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spk05: Good day and thank you for standing by. Welcome to the G1 Therapeutics Second Quarter 2022 Financial Results Call. At this time, all participants are in the listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker for today, Mr. William Roberts. Please go ahead.
spk07: Thank you, Mikey. Good morning, everyone, and welcome to the G1 conference call to discuss our second quarter 22 financial results and business update. The press release on these financial results was issued this morning and can be found in the news section of our corporate website, g1therapeutics.com. On this morning's call, the team will provide a business overview of the second quarter of 22 including an update on our clinical programs and our commercial progress in that period with COSELLA, which is approved and commercially available to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum and toposide-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 want to remind you that today's webcast contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements represent management's judgment as of today and may involve risk and uncertainties that could cause actual results to differ materially from those expressed in or implied by these statements. For more information on such risk 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, August 3rd, 2022. Joining me on the call today are Jack Bailey, our Chief Executive Officer, Andrew Perry, our Chief Commercial Officer, Raj Malik, our Chief Medical Officer, and Jen Moses, our Chief Financial Officer. And with that, I'll turn the call over to Jack.
spk01: Thanks, Will, and good morning, everyone. Thanks for joining us on the call. Today's headline is that we have achieved a variety of important foundational milestones that we set for ourselves for the first half of 2022. I'll briefly touch on three of them. First, I'm proud of the decisiveness and strategic execution shown by the G1 team over the past few quarters regarding the commercialization of COSELLA. We identified the issue of needing to better access top target prescribers and accounts, We made the right decisions quickly and executed decisively to correct course, including building our own Costella-focused sales team. And as a result, during the quarter, we saw an inflection in sales. The momentum we experienced in the quarter is evident as our team worked to bring this innovative drug to more patients with small cell lung cancer than ever before. Costella is an important and unique drug. It is proactively administered and covers multiple lineages, enabling oncologists for the first time to reduce or prevent the serious hematologic side effects of chemotherapy preemptively, rather than waiting for treating them reactively with a variety of single lineage interventions, which of course carry their own unintended and potentially dangerous consequences. As you'll hear from Andrew, we experienced good growth during the quarter. including growing vial volume by almost 60% period over period. Second, the team has executed the majority of our clinical programs extremely well during a period of significant headwinds, including COVID-19 and the ongoing crisis in Ukraine, which impacted many clinical trials of different products. Most importantly, we achieved the important milestone in the second quarter of completing enrollment in our Phase III Line Extension Trial of Trilocyclib in 326 participants with metastatic colorectal cancer. We expect the initial results, including those from the primary endpoint, in the first quarter of 2023. And, as you read in this morning's press release, We recently also had key enrollment milestones in both our Phase II bladder and our Phase II trial assessing the mechanism of action for tritocycline. Further, as you will hear from Raj, we expect to provide the initial results from each of our five ongoing Phase II and Phase III clinical trials over the coming 18 months, starting in the fourth quarter of this year. Third, from a corporate perspective, we were recently very pleased to share that the China National Medical Products Administration had conditionally approved the marketing authorization for COSELLA, which was jointly developed for use in Greater China in partnership with Sincere. As a result, G1 will receive a $13 million milestone payment from Sincere, part of a total milestone consideration of up to $156 million. We also expect to receive double-digit royalties on future annual net sales of Procella in China, which Jen will describe later in the call. This morning, I will first ask Anju to cover our recent commercial progress, including an update on our efforts of our new field sales team during the second quarter of 2022. Raj will then provide a snapshot of our clinical momentum, including timelines and data expectations. Finally, Jen will provide the financial results for the quarter, including an update on financial ramifications of the sincere approval and a reminder that our cash runway takes us into 2024. Then I'll be back for some concluding comments. With that, I'll turn the call over to Andrew.
spk10: Thank you, Jack. I'm glad to be with you today to provide an update on a number of commercial topics, including second quarter sales performance and leading indicators of growth. The second quarter was our first complete period during which Cosella was promoted solely by our own team of G1 oncology sales account managers, or OSAMs, following their full deployment in mid-February and the termination of our co-promotion agreement with Boring or Ingelheim in early March. Our goal in the second quarter was to demonstrate significant volume growth with a focus on the top 100 organizations who see around 50% of patients with extensive stage small cell lung cancer. We also wanted to build a platform for future growth by demonstrating both breadth and depth of utilization across the U.S., beginning with sales activity. We ended the quarter with $8.7 million in net sales of Cozella, representing nearly 60% file volume growth quarter over quarter. This was our highest quarterly growth rate since the initial launch period and has almost tripled the growth rates we saw in Q4 of last year and in Q1 of this year. Compared to the same quarter in 2021, which was our first full quarter after launch, the growth in vial volume was 268%. Each month in the second quarter showed positive month-over-month growth in volumes. However, the small cell lung cancer market can show variability from month to month due to patient flow and pressure on staffing in healthcare organizations at different times of the year. And similar to last year, our rate of growth in July did not reflect the pattern we saw in prior months. However, we do anticipate continued quarter-over-quarter growth, and we've taken the opportunity to initiate a number of sales and marketing initiatives designed to further improve our execution and restore stronger growth. We saw 77 percent of volume in the quarter come through community clinics and hospitals, and 23 percent of volume come from academic centers. 98% of our volume in the quarter was in commercial supply, with 2% coming through our patient assistance program. And our repair mix remained broadly unchanged, with 65% covered by Medicare, 27% covered by commercial, and the remainder in Medicaid or government programs. As I mentioned earlier, our goal was to not only deliver higher growth, but also to deliver a platform for future growth by broadening our base of utilization and driving debt in key accounts. I'm pleased to report that all four of our sales regions in the U.S. contributed to our national quarterly growth, with regional growth rates during the quarter ranging from 22% to 85%. In fact, 13 of our 34 territories demonstrated growth of over 100% in the quarter. We also wanted to expand our reach and uptake in the important top 100 organizations which treat around 50% of patients with extensive stage small cell lung cancer, and we have added seven top 100 organizations since the end of Q1, giving us a total of 60 of the top 100 which have trialed CoSELLA. Approximately 80% of those organizations had repeat orders during the second quarter. The proportion of our Q2 business and top 100 organizations was 53%, and our quarterly growth in those top 100 was 52%. Moving to some measures of overall commercial execution, Costella brand awareness remains high, at around 80%, with over 90% of physicians who are aware of Costella intending to prescribe within 12 months, and over 50% intending to prescribe within three months. Message effectiveness for the majority of Costella key messages is at or above oncology brand industry averages. third-party payer reimbursement has remained strong, and we have had very few payer rejections to date. We've also seen an increase in opportunities for face-to-face engagement with customers, with the majority of our calls now in person, and we were excited to have our commercial and medical teams representing G1 Therapeutics and Cosetla at major conferences such as ONS and ASCO this quarter. Overall, we're pleased with our progress in Q2. We delivered significantly stronger growth, and built a broader base of business across the key customer organizations, which can continue to support growth going forward. Our key lead measures of success all show even more potential for Cosella in the future. As a result, we remain ambitious for the potential of Cosella to benefit many more patients with extensive stage-fall cell lung cancer, and we're committed to ensuring their healthcare providers have the necessary information and resources to include Cosella in their regimens. With that, I'll turn the call over to Raj for a medical and clinical update. Raj?
spk03: Thanks, Andrew, and good morning, everyone. As Jack mentioned, I can report that as of today, we expect to provide the initial results from our five ongoing clinical trials in the timelines we have previously disclosed. As context for the studies where assessment of antitumor efficacy is the primary objective, it is important to understand the Phase II triple negative breast cancer data that were published in 2019 in Lancet Oncology. as we think about the initial and final data that will be reported in the fourth quarter of this year and through 2023. As you may recall from the TMBC Phase 2 data, we observed robust, statistically significant improvements in the most clinically meaningful endpoint of overall survival in patients receiving Trelacyclib compared to patients in the control group with hazard ratios of 0.31 and 0.4 in the two Trelacyclib groups. The effect on progression-free survival was strong, but not as robust as overall survival, and the least difference between the trialocyclib arms and control was in response rate. Our hypothesis for expecting to see a greater effect on EFS and OS compared to response rate is that the immune-modulating mechanism of action of trialocyclib could improve survival more so than response rate. This is consistent with data from therapies that modulate the immune system, such as immune checkpoint inhibitors. Specifically, we believe that the durability of effect may occur through increased formation of memory CD8-positive T cells, which could improve long-term immune surveillance. Therefore, for our Phase II studies focused on assessing antitumor efficacy, We expect to see a greater effect of Tala-Cyclib on progression-free or overall survival and the least on response rate. I remind you of our expected timeline for data over the coming 18 months, starting with our Phase III pivotal trials and then moving on to our Phase II program. First and foremost, we recently achieved an important milestone as we completed enrollment in our 326-station trial of Trilocyte-Lib in first-line metastatic colorectal cancer called Preserve-1. Folpoxiri is the most effective and also the most myelotoxic regimen for metastatic colorectal cancer. Improving myelotoxicity could result in a greater exposure to chemotherapy and potentially also improve antitumor efficacy. We expect to release initial results from this trial including those from the primary endpoint of myeloprotection and from the secondary endpoint of overall response rate in the first quarter of 2023. The secondary survival endpoints of PFS and OS will come later. If the myeloprotection data are positive, we will meet with regulatory authorities to discuss filing for approval in this indication. Second, regarding PRESERV-2, our first-line TMBC pivotal trial in approximately 170 patients with PD-L1 positive and negative tumors. We expect the interim overall survival analysis to be conducted by a data monitoring committee in the second half of next year. If the trial meets the interim analysis stopping rule, it will terminate, and we will report the top line results. If it does not, the trial will continue to the final analysis. Next, regarding our phase two trials, We currently expect initial data from the following three in the fourth quarter of this year. Starting with Preserve 3, our study of Tralacycline with chemotherapy and the immune checkpoint inhibitor, Avalumab, in patients with bladder cancer receiving first-line treatment. As Jack mentioned, we announced this morning that we have achieved our target enrollment in this approximately 90-patient trial. The last few patients who have consented to enroll should do so shortly, so we should achieve last patient in in the upcoming days. As such, we can confirm that we expect to provide initial top-line response rate and model protection data in the fourth quarter of this year, followed by data on the primary endpoint of PFS in 2023. Second, we've also completed enrollment in our 24-patient trial clarify the mechanism of action of Trialacyclid in participants with neoadjuvant triple negative breast cancer. We expect to provide initial immune endpoint results from this trial, including Trialacyclid's impact on CD8 positive T cells and regulatory T cells, or Tregs, in the tumor microenvironment in the fourth quarter of this year, with pathological complete response and other immune and profiling data in 2023. And third, We expect to present preliminary safety data from our Phase II trial in triple-negative breast cancer designed to evaluate the additive combination potential of Trialacyclib with the antibody drug conjugate sasituzumab Govitecan. The treatment landscape has continued to change in the U.S., with greater usage of pembrolizumab in the neoadjuvant and adjuvant setting, resulting in slower progression of disease, which is great news for patients. As a result, the time until a patient could become eligible for our trial has pushed out, which appears to be one of the factors that has contributed to slower enrollment. We are in the process of mitigating this in a variety of ways, including adding additional sites. As a result, we'll have preliminary safety data late this year from as many patients as possible, and the bulk of the data, including efficacy, next year. It's worth noting that this landscape evolution is a U.S. effect only. We are not seeing these enrollment hurdles in the global pivotal TMBC trial. Finally, there is significant strategic importance to expediting the evaluation of the combination of trialacyclid with a checkpoint inhibitor and chemotherapy in first-line non-small cell lung cancer. As such, rather than supporting an investigator-initiated study, We're exploring other means of evaluation, such as sponsoring it ourselves or with a partner. We will provide an update on this as soon as possible and also keep you abreast of our ongoing ISS program as those trials initiate. With that, I'll turn the call over to Jen for a review of the financial results for the second quarter of 2022.
spk06: Thanks, Raj, and good morning, everyone. As Will mentioned, full financial results for the second quarter of 2022 are available in this morning's press release and will be in the 10Q, which we intend to file today after market close. Our total revenue for the second quarter of 2022 was $10.6 million, comprised of net co-seller revenue of $8.7 million and license revenue of $1.9 million, compared to $6.6 million of total revenue for the same period in 2021. Cost of goods sold for the three months ended June 30th, 2022 was 1 million compared to 0.8 million for the same period in 2021. As a reminder, a portion of the manufacturing costs related to Goose Bella sales were incurred prior to FDA approval and therefore were recorded as R&D expense in prior periods. The majority of prelaunch inventory has been depleted and the treatment of these costs will now have a nominal impact on cost of goods sold going forward. Our research and development expenses for the second quarter of 2022 were 20.8 million, compared to 18.8 million for the second quarter of 2021. The increase in R&D expense was primarily due to an increase in clinical trial spend, offset by a decrease in cost for manufacturing of active pharmaceutical ingredients and drug product for clinical trials. As we mentioned on the last call, we expect annual 2022 R&D spend to come in above 2021 levels, with the first quarter of 2022 as the outlier and the third and fourth quarter more in line with what we saw in the second quarter of this year. Our selling, general, and administrative expenses for the second quarter of 2022 were $25.7 million, compared to $25.2 million for the second quarter of 2021. The increase in SG&A expenses quarter over quarter was largely due to an increase in personnel costs related to headcount, offset by a decrease in medical affairs costs, commercialization activities, professional and legal fees, and IT-related costs. We continue to monitor our expenses in a disciplined manner. While we are investing in customer-facing commercial activities and prioritizing spend that allows us to meet enrollment and data readout timelines for our trials, we are continuing to monitor other ancillary expenses. We have reduced or delayed spend in many areas while we allow time to grow our product revenue lines. Regarding our cash position, as described in the press release this morning, we ended the second quarter with cash and cash equivalents of $144 million compared to $221.2 million as of December 31, 2021. We expect this to be sufficient to fund our operations and capital expenditures into 2024. This projection of cash runway includes a future draw of an additional $25 million on our debt facility with Hercules, which is currently available to us at our discretion. As Jack mentioned, we will receive a $13 million milestone payment in the third quarter from Sincere as a result of their recent approval of Cosella in China. We also expect to receive double-digit royalties on annual net sales of Cosella in China. Although we may earn some royalties this year for our internal modeling purposes, our assumptions are that these royalties will begin in 2023. With that, I'll turn the call back over to Jack for some closing comments. Jack?
spk01: Thank you, Jen, Raj, Andrew, and Will. And as always, I want to thank people living with cancer for your inspiration. You drive us toward our goals each and every day. Before we move to Q&A, let me just recap some of the points that you have heard today. The second quarter was our first full period during which COSELLA was promoted solely by our own team of G1 OSAMs. following their deployment in mid-February. We ended the quarter with nearly 60% file volume growth quarter over quarter. This was our highest quarterly growth rate since the initial launch period. Third-party payer reimbursement has remained strong, and we have had very few payer rejections to date. During the quarter, we completed enrollment in our Phase III registrational trial in colorectal cancer, and more recently completed enrollment in our Phase II mechanism of action trial, and hit our enrollment target in our Phase II bladder cancer study. And finally, as Raj described, we expect to provide initial results from our two ongoing pivotal trials in CRC and triple negative breast cancer next year, starting with the CRC data in the first quarter of 2023, and data from our three Phase II trials later this year, the bladder study, the MOA study, and the ADC combination studies. Now, regarding COSELLA guidance, as we have previously communicated, we intend to provide formal guidance as soon as we have enough data on performance and impact of our G1 sales team to do so. However, given the month-over-month tempering of sales in July, we need a better understanding of these market dynamics before we can do so. As such, as of today, we remain comfortable with analyst consensus for COSELLA net sales in 2022 currently sitting just under $40 million. With a strong quarter of sales under our belts and a data-rich period through the end of 2023 ahead of us, I could not be more excited about where we are heading and the potential for Trilocycloid to impact the lives of many patients living with various cancers. Thank you for your time this morning. We will speak again in this format in November on the third quarter 2022 call. However, you will hear from us next at our upcoming virtual R&D day on September 15th. We expect to discuss a variety of topics, including a more robust discussion on the trialocyclic mechanism of action, readouts from our preclinical work assessing the potential synergies with other anti-cancer drugs, updates on our clinical program and data expectations, and the future potential of trialocyclic, all ahead of the key readouts from our clinical trials. So please keep an eye out for invitations and dial-in instructions over the coming weeks. With that, I will close the call and turn it over to Q&A. Operator, would you please remind our listeners how to ask a question?
spk05: As a reminder to ask a question, you will need to press star 1-1 on your telephone. Please stand by while we compile the Q&A roster. Your first question comes from the line of Hill Blum of Needham & Company. Your line is open.
spk12: All right. Good morning, everyone. Congrats on the progress. So we kind of discussed a few potential items on the commercial side that show signs of improvement. I'm just curious as to what is the company's view on the most important factor in driving future growth? Is it adding more top 100 facilities? Is it improving penetration in those facilities? Whichever you think is the most important.
spk10: Yeah, hey, Bill, happy to take that. Yeah, I mean, I think you nailed it, but we've obviously got to a significant portion of those top 100 right now, those 60 organizations that we have now seen an order from, and, of course, we've seen an 80%. reorder rate from those organizations which we're really happy about. But the overall depth of penetration has just a ton of potential there. I mean, clearly, there is a lot of runway even within the 60 organizations that have already ordered the product to actually see increased uptake. And very often with these types of organizations, there's a period where they initially use the product, they take a look at the results, but it might not be on all of their pathways or in all of their systems. And there's a period of us optimizing the placement of the product and then communicating how to use the product across all of the satellite locations. And that's the process that we're in the middle of right now. We've actually seen in Q2 some amazing success in some organizations through doing that process. And so that's what our team is really focused on in Q3 and Q4. Okay.
spk12: Thank you. And considering that several of your clinical studies have helped complete their enrollments, Should we expect a slowing in R&D operation expenses moving forward or just kind of remaining flat?
spk06: I would expect it to remain flat. We have, the studies are enrolled, but we are, we will have data processing. We'll have just a number of things to close out studies. So they'll continue to be, I would estimate them to be around where they were for the second quarter and continue that going forward.
spk12: Okay, excellent. Thank you for taking my question. Thank you, Gil.
spk05: Your next question comes from the line of Kari Polman of BTIG. Your line is open.
spk04: Yeah, good morning. Thanks for taking my question. So, for TNBC, has the change in treatment landscape impacted enrollment in the first-line TNBC Phase III trial?
spk01: Yes, thanks for the question, Kavari. This is Jack. It has not changed the enrollment timeline on the first line, phase three, first line TMBC. That's a global study, so we've got an enormous number of sites outside of the U.S. The ADC combination study is solely a U.S.-based study, and since Kachuta's approval at the end of 2020, or 2021, I guess it was, that is really only impacting the U.S. sites in terms of a bit more watch and wait and these patients taking longer to get to a time where they would be eligible for our study. So no on the first-line phase 3 study, no impact.
spk04: Got it. That's helpful. And for TNBC Tridelvi, do you expect the use of Keytruda in the new adjuvant setting to impact trilocyclic efficacy in the first-line setting? I mean, in patients who previously received and progressed on this immunotherapy?
spk03: Hey, Kaveri, this is Raj. I can take that one. You know, we do not. You know, based on the mechanism of action of Tralacycline and its impact on various aspects of that cancer immunity cycle, we think that there is a potential that we could work even in patients who have previously received an immune checkpoint inhibitor.
spk04: Great, thanks, and congrats on the progress.
spk00: Thank you.
spk05: Next question is from Tony Butler of Ross Capital. Your line is open.
spk09: Yes, good morning. Andrew, you made a comment about July, and then you made a statement about some sales initiatives, and I didn't quite get what those sales initiatives might be. I wondered if you could make a statement about if you could, about what those new sales initiatives would be. And then two additional questions. Raj, on the Preserve 2, while you're enrolling PD-L1 positive and negative patients, is there a net number of PD-L1 positive versus negative patients that are most desired from the 170? Because even though You had seen some positive data in both cohorts. It's not exactly equivalent. That could play into the futility next year. And then finally, when you mention you'll make comments about myelopreservation, for example, in CRC in Q1, exactly what will you say about myelopreservation or what can you say about myelopreservation given the trials continuing? Thank you very much.
spk10: Thanks, Tony. I'll take the first one. Yeah, you know, obviously in oncology, patient flow in the summer months can vary a little bit, and it does appear to have been affected by some trends in patient flow and perhaps healthcare staff availability as well for various reasons. I did mention a couple of the initiatives that are underway. And so the first is just focusing on those high-growth opportunity accounts at the national, regional, and territory level and creating some accountability around progress there. We're also developing an early warning system, which will highlight accounts to us when they drop in utilization, because quite often that's not because of a lack of confidence. which we can actually intercept much earlier if we flag it earlier. We're also following through more effectively where we see a patient come on board to make sure the providers have all the information they need about how to use the product appropriately. We've shifted some digital advertising to focus on our key accounts, and we have some new marketing materials and resources coming out in Q3 as well to keep our messages front of mind. So we've taken the opportunity to sharpen execution across a number of elements of our commercial model
spk03: Thank you. Hey, Tony. This is Raj. So initially, so the first for Preserve 2, you're right, we're enrolling all comers, so PD-L1 positive and negative. If you look at the data, approximately 40% of patients have PD-L1 positive tumors. We are stratifying by PD-L1 status. So, you know, we anticipate that that the approximate distribution of PD-L1 in this tumor population is what will be represented in the trial, so in that 40 to 50 percent. And because we're stratifying, we think it's going to be a, you know, it's the appropriate way to evaluate the effect in both. And even in the PD-L1 negative, if you recall, the hazard ratio was still less than 0.5, so there was definitely a meaningful effect there. And then to preserve one, The data that we'll be analyzing and reporting will be the primary and key second data, so duration of severe neutropenia, severe neutropenia, and patient reported outcomes. We will be blinded to any event-driven outcomes, so the trial will continue. Event-driven outcomes, so the trial will continue. for those PFS and OS readouts. So we will be able to report the myeloma protection data as well as the response rate data.
spk09: Very helpful. Thanks so much. Sure. Thank you, Tony.
spk05: Your next question is from Ed White of HC Wainwright. Please ask your question.
spk02: Good morning. Thanks for taking my questions. I'm just curious if you have any data on potential off-label use of COSELLA.
spk10: Yeah, thanks, Ted. You know, we get information that has quite a significant lag on it because it has to come through claim sources, so I don't have a lot of information that pertains to the second quarter, but I would estimate it's single-digit percentages of off-label use.
spk02: Okay, thanks. And then, Andrew, you had mentioned earlier that you now see a majority of live versus virtual sales calls. Maybe you could just review with us the importance of that, and do you expect this to continue going forward?
spk10: Yeah, thanks. I do anticipate it will continue going forward, actually. And the big advantage, I think, and maybe I'm a little old school in this, but when an oncology salesperson who is competent and capable and is engaged with the product goes into an office, they're not only calling on a prescriber. They're calling on the nursing staff. They're calling on whoever channels reimbursement. They're calling on the front office staff. and they built, they're calling them pharmacy, and they build up a whole picture of activities across the account, which can vastly accelerate adoption of a product. You know, the idea of just getting to a prescriber is, you know, a very one-dimensional view of what it takes to sell any specialty product, never mind an oncology product, and there's no substitute to my mind for getting into the office and having that total call.
spk02: Thanks, Andrew. And perhaps my last question for you is just, You mentioned a lot of positives going on during the launch. I'm wondering what sales headwinds that you're seeing and what potential solutions that you have to those headwinds. Thank you.
spk10: Yeah, thanks. I don't think they've really changed too much. I think it's converting the awareness of the product and the willingness to prescribe into identifying a patient and We've been really pleased, actually, to see some real-world data recently presented at NCCN where it really showed the burden of myelosuppression, which is much more profound, I think, maybe than any of us had thought, and we're starting to evaluate how we can get that into promotion because that creates a conversation about how we can do better together with the healthcare provider. And then the next part is really just shifting that kind of 20 years of habit of waiting for a problem to happen versus dealing with it proactively and getting the benefits of multi-lineage myeloid protection, which only Grusella can offer. And then finally, there's the process component, which is, you know, many of these institutions, organizations, networks are deeply embedded with an EMR system or an IT system, and they've You know, providers rely on that now for quality of care and for efficiency of care, and so working out the optimal placement for COSELLA in those systems, even when you have formulary review, even when you have P&T review, even when you have enthusiastic physician support, you still need to make sure you're in those systems, and that takes a little bit of navigation behind the scenes.
spk02: Great. Thanks, Andrew. Thank you, Ed.
spk05: Your next question is from David Niren-Garten of Wedbush Securities. Your line is open.
spk11: Hey, thanks for taking the questions, and congrats on all the progress here, especially on the clinical side. It's impressive. A couple questions on the clinical side. For the ADC combination study and the bladder cancer study, I know the primary endpoint is PFS, but thinking about myelopreservation in those settings, are there you know, anything we should know? You know, are there nuances to how, you know, that'll come out? Or is it going to be a straight, you know, read on, you know, neutropenia rates or things like that? And maybe another way to ask the question is, you know, is there a significant background, you know, myelosuppression in those patients? And is it currently, you know, generally treated with, you know, Neulaster or the other agents out there? Just, you know, trying to get a feel for what we could expect for, you know, kind of background rates and effects of trilocyclic on myelopreservation there. Thanks.
spk03: Yeah. Hey, David. This is Raj. Yeah. So, we will be looking at, you know, the outcomes of myelosuppression. So, neutropenia, anemia, thrombocytopenia. Starting with Tredelvi, it does have actually quite significant rates of neutropenia, so we feel there's an opportunity there to show potential improvement, which could translate to better tolerability of the combination. You know, one of the things that this was actually reported at ASCO this year, that that efficacy of Tredelby was associated with a greater AUC, and they did an exposure response analysis looking at a POP-PK model. And so maintaining dose intensity could be important for Tredelby. So that is something that we'll be looking at in that study. On the bladder, the chemo regimen, as you know, is gemplatinib. So this includes both cis and carbo, and it's given in a day 1-8 regimen. schedule, I should say, which is similar to our TMBC study. And it's going to be the same readout, so we'll be looking at, you know, model suppression does occur with, you know, with those combinations as well.
spk11: And just to double check, it's a secondary endpoint that you'll be able to report a statistical benefit? Yeah. Thank you. Yeah.
spk03: Sorry, David, just to clarify, it is a secondary objective, and there's no alpha assigned, so it will be descriptive, but it will be important additional data as we evaluate model protection across different regiments. Thank you. Thanks, Dave.
spk05: Once again, to ask a question, you may press star 11 on your telephone. Your next question is from Anupam Rama of JP Morgan. Your line is open.
spk13: Hey, guys. Thanks so much for taking the question. Just a question on the Trilocyclib MOA study, the mechanism of action study. Kind of what's the win scenario there, in your opinion, and how might that change the view of, say, Preserve 1 versus some of the efficacy studies that have been cited on this call? Thanks so much.
spk03: Yeah, hey, Anupam Raj here. So, yeah, so it's, you know, what we've shown previously in preclinical studies as well as with peripheral blood analysis from our clinical studies is that the impact of trisomyclib is in the T cell compartment largely. So we'll be looking at effect on CD8 positive T cells, G regulatory cells, but not just the numbers by immunohistochemistry, but also sort of more functional readouts. Are the cells activated? Which subsets are present? One of the interesting things that I think we've discussed in the past is that transient CDK4-6 inhibition can increase the formulation of memory CD8-positive T cells. So that could be something that we'll be interested in looking at as well. So it's going to be a very holistic assessment of the immune mechanism. We're also going to look at peripheral blood from these patients so we can make correlations with what's happening in the tumor with the peripheral blood. And this would, of course, help us going forward because it's much easier to look at peripheral blood going forward rather than looking within the tumor microenvironment. So a win scenario in your terminology would really be showing that trotocyclic can modulate the tumor-immune microenvironment in a variety of ways.
spk00: Thanks for taking our question. Sure. Thanks, Anupam.
spk05: And your next question is from Troy Langford of Calvin. Your line is open.
spk08: Hi, everyone. Thanks for taking our question and congrats on all the great progress in the quarter. Just two quick ones on the Cosella launch from us. First, on the new sales initiative, how long do you think it will take before we all see an effect on quarterly sales? So do you think we could see an effect over a quarter or two? Do you think it'll play out over a longer period of time? And then I have a follow up after that.
spk10: You know, I think we're not in a position necessarily to provide too many predictions there. What I would say is that at the account-by-account level, we can see rapid improvement due to execution improvement, so we'll be looking for that account-by-account. As to how it lathers up quarter-to-quarter, I don't want to second-guess that at this point.
spk08: Okay, great. That helps, definitely. And then the next question I have is just, does anything in particular distinguish the last handful of top Coachella accounts that you all haven't reached yet? Like, do these represent bigger systems that are more difficult to break into or something else like that?
spk10: Yeah, I mean, it can be a variety. So sometimes they are accounts or organizations that are completely no-see, no access to commercial, and they can be a mixture of academic and community in some cases. And those ones we always knew would take longer because there's just many, many fewer shots on goal. In some cases, it's organizations that looked at Costella very, very early in the launch period, maybe didn't have all the information they needed. and our job there is really to get them to re-evaluate the product and get more of our recent information out in front of them. And, of course, these organizations, they don't like to retread, so once they've made a decision, they don't like to go back. So getting on the docket for those decisions can take a little bit of time. We're happy we've got some plans in place across both academic and community organizations in that top 100 that have not yet adopted that we hope will continue to bear fruit. And, of course, those organizations are looking at their peers across the healthcare environment, and as they see more experience with Costella and more success with Costella, I'm sure they're going to be excited to actually have those discussions with us.
spk08: Okay, great. Thanks for all the color. Thank you, Troy.
spk05: No further questions at this time. I would now like to turn the conference back to Mr. Jack Bailey for closing remarks.
spk01: Great. Thank you, Operator. As always, we look forward to keeping you updated as we progress. Thank you for joining us today and certainly hope you all stay well. Thank you.
spk05: This concludes today's conference call. Thank you all for participating. You may now disconnect.
spk00: The conference will begin shortly. To raise your hand during Q&A, you can dial star 11.
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