G1 Therapeutics, Inc.

Ladies and gentlemen, thank you for standing by, and welcome to G1 Therapeutics Fourth Quarter 2020 Financial Results Conference Call. At this time, all participants are on listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press the star, then the one key on your touch-tone telephone. Please be advised that today's conference may be recorded. If you recall our persistence, please press star, then zero. I would now like to hand the conference over to your speaker host today, Will Roberts, Head of Investor Relations at G1 Therapeutics. Please go ahead.

Thank you, Livia. Good afternoon, everybody, and welcome to the G1 conference call to discuss our fourth quarter and full year 2020 financial results and business update. The press release on these financial results was issued after market closed this afternoon and can be found in our news section of our corporate website, g1therapeutics.com. On this afternoon's call, the team will provide an overview of the fourth quarter and full year 2020, including an update on our launch progress with COSELLA, which was approved by the U.S. Food and Drug Administration on February 12, 2021, to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum etoposide-containing regimen or topotecan-containing regimen for extensive stage small cell lung cancer, or ES SCLC. A question and answer session will follow the prepared remarks. Before we begin, I'd like to remind you that today's webcast contains forward-looking statements within the meaning of the Private Security Litigation Reform Act of 1995. Such statements represent management's judgment as of today and may involve certain risks and uncertainty that could cause actual results to differ materially from those expressed in or implied by these statements. For more information on such risks and uncertainties, please refer to our filings with the Securities and Exchange Commission, which are available from the SEC or on our corporate website. Any forward-looking statements represent our views as of today, February 24, 2021. Joining me on the call today are Jack Bailey, our Chief Executive Officer, Raj Malek, our Chief Medical Officer, Soma Gupta, our Chief Commercial Officer, and Jen Moses, our Chief Financial Officer. I'll now turn the call over to Jack Bailey, our CEO.

Jack? Thanks, Will. Good afternoon, everyone, and thank you for joining us on the call today. We hope that you and your families are well. Today's headline is that G1 is a very different company than it was a year ago or even last quarter. Only eight days ago, we were on a call with you to announce the FDA approval of COSELLA, the first and only FDA-approved therapy that is administered proactively to deliver multi-lineage myeloprotective benefits to patients with extensive stage small cell lung cancer. The entire G1 team is energized to be making this important therapy available to cancer patients. But of equal importance is our rapidly evolving clinical pipeline, intelligently designed to help address the unmet needs of people with a variety of different cancers who require a range of chemotherapy. we are initiating and conducting clinical trials evaluating COSELLA across an array of cancers and chemotherapy regimens. Within the first half of 2021, we expect to have two registrational trials underway, one in colorectal cancer, in which we began dosing patients last month, and another in metastatic triple negative breast cancer, which we'll initiate in the first half of this year. we will also have three Phase II studies underway. These include our I-SPI-2 neoadjuvant breast cancer trial, which was initiated last year. And as we announced in January at the J.P. Morgan Conference, we expect to initiate Phase II trials in both non-small cell lung cancer and bladder cancer in the first half of 2021, with each study having anti-tumor efficacy as the primary endpoint. Regarding the bladder cancer trial, we announced an important supply agreement with Merck KGA of Darmstadt, Germany, and Pfizer in our press release this afternoon, which Roz will describe in more detail. G1 was founded with the sole purpose of making a difference in the lives of people living with cancer. The launch of COSELLIT is the first step. We believe that COSELLIT will be an important therapy in the arsenal for improving the lives of patients with a variety of cancer diagnoses as we work toward the goal of developing it as a tumor agnostic solution for patients with cancer. And it also represents an excellent opportunity to bring strong value to our shareholders. This is a transitional call for us, given that we are only a few days past turning the corner to becoming a commercial organization, and just a few days past our last call with you all on the commercial launch readiness. So while Jen will cover our financial results for the fourth quarter and full year 2020 toward the back end of the call, the rest of the call will largely be forward-looking. I will ask Raj to cover our clinical focus with COSELLA, including a reminder of its mechanism of action, which we believe will be broadly applicable. SOMA will then briefly provide an update on some of our launch efforts over the past eight days, including the ongoing launch meeting being held this week. then I'll be back for some concluding comments. I'll now turn the call over to Raj for an update on COSELLA in the clinic. Raj?

Thanks, Jack, and good afternoon, everyone who is on the call with us. This is a very exciting time at G1 as we are in the process of launching COSELLA for patients with extensive stage small cell lung cancer and at the same time developing it in the clinic for a variety of other solid tumors. Over the past few weeks, There has been considerable interest in the single mechanism potential dual benefit of Casella, so I want to take some time this afternoon to walk you through it as it will help to clarify the educated approach that we are taking to determining the cancers to pursue in the clinic. Casella is administered as a 30-minute intravenous infusion completed within four hours prior to the start of chemotherapy. It has a single mechanism of transient G1 cell cycle arrest due to transient CDK4-6 inhibition in susceptible host cells, which temporarily blocks progression of these cells through the cell cycle. In cancers like small cell lung cancer, chemotherapy is highly myelosuppressive and given multiple days in a row. Chemotherapy is an essential treatment for most tumors, but it kills proliferating cells indiscriminately, causing damage to tumor cells and host cells like hematopoietic stem and progenitor cells or HSPCs alike. COSELLA transiently arrests the HSPCs in the G1 phase of the cell cycle. thereby protecting and preserving myeloid cell lineages like neutrophils and erythrocytes and lymphoid cell lineages like T and B lymphocytes from the myelosuppressive damage caused by chemotherapy. The half-life of Casella is relatively short, approximately 14 hours, and as a result, the HSPCs quickly recover and start to produce mature blood cells. This myeloprotection benefit was conclusively demonstrated in our three double-blind placebo-controlled trials in extensive-state small-cell lung cancer, which led to the approval of Casella by the FDA to decrease the incidence of chemo-induced myelosuppression in patients with extensive-state small-cell lung cancer. We are also exploring whether Casella has the potential to improve antitumor efficacy through a combination of factors. through the protection of the immune system, allowing it to function after chemotherapy, and two, by enhancing anti-tumor immune response by increasing the ratio of effector CD8 positive T cells to immunosuppressive T regulatory cells, which is important to immune priming, by directly activating CD8 positive T cells to improve T cell mediated response, and by increasing clonal expansion of T cells. In addition, COSELLA may increase the patient's ability to receive a longer duration of chemotherapy, and as such, can also contribute to improving antitumor efficacy. COSELLA appears to activate a T cell-mediated immune response with clinical evidence of improved antitumor efficacy when the tumor is immune-responsive. This benefit was shown in the clinical data from the triple negative breast cancer phase two trial, which we presented in December at the 2020 San Antonio Breast Cancer Symposium and was previously published in the Lancet Oncology. This randomized open label phase two trial of Casella in combination with gemcitabine and carboplatin, a current standard of care for metastatic triple negative breast cancer, enrolled 102 patients who had received up to two prior chemotherapy regimens for locally recurrent or metastatic triple negative breast cancer. In this three-armed trial, all three groups received a chemotherapy regimen of gemcitabine and carboplatin. Patients were randomized to receive either GemCarbo only in group one, GemCarbo plus Casella administered on the day of chemotherapy, group two, for Gemcarbo plus Casella administered the day prior to and the day of chemotherapy, group three. The survival results were pretty remarkable, and compared to Gemcarbo alone, overall survival was significantly improved in both Casella arms. And importantly, patients with both PD-L1 positive and PD-L1 negative tumors treated with Casella prior to their Gemcarbo demonstrated improvement in OS compared to patients receiving GemCarbo alone, with the PD-L1 positive subset achieving statistically significant improvement. We will initiate a registrational trial in patients with metastatic triple negative breast cancer in the first half of this year to evaluate Casella in combination with the chemotherapy regimen of GemCarbo in two separate cohorts. as first-line treatment in 170 patients who are checkpoint inhibitor treatment naive, and as second-line treatment in 80 patients whose disease has progressed following prior checkpoint inhibitors. Both cohorts are adequately and independently powered, and we will provide more information on trial design when we announce initiation of this trial. Another thing we have learned is that the best place to see the bioprotection benefit I discussed earlier is in chemotherapeutic regimens that require administration of chemotherapy on multiple days in a row. That leads us to our approximately 300-patient registrational trial in colorectal cancer, which began enrolling patients in January. In this trial, Patients receive folfoxiri and bevacizumab, the most efficacious chemo regimen in colorectal cancer, but also the most myelosuppressive. Patients receiving folfoxiri are administered arenotecan, oxaliplatin, and bevacizumab on day one, and then a continuous infusion of 5-FU over 48 hours starting on day one. After 12 two-week induction cycles with all chemotherapy agents, 5-FU and Velocizumab are continued in maintenance until disease progression. Patients will receive Casella or placebo prior to chemotherapy on day one and again on day two during the 5-FU infusion with every cycle during induction and maintenance. The primary endpoints for myeloprotection include duration of severe neutropenia in cycle one and occurrence of severe neutropenia And the secondary endpoints include progression-free survival and overall survival and patient-reported outcomes. Eighty percent of the alpha is reserved for the model protection endpoints, but we have reserved 20 percent of the alpha for the antitumor efficacy endpoints. We expect the data readout in the first half of 2023. In addition to those registrational trials, we announced in January that we expect to initiate two additional phase two trials of COSELLA in known immunogenic tumors in the first half of this year. The first is a randomized open label trial in first line locally advanced for metastatic bladder cancer, also called locally advanced or metastatic urothelial carcinoma. COSELLA will be administered prior to gemcitabine platinum chemotherapy which is a similar regimen to the one we used in the triple negative breast cancer trial, followed by maintenance therapy of Casella in combination with the checkpoint inhibitor of Elumab until disease progression. To that end, we were happy to announce this afternoon in our financial results and business update press release that we have entered into a clinical trial collaboration with Merck KGAA, Darmstadt, Germany, and Pfizer whereby the alliance will contribute clinical supply of Evalumab to this first-line metastatic urothelial carcinoma trial. The primary efficacy measure of the trial is antitumor efficacy, and we expect to have initial data in late 2022. The second is a randomized double-blind Phase II trial in second-line and third-line patients with non-small-cell lung cancer who have progressed following checkpoint inhibitors. Patients will receive Casella or placebo prior to each administration of docetaxel. The primary efficacy measure of the trial is, again, anti-tumor efficacy, and we expect interim data in the first half of 2023. We also intend to support a variety of investigator-sponsored studies starting this year. We opened our online portal to receive requests for investigator-sponsored studies late in 2020 and the interest has been strong. We expect these to be small, open-label studies with quick data readouts, so you can expect a consistent cadence of data. We will keep you updated as the investigator-sponsored studies get up and running. I want to touch briefly on our oral SIRT rintodestrant as well. The mature monotherapy data from our Phase 1b trial a heavily pretreated population of ER-positive HER2-negative patients were presented at the 2020 San Antonio Breast Cancer Symposium, confirming the results of the preliminary analysis. We reported good safety and tolerability, which is important for an oral CERN. We also saw robust target engagement and a clinical benefit rate, or CBR, of 30% in the ballpark of what is seen with other oral CERNs. We advanced an 800 milligram dose of rintodestrin into a phase two combination trial with albacyclib last year in 40 patients who are somewhat less heavily pretreated than those in the phase 1B. Enrollment was completed in October 2020, and we expect to announce initial safety and efficacy results in the second quarter of 2021. With that, I'll turn the call over to Soma for her update on the first couple of weeks of the COSELLA launch. Soma?

Thanks, Raj, and good afternoon, everyone. Thanks for joining us on the call. These are exciting and very busy times as we are commercially launching COSELLA, completing the training of our field force, and generating broad interest as we prepare for product availability in the coming days. We provided a very robust update just a few days ago on our approval call but today's prepared comments will be fewer and focused on what we've accomplished in the last week or so. I will first briefly comment on our baseline awareness pre-approval. G1 conducted a series of surveys over the past several months to assess awareness and interest in usage, and we will continue to do so going forward. Based on our final pre-approval survey, awareness trends have continued to go our way. In a sample of 75 physicians with a 70% community, 30% academic split, aided awareness is at 50%, which is a significant jump from 30% in November and is in line with what we would expect from similar benchmarks in this space. Also, the percentage of oncologists who are engaging in prophylaxis for some portion of their patients, what we think of as providers who will be most receptive to the CoSALA proactive protection message, has increased from 66% in June of last year to 77% today, likely driven at least in part by heightened sensitivity in the COVID-19 pandemic environment. We were also glad to see the latest metrics for our mild suppression disease state education campaign indicate that 30% of our Tier 1 to 3 targets have engaged with the content. As many of you know, this is well above the expected benchmark of 8 to 10%, suggesting that this is a topic providers have interest in learning more about. Interestingly, our survey data also indicate a steady increase in unaided mentions of non-neutropenia-related concerns of chemo-induced mild suppression, like severe anemia and dose reductions or delays, more than a doubling from prior to the campaign, and even higher if you ask nurses. All in all, a good foundation on which to launch COSELLA. As of day one of COSELLA approval, which was February 12th, The field force, including our GPO account managers, clinical nurse educators, our national accounts team, managed markets, and the Beringer Ingleheim sales reps, have begun their outreach to set up appointments with our Tier 1 target providers. Detailing and presentations will start immediately after our reps are certified as of the end of this week. I'm happy to confirm Drug is planned to be in channel around this time also as we are on target for March 2nd. Our MSLs have been engaging with physicians for months in peer-to-peer discussions about the multi-lineage impacts of mild suppression and have now added the approval of the product to their conversations. So far, the early anecdotal feedback has been very positive. For example, one community provider told us that this is exactly what we want to see in our practices and to know that giving this drug can save patients from adverse events and hospitalizations. Similar positivity from payers has included comments like the following from a national plan medical director who said, I applaud G1 for finding a way to achieve one therapy to address mild suppression as opposed to multiple treatments we use now. This is just a sampling of the positive feedback we have received thus far. Also, since approval, our GPL account directors indicate several of the large community practices already taking initial steps to get trial cyclists reviewed and added to formulary. Our launch sequence has been very intentional, and the activities for days one through seven of approval support the goals of, first, getting our NCCN submission in to get COSELLA quickly added to the guidelines, second, completing all pricing compendia submissions to enable reimbursement, ordering, and flow treatment guidelines into EHRs, and third, getting the sales team certified on the label and on core marketing materials. Regarding NCCN, Raj's medical affairs team has already completed our formal NCCN submission. We hope to see Coachella added to the guidelines in a few months. Regarding the pricing compendia submission, our market access team has submitted to all pricing compendia, and medical affairs team has submitted to all other clinical compendia as well. Regarding the sales team, they completed their initial training on the label last week. Today is day two of the four-day Cosella launch meeting, which has a strong emphasis on training and practice workshops. It is important to clarify that we are doing this launch meeting remotely and virtually with a socially distanced set and adherence to COVID-19 mitigation procedures. Despite being in a virtual setting, this launch meeting has all the hallmarks of a traditional in-person one, including training sessions on various topics such as MOA, package insert, and the core interactive sales aid. There will be exercises focused on effectively overcoming objections, education panels featuring HCPs and oncology nurses, and inspirational sessions devoted to patient journey and caregiver stories. In parallel, we are also activating a robust branded digital campaign to drive awareness and augment the Salesforce efforts. At the end of this program, every rep will be fully trained, certified, and ready to sell in person where possible, virtual where needed or preferred, early next week, with product and channel ready to order on March 2nd. The team has already started to invite our target physicians, nurses, and pharmacists to our upcoming national broadcast. Some of the most experienced oncologists will educate their peers on the impact of chemo-induced mild suppression and COSELLA clinical trial data at this session. The national broadcast is scheduled for March 25th with an encore on the 26th. The broadcast will include a panel presentation and discussion with Dr. Ed Kim, Vice Physician-in-Chief at City of Hope National Medical Center, Dr. Mohamed Mohamed, Director of Thoracic Oncology at Cone Health Cancer Center, and Dana Herndon, a Thoracic Oncology Nurse also at Cone Health. it's probably worth reminding folks that about 1,500 first-line small cell lung cancer patients are treated each month across the country. We expect COSELLA to be considered for use in newly incident patients versus the pent-up demand we might see for therapeutics. We therefore expect this to be a steady climb over the first few months where providers first learn about COSELLA, then find an appropriate patient and whom to gain some experience, and then move it into their practice more broadly. All of this to say that by beginning of next week, we'll be fully teed up with branded Cosella marketing materials to actively promote Cosella and supporting its use to oncologists, oncology nurses, and payers. We expect the entirety of our field force to communicate the advantages of Cosella with materials in hand and products in channel ready to improve the chemotherapy experience of small cell lung cancer patients. It's a very exciting time for both the commercial teams at G1 and BI. And with that, I'll turn the call over to Jen Moses.

Jen? Thanks, Thelma, and good afternoon, everyone. As Will mentioned, full financial results for the fourth quarter and full year 2020 are available in our press release and 10-K. Today I'd like to focus on a few key points from our disclosures. License revenue for the fourth quarter of 2020 was $16.5 million. primarily related to an upfront payment for our license agreement with Sincere, which provides them with development and commercialization rights for Trilocyclib across all indications in Greater China. This payment was recognized following the transfer of the related technology and know-how, which occurred during the period. In addition, we recognized revenue for existing inventory transfers related to our license agreements with Genor and EQRX for Lerocyclib, as well as revenue for reimbursable clinical trial costs due from EQRx. License revenue for the full year 2020 was $45.3 million. G1's research and development expenses for the fourth quarter of 2020 were $16.4 million, down from $24.5 million for the fourth quarter of 2019. The decrease was primarily due to a decrease in clinical program costs, external costs related to discovery and preclinical development, and costs for manufacturing pharmaceutical active ingredients. We expect our clinical program costs to increase as we initiate our two new phase two trials and our registrational trial in TNBC later this year. Our general and administrative expenses for the fourth quarter of 2020 were 24.3 million, double the 12.1 million in the fourth quarter of 2019. As would be expected, the increase was largely due to an increase in compensation due to additional headcount and increases in pre-commercialization activities and medical affairs costs related to preparing the company and the market for the launch of Casella. We ended the year with cash and cash equivalents of $207 million, slightly above our year-end cash guidance of $200 to $205 million. Subsequent to the reporting period between January 14th and February 9th of 2021, we sold 3,513,027 shares of common stock pursuant to our 2018 sales agreement for at-the-market offerings with Cowan & Company, resulting in 86.4 million in that proceeds. This activity utilized all remaining capacity under the sales agreement, so this ATM offering is now closed. Also, the company now has access to $30 million of the remaining $80 million of our debt financing facility with Hercules Capital upon achievement of the FDA approval of Cosella Milestone. We now expect our current financial position to be sufficient to fund operations into 2023. With that, I'll turn the call back over to Jack.

Jack? Thank you, Jen, Selma, and Raj. Before we close the call, I want to underscore that without the participation small cell lung cancer, and their families, doctors, nurses, and caregivers, we would not be making COSELLA available today. We are grateful for their support and humbled to be part of your community. We will work hard every day to improve the chemotherapeutic experience of people living with extensive stage small cell lung cancer. Now, as I mentioned at the start, we are a very different company than we were a year ago or even a quarter ago. Our first product, COSELLA, is approved and will soon be available for patients living with extensive stage small cell lung cancer. We are developing a broad and growing clinical pipeline of intelligently designed trials across an array of cancers and chemotherapeutic regimens with both myeloprotection and antitumor efficacy endpoints to deliver on our tumor agnostic vision for COSELLA With the additional $86 million from our at-the-market, which is now closed, we believe that our cash runway will take us into 2023. This ATM offering has provided us with the capital that we believe we need to run the company, and as such, we have no plans for any additional offerings in the near term. And we have a team of experienced professionals throughout G1 solely dedicated to bringing new therapies to cancer patients who need them. This all gives me the confidence as we turn the corner to commercialization while at the same time advancing the development of COSELLA in a tumor-agnostic manner. As we proceed with commercializing COSELLA, we will be open and transparent to help you track our performance. While we will not be providing revenue guidance for 2021, we will consistently provide you with both qualitative and quantitative metrics of both leading and lagging indicators of interest and uptake along with our revenue results every quarter, starting with the results of the current quarter. With that, I'll close the call and turn it over into Q&A. Operator, would you please remind our listeners how to ask a question?

Thank you, ladies and gentlemen. As a reminder to ask a question, you will need to press the start and the 1 key on your touchtone telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Now, first question coming from the line of Ed White with HC Wainwright. Your line is open.

Hi. Thanks for taking my questions. So maybe just start off with a couple of questions for Jen. That last $50 million from Hercules, what is the trigger for that to become available? And is that $80 million that's available included in the – guidance for cash to last through 2023?

Thanks, Ed. The full $80 million is not included. Because we have ability to access the $30 million, I'm including that in the guidance into 2023. To access the additional portion of the Hercules facility, it's revenue-based for $30 million of it, and the additional $20 million is at their discretion. So we expect to meet additional milestones later in this year.

Great, thank you. And then a question for Soma. Just one thing you had mentioned was that non-aided patients had concerns over myelosuppression. I'm just wondering if you have plans for any DTC advertising.

Yeah, sure. Sure, happy to take that. So what we actually think, because small cell is an urgently presenting disease, broad-based DTC for small cell probably doesn't make sense. But what we do think is critical is working with advocacy. So we've actually been doing quite a bit with GoToFoundation and Longevity because we think that what will happen is once they get a diagnosis, they will very quickly – seek out the major advocacy organizations to get their information. So we actually think that that's the best way to get that in their hands versus big DTC, you know, which obviously can be a significant expense, but more importantly, probably won't get to them at the time that they actually need to make the decision. So we're being very targeted about it. We are doing some digital consumer things. But in general, we do think advocacy has the greatest role to play here, just given the urgency of the diagnosis and how quickly they go on treatment.

Great. Thank you. And then my last question is for Raj. You gave great guidance over the timing of data for some of the trials. I'm just wondering if you can give us some thoughts on timing for data for the triple negative breast cancer and also the bladder cancer. Thank you.

Yeah, hi, Ed. Yeah, for the TMBC, it will be the second half of 2023. And for the bladder cancer, we expect initial data later next year, towards the end of 2022.

Okay, great. Thank you very much for taking my questions.

Now, next question coming from the line-up. Chad Messer with Neham. Your line is open.

Great. Thanks for taking my questions. Maybe to start, you know, as you're out there, you know, preparing to bring this drug to patients, is there a profile that you think doctors have for the initial patients they might try to get this on, maybe by risk factor or liar treatment or something like that, or Or do you think, you know, kind of, you know, first available as of March 2nd?

Yeah, thanks, Chad, for that question. I really think because of the profile and the benefits that COSELLA brings, really any patient who's got extensive stage small cell lung cancer is really the target. And we talk about first time every time they get put on chemotherapy. So given that every patient in that first line regimen that we studied and have on our label get those benefits, both in terms of the reductions in levels, but also feeling better, we believe that ultimately it's not a question of parsing out patients, but rather it's really every patient, first time, every time, who's got extent to state small cell lung cancer.

Yeah, no, I think given small cell is like, that makes sense. Perhaps just one on the Rento data that's coming up. Can you help us benchmark what good efficacy, you know, based on, you know, sort of the competitive landscape would look like in combination with Palo Alto?

Go ahead, Raj. Yeah, hey, Chad. Raj here. Yeah, so in this 40-patient data set where Rinto was combined with Palvo, the patient population was less heavily pretreated compared to our monotherapy data set, closer to the population that was enrolled in the Paloma 3 trial. And in that trial, the clinical benefit rate at six months was 64%. So what we will be looking for is, you know, continued good safety and tolerability, the profile we saw as a monotherapy, and a CBR rate in that 60% to 65% range.

All right, great. Thank you. Very helpful. Welcome.

Our next question coming from the line of Phil Bindu with Cowan. Your line is open. Thank you.

Good afternoon. Thanks for taking my questions. A couple on the commercial side. You mentioned compendia that submissions have been made. Can you remind us, are some compendia more important than others? Which are the ones that are particularly influential?

Salma, can you handle that, please?

Yeah, sure. So obviously, you know, compendium is a pretty broad category of things. I think NCCN is sort of a compendium of itself. So that is clearly the gold standard. There are additional ones, though, that are in the mix that drive pathways for, you know, kind of within a larger GPO type environment. And those are ones that we have submitted to on the clinical side. And then On the kind of more payer access side, things like Micromedex, Lexidrug, things like that we've also submitted to so that they can sort of flow in through the EHR systems. So there's multiple different ones, and we're actively pursuing each one. But NCCN is the go-to guide for Compendia. So while it is very influential on the other pathways, I guess is the best way to put it.

Got it. Okay, that's very helpful. In terms of NCCN specifically, do they host meetings where they come to determinations, or is there a defined protocol that they work through as they're assessing new drugs, or is it done more on the fly just as drugs are available, they tend to consider them?

Yeah, I'm going to have Raj answer this.

Yeah, hey, so, yeah, so we submitted the applications to both the small cell lung cancer and the hematopoietic growth factor guideline committees. Typically what they will do is with new drug approvals, they will meet, you know, whenever they're able to pull the guideline committees together and review the evidence. So that's why we think it would, you know, take a few months. But they often do that outside of their regularly scheduled meetings, which occur, you know, annually.

Got it. And maybe last question from us. Before the NCCN comes out, is utilization likely? I guess how closely do physicians and practices adhere to the NCCN guidelines? Will they adopt new medicines prior to the guidelines, or is it secondary? similar to the ACIP recommendation for a vaccine where the NCCN guidelines are a major catalyst for uptake?

Yeah, Phil, this is Jack. Thanks for the question. We will get some utilization prior to NCCN, but that is an important point or catalyst to Soma's earlier point, as that triggers the regional pathway organizations and it enables a lot of times organizations to then get into things like order sets. But you will get some utilization. It's a very helpful endorsement, obviously, in the oncology space to get them to endorse it. And as Raj said, it will probably be a couple months until we get that.

Perfect. Thanks for taking my questions, and congratulations on the progress. Thank you, Phil.

Our next question coming from the line of Tony Butler with Watt Capital. Your line is open.

Yes. Hey, Raj. I want to just touch on the trial in bladder cancer with the Velumab. And I wanted to understand, would the trial actually mimic JAVELIN 100? That's effectively the first question. And secondly, the key is, do you actually utilize Casella during the, because you do have first-line platinum chemo, before you actually put the Vincio on top with respect to maintenance. Do you actually put Casella on board just during the chemotherapy phase and then it stops as Avilumab comes on board? I just want to clarify. Thanks.

Yeah. Hi, Tony. Yeah, you're actually right. Javelin 100 is sort of the model, if you will. I mean, that's the – you know, the standard with Avalumab maintenance following up to six cycles of gem platinum therapy. So our trial is going to include COSELLA administered with the chemotherapy and with the Avalumab maintenance, with the control arm being, of course, just the chemotherapy alone and Avalumab maintenance. So essentially it's an add-on to that standard of care.

That's great. And then again, if I may, the readout is overall survival. Is that fair or is there a PFS readout? I'm asking what in effect would be the primary?

Yeah, so, you know, we'll provide more details on that, Tony, when we describe the trial, but these will all be anti-tumor efficacy readouts with the initial readouts being, you know, towards the end of next year, as I mentioned, which will likely be more response rate focused with others to follow.

Thanks, Raj. Appreciate it. Sure.

Sure.

And our next question coming from the line of Dan Leon with Raymond James. Your line is open.

Hi. Thank you for taking the questions. Congratulations on the launch, and thank you for providing the details around that. I just wanted to ask more of a strategic question. When we think about the company going into the launch of Trilocyclib and potentially expanding indications over the next couple of years, How do you think about other assets around that that I guess you may think about acquiring externally or bringing in? Do you view G1 Therapeutics as focused more on supportive care for oncology at this point, and that's where the synergy would be with the channel you're building? Or would you also look at more traditional assets that would be directly targeting the tumors as well? How are you thinking about the company's strategy as it's kind of changing right now? Thank you.

All right. Thank you, James. Appreciate the question. Yeah, I think for the foreseeable future, we've really tightened the strategic aperture around Trila, just given this sort of pipeline and a molecule potential that it has, given the dual benefits of both myeloprotection and antitumor efficacy and an array of different tumor types and chemo regimens. So, From a capital allocation strategy, that's really where we're highly focused on making sure that we both have a successful launch year and the initial indication, along with obviously getting this development plan, all of those studies initiated in the first half of this year. So for the foreseeable future, it really is trial and focus. Obviously, we do have rent or debt strength. We'll get the readout next quarter on that. But the primary focus for us is really around trial here for the foreseeable future.

Great. Thank you.

Our next question coming from the line of Anupam Rama with JP Morgan. Your line is open.

Yeah. Hey, guys. This is Tess on the call tonight for Anupam. Thanks for taking our question. Just a quick one on the pipeline, actually, sort of bridging from a prior question that Thinking about the expansion data that we're going to get in 2Q, I was wondering, Raj, or anyone else, can you get a little bit more granular for us what a win looks like from a safety perspective? And then just kind of a logistical one, is this plan to be like a PR or a medical meeting presentation? How are you thinking about that? Thanks so much.

Yeah, hey, Tessa. So, yeah, from a safety perspective, you know, continued good safety profile. We were very, you know, quite favorable in terms of GI tolerability, and that's what we want to continue to see. Obviously, no bradycardia and no, you know, no ocular toxicities, which have been issues with some of the other agents. you know, as well as cytopenias. So I think those are the safety signals we would be looking for. And we would expect to present the data at a medical meeting.

Okay. Okay, great. Thanks for taking our questions.

Sure.

And our next question coming from the line of Tom Schroeder with BTIG. Your line is now open.

Hi, this is Kaveri Pullman for Tom. Thanks for taking our question. For your first line trial, can you tell us why you chose bladder cancer, given C-gens and FODMAP-vidodin is going to be in bladder cancer soon, whereas a front line in non-small cell lung cancer is more static? And a follow-up on that, do you plan to do a trial in combination with ADCs? Because neutropenia is the dose-limiting toxicity for almost all of them.

Yes, good question. So regarding bladder, you know, our strategic interest in that particular study was to generate data in combination with checkpoint inhibitors, and so that was certainly the driving force there. Fully understand your comment about PADSEV and that ADC, so we'll have to obviously follow that data in first line when that matures. Yes, in terms of combinations of ADCs, that is an area that we're also exploring exactly for the reason you mentioned. We actually think there could be two potential ways that we could add to ADCs, not only by improving myelosuppression, but also through this immune-enhancing property of, you know, of COSELLA. Because, you know, at the end of the day, the ADC is chemotherapy. to Gemcarbo and triple negative breast cancer. So, yes, I think it makes sense definitely to combine with ADCs and we're exploring that.

Got it. And for a triple negative breast cancer, can you talk about your rationale for not using a checkpoint inhibitor combination? Because that, to some extent, to some point, is more immunogenic tumor and Atezo is already approved in the frontline settings.

Yeah, you know, I think it goes back to our data where we saw activity in both PD-L1 positive and PD-L1 negative, and the checkpoints are only approved in PD-L1 positive, about 40% of the population of metastatic triple negative breast cancer. So we wanted to enroll all comers in both PD-L1 positive and PD-L1 negative. If you look at our data, you know, we showed in a relatively small trial an improvement in survival, which has not been seen with either checkpoint inhibitor. So if we're able to reproduce those data, in fact, a combination of trialocyclic with chemo could even potentially be an alternative to a checkpoint inhibitor. So that was our rationale in first line. In second line, it is post-checkpoint inhibitor. And given the immune mechanism of action, and since Trilocyclob is a CDK4-6 inhibitor, you know, it has a different immune mechanism to checkpoints, we believe there's an opportunity to see activity in the post-checkpoint setting, which is clearly an unmet need as well. So that was our rationale behind the design in triple negative breast cancer. And our second, third line, non-small cell lung cancer study is also in a post-checkpoint setting.

Got it. Great. Thanks, and congrats on the progress.

Thank you.

Our next question coming from the line of David Newton-Garten with Red Bush Securities. Your line is open.

Hey, thanks for taking the questions. I had two, if I may. First off, on the bladder cancer study, I'm curious, you know, obviously it's a bit different than presentation than the triple negative where you have a fixed cycle of chemo where you're planning to dose Casella and then dose Casella in combination with an IOH and afterwards. So I was a little curious if there was any way to analyze or break apart the data or potential benefit of Casella between, you know, the, as you think about the study, between the chemo portion and the maintenance therapy with abeliumab. And then quickly on the TASH guidance into 2023, is that incorporating OPEX only or presumed revenues? Thanks.

Yeah, David, so in terms of that's exactly what we will do. What we're interested in is to look at, so for example, you know, patients get up to six cycles of gem platinum in this regimen, and then if they have not progress, they go on to receive a value map. So one of the things we'd be interested in looking at, given our data with GemCarbo and triple negative breast cancer, is do more patients actually make it to maintenance value map? And so we will be looking at that. And then, of course, we'll be looking at, you know, survival and PFS across the entirety of the study, but also from the initiation of maintenance so that we can, you know, have a, you know, evaluated versus the javelin data. because obviously that trial started from the maintenance portion because only patients who made it onto a value map were included in that trial. So, yes, we'll be looking at the trial overall and breaking it apart into those two components.

David, it's Jen. So on the runway, When we're looking at – we actually have a number of ways to get into 2023, and I'm being kind of cautious saying into 2023 and not giving further guidance on it. So if you look at the cash balance we have after the ATM, you look at the ability to draw down debt, even if we just look at the $30 million that's available right now. Also, we are expecting some milestone payments from our partners, not as large as we thought. obviously in 2020, but to add to that runway. And then we would be anticipating revenue. We ran it with a range of revenues, and so feel very comfortable giving guidance into 2023.

Okay, got it. Thank you.

That's all the time we have for questions today. I would now like to turn the call back over to Jack Bailey for closing remarks.

Thank you, Operator. So in summary, 2020 was a strong year of progress for the company. We look forward to keeping you all updated as we continue to progress in 2021. We are excited to bring Cosella to patients with extensive stage small cell lung cancer and look forward to keeping you updated as we move forward. To everyone listening, thank you for joining us today and please stay well.

Ladies and gentlemen, that does end our conference for today. Thank you for your participation. You may all