense potential. Indeed, it is the only CDK4/6 inhibitor that is being developed with this concept specifically in mind. I think there are a number of features, with respect to trilaciclib that make it an excellent candidate to try and exploit this, these properties. The first of these is the fact that it's administered intravenously. What we are beginning to learn about this immunomodulatory effect with CDK4/6 inhibitors is that it really does involve a careful balance between immune cell number and immune cell function. One needs to dose the CDK4/6 inhibitor precisely and probably intermittently. That's where trilaciclib has an advantage because it is dosed intravenously, and therefore, there is greater precision with respect to the timing of dosing. What that ultimately allows is for us to very precisely change the transcriptome or the gene expression profile in T lymphocytes in ways that we would like over the course of a patient's treatment. The other good thing about giving trilaciclib intermittently and intravenously is that it is very easy, I think, to integrate trilaciclib therapy with existing standards of care, whether that be intravenously administered chemotherapy, or for that matter, immune checkpoint inhibitors. As a result, I think, to summarize, I think this drug really does carry great potential, to in a wide range of cancer types when combined with, chemotherapy and immunotherapy, et cetera. With all of this in mind, I'm really extremely supportive of and excited by this plan to develop trilaciclib in this way. I think that the preclinical data and the available clinical data strongly support this concept, and I think that with careful strategy, I'm optimistic that we'll see this drug used as an adjunct to many cancer therapies where an immune process underlies part or all of the mechanism of that therapy's action. With that, I'd like to thank you very much for your attention, and I'll turn it over to John. Thank you, Shom. Dr. Goel has outlined a role for trilaciclib in anti-tumor efficacy, and my section will highlight key trilaciclib-induced immune modulations that support its synergistic potential. A method to evaluate a drug's immune modulatory property is to identify how it contributes to the cancer-immunity cycle. Before sharing our data, I would like to familiarize the audience with the cancer-immunity cycle. The cancer-immunity cycle highlights key processes that are required for an optimal anti-tumor response with the focus on T cells. The cycle starts with the release of cancer cell antigens induced by agents such as chemotherapy or ADCs. The cancer antigens are then processed and presented to T cells by antigen-presenting cells, initiating a cascade of T cell activation, trafficking, and infiltration of T cells into the tumor. Once the T cells are in the tumor microenvironment, T cells can initiate further tumor killing. As we come to realize, this cycle is not as straightforward as immune cells navigate an immunosuppressive microenvironment and tumor cells evade immune recognition. Notably, current strategies to overcome the immunosuppressive roadblocks, such as inhibitory receptor blockade, are specific for a process within the cancer immunity cycle, and therefore may not be as efficient if other processes in the cycle are interrupted. In the following slide, I will highlight trilaciclib's impact on the cancer immunity cycle. Our clinical data strongly demonstrates a broad effect of trilaciclib on the cancer immunity cycle. Compared to the therapeutic interventions in red, trilaciclib's role, seen in blue, supports several processes through MHC upregulation, increase in cytokine and chemokine production, modulation of an immunosuppressive type of T cells known as Tregs, and differentiation of T cells into a memory T cell population. Collectively, the effects of trilaciclib can be grouped into three immune mechanisms, enhancement of T cell activation, favorable alteration of the tumor microenvironment, and improvement of long-term immune surveillance. Based on the mechanisms of action of trilaciclib and its broad effects, trilaciclib is ideal for combination use in enhancing the efficacy of these therapeutic interventions. We believe that trilaciclib has a broad impact on the immune response based on its ability to modulate gene expression within T cells. In collaboration with Dr. Shom Goel, we demonstrate this by treating mice with a single dose of trilaciclib in a breast cancer model. Controls were left untreated. After 24 hours, tumors were dissociated, and CD3 positive T cells were isolated for single-cell RNA sequencing. The figures presented visually demonstrate the subpopulation of T cells and changes in T cell gene profiles in a dimension reduction analysis. A dot represents an individual T cell, and each color-coded cluster of cells identify a subset of T cells. The fact that the populations of T cells in the control and trilaciclib groups do not overlap signifies differences in the gene profile of a T cell subset, even though they are identified as the same cell type. We also observe a loss of T cell subsets following trilaciclib administration, notably in the red and blue clusters in the bottom portion of the figure in the control group. We are excited about this early data because the study suggests that trilaciclib's effect on gene expression is immediate, and the breadth of gene expression changes support the broad cellular changes observed. In the next set of slides, I will refer back to the cancer-immunity cycle and show how trilaciclib enhances T cell activation, favorably alters the tumor microenvironment, and improves long-term immune surveillance. To determine whether trilaciclib can enhance antigen presentation on tumor cells, human peripheral blood mononuclear cells were stimulated in the presence and absence of trilaciclib. Subsequently, supernatant from the T cell stimulation were cultured with MCF-7 breast cancer cell line prior to MHC class I and II and PD-L1 expression analysis by flow cytometry, shown in the figure on the left. Compared to controls, supernatant from trilaciclib-treated PBMCs enhanced antigen presentation based on up-regulation of MHC class I and II, and we also observed an increase in PD-L1. Fold change for individual patients are shown on the bar graphs. To assess T cell activation, we performed a set of in vivo studies which I'll refer back to over the course of this presentation. In this study depicted on the right side of the screen, we compare the addition of trilaciclib in a combination of chemotherapy and anti-PD-L1 therapy in an MC38 colorectal cancer model. five days after treatment, early activation was quantitated by detecting the expression level of an activation marker called CD69 on splenocytes. The orange bars representing the addition of trilaciclib demonstrate the increase in the frequency of activated CD4 and CD8 T cells. Enhancement in these two mechanisms highlighted in these slides support trilaciclib's role in T cell activation. These next sets of studies demonstrate trilaciclib's potential in modulating the tumor microenvironment. To determine whether trilaciclib can affect trafficking of T cells, an in vitro study was conducted using an organoid system derived from tumors from five individual non-small cell lung cancer patients. In the figure on the left side of the screen, the tumor organoids were exposed to trilaciclib and cytokine and chemokines measured on day three. Overall, exposure to trilaciclib increased chemokine production, notably CXCL9 and CXCL10. This result is in line with a recent publication highlighting an increase in CXCL9 and CXCL10 in recruiting activated CD8 T cells, but not Tregs into the tumor. To examine trilaciclib's effect on the tumor microenvironment, I want to refer back to the in vivo study of trilaciclib in combination with chemotherapy and anti-PD-L1. For this study shown in the middle, tumor was collected on days two, four, and seven to isolate and characterize the tumor-infiltrating lymphocytes. Changes within the tumor microenvironment was assessed by measuring the proliferative kinetics of CD8 T cells and Tregs on days two, four, and seven following a single dose of trilaciclib. Initially, we observed an expected dip in the relative proliferation of the trilaciclib-treated groups on day two. By days four and seven, the CD8 T cells rebounded to levels on par with controls. Interestingly, this rebound back to control levels did not occur in the Tregs because we observed a prolonged arrest of Treg proliferation. This data suggests that the disparity in proliferation between CD8 T cells and Tregs can result in a higher ratio of CD8 to Tregs in the tumor microenvironment, and thereby promote a favorable tumor microenvironment. To follow up on the data showing proliferative sensitivity of Tregs to trilaciclib, we next examine whether trilaciclib can modulate Treg function. To address this, we performed a Treg suppression assay, which measures the ability of Tregs to suppress the proliferation of activated CD8 T cells. Prior to combining CD8 T cells and Tregs were pre-treated with increasing concentrations of trilaciclib. The figure on the right show a 50% decrease in CD8 T cell proliferation, a sign of Treg suppression when Tregs were not pre-treated with trilaciclib. When Tregs were pre-treated with trilaciclib, we observed a stepwise increase in CD8 T cell proliferation, demonstrating a loss of suppressive function within Tregs when exposed to trilaciclib. Overall, trilaciclib supports immune cell infiltration into the tumor and has both quantitative and qualitative effects on Tregs that could diminish the immunosuppressive niche within the tumor microenvironment and enhance anti-tumor response. To confirm our non-clinical findings, we have an ongoing phase II trial in neoadjuvant TNBC, where we will have the opportunity to investigate changes within the tumor microenvironment between baseline and day seven following trilaciclib monotherapy. Generation of memory T cells is critical for a durable anti-tumor response and immune surveillance. Assessment of T cell memory at early time points reveal a skewing towards a memory phenotype when trilaciclib is administered. In a single cell analysis of CD8 T cells from tumor-bearing mice treated with trilaciclib, genes associated with memory differentiation were upregulated compared to controls on day seven. These genes shown on the left include cell, IL-7 receptor, and TCF7. When we hone in on the tumor microenvironment at day seven following treatment and survey the maturation status of the residing intratumor CD8 T cells on the right side of the screen, we observe an increase in effector memory CD8 T cells in mice treated with trilaciclib. The reason we're excited about this data is that the enhancement of memory CD8 T cell generation potentiated by trilaciclib can promote a durable response and long-term survival. Ongoing efforts are focused on better understanding the mechanisms of memory T cell differentiation in response to transient CDK4/6 arrest. The broad immunomodulatory effects elicited by trilaciclib support several steps outlined in the cancer-immunity cycle. Therefore, the combination therapy with trilaciclib should provide a synergistic benefit. To address this, we performed two sets of studies investigating the potential for trilaciclib to combine with a checkpoint inhibitor and to investigate the requirement of chemotherapy in this combination. The study on the left was focused on the combination of trilaciclib and anti-PD-1. The efficacy study performed in an MC38 model reveals an added benefit to tumor suppression when anti-PD-1 and trilaciclib are combined. The effectiveness of tumor suppression was supported by an increase in T cell function, highlighted by the increase in the frequency of IL-2 and interferon-gamma pro-inflammatory cytokines. When trilaciclib was combined with anti-PD-1 or PD-L1 in chemotherapy, we observed beneficial outcomes no matter the type of chemotherapy, type of inhibitors targeting PD-1 or PD-L1, and mouse model. For the three studies on the right, the addition of trilaciclib to chemotherapy and checkpoint inhibitor enhanced efficacy and increased survival. These efficacy studies highlight the immune modulatory properties of trilaciclib and suggest that trilaciclib can provide an added benefit to current checkpoint inhibitor therapy. The synergistic effect that we observed with trilaciclib and PD-1 blockade has led us to investigate other combination opportunities. We chose to investigate whether trilaciclib would provide an added benefit to the combination of LAG-3 and PD-1 since this combination has been approved in melanoma. We also examined the adenosine pathway, which is independent of checkpoint inhibitors. When a weekly dose of trilaciclib was administered on top of the combination of anti-LAG-3 and PD-1, we observed an early diminishment of tumor growth that was maintained through the course of the study. The triple combination resulted in seven of eight mice reaching a complete response. Trilaciclib also provided a survival benefit in the triple combination. The inhibition of the adenosine pathway is another area of interest to enhance anti-tumor response. Adenosine can aid in cancer cell proliferation, angiogenesis, and anti-tumor immunosuppression. CD73 is a critical protein in generating adenosine from ATP and is a developing target for immunotherapy. Similar to the LAG-3 triple combination, the addition of trilaciclib to a PD-1 and anti-CD73 further suppressed tumor growth and enhanced survival of the CT26-bearing mice. Overall, trilaciclib provides an added benefit to current strategies utilizing checkpoint inhibitors. As I mentioned previously, we believe that trilaciclib's broad immune MOA within the cancer-immunity cycle allows for the benefit in efficacy when combined with inhibitory receptor blockade. We're excited to have shared with the audience our data highlighting trilaciclib's potential as an immune modulator to enhance the anti-tumor immune response. We believe that the transient arrest induced by trilaciclib initiates a cascade of molecular changes within T cells that enhances T cell activation, favorably alters the tumor microenvironment, and improves long-term immune surveillance. This was corroborated with the in vivo efficacy data supporting a synergistic effect when combined with checkpoint and adenosine pathway inhibitor. The work to better understand the MOA is ongoing, and we will report some of our new findings at an upcoming medical meeting this year. We also have an ongoing phase II TNBC MOA study that will provide us with clinical information into the immunological changes within the tumor microenvironment with trilaciclib monotherapy. We will report some of that data at another medical meeting in Q4. Now I want to introduce you to Samantha Melamed, who will provide information on our clinical development. Thanks, John. I'm Samantha Melamed, the VP of Clinical Development at G1 Therapeutics, and I'm looking forward to talking to you today about the ongoing studies for trilaciclib. Trilaciclib's unique mechanism provides multiple opportunities to improve on standard of care, depending on the properties of the underlying therapy, length of time on treatment, and characteristics of the tumor type. In colorectal cancer, we have an ongoing phase three study with myeloprotection and patient-reported outcomes as primary endpoints. On this trial, extended cycles of therapy give trilaciclib the opportunity to have a greater impact on time to event outcomes such as PFS and OS, much longer than those obtainable in extensive stage small cell lung cancer. Positive data from this study will be sufficient for filing a label expansion with FDA. As we look at our ongoing phase II study in combination with sacituzumab govitecan, referred to for the rest of the presentation as SG, we have the potential to leverage myeloprotection effects of trilaciclib for SG's SN38 payload. Based on the results of the ASCENT study, SG is administered until disease progression, which provides the opportunity for extended cycles of trilaciclib in this combination. Trilaciclib added to SG also has the ability to improve tolerability of this effective regimen, increase the length of time patients remain on therapy, all with the potential to improve time to event endpoints such as PFS and OS. In addition, TNBC is a known immunogenic tumor where trilaciclib has phase II efficacy data demonstrating an improvement in survival, so there's potential synergy with these two effective regimens. Finally, the results of the study will provide foundational data for future combinations and other tumor types where SG has the potential to be a meaningful regimen across breast, lung, and bladder cancer. Next, we turn to our ongoing phase III pivotal study, which is a confirmatory trial for the phase II data in TNBC discussed previously by Raj. This study is testing the hypothesis that the unique mechanism of action of trilaciclib in immune modulation in a background of a known immunogenic tumor treated with extended cycles of therapy of trilaciclib will again result in an improvement in overall survival. As Raj mentioned, based on the previous phase II study, we do not expect an improvement in myeloprotection endpoints. A positive study will be discussed with global agencies with the opportunity for label expansion based on an improvement on overall survival. In our ongoing bladder cancer study that has recently fully enrolled, trilaciclib is administered in both the induction phase with chemotherapy and with maintenance of avelumab based on the results of the JAVELIN Bladder 100 study. This provides the opportunity for extended cycles of trilaciclib therapy with trilaciclib in bladder cancer as a known immunogenic tumor. Combination data with avelumab alone in maintenance therapy allows us to test in the clinic the data we observed in preclinical models of improved activity of trilaciclib in combination with an immune checkpoint inhibitor, which will be foundational data for future development in trilaciclib combo, both in bladder cancer and with an immune checkpoint inhibitor in other tumor types. Given data from the phase II TNBC trilaciclib study with the same underlying regimen of gemcitabine plus platinum, we do not expect an improvement in myeloprotection for the chemotherapy phase of this trial. Finally, we turn to our ongoing study in neoadjuvant TNBC, which also recently fully enrolled and has a primary biomarker endpoint. This study will provide important mechanism of action data for trilaciclib. In this study, trilaciclib has multiple areas to provide benefit due to extended cycles of treatment in a known immunogenic tumor and in combination with an immune checkpoint inhibitor, pembrolizumab, based on the KEYNOTE-522 regimen. Patients will be treated with trilaciclib plus standard of care neoadjuvant treatment prior to definitive surgery, and on-treatment biopsies will report important mechanistic data, and the pCR endpoint based on the entire treatment regimen will provide efficacy results in early-stage breast cancer and can be leveraged in our future development plans. Next, we will turn to the details on our ongoing pivotal phase III studies. This is the foundational data for ongoing pivotal phase III in colorectal cancer based on a meta-analysis comparing FOLFOXIRI plus Bev compared to doublet chemotherapy plus bevacizumab. In these studies, efficacy outcomes improved with FOLFOXIRI plus Bev as compared to doublet chemotherapy plus Bev, but come with significant toxicity, including a doubling in neutropenia, which has limited the use of the regimen to fitter patients. Of note, the patient population enrolled on these studies may be different than those enrolled in PRESERVE 1, as those patients had the opportunity to receive doublet therapy. Given all patients on our trial receive FOLFOXIRI, they may be younger with a higher disease burdens and their outcomes reflective of this difference. Next, we turn to a schema of our ongoing pivotal phase III study with primary endpoints of myeloprotection and patient-reported outcomes assigned to 0.04 alpha, and the later readout of time-to-event endpoints of PFS and OS assigned to 0.01 alpha. Assuming a positive endpoint for the co-primary endpoints, this allows us to conserve alpha for time-to-event analyses and assess these endpoints when the final number of events occur. Of note, in December 2021, Rossini et al. Published a meta-analysis of the FOLFOXIRI plus Bev versus doublet plus Bev phase III TRIBE studies demonstrating the majority of severe neutropenia with FOLFOXIRI occurred in Cycles 1 through 4 of induction. Our initial primary endpoint of PRESERVE 1 was confined to Cycle 1 alone, similar to our small cell lung cancer trials. To reflect this clinically relevant time point derived from foundational studies for PRESERVE 1, G1 worked with the FDA to update the primary endpoint from duration of severe neutropenia in Cycle 1 to duration of severe neutropenia across Cycles 1 through 4. The study is currently being amended, and the data readout in Q1 of 2023 will reflect this change in endpoint. The initial readout next year will be for the primary endpoints of myeloprotection and patient-reported outcomes. Positive data will be discussed with FDA to file for a potential label expansion. We believe the longer-term treatment with trilaciclib and improved ability to tolerate FOLFOXIRI and bevacizumab will improve time-to-event endpoints such as PFS and OS. However, those will read out at a later date. Initial efficacy data at the primary analysis will be response rate, where we expect the benefit of trilaciclib to be more modest. Next, I wanted to highlight the phase II data that Raj presented previously and led to us initiating a phase III study for trilaciclib in combination with gemcitabine and carboplatin in metastatic TNBC. This study demonstrated substantial improvement in overall survival, with a 60%-70% reduction in risk of death, with extended cycles of trilaciclib treatment in a known immunogenic tumor. Based on the results of this trial, trilaciclib was granted Fast Track designation a year ago, and this study provided foundational data to confirm in a phase III study. The next slide describes the schema of this randomized double-blind, placebo-controlled pivotal phase III trial with a primary endpoint of overall survival. There is an interim analysis in the H2 of 2023 when 70% of the survival events will be reported. G1 will remain blinded, and if the study re-meets predetermined stopping rules, the study can be declared positive. If not, the trial will continue to the final analysis. A positive study will be discussed with global regulators with the potential of a label expansion based on significantly improved overall survival. Next, we turn to the details of our ongoing phase II studies. Three phase II trials will provide data to further elucidate the mechanism of trilaciclib and to indicate future development for our pipeline within a molecule. First, in combination with SG, we can leverage both the myeloprotection properties of trilaciclib to improve tolerability, exposure, and length of time on therapy, and the activity of trilaciclib in TNBC with the goal of continuing to optimize the ASCENT data with increased OS and PFS. Combinations with ADCs, including SG, provide a platform potential for future development of trilaciclib. For bladder cancer, this is an opportunity for trilaciclib to demonstrate an improvement in overall survival beyond triple-negative breast cancer and to explore the synergy seen pre-clinically of trilaciclib in combination with an immune checkpoint inhibitor. These treatments are foundational in most tumor types, and synergy of trilaciclib in combination will be an important aspect of future combination studies. Finally, our ongoing neoadjuvant TNBC study will provide detailed clinical mechanistic data for trilaciclib as an immune modulatory agent, as well as an efficacy signal in earlier stage disease in a tumor type with demonstrated activity with trilaciclib. Together, this portfolio of phase II studies will provide meaningful data to expand upon in our next series of phase III trials. turning to the schema for our phase II SG combination, this single-arm study is ongoing and continues to enroll patients. The primary endpoint for the trial is progression-free survival, with secondary endpoints of ORR and OS, as well as myeloprotection. We expect to see initial results from the study in the Q4 of this year, and an abstract has been submitted for an upcoming medical meeting in December. More mature data will be reported out through 2023. Our ongoing phase II bladder cancer study has recently completed enrollment. This trial is a randomized study with trilaciclib administered both during platinum-based induction chemotherapy and with avelumab in the maintenance phase of treatment. The primary endpoint is PFS, with secondary endpoints of ORR, OS, and myeloprotection. Efficacy for the study will be examined both for the overall study period as well as separately for induction and maintenance. Initial data will be available in Q4 this year for safety and response rate. We expect the major benefit of trilaciclib in this patient population to be on time to event endpoints of PFS and OS. PFS is projected to read out later in 2023. Finally, I would like to discuss our ongoing phase II single-arm study in neoadjuvant TNBC. This trial has also recently completed enrollment, and the primary endpoint describes the immune-based mechanism of action of trilaciclib, with initial data available in Q4 this year and an abstract submitted to an upcoming medical meeting in December. The study is signal generating for activity of trilaciclib in earlier stage disease and in combination with an immune checkpoint inhibitor. The secondary endpoint of pCR will provide proof-of-concept data for future development in earlier stage cancers when it reads out next year. In summary, the ongoing clinical portfolio for trilaciclib has the potential for near-term label expansion based on the phase III trials. The phase II studies are uniquely poised to answer relevant questions about the biology of trilaciclib and provide proof of concept in multiple treatment combinations with drug classes expected to be foundational in future standard of care. Thank you for your time, and I will now hand off to Norman Nagl. Thanks so much, Sam. My name is Norman Nagl. I'm Vice President of Medical Affairs at G1 Therapeutics. We're happy to be joined today by Dr. Richard Goldberg, who is Professor Emeritus and former Director of the West Virginia University Cancer Institute, who is an internationally recognized expert in colorectal cancer and GI malignancies. Thanks for joining us, Dr. Goldberg. We're gonna have a little bit of a discussion here around the current standard of care for patients with first-line metastatic colorectal cancer, as well as what some of those unmet needs are in that space. Thanks so much for joining us. We have a couple of questions for you. Please go ahead. Thanks for the opportunity to be here. Our first question. What do you feel are some of the main chemotherapy regimens that are used to treat patients with metastatic colorectal cancer in that first-line setting? Chemotherapy for metastatic colorectal cancers evolved a lot from the days when we used 5-FU as a single agent, now to the point where we're using multiple drugs as first-line therapy. Not just cytotoxics, but also biologics. As we have gone to multiple drug regimens, we've had to compromise in terms of expecting more toxicity, but have applauded the advances in terms of progression-free survival and overall survival. The principle now is multi-drug chemotherapy coupled with biologics. Commonly, we're using irinotecan and oxaliplatin-based regimens with 5-FU, and sometimes all three drugs together. FOLFOX, I think, is still the standard of care, particularly in the U.S., for first-line regimens. In Europe, FOLFIRI is commonly used, more commonly than in the U.S. The FOLFOXIRI regimen, which combines 5-FU, irinotecan, and oxaliplatin, in a single drug regimen, is more commonly being used. The data for that comes from studies mainly done in Italy, which have shown really promising results in terms of extending progression-free and overall survival. There's an interest, particularly in younger, fitter patients, and unfortunately, we're seeing more younger patients with colorectal cancer, to push the intensity of the drug regimens in hopes of increasing both response rate and overall survival. Of those regimens that you just described, FOLFOX, FOLFOXIRI, or FOLFIRI in that first-line setting, which has been shown to provide the most clinical benefit with regard to efficacy? Well, in terms of outcomes, there are good randomized studies done by the GONO group in Italy that have really shown that FOLFOXIRI, often given with bevacizumab, provides the best outcomes. So, the studies have shown that progression-free survival of about 19 months with FOLFOXIRI plus Bev in comparison to FOLFOX plus Bev at 16.4 months is among the best outcomes that we've seen with any regimens in the first-line metastatic disease setting. I would mention that FOLFOXIRI is not given for an indefinite number of cycles but is generally given for a finite number of cycles. Part of the reason for that is the toxicity of the regimen can be daunting in some patients. We don't even consider it in some patients who are compromised in terms of performance score or comorbidities, because of the intensity of the regimen. Given those statements, what really helps inform the clinical decision-making process, with regard to which patients need that more aggressive first-line treatment with FOLFOXIRI? Well, certainly the most important is patient preference. As you describe to a patient the potential regimens that you can use, you need to understand what their goals are. For a patient who is young and interested in the best possible outcomes, they often will wanna choose the most aggressive therapy. For a patient that has multiple comorbid conditions and is not fit, maybe a performance score of one+ or two, the choices are different. When the goal is to try and treat somebody with metastatic disease in hopes that their liver disease or their lung disease will respond sufficiently so that they can be resected for a cure, the most aggressive therapy is what's most likely to get you to that place. Understanding goals of therapy is important. Of course, safety considerations, which, as a physician trying to not do harm to patients, are really important to both the physician and the patient. As a clinician, what are some of the most concerning side effects with FOLFOXIRI from your perspective? Second part to the question, what about patients? What do patients feel are the most concerning adverse events with FOLFOXIRI? Well, the most obvious is the rate of high-grade toxicity. Grade 4, meaning severe toxicity, and grade 5 meaning lethal toxicity, are really important issues. In metastatic disease, of course, you're contending with the complications of the disease, and some patients will get progressive disease and have severe consequences as a result of that. The thing that's most concerning is for patients to have very severe or lethal toxicity as a consequence to drug side effects. The most concerning is neutropenia, which can lead to sepsis and death. In the trials run by our Italian colleagues, there have been deaths related to sepsis in the FOLFOXIRI arms, while in the FOLFOX arms of their studies, that has not been seen. The last thing that any physician wants or any patient or family member wants is to be subject to this severe and potentially lethal toxicity. The other side effects that we see are the side effects of the multiple drugs. irinotecan is not only associated with neutropenia but also with diarrhea, nausea, and fatigue. oxaliplatin also can cause neutropenia, fatigue, and of course, peripheral neuropathy. 5-FU is less likely to cause neutropenia because it's given as an infusion in these circumstances, and you don't have the high peak levels of the drug that are associated with neutropenia. but I would say GI side effects, bone marrow toxicities, including both neutropenia and low platelet counts, can be daunting toxicities. Fatigue and just the debilitating effects of having to deal with both a stage four diagnosis and the consequences of its therapy are paramount in my thinking as I make decisions for patients. I think patients often don't really have a sense of what they're getting into, so they rely on my descriptions. Quality of life is a very important consideration for patients, most of whom will not end up with an option for curative therapy in this setting. The ability to enjoy life while maintaining disease control, I think is what often is paramount in their minds. Great insight. Thank you. Since FOLFOXIRI, as you mentioned, is very effective, but also is associated with some side effects, what are some of your thoughts on ways to potentially improve, so certainly the tolerability but then also potentially efficacy of the regimen as well? Well, you constantly walk the tightrope between dose intensity and toxicity intensity. I think the fact that FOLFOXIRI has emerged as the most effective regimen shows that dose intensity is important. How do patients moderate the toxic effects of this? Well, one is to go into it with a good understanding of the supportive care regimens that are available, such as antidiarrheal treatments, anti-nausea treatments, to maintain a good intake so that their calorie balance is at least neutral and potentially positive, if possible. To be sure that they're aware of the potential for infection and life-threatening infection, so that if they get fevers, they manage them appropriately, including getting in touch with their oncology team and being sure that they get a CBC check to know if they're neutropenic. We often in patients who do manifest neutropenia in the first few cycles of treatment end up going to G-CSF as a supportive care regimen. That too has downsides both in terms of cost and the fact that some patients can have side effects as a consequence of getting G-CSF injections. All of those supportive care measures I think are important. Increasingly the importance of continuing activity, whether it's walking or more vigorous exercise, as an adjunct to treatment, is being recognized as an important way of maintaining patient health and well-being. Great. Thank you. Last question. If FOLFOXIRI had similar or even reduced toxicity, particularly myelotoxicity, with regard to something like FOLFOX, do you think that this would change how the triplet regimen is used today versus how it's currently seen in clinical practice? Well, I do believe that the potential for FOLFOXIRI is underutilized by oncologists in general. In the United States, it's not the default regimen I think for many patients. I think in Italy it is the default regimen, but in other parts of Europe it's less commonly used, and I'm not sure about the practice patterns in Asia, so I can't speak to that as well. I do think that if toxicity could be better controlled, that it would be used more commonly by oncologists and would have greater acceptance, particularly in the U.S. I do think toxicity concerns are an inhibitor of routine use of this regimen despite its activity statistics. Great. Dr. Goldberg, thank you so much for your insight, as well as your time. I know myself and my colleagues found it very informative and helpful. With that, I'd like to turn things over to my colleague, Mark Avagliano. Mark. Thanks, Norm, and a special thanks to Dr. Goldberg for joining us today and sharing his insights. I'll take a few moments to share our thoughts about the trilaciclib market opportunity as we see it and where we are focusing our efforts to maximize this pipeline in a molecule product. Turning to our first slide, I just wanna recap where we're primarily focused in our current efforts as a company. As you see on this chart, we're active in four of the six most common tumor types by annual incidence, each of which have significant unmet need. Looking at the right side of this slide, we currently market trilaciclib as COSELA in the U.S. for small cell lung cancer patients, and our partner, Simcere, recently received approval to start marketing COSELA in China there as well. We have our two pivotal studies ongoing in first-line triple-negative breast cancer and first-line colorectal cancer, as Sam highlighted earlier today, and I will dig into those two opportunities a little further shortly. Lastly, we have multiple phase II studies either ongoing or planned across breast cancer, lung cancer, and bladder cancer, with initial data from three of the ongoing studies expected at the end of this year. In terms of our ongoing pivotal study in colorectal cancer, we see a meaningful opportunity to help a large segment of patients that desperately need new treatment options. As you see on the left side of this chart, we estimate there to be approximately 47,000 first-line patients with microsatellite stable disease treated each year. This represents the vast majority of all first-line treated colorectal cancer patients. There has been limited new treatment innovations in this space, and chemotherapy remains the primary backbone treatment. As we just heard from Dr. Goldberg, FOLFOXIRI is the most efficacious regimen but is less commonly used given its toxicities. We estimate FOLFOXIRI to be used in approximately 10%-20% of patients, mostly in younger, healthier patients with high tumor burden, where the efficacy needs outweigh the toxicity concerns. We believe trilaciclib can potentially meaningfully decrease the myelotoxicities of FOLFOXIRI and enable greater use of this regimen across a broader segment of patients. Additionally, we believe trilaciclib's unique ability to enable patients to receive even greater exposure to FOLFOXIRI than they would have otherwise while protecting their immune systems can potentially further increase the efficacy of this regimen. We look forward to those data further down the line. Switching to the potential opportunity of first-line triple-negative breast cancer, this is a smaller opportunity than CRC, with approximately 9,000 patients treated each year. However, these patients desperately need new treatment options, as TNBC is the most challenging breast cancer segment to treat. Chemotherapy currently remains the standard of care in first-line TNBC, either with or without targeted therapies, and there is an urgent need for new therapies, particularly that work broadly and without added toxicities. Based on our previous phase II data, as both Raj and Sam discussed earlier, we believe trilaciclib could be a meaningful new treatment option with benefit to patients that have either PD-L1 positive or PD-L1 negative tumors. We are excited for the expected readout of this trial in the H2 of 2023 if the interim analysis is positive. Moving to our proof of concept studies. Each of these three ongoing studies will be critical, not only for evaluating trilaciclib in these specific tumor types and populations, but also for demonstrating how broadly applicable these benefits may be, including in combination with important existing and emerging foundational therapies, as Sam mentioned earlier. For example, the second-line, third-line triple-negative breast cancer study shown at the top of this page will provide proof of concept combination data for trilaciclib added to the ADC sacituzumab that could be applicable to any other setting where sacituzumab is used. Similarly, the first-line bladder cancer study shown in the middle of this page could provide insights for the benefits of adding trilaciclib to checkpoint inhibitor treatment regardless of tumor type, and was generally observed in our preclinical findings. Lastly, the neoadjuvant triple-negative breast cancer study shown at the bottom of this page could demonstrate a benefit of adding trilaciclib to chemotherapy and checkpoint inhibitor treatment together, particularly in early stage cancers. Moving to this next slide, I wanted to briefly talk through how we're thinking about our next wave of trilaciclib studies, which will be generally based on the two key benefits we have been discussing throughout today. As you see on the top portion of this slide, we believe there are multiple meaningful opportunities to leverage the myeloprotection benefits of trilaciclib with important therapies such as ADCs, ADC combinations, and other highly myelotoxic regimens in a tumor-agnostic approach. For example, if trilaciclib adds meaningful benefit to the ADC sacituzumab, we can potentially pursue this combination in any setting where sacituzumab is or will likely be used in the future. This could also apply to other ADCs or other highly myelotoxic regimens, such as the example listed on the right-hand side of this slide, FOLFIRINOX, which is a similar regimen to the chemotherapy we're evaluating in our first-line colorectal cancer study. As shown in the bottom half of this slide, we think there are many settings where the immunomodulation properties of trilaciclib may provide benefit, particularly in combination with checkpoint inhibitors. For example, if trilaciclib adds benefit to avelumab maintenance in our ongoing bladder study, there could be many meaningful opportunities to pursue wherever checkpoint inhibitor maintenance treatment is used. This slide provides an overview of how all the pieces come together with the multiple upcoming data readouts and determining which trilaciclib studies likely make most sense to pursue next. As you've heard today, we believe trilaciclib may work broadly in many different settings, and we wanna be aggressive to get to as many patients as quickly as possible. However, we also want to have an update in hand to ensure we are making the best decisions possible before initiating additional large pivotal studies. Therefore, we are currently expecting to initiate the bulk of our next wave of studies, likely towards the middle of next year, once we have a fuller picture of the data across our ongoing studies. This timing also lines up with our broader partnering plans as we anticipate identifying a partner ahead of initiating these additional phase III studies that will be able to help us maximize the development and commercialization of this product globally. Turning to the last slide here, which we have shared previously, I just want to reinforce our excitement for the potential of this unique pipeline and a molecule product. We are looking forward to the near-term data readouts ahead to potentially expand into new indications and demonstrate the breadth of opportunity for this asset. As mentioned, we hope to expand on our initial small-cell lung cancer indication with two important near-term commercial opportunities in first-line colorectal cancer and first-line triple-negative breast cancer, both with expected pivotal data readouts next year. We have 3 current phase II studies with data readouts expected by the end of this year that will help us refine our study plans for where we go next. Our ultimate goal is to help as many patients as possible by pursuing a tumor-agnostic approach for this unique product, including in combination with existing and future foundational therapies. With that, I'll turn it back to Jack for some closing remarks. Jack? Thanks, Mark, and I want to thank everyone for joining us today. We hope you have found the data and presentations helpful to better understand the exciting and broad opportunities we believe are in front of trilaciclib. Now, before we go into Q&A, let me underscore what you have heard today. First, that trilaciclib's unique effect on the bone marrow is directly attributable to the transient, potent, and selective CDK4/6 inhibition and the fact that it directly targets the host. Second, that trilaciclib enhances multiple immunological processes within the cancer-immunity cycle. Third, that trilaciclib has the potential for improved survival via both improved immune response and increased cytotoxic exposure while protecting the immune system. Fourth, new preclinical data that shows consistent synergistic potential with multiple combination treatments. Fifth, we have meaningful clinical readouts starting in the next three months and continuing throughout next year. Finally, that trilaciclib represents a true pipeline-in-a-molecule opportunity with significant expansion opportunities in future standards of care. Now, with that, we will now go into our Q&A session. To lead us through that, I will turn it back to Will Roberts again. Will? Hello. Thank you, Jack, and hello again, everybody. This, as Jack mentioned, is the Q&A session with the G1 leadership team. While we certainly appreciate the content and input from Dr. Goel and Dr. Goldberg, they're not participating in this portion of it. While the G1 team assembles for the Q&A, just a couple of reminders for our listeners. First of all, I'll remind you that the forward-looking statement commentary that I provided at the beginning of this presentation applies to the Q&A as well. Secondly, a reminder again that today is really all about trilaciclib, its mechanism of action, its broad applicability, the clinical evaluations we're doing, the new synergistic data that we've talked about, and we're gonna limit the questions to those topics. Third, thank you for all the great questions. They're terrific. We have quite a few. I'm gonna do my very best to get to them all. I'll combine them into hopefully bite-sized pieces, but we'll do our very best to get to as many as we can. Finally, as Jack mentioned, I'm quarterbacking this. I'll be asking the questions of the team. One thing to keep in mind is that a few folks have asked that I leave out the name and affiliation of the folks who are asking the question. I respect that, and we're gonna apply that rule to all the questions that have come in. With that, I'd ask the engineer to please hopefully bring in the entire team for the Q&A portion. Hi, gang. Can everybody hear me? Awesome. As a reminder to our listeners who are attending today, we have Jack Bailey, Raj Malik, Mark Avagliano, Samantha Melamed, and John Yi, and we'll start the Q&A immediately. Raj, way up in the trees, we've gotten a few questions about sort of generalizing the content and asking, in summary, how would we define success this fall in those three phase twos? Yeah, happy to. Will, starting with bladder, we believe that improvement of efficacy in this trial is gonna be driven by the immune modulatory effects of trilaciclib, enhancing the antitumor immune response, as you heard from John Yi. What we also expect is that this effect will be more on the longer-term, event-driven endpoints, particularly PFS, which is actually our primary endpoint of the trial, and overall survival, and the least effect on the response rate. With regards to the data available in the Q4, what we will be looking for is indications of the data at that time and how it could potentially translate to improvement in the longer-term, endpoints that I mentioned. For example, the duration of exposure of trilaciclib and avelumab or chemotherapy, the duration of response, what does the response look like in the chemotherapy part of the trial and the avelumab part of the trial? Those are some of the things we'll be looking at. Important to mention that we do not expect to see myeloprotection benefits, and I went into this and reasons for this during my presentation a little while ago. Moving to the ADC trial, which is with sacituzumab govitecan. As everyone will be aware, while sacituzumab is quite effective, it also has a fair amount of myelosuppression and other toxicities which can limit its dose intensity. In fact, about 30% of patients require a dose reduction. There were data presented earlier this year at ASCO, which showed a nice correlation between increased exposure to sacituzumab and better antitumor efficacy. We believe that the way that we could improve the efficacy of sacituzumab is by myeloprotection, allowing that increased exposure. In addition, TNBC is an immunogenic tumor, so the enhancement of antitumor immune response could also play a role. In terms of data in the Q4 and how it translates to the eventual PFS readout, which will occur next year, you know, we will be looking at. It's primarily gonna be a safety readout, so we'll be looking at myeloprotection, indications of durability of effect with sacituzumab, and additional safety and efficacy data will come out next year. Finally, on the MOA study, this study, as John covered, is really focused on a better understanding of the changes in the tumor immune microenvironment. What we'll be looking at and reporting in the Q4 of this year is particularly changes in the T cells, so CD8 positive T cells and T regulatory cells. Those are some of the highlights from the studies reading out later this year. Thanks, Raj. Sam, this one I think is for you. We got a few questions who are asking various questions about the colorectal cancer trial and the change in endpoint. I think to summarize what those questions are asking, can you provide more color into what drove us to make that change? Just any more color would be helpful. Yeah, absolutely. At the end of 2021, Rossini et al. published a meta-analysis of 1,155 metastatic colorectal cancer patients that received FOLFIRINOX plus bevacizumab in the TRIBE and TRIBE2 studies. In this analysis, about 79% of the grade 3 and 4 neutropenia events occurred in the first two months or the first 4 cycles of treatment. This was in contrast to our historical data and experience in small cell lung cancer. We believe that this new data that we received about the occurrence of severe neutropenia with a FOLFIRINOX regimen warranted a reevaluation of our endpoint. We had our analysis occurring in cycle 1, and we thought that changing the measuring duration of severe neutropenia in cycles 1 through 4 will provide a more appropriate assessment of the risk of febrile neutropenia during the time of the greatest clinical risk to patients. As a reminder, this study is 90% powered to pick up a meaningful difference at a two-sided p-value of 0.04 for the myeloprotection endpoint. We aligned on this approach with FDA to change the primary endpoint from measuring DSN just in cycle 1 to cycles 1 through 4. This amendment is currently in progress, and the data will be reflected in our primary analysis in the Q1 of 2023. Terrific. Thank you, Sam. Raj, we've received a couple of specific questions about triple-negative breast cancer, so I'll ask these two in a row. The first one is really about the mechanism. TriLA has a variety of mechanisms by which it may work. Can you use the phase II TNBC data to clarify what we should expect a myeloprotection combination contribution versus an immune contribution? In that study, going back to the data, we saw the greatest improvement in overall survival, which was highly statistically significant. We did see an improvement in progression-free survival as well, which was clinically meaningful, but given the small study, did not meet stat sig, and the least improvement was in response rate. We think that this type of improvement on the longer-term event-driven endpoints is likely to be due to the immune modulation and enhancement of antitumor immune response by trilaciclib. We did not see any myeloprotection in the study, so you know, specifically, we did not see an improvement in the neutropenia endpoints. However, patients on trilaciclib did receive fewer red cell transfusions. On balance, we think it's likely an immune effect that resulted in that outcome. Thanks. The second question on the triple-negative line of question is, with the changing first-line triple-negative breast cancer landscape, has enrollment been impacted either on a timing basis or on a geographic basis? Meaning, are you getting more patients outside the US versus in the US compared to your initial expectation? Yeah. First on the enrollment, actually it has not because this is a global study, and we enroll patients, you know, obviously in the US and across a number of countries in Europe. Enrollment was not impacted, and we're very close to completing enrollment, and we'll announce that when that happens. The second part of the question, Will? Oh, the second part, yeah, it was just about timing basis or on a geographic basis. Going in, we anticipated that the majority of patients would actually come from outside the U.S., and that's also the case. But we do have patients who have enrolled in the U.S. to allow us to evaluate the effects, you know, across different regions from the trial. Great. Thank you. Raj, this one is probably for you as well. We've gotten a few questions about other regimens and specifically about ADCs. Please clarify which other regimens you're interested in. Specifically, can you dive further into why trilaciclib could be synergistic or additive to ADC therapy regardless of payload? Thoughts on how that might expand the ADC market. Thoughts on where trilaciclib might fit into that treatment paradigm. Yeah. We're very interested in ADC combinations. I mean, this is a class that's really emerging, lots of trials, lots of ADCs. We're sort of, if you will, at the start of the wave, and we wanna catch that wave. You know, we think that we could make ADCs work better either by themselves or potentially even in combination with a checkpoint inhibitor for the reasons that John went into. We have, in terms of preclinical characterization, I think there were some questions that came up on this as well. It's just important to note that, you know, most of the ADC studies done preclinically were actually done in an immunocompromised setting because those companies were really interested in the effect of the payload on the tumor. That really doesn't address what we're trying to do, which is to evaluate the effect of trilaciclib on the immune system, and therefore, how it could improve the efficacy of an ADC when combined with trilaciclib. To do that, we've actually had to create, and are in the process of doing that, the appropriate models to do that. Specifically, murine tumor models that express a human target that you can then put into that tumor model and evaluate the combinations. We are very interested in evaluating combinations across different payloads, across combinations with checkpoints as well. Getting back to the clinical situation, we think we can improve the efficacy of ADCs really in a couple of different ways. One is by myeloprotection, allowing increased exposure, and the second is by immune modulation, increasing the antitumor immune response. Of course, these two are not mutually exclusive and can certainly happen together as well. Getting to your question about payloads, and this is actually really interesting and where trilaciclib can, we think, be a good partner with a number of different ADCs, is that if you look at ADCs where, for example, myelosuppression is a major toxicity and therefore can impact the dose intensity of that ADC, and that by reducing that dose intensity, you can in fact decrease antitumor efficacy, myeloprotection with trilaciclib, so a case in point would be our study ongoing with sacituzumab govitecan, could potentially allow extension of the duration of therapy of that ADC and thereby improve antitumor efficacy. Turning now to another class of payloads that are in development and approved, this includes the MMAE payload, which is thought to cause more immunogenic cell death. Here we believe that the enhancement of antitumor immune response is likely to be more important in that additivity between trilaciclib and the ADC. We're very excited about not only the sacituzumab study but also thinking about other development with the ADC class down the road. Thanks, Raj, I'm gonna give you a breather. John, I'm gonna over-index on you for a minute. We've gotten quite a few follow-up questions to the new data that you presented, and I'll kind of run them all together. The first one is there any influence of trilaciclib on innate immune cells, i.e., NK and macrophages? Our current studies have been focused on T cells right now. With the MOA study, it should be a very expansive data set. This is something that we are going to investigate, both the NK cells and also the monocytes. We do have some hints that trilaciclib does impact those cell types. In our SITC poster that we presented last year, we have peripheral blood data showing that with trilaciclib, with chemotherapy, that we do see decreases in MDSCs. This is an opportunity for us that we'll investigate with the MOA study. Good segue there into the MOA trial itself. A question or two about the data that we would expect. Regarding the primary endpoint, we said, immune-based MOA, what data beyond the CD8 positive T cells to Tregs ratio will we see? In regard to the secondary endpoints, we mentioned immune response and profiling measures. What are those measures? Okay, great. Yeah. This is definitely a study that goes beyond the CD8s and Tregs. This is an exploratory study that was designed for us to have a unique opportunity to investigate the effects of trilaciclib, both in the tumor microenvironment and also in the peripheral blood. Just to refresh everyone's memory that this is a phase II neoadjuvant TNBC study, and we're collecting baseline biopsies and also on-treatment biopsy at day seven following one dose of trilaciclib in a neoadjuvant setting. With the biosample that we're collecting, we're doing in-depth analysis of the tumor microenvironment through RNA sequencing, TCR sequencing, multiplex IHC. In parallel in the blood, we're also doing some high-dimensional cellular profiling with CyTOF analysis and with flow cytometry analysis to look at activation, maturation, and function. All those datasets combined will equate to that secondary endpoint where we're looking for biomarkers, we're looking for immune signatures that correlate with trilaciclib monotherapy. We'll use that dataset to potentially confirm our preclinical findings and then provide clinical data to support future clinical studies. Regarding Tregs and CD8 positive T cells, here's a run-on question for you. Why would there be a different effect for Tregs versus CD8 T cells with trilaciclib? Was it predictable? Sort of a cause-and-effect question, do the CD8 positive T cells recover faster, or are Tregs blocked longer? Yeah. Short answer is that we believe that the difference is due to CDK6 expression. We know that Tregs have a higher expression of CDK6 compared to the CD8 T cells. For Tregs, the consequence of this transient arrest suppresses their immunosuppressive function. I've demonstrated that in my talk earlier, where we see a decrease in CD8 T cell or increase in CD8 T cell proliferation when Tregs are incubated with trilaciclib. What's also interesting about Tregs is that these T helper cells are plastic, meaning they're not permanently Tregs once they become Tregs, but they can convert to TH1s that can produce immunoinflammatory cytokines. This is an area of interest, and this can contribute to the favorable tumor microenvironment. Did that answer that question? Oh, in terms of the proliferation. Right. We think that it is a slower recovery for the Tregs because of the sensitivity to CDK6. Okay. Thanks, John. One more for you right now. Is there evidence for the maturity of trilaciclib-protected cells? Are there more or most earlier progenitor cells, or does trilaciclib also protect more adult effector immune cells? In mature cells, we observe dual benefit. We see both protection, and we also see enhancement of effector function. Whereas in the progenitors, we're only seeing protection. We believe that this could be due to discrepancies in the antigen in the bone marrow versus the tumor. We do see both protection and differentiation of these T cells, mature T cells into effector cells and central memory T cell populations. Thanks, John. Raj, back over to you for this one, I think. A couple folks have mentioned the commentary about expecting a larger impact on survival and less on response rate. Can you comment a little bit deeper on that? What it's in the mechanism of trilaciclib that would cause that? Yeah. I think it goes back to what John just mentioned regarding the memory T cells. You know, we think that this is likely happening due to a better long-term immune surveillance. By this transient CDK4/6 inhibition by trilaciclib, increasing the formation of memory CD8 T cells, we believe could help with this long-term immune surveillance and result in a greater effect on overall survival, you know, and PFS compared to shorter-term readouts such as response rate. It's really a durability of effect, if you will, as a result of these memory T cells. Thanks. Switching now to a question about myeloprotection. A few folks have asked a question about a broad myeloprotection label. Is there an opportunity for a broader myeloprotection label across a variety of different tumor types with positive data? Yeah. You know, the first place we're gonna evaluate that is actually in the GI malignancy space. Here, 5-FU based chemotherapies, whether they're triplets like FOLFOXIRI or FOLFIRINOX, which is used in pancreatic cancer more commonly, or doublets like FOLFOX and FOLFIRI, these are pretty much standards of care chemotherapeutic regimens across the GI malignancy space, where 5-FU is given as a 48-hour infusion in these combinations. If our colorectal trial is positive, you know, clearly we'll be meeting with the agency about the potential for filing the data. As part of that discussion, we will broach this broad 5-FU based chemotherapy indication to have a dialogue with the agency. In addition, you know, we have an investigator-sponsored studies plan as well, where, you know, we will conduct studies with trilaciclib, plus some of these other 5-FU based regimens that I mentioned, to really build datasets that we show this model of protection across other chemo regimens as well. You know, that could, you know, add to the compendia component of the literature and could then be helpful for reimbursement as well. Great. One for you, Mark. How do we think about the total market values associated with the CRC and the triple-negative breast cancer indication, you know, number of vials expected to use by patients in these two populations? Sure. Thanks, Will. Yeah, happy to provide some additional color there. As we talked about before, colorectal is a meaningful opportunity as we see it. It's about 47,000 patients with microsatellite stable disease that are treated each year in the U.S. alone. As you heard from Dr. Goldberg, the biggest issue with FOLFOXIRI, it is the most efficacious regimen, but it has the myelotoxicities, which is what limits its use in the broader population. If we do show a significant reduction in myelotoxicities in our phase III study, we would expect significant uptake across the broader population, which is quite large, as I mentioned. I guess the key question comes down to really how long will patients stay on therapy? We know it's a large patient population. When you look at the literature, it seems like roughly about 60% of patients that start FOLFOXIRI for induction complete the 12 cycles, the majority of which then go on to maintenance therapy. Based on what we talked about today, we believe trilaciclib could actually increase that number beyond 60% to get patients to stay on FOLFOXIRI even longer and continue on through maintenance. The average cycles per patient, we estimate somewhere between 12-24 cycles based on that data. We'll confirm that obviously in the phase III data. The key thing to remember is trilaciclib, the vials are given four vials per cycle. Twelve to 24 cycles translates to about 24-48, I'm sorry, 48-96 vials per patient. If you remember, small cell patients on average get about 24 cycles. Here, again, 48-96 vials per cycle is roughly two-four times the amount of vials each small cell patient gets on average. Again, a much larger patient population and a significant more amount of vials assumed per patient. A really meaningful opportunity here from a commercial perspective. Triple-negative is a smaller opportunity. As we talked about before, about 9,000 patients treated annually for first-line triple-negative breast cancer. Based on our previous phase II data, patients received a median of 8 cycles of therapy for trilaciclib plus chemotherapy. The key thing to remember in that study was it was a mixed population of first-line, second-line, third-line patients. The phase III is only first-line patients, so it's more a pure population of first-line triple-negative breast cancer patients. We'd expect patients to actually stay on drug longer. The 8 cycles translates to 32 vials for triple-negative breast cancer. Given that this is a first-line study, we expect the number to be somewhere north of that. Again, the vial question, I'd say colorectal, roughly somewhere between 48-96 vials on average per patient and triple-negative breast cancer, more north of 32. Hopefully, that addresses the question. Yeah. Thank you, Mark. Sam, I think one for you regarding the pivotal triple-negative breast cancer trial. Can you provide an update on the number of patients that have enrolled and when the company expects enrollment to be complete, please? Yeah. Just to reinforce what Raj mentioned before that it's 180-patient pivotal phase III, and we're discussing, and we're enrolling the last handful of patients on that study and expect to be done with enrollment soon. We will announce that when we complete. Thank you. One for John Yi regarding the preclinical data that you presented. Good comments. A question from a couple saying, "What additional work is ongoing, and when do you expect to publish or present some additional data? The data that we're generating is really, really exciting. We're conducting follow-up studies to basically identify the key genes and pathways associated with trilaciclib administration. For my team, our focus for the preclinical studies are sort of divided into two goals. The first one being determine how trilaciclib regulates effector T cell function and memory differentiation. Just getting at the nitty-gritty of pathways and genes that are regulated. The second focus is to determine synergistic combinations with trilaciclib that can translate to clinical studies. This will give us a sort of preview of what upcoming combinations that trilaciclib could synergize with. That's two focus for our group. With the data that we'll generate, our goal was to present new data at major upcoming immuno-oncology meetings that are coming up this year and also next year. Thanks, John. Mark, another for you. We've had a couple of questions that have come in about the potential for partnerships with other companies to potentially address some of these other indications. When you think about partnerships, Mark, what are you looking for in a partner? What's interest been like to date? Sure. The couple of comments I would mention is really the main goal is to be able to get trilaciclib to as many patients globally as quickly as possible. That's really kind of our compass, how we're evaluating partners. There's really two dimensions to that. As you know, we're not planning on building an ex-U.S. infrastructure. We own or retain all global rights to the product outside of China, where we partner with Simcere, but it's a fully unencumbered product outside of Greater China. It really comes down to finding a partner with good commercialization capabilities to get it to as many patients as possible globally. I think the second piece, as you heard today, we really believe this product is broadly applicable across tumor types, treatment combinations, and we have a lot of hope for this product. The second thing we're really looking for is a partner to bring the resources and development capabilities to help us maximize this product for patients. Regarding the interest point, all I would say right now is we have meaningful interest to date. We really look forward to progressing these conversations as the data becomes available in the coming months. Thank you, Mark. Sam, in terms of cold tumors, how different is microsatellite stable CRC versus SCLC? Can you elaborate on why you'd expect to see longer survival there? Yeah, for colorectal cancer. It's a great question. Mm-hmm. Both these cancers are relatively insensitive to immune modulation. Just to reinforce some of the points that Mark mentioned earlier when we're thinking about trilaciclib in both of these cancers. With small cell lung cancer, we only have the opportunity to treat for four cycles of therapy. For colorectal cancer, we believe the longer-term treatment with trilaciclib, with the regimen that we're investigating, and the improved ability to tolerate FOLFOXIRI and bevacizumab will improve time to event endpoints such as PFS and OS, and we're looking forward to those reading out in the future. Great. Raj, I'm sensitive to time here. A question for you on CDK4/6-dependent cells. Can you comment on any effects that you're seeing or would expect to see on alopecia or any other CDK4/6-dependent cells? Yeah, this is an interesting question and you know, one that we are continuing to accumulate data on. You know, we certainly know about the bone marrow and the immune system that was covered today. We have data from our small cell studies where in our first-line small cell studies, there appeared to be, or there was a reduction in alopecia, in fact. We think that this could actually be an on-mechanism effect in that the hair cells, particularly the stem-like hair cells, could be CDK4/6 dependent, and we're actually potentially protecting these during multi-day chemotherapy regimens. You know, that's one adverse event that we're gonna continue to accumulate data on with our studies. The second one that is interesting, and we really don't have any clinical data, but the upcoming studies will tell us if we could potentially see an improvement here, is that the cells in the intestinal crypts are also thought to be CDK4/6 dependent. These are not the highly proliferative cells that are closer to the lining of the small intestine, but really more of the stem-like cells at the bottom of the intestinal crypt. These cells could potentially also be CDK4/6 dependent. One adverse event that we're following very closely in our study is with regimens that actually have a greater rate of diarrhea than what we've used up until now. This includes the colorectal trial with irinotecan, as well as, in fact, the sacituzumab govitecan trial, which has SN-38, which is essentially irinotecan as its payload. We will see if we see, you know, we have any impact on diarrhea with trilaciclib as well. Great. We have about 3 minutes left to the top of the hour. I think I've gotten through a vast majority of the questions that are out there, either individually or combined. Maybe, Jack, I'll give you the last question, then ask you to close the call, if that's okay. A couple of questions that are commercial related but specific to trilaciclib and colorectal cancer. Assuming we are successful in the study and assuming a label in myeloprotection. What would be the commercial strategy in that setting? Do we need a new sales force? Can we use the old sales force? Where are the synergies, how can an investor think about where the synergies may not be? Yeah, great question. Certainly we are doing work right now, and we'll continue leading up to the readout. I think the headline is, when Andrew and the team built the existing sales force of 34 territories covering the entire United States and hitting both the large community practices and the key academic centers, we feel it matches up really well, should we get a positive readout in Q1 for CRC and go on to get a labeled indication there that we've got it covered. From our standpoint, first and foremost, there's a lot of synergy there. Second of all, obviously, because to Mark's point, then it's a bigger tumor type in terms of the number of patients, and there's likely much higher vial use per patient. It's a real opportunity to reinforce the habit of using an agent like trilaciclib to proactively prevent all these downstream problems that in the case of colorectal and the use of FOLFIRINOX has obviously reduced its utilization. I think we heard from our experts 10%-20% of the time they're using it. Obviously, being able to have a product like trilaciclib added could significantly hopefully increase the utilization of FOLFIRINOX you heard from Dr. Goldberg. From our standpoint, we've got the major facilities covered. There's synergy with the sales force, and it's a more prevalent tumor that will enable even greater reinforcement of the habit of trilaciclib going forward. Thanks, Jack, and maybe a couple of closing comments before we close the call down. Yeah, absolutely. First and foremost, thank you all for joining us today on the science of trilaciclib. Hopefully, you found it to be informative and helpful. Certainly, we're very excited here as we stand on the cusp of an array of readouts starting in the Q4 of this year and extending into next year. You can tell by the development plan reviewed by Sam that, you know, it's covering an array of tumor types, chemo regimens, and the work by John that has us believing that there's even more opportunity beyond that. Thank you today for all your questions. I think we got to most of them. For those that we didn't, we'll certainly follow up with you. Again, we appreciate you taking the time. This officially closes our program. Thank you very much, and we look forward to being in touch.