G1 Therapeutics Inc (GTHX) 2022 Q4 法說會逐字稿

Good day, and welcome to the G1 Therapeutics Fourth Quarter Financial Results Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded. It is now my pleasure to introduce Vice President of Communications, Will Roberts.

Thank you, Andrew. Good morning, everyone, and welcome to the G1 conference call to discuss our fourth quarter and full year 2022 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 fourth quarter of 2022, including an update on our clinical programs and our commercial progress in that period with COSELA, which is approved and commercially available to decrease the incidence of chemotherapy-induced myelosuppression in adult patients who were administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive stage small cell lung cancer. A Q&A 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 Securities Litigation Reform Act of 1995. Such statements represent management's 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 these statements. For more information on such risks and uncertainties, please refer to our filings with the Securities and Exchange Commission, which were available from the SEC or on our corporate website. Any forward-looking statements represent our views as of today, March 1, 2023.

Joining me on the call today are Jack Bailey, our Chief Executive Officer; Raj Malik, our Chief Medical Officer; Andrew Perry, our Chief Commercial Officer; and Jen Moses, our Chief Financial Officer.

And with that, I'll turn the call over to Jack.

Thanks, Will. Good morning, everyone, and thank you for joining us on the call today. We spoke with you just a couple of weeks ago on the PRESERVE 1 results. Since that time, we continue to move forward with urgency on the rest of the business, focusing on 3 core goals.

First, regarding sales in small cell lung cancer, we remain confident in the sales trajectory for COSELA in our first lung cancer indication. As you will hear from Andrew, our sales and marketing teams have executed well since the start of the fourth quarter of 2022 and vial volume growth returned after experiencing a flat third quarter. This has continued into the first quarter of 2023 with a record month of sales in January and our highest week ever of sales in February. Based on what we are seeing today, we expect our 2023 net COSELA sales to be in the range of $50 million to $60 million, an increase of up to 92% over 2022.

Second, as Raj will describe, we are focused on executing on our ongoing clinical trials to achieve near-term data readouts, in particular, our ADC and MOA Phase IIs and our Phase III in triple-negative breast cancer. Regarding the 2 Phase IIs, initial data were compelling. We observed clinically meaningful on-target effects of trilaciclib to reduce the rates of multiple adverse events when administered prior to the ADC sacituzumab, including myelosuppression and diarrhea. And the initial results from our mechanism of action trial in neoadjuvant TNBC showed favorable alterations in the tumor micro environment from just a single dose of trilaciclib monotherapy.

And third, we have moved quickly to make the necessary organizational changes to preserve capital, including reducing the workforce by nearly 30%, though the sales team remains intact. And also other prudent decisions to reduce spend and extend our cash runway through each of our clinical readouts, including the TNBC pivotal trial. Jen will provide more color on these topics.

We will take these 3 goals in order. Andrew will first cover our recent commercial efforts since the start of the fourth quarter of 2022. Raj will then provide an update on our clinical program, including a brief overview of the results of PRESERVE 1 and our efforts to understand those results. Finally, Jen will provide financial results for the quarter, and as mentioned, discuss the actions we have taken to extend our cash runway. Then I'll be back for some concluding comments.

With that, I'll turn the call over to Andrew.

Thank you, John. I'm glad to be with you today to provide an update on our fourth quarter 2022 sales performance, the actions we took to drive growth in the fourth quarter and how those actions have continued to deliver growth into Q1 2023.

Our goals in the fourth quarter were to restore volume growth after a flat third quarter and to build a broader platform for future growth based on more customer organizations driving significant volume each quarter. We delivered on both of those goals in Q4, and I will discuss some of the factors underlying our performance to date.

Beginning with sales results, we ended the quarter with $8.9 million in net sales of COSELA, representing 8% vial volume growth compared with Q3. Volume growth compared with fourth quarter in 2021 was 103%, demonstrating the continued progress we have made with sales execution. Volumes grew month-over-month throughout Q4 and have continued to grow in January and February 2023. In fact, January was our highest volume month launch to date with volume strength continuing throughout February.

Two months into Q1, our quarterly growth is tracking well above the 8% growth we are reporting today for Q4. As we stated on our last call, an extensive-stage small cell lung cancer market, our quarterly growth is highly reliant on gaining new patients either from new accounts or from existing accounts in order to compensate for patients who complete their chemotherapy regimen and [drop all] therapy. I'm happy to report that we significantly increased the number of new accounts ordering COSELA in Q4. We brought on board almost 100 new accounts in Q4 compared with around 70 in Q3.

Moving into 2023, we have continued to add new accounts at a rate of around 1 per day. Many of these new accounts are affiliated with larger parent organizations, and we added 8 new top 100 organizations in Q4 and 2 so far in Q1, giving us a total of 71 of the top 100, which have ordered COSELA launched to date. The most recent of these from just last week was one of the largest academic centers in the U.S. and demonstrates the continued interest and the unique benefits of COSELA.

Within Q4, 54 of those organizations had orders, which supports our continued high overall reorder rate of around 80%. Our estimate of COSELA patient share continues to grow, and in Q4 increased to approximately 9% in the first-line market, which represents the majority of our use. One of our goals as we grow our business is to create a broader platform of organizations with deep adoption. For most quarters since launch, 3 customer organizations have driven around 20% of volume in each quarter. In Q4, we saw 5 organizations driving 20% of volume. In fact, the highest volume organization in the fourth quarter grew over 400% from Q3 to Q4.

In a relatively rare tumor types, such as small cell lung cancer, having more customers with deep adoption should provide more stability in our quarterly volumes. We saw 77% of volume in the quarter come through community clinics and hospitals, and 23% of volume from academic centers, which reflects some of the high growth we saw in the quarter from large community clinic networks. 98% of our volume in the quarter was in commercial supply with 2% provided through our patient assistance program. Our payer mix remains stable with the majority covered by Medicare and third-party payer reimbursement has remained strong.

Looking into Q1 2023, with several new top 100 organizations and many new accounts added in the prior quarter, we entered Q1 in a better position than the last quarter and have been encouraged by January and February demand. Our focus going forward is continuing to build a broader base of deeply [adopting] customers with emphasis on community clinic networks.

We now have 3 volume-based agreements with large community oncology provider networks and are progressing additional contract opportunities. While these contracts can take a little time to fully get up to speed, we've already seen Q1 quarter to date increases in demand in these contracted organizations of over 30% so far. We have also continued to make operational efficiencies where it made sense, including some consolidation of territories and the redeployment of one sales representative to a virtual hybrid role that can augment our digital marketing and provide support for unstaffed territories.

Overall, this was a quarter where we focused our execution on building a broader base of customers with high growth potential, and we're able to create sustained volume growth, while also driving some efficiencies in our commercial model. Our performance in Q4 2022 and midway into Q1 2023 confirms that there remains significant growth potential in small cell for COSELA.

With that, I'll turn the call over to Raj.

Thanks, Andrew, and good morning, everyone. As Jack mentioned, we've had a number of important data readouts since the end of the third quarter, although the most important of them, the Phase III readout from the pivotal PRESERVE 1 trial did not work out as we had hoped. I'll touch on each of them, starting with colorectal cancer, so I won't go into the same level of detail as I did on the call 2 weeks ago.

Although the results were confounded by less favorable preliminary antitumor efficacy results, including early indicators of survival, PRESERVE 1 yet again confirmed the myeloprotection benefit of trilaciclib. For example, the inclusion of trilaciclib to FOLFOXIRI and bevacizumab reduced the rates of many measures of myelosuppression compared to placebo, including achieving the co-primary end points with statistical significance.

However, we decided to discontinue the trial given the low likelihood of achieving the PFS and OS endpoints based on the preliminary antitumor efficacy data to date. This adverse effect on antitumor efficacy appears to be limited to this chemotherapy regimen used in colorectal cancer, as other clinical trials of trilaciclib in combination with different chemotherapies in patients with extensive-stage small cell lung cancer and triple-negative breast cancer did not demonstrate this adverse antitumor efficacy signal.

In fact, in the Phase II triple-negative breast cancer study, we saw the opposite, a statistically significant improvement in overall survival in patients receiving trilaciclib compared to placebo. We are conducting a variety of analyses to understand the results. For example, we are looking into the possibility that trilaciclib may have had an unanticipated negative interaction with 5-FU, which would not have been identified as a risk in any of the preclinical assessments we performed. We look to communicate the results of these and other analyses over the coming few months.

Since the start of the fourth quarter, we also had readouts from each of our ongoing Phase II trials. Starting with the ADC trial in combination with sacituzumab, initial results on the first 18 patients showed a clinically meaningful on-target effect of trilaciclib to reduce the rates of multiple adverse events compared to sacituzumab single-agent data from the ASCENT trial, including any grade and grade 3/4 neutropenia and any grade and grade 3/4 diarrhea.

We expect to complete enrollment in this trial this week. We expect to present a more comprehensive data set, including safety and initial efficacy results, including outcome by tumor PD-L1 status at a medical meeting in the second quarter of this year.

In December, we presented initial results from our mechanism of action trial in neoadjuvant triple negative breast cancer at the San Antonio Breast Cancer Symposium. We noted favorable alterations in the tumor microenvironment following a single dose of trilaciclib monotherapy, with a trend towards an increased CD8 T cell to T regulatory cell ratio, which is consistent with prior data. We expect to present initial tumor pathological complete response results, again including outcome by tumor PD-L1 status in the second quarter of this year.

And in January, we provided an initial update on PRESERVE 3 in bladder cancer, showing similar but numerically lower response rate in the trilaciclib arm. We anticipate additional safety and efficacy data, including preliminary progression-free survival data in the middle of this year.

Finally, our Phase III trial in triple-negative breast cancer is based on the foundational data from our Phase II trial that showed a statistically significant survival advantage for patients enrolled in both trilaciclib arms compared to placebo. We have previously said that the interim overall survival analysis was expected in the second half of 2023, following the occurrence of 70% of the events required for the final analysis.

Since the interim analysis is dependent on having a protocol defined number of events, we tracked the occurrence of events in a blinded way at a regular interval. Based on recent evaluations, the number of actual events appear to be occurring more slowly than predicted. Therefore, we now expect the interim OS analysis to be conducted in the first half of 2024. As events accumulate, we'll be able to refine this estimate further. So a lot of data coming over the next several months.

With that, I'll turn the call over to Jen for a review of the financial results. Jen?

Thanks, Raj, and good morning, everyone. As Will mentioned, full financial results for the fourth quarter and full year 2022 are available in this morning's press release and will be in the 10-K, which we intend to file today after market close.

Our total revenue for the fourth quarter of 2022 was $10.3 million, comprised of net COSELA revenue of $8.9 million and license revenue of $1.4 million. The license revenue from the current quarter is primarily related to clinical trial reimbursement from our partners, Simcere and EQRx.

For the same period in 2021, total revenue was $5.7 million, including $4.4 million of net product revenue. For the full year of 2022, total revenue was $51.3 million, comprised of $31.3 million in net COSELA revenue and license revenue of $20 million. Cost of goods sold for the 3 months ended December 31, 2022 was $1 million compared to $0.4 million for the same period in 2021. Cost of goods sold for the full year 2022 was $3.7 million compared to $2 million for the prior year.

Our research and development expenses for the fourth quarter of 2022 were $16.6 million compared to $19.8 million for the fourth quarter of 2021. The period-over-period decrease in R&D expenses was primarily due to reduced clinical trial costs. R&D expenses for the full year 2022 were $83.3 million compared to $76.2 million for the prior year.

Our selling, general and administrative expenses for the fourth quarter of 2022 were $23.6 million, relatively flat with the $23.2 million for the fourth quarter of 2021. Comparing the 2 periods, increases in personnel costs due to increased headcount and sales were offset by a decrease in fees paid to BI and decreased professional and administrative expenses. SG&A for the full year 2022 was $100.4 million compared to $95.7 million for 2021. Regarding our cash position, we ended 2022 with cash, cash equivalents and liquid securities of $145.1 million, compared to $221.2 million as of December 31, 2021. This includes $52 million in net proceeds from our fourth quarter 2022 underwritten public offering.

Finally, regarding revenue, expense and cash runway guidance for 2023. As Jack mentioned, our net product revenue guidance for 2023 is a range between $50 million and $60 million. This guidance reflects an adjustment to our anticipated gross to net percentage. Our gross to net adjustment in 2022 was in the mid- to high teens. Going forward, we expect it to be in the low to mid-20s, primarily due to the potential impact of the wastage provision of the 2021 Infrastructure Bill. When forecasting our license revenue, we anticipate receiving a $5 million milestone payment from EQRx in the first half of 2023 due upon dosing of their first patient in their pivotal trial for lerociclib.

Regarding expense guidance, we've completed a reduction in force of approximately 30% and have also reduced anticipated spend throughout the organization. We currently expect our 2023 operating expenses to be 20% to 30% lower than that of 2022. While we won't see an impact in the first quarter due to severance and costs associated with reading out and winding down PRESERVE 1, we'll start to experience these savings in the second quarter, with most of it occurring in the back half of the year.

With these adjustments to OpEx, the top line guidance provided and other assumptions around partner revenue, we anticipate a year-end cash, cash equivalents and marketable securities balance of approximately $70 million to $80 million.

With that, I'll turn the call back over to Jack for some closing comments. Jeff?

Thank you, Jen, Raj, Andrew and Will. As always, I also want to thank people living with cancer for your inspiration. You drive us toward our goals every day.

Now as I mentioned at the start, we have 3 core goals for the remainder of the year. First, we remain confident in the potential of COSELA in lung cancer. And as you heard from Andrew, we made good progress since the end of the third quarter, including returning to vial volume growth in the fourth quarter of 2022 with month-over-month growth throughout the fourth quarter, January being our highest vial volume month since launch, and volume strength has continued through February.

We've added nearly 100 new accounts in the fourth quarter, including 8 new top 100 organizations with 2 more added since the start of Q1 to continue to build that broad platform for future growth. Given our progress, we have provided formal guidance this morning of between $50 million and $60 million in net COSELA revenue in 2023.

Second, clinical trial execution. Our initial Phase II readouts over the past several months have been compelling, in particular, from the ADC and MOA trials. As you heard from Raj, we expect to present more comprehensive data from both of those in the second quarter, followed by additional data from the bladder cancer trial midyear.

We believe that positive data from any of them should be important value drivers for us as they will clarify the next indications and combinations we will pursue. And given that the number of events occurring more slowly than anticipated, the interim OS analysis for the pivotal TNBC trial is now expected in the first half of 2024.

And third, capital preservation. Although it's difficult to make these decisions, we are, as of yesterday, smaller than we were on our February 13 call, and we are making prudent reductions to our spend to extend our cash runway throughout each of our clinical readouts.

Finally, as you saw in this morning's press release, this will be Jen's last call with us as Chief Financial Officer. As part of our succession planning, Jen has resigned from G1 effective on the 15th of this month, but will remain on as a senior adviser for 1 year. On behalf of the entire executive team, I want to express my gratitude to her for everything she brought to the CFO role and for her dedication to the cancer patients we seek to treat.

At the same time, I'm pleased to announce that our Controller, John Umstead, will be appointed to the role of CFO. John has been with G1 since 2018, after 5 years with PricewaterhouseCoopers before that. And we look forward to introducing him on our next call.

Thank you for your time this morning. We will speak again in this format on the first quarter 2023 call, and we'll have a variety of opportunities to communicate the upcoming data from our Phase II trials throughout the year.

With that, I'll close the call and turn it over to the Q&A. Operator, would you please remind our listeners how to ask a question.

(Operator Instructions) Your first question comes from the line of Gil Blum with Needham & Company.

Just to make sure I fully -- I got this sort of correct. So the pivotal breast cancer study will be reading its interim next year due to a slow accumulation of events or difficulty in enrolling?

Gil, I can address that one. No, it's a slower accumulation of events. The trial is fully enrolled with 187 patients.

Okay. That's important to [testing]. The other question that I have is you discussed some postmortem analysis on the PRESERVE 1 study. Any potential time line guidance on when we might be able to see that data?

Yes. Those are active analyses now. And so I'd say over the upcoming months, we should have more information. Our leading hypothesis, as I mentioned, is really 5-FU. And we're looking at how patients did both on the adoption part of the study and the maintenance part of the study, and we have some thoughts on what might have happened. But we need to do some more analyses to sort of gain more firm footing on that hypothesis.

Okay. On the commercial end, it appears that you've been broadening the number of accounts in order to increase the flow of patients, given relatively fast turnover because of the way the treatment is provided. How are you planning to drive more growth here? Is there more white space to be had?

Thanks, Gil. Yes. So many of those new accounts, and we talked about roughly 100 new accounts coming on board in Q4 and expanding it around 1 per day going into Q1. Many of those accounts are actually affiliated with a large parent organization. One of the top 100 or beyond the top 100. So really, it becomes a measure of depth when a new account comes on board in the vast majority of cases. And that can be driven by standardization in the EMR, which we've seen can very quickly drive COSELA uptake on the EMR has COSELA as a standard option for patients coming in receiving chemotherapies.

Or, in some cases, it can be driven by internal marketing from the large organization that has discovered that COSELA is aligned with their corporate interest and they want all of their related accounts to use the product. Or it can be related to, in some cases, our large organization community contracts, community oncology contracts, where the parent organization determents that COSELA is on contract system with their organizational goals. And they cascade the use of COSELA through the organization and then new accounts become aware of it as the parent organization cascades that information.

And our next question comes from the line of Joseph Thome with Cowen.

Maybe the first one, just on the combination with TRODELVY. What sort of PFS improvement are you looking for when we see that data update? Is it the correct comp sort of 5 months here? And then when you think about the decision to go forward and maybe advance this to next step, would you be waiting for overall survival? And could we see those data maybe closer to the end of this year?

Joe, yes, the comp, as you said, in this sense, it's around that 5-month mark for PFS. But we'll be looking at all of the data, the response rate, duration of response. And as I mentioned, also the tumor PD-L1 status, so it will be a totality of the data that we'll see. And those will be the key drivers for the next step. Yes, we wouldn't wait for overall survival. It would really be what these early indicators of efficacy show.

Great. And then maybe just a commercial question. What's sort of the average length of time a patient is on COSELA in the real world? And as some of these new accounts are coming on in the fourth quarter, are you seeing them being used in different patients that sort of overall usage time line could potentially expand in the years to come? How do you think about average -- averages?

Yes. Thanks. So as you know, in the first-line setting, you would expect around 4 cycles on 21-day cycles. And on average, we see probably around about 3.3 to 3.5 cycles. Sometimes that's due to patients starting in the second cycle or the third cycle. Sometimes it's also due to patients being initiated in an inpatient setting where they will only receive 1 cycle and then being discharged to the community, where they will receive the subsequent cycles. And of course, our analysis doesn't always pick up on that. So we're -- when people use COSELA in that setting, they do tend to use it for every cycle.

And our next question comes from the line of Dane Leone with Raymond James.

Congratulations on the progress. So your commentary around the start of the year for COSELA uptake was obviously highly encouraging with the explicit financial guidance. But can you just take us through what you think has catalyzed the expanded use and adoption of COSELA. Obviously, for the prior 3 quarters in 2022, sales were relatively flat. But it seems like you've been able to invigorate some growth there. So anything you can elucidate in terms of what's driving that, I think, would be super helpful.

Yes. Thanks. So obviously, we had great success in Q2, and we saw 60% volume growth within the quarter of Q2. Much of that was driven by the addition of new accounts and new patients. We were not as successful in driving new accounts in new patients in Q3. We only added 17 in Q3 compared with over 100 in Q2. In Q4, we were back to strength, adding new accounts in Q4 and new patients in Q4, and that's really been the driver because as those new accounts come on board, some of that new account business then goes into Q1 of 2023. So it gave us a much better exit path into the next quarter.

The reasons for that, so we focused very much on pull-through in the community and on improving our ability to execute within community clinics. We've discovered that the reasons for that are improved access, the opportunity for standardized EMRs that I referred to earlier, obviously the success so far of our contracts and the potential for more of that, and the economic value proposition that COSELA has had ever since launch, which is very appealing in the community setting.

And some of those community organizations as they come on board, they can range from 5, 6, 10 individual accounts. There's sometimes 80 to 100 individual accounts within one organization. And as you see trial and then the physicians prescribing the product, seeing the benefits of the product, wanting to communicate that through peer to peer, you can see a very rapid option throughout the rest of our community oncology network. So that's definitely been our sweet spot for execution in Q4, we've doubled down there, and we've seen that success continue into Q1.

Great. And maybe another follow-up question for me. Can you just contextualize what the scale and scope of the data from the Phase II study with sacituzumab govitecan will be in the second quarter? I guess, number of patients and median duration of follow-up would be super helpful for people to set expectations.

Dane, so we'll -- this is Raj. We'll provide, of course, updated safety data and data on all the patients. As I said, we'll be completing the enrollment. We expect approximately 30 patients worth of data at the time. Enrollment has been going on for longer than a year, or about a year and 2 or 3 months. So I couldn't tell you what the median duration of follow-up would be at the time of the presentation. But obviously, it will be long enough for us to make a call and at least preliminary PFS. And I think the other point is, since tumor PD-L1 status is an important consideration, and we're also evaluating the immune hypothesis here for trila, that will be another important aspect of the mechanism, and we will be also currently evaluating and then presenting.

And sorry, one last one for me. The question, I think we're getting in is related to some of the earlier questions. But is -- does PRESERVE 2 actually have a futility analysis on OS designed into the study that could be evaluated before the readout in the first half of '24. I think people are asking that question within the context of understanding what the actual hazard ratio needs to be on OS as an endpoint, and whether it would be prudent to maybe look at the interim and see if there could be futility and continuing the study.

Yes, Dane, we did not include a futility analysis. It was really an interim for improvement in efficacy and primarily because of the signal we saw from our Phase II study. So obviously, the other comment I'd make is the data monitoring committee reviews the data regularly. So if they feel like they need to run a futility analysis, they could, of course, do that on their own as well.

(Operator Instructions) One moment, please. And our next question comes from the line of Priyanka Grover with JPMorgan.

It's Priyanka, on for Anupam Rama. We just had a quick question. What exactly -- or could you provide some color what's driving the delta between the 2023 guidance of $50 million to $60 million on metrics? Is it just penetration? Or is there some seasonality like in the third quarter in SCLC?

Yes. So what's driving it is the rate of increase that we have seen in our success, mainly in these community clinics, the rate of continued adoption in new accounts and our estimate of how that will extend through the year based on what the round so far about the COSELA [path] of adoption. Again, I would say that the single biggest thing that will drive our success in this market is when we move quickly from trial to adoption and one -- the first patient to multiple patients and then multiple accounts within an organization with multiple patients.

We've seen great success over the last few months with that strategy. We're doubling down on that strategy going into this year. And our forecast is really based on that dynamic. And I think it's important to remember, this is several hundred million dollar market -- $700 million market. We are scratching the surface of the potential here. There is plenty of room for us to grow and achieve these targets.

Thank you. And I'm showing no further questions. So with that, I'll hand the call back over to CEO, Jack Bailey for any closing remarks.

Great. Thank you, operator. As always, we look forward to keeping everybody updated on our progress. But for now, that concludes this call. Thank you for joining us today. We look forward to being in touch.

Ladies and gentlemen, this does conclude today's program. You may now disconnect.