G1 Therapeutics Inc (GTHX) 2018 Q1 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the G1 Therapeutics First Quarter 2018 Corporate and Financial Update. (Operator Instructions) As a reminder, this call is being recorded.

I would now like to introduce your host for today's conference, Mr. Jeff Macdonald. Sir, you may begin.

Thank you, operator. Good afternoon, and welcome to G1 Therapeutics First Quarter 2018 Corporate Update Conference Call. Joining me are Mark Velleca, Chief Executive Officer; Raj Malik, Chief Medical Officer and Senior Vice President, R&D; and Buck Phillips, Chief Financial Officer and Senior Vice President, Corporate Development. Terry Murdock, our Senior Vice President, Development Operations, will also be available during the Q&A portion of this call.

Before I turn the call over to Mark, I would like to remind you that today's call will include forward-looking statements based on current expectations. Such statements represent management's judgment as of today and may involve risks and uncertainties that could cause actual results to differ materially from expected results. Please refer to our filings with the SEC, which are available from the SEC or on our corporate website, for information concerning risk factors that could affect the company.

I'll now turn the call over to Mark.

Thanks, Jeff. Good afternoon, everyone, and thank you for joining us today. In the first quarter of 2018, we continue to build on a successful 2017. On today's call, we'll review key milestones for our 3 programs: Trilaciclib; G1T38; and G1T48. After our prepared remarks, we'll be available to take your questions.

I'll begin with our most advanced clinical program trilaciclib, our short-acting CDK4/6 inhibitor, that is administered intravenously prior to chemotherapy. In March, we announced positive Phase IIa top line data, showing robust myelopreservation benefit to trilaciclib versus placebo in small cell lung cancer patients receiving first-line chemotherapy. I would encourage you to review the press release we issued on March 5, for more details on the findings, and remind you that we plan to present these data at a medical meeting in the fourth quarter.

Based on the strength of the clinical data across multiple hematopoietic lineages, we have accelerated our time line for interactions with regulators, which we had originally planned for early 2019. We now have meetings scheduled for this summer with the FDA and European regulatory authorities. We'll provide an update regarding this ongoing dialogue later this year, as appropriate.

Data from the trilaciclib second-/third-line small cell and triple-negative breast cancer trials, which we'll read out in the fourth quarter of this year, will also inform our development and regulatory plans. Clarity on the path to approval will be dependent on the results of ongoing clinical trials and subsequent regulatory discussions. Potential plans that may include initiating a Phase III study in 2019.

Now let me turn to G1T38, our potential best-in-class oral CDK4/6 inhibitor. We are presenting early Phase Ib data at ASCO next month on the combination study with Faslodex in breast cancer. Raj will discuss that in more detail in just a moment.

In April, we announced the initiation of another G1T38 combination trial, this one with Tagrisso for non-small cell lung cancer. Given recent data on Tagrisso presented at AACR and its approval as first-line therapy, we're excited about how G1T38 may further improve patient outcomes.

Finally, we are on track to initiate the first clinical trial of G1T48, our oral selective estrogen receptor degrader, or SERD, later this quarter. This trial will initially consist of G1T48 monotherapy in ER-positive, HER2-negative breast cancer. Our plan is to combine G1T38 with G1T48. And that combination trial could initiate in 2019.

I will now turn the call over to Raj to provide more color around the upcoming G1T38 data presentation at ASCO.

Thanks, Mark, and good afternoon, everyone. As Mark mentioned, we are presenting the first data from our ongoing Phase I/II trial of G1T38 in patients with ER-positive, HER2-negative breast cancer at ASCO on June 2. This is an open-label trial in patients receiving a combination of oral G1T38 and Faslodex given intramuscularly. We are testing 2 different schedules of G1T38, with a drug given once a day or twice a day continuously without a drug holiday. The trial design consists of 2 parts: dose finding; and expansion. Once we complete the dose escalation, which is currently ongoing, we expect to enroll approximately 30 participants in the expansion phase.

The primary outcomes of the trial are assessing dose-limiting toxicities, identifying a recommended Phase II dosing schedule and safety. Secondary outcomes include pharmacokinetics, pharmacodynamics, tumor response, progression-free survival and overall survival. The data at ASCO will include preliminary findings from the ongoing dose escalation portion of the trial. This is positive from a safety perspective since we have been able to progress through several dose escalations. We will present early safety and tolerability findings and PK data.

We are also following effects on neutrophil counts when G1T38 dosed continuously without a drug holiday. In our 28-day toxicology studies, we were able to give G1T38 continuously. We observed that neutrophil counts decreased over the first 14 days as expected, and then plateaued without a further decrease for the remainder of the 28-day dosing period. We're doing similar analyses with the early clinical data, and we'll report these findings at ASCO.

We will also report early efficacy data consisting our tumor response assessments. It is important to keep in mind that since we are still in the dose escalation portion, the efficacy data are preliminary.

I will turn the call over to Buck for a discussion of the first quarter financials. Buck?

Thank you, Raj, and good afternoon, everyone. Our first quarter financial results can be found in our earnings press release, which is available on our website. Let me take a moment to walk you through the financial highlights contained in that release.

We reported a net loss of $20.4 million for the first quarter of 2018 compared to $12.3 million for the first quarter of 2017. Operating expenses were up $20.7 million for the quarter compared to $12.4 million for the prior-year period. GAAP operating expenses include noncash stock compensation expense of $1.6 million for the first quarter of 2008 (sic) [2018] compared to $0.5 million for Q1 '17.

Research and development expenses for the first quarter of 2018 were $17.3 million compared to $11.1 million for the prior year period. The increase in expenses was driven by an increase in clinical program costs, drug manufacturing costs to support clinical programs and personnel cost related to additional headcount.

General and administrative expense for the first quarter of '18 were $3.4 million compared to $1.3 million for the first quarter of '17. The increase in expense was largely driven by an increase in professional fees and personnel-related costs.

As of March 31, 2018, we had $194.4 million in cash, cash equivalents and short-term investments. This includes the $107.9 million in net proceeds from our March offering. This compares to $103.8 million on December 31 of 2017.

As discussed on this call, the positive trilaciclib clinical data presented in March has accelerated our time line for interaction with regulators and potential paths to approval that may include initiating a Phase III clinical trial in 2019. Therefore, the company will make additional investments in trilaciclib including manufacturing, regulatory activities to facilitate future filings, pre-commercialization initiatives, including: value and access studies; pharmaeconomic and pricing analysis; and market research, and additional headcount and corporate infrastructure to support these activities.

Based on the additional investments, we are revising our cash burn guidance for 2018 from a range of $65 million to $75 million to a new range of $75 million to $85 million.

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

Thanks, Buck. To summarize our upcoming milestones, we will provide an update on our regulatory dialogue with U.S. and European regulatory authorities on trilaciclib later this year. By the end of June, we expect to complete enrollment in the Phase II trials of trilaciclib in second-/third-line small cell lung cancer and triple-negative breast cancer. Preliminary data from both trials are expected in the fourth quarter of 2018. We're presenting preliminary data from the Phase I/II trial of G1T38 plus Faslodex in ER-positive, HER2-negative breast cancer at ASCO on June 2. And we are on track to initiate a Phase I trial of G1T48 in ER-positive, HER2-negative breast cancer by the end of this quarter.

That concludes our prepared remarks. Operator, please open the call for questions.

(Operator Instructions) Our first question comes from Anupam Rama with JPMorgan.

This is Tessa on for Anupam this evening. I guess, one from us. With the initial Phase Ib data in ER-positive breast cancer expected here at ASCO in 2Q, what should be anticipated with respect to what will be continued within the preliminary efficacy and safety data that you are presenting? And what might we have to wait for in the follow-up? And then maybe help us that, from the expectations from your standpoint on what the benchmarks for success are in the study? And then finally, if I could one more. Just -- should we expect there to be any data in the abstract or we have to wait for the full data presentation at ASCO?

Thank you, Tessa. I'm going to let Raj take that question.

Great. Hey, Tessa. So yes -- so keep in mind, first of all, this is early Phase I data, so the focus will be on safety, tolerability and PK. And we will present longitudinal neutrophil data. I alluded to that in my remarks. So we will present that data and what the neutrophil counts look like with continuous dosing of G1T38, which cannot be achieved, as you know, with 2 of the other 3 CDK4/6 inhibitors. The -- we will present response data. However, other PFS and OS data are immature. But just to remind you in -- the study is similar to the PALOMA-3 study, which was the pivotal study of palbociclib with fulvestrant. And in that study, the median PFS was about 10 months, and the median time to response was around 16 weeks, which is why the trial has been going a little bit over a year, and hence, the data should still be considered premature or not immature, early I should say. So I hope that answers your first 2 parts in terms of what data we're presenting and the benchmarks. We do have data in the abstract, that you will see. It's going to be on 24 patients worth of data, and we expect to have a few more patients at the presentation itself.

Our next question comes from Joseph Thome with Cowen and Company.

Just a couple from me. I guess, in terms of the development path forward for trilaciclib after these summer meetings, will you need to meet with the agencies again following the Q4 data readouts? And maybe what would a Phase III program for trilaciclib look like, especially if you are going after more of a chemo-agnostic label? And then, I guess, when -- in terms of the combination studies with G1T38 and 48, this might be a little bit premature, but I guess, what would you be looking for to see in the early study of 48 if you are confident going forward with the combinations in the future?

Thanks, Joe. I'll just answer the very first part of your question and turn it over Raj. We do expect to have a continued ongoing discussion with both FDA and European regulators. We do have meetings scheduled this summer. We expect to be back in front of them early next year with the Phase II data from the ongoing trial. So that will be an ongoing dialogue, and we will update you as appropriate.

Yes, and just to add Joe, the data are very strong, and we just want to get in front of the regulators to discuss the data. Our early meetings with them really were focused around the Phase I open label data, and so this is an opportunity to get in front of them with the robust myelopreservation benefits that we've seen. And as Mark mentioned, it's really an ongoing dialogue. We certainly can't comment on what the Phase III would look like, I mean, that's obviously a matter of discussion with the agencies.

Great. And then the final one -- sorry, was just on, what are you looking for with G1T48 to maybe be confident that it's combinable, yes?

Thanks, yes. So the initial part of the 48 is a monotherapy dose escalation. So we'll be looking at safety PK, but importantly, it also has a FES-PET component. So we're going to be looking at what happens to reduction of the tracer uptake following administration of 48, and this has been used with other [serves] as you know. So we'll be really looking at safety as well as PK as well as PD effects in defining the dose. And once we've defined the dose, the recommended Phase II dose, which will be likely some time in '19, that's what would trigger the combination with 38.

Our next question comes from Dane Leone with BTIG.

We look forward to the data at ASCO. I just wanted to clarify kind of the context of some of the safety data. I appreciate the neutrophil count being looked at, but do you have a perspective on looking at some of the GI talks that we've seen with some of the other agents or any characterization on that front?

Yes. We will absolutely present that data. And you will see that it's differentiated from really the -- both of the agents, both Kisqali and [panthema] in terms of the safety profile. So yes, we'll be presenting GI tolerability data, which are more in line with palbo and ribo, I should say.

And just to clarify, because in these early studies always scares me when response rates are promised and best-in-class is used. Could you just be a kind of crystal clear in terms of -- for a cohort, where you think patients are at a therapeutic dose level that will be presented at the meeting? How robust is that size of the cohort going to be? And then kind of relative follow-up on that cohort specifically?

Yes, thanks, Dan. To be clear, we think based on everything we've seen with 38, that it has best-in-class potential. Also to be clear, the data at ASCO is going to be from dose escalation cohorts. So there should be no expectation that we're going to have a robust data set on several patients who are at our go-forward Phase II devs. That dose expansion phase will start enrolling, we expect, some time middle of this year and complete enrollment by the end of this year. And it would be from those patients, those 30 patients that Raj alluded to that you would expect to see robust efficacy reads.

Okay. And so that -- those 24 patients you mentioned in the abstract, could you tell us what percentage of those patients would be understandably below what you consider a therapeutic dose level?

Yes. So Dan, this is Raj. I mean, we are -- we think we're getting close to the recommended Phase II dose. And so you can imagine that those patients have been on study the least, in terms of duration. So most of the efficacy data from a long-standing perspective are -- will be from lower dose levels. We also are testing once a day and twice a day cohorts in the study. So you'll see data on both of those cohorts as well. And we wanted to test that because of the shorter half life of the drug and just to make sure that they weren't clear differences between the 2 cohorts or 2 schedules, I should say.

Our next question comes from Chad Messer with Needham & Company.

Well understood that your conversations with regulatory agencies are kind of an ongoing issue, but given that you kind of went out your way to accelerate getting in front of them based on the strength of the trilaciclib data, just wondering if you could share with us any specific issues or questions or any objectives that you're hoping to get out of these initial meetings?

I'll just take -- I'll remind you, they're not initial meetings. We have had a prior dialogue, a really good end of Phase I discussion last year, but I'll turn it over to Raj on expectations for feedback from these upcoming discussions.

Yes. So as you know, Chad, the data are very compelling. It is a -- it's a novel mechanism of action with a multi-lineage effects that we saw. And when you're going and doing something that is a little bit different, the more chances you have to get in front of the regulators and get a sense of how they're thinking, really helps the development program. So that's really the main intention here, get in front of them, get there, first of all, reaction to the data, make sure that they are as excited as we are. And secondly -- obviously, we'll be talking about end points and things like that and getting their thoughts on our proposals.

At this time, I'm showing no further questions. I'd now like to turn the call back over to Dr. Velleca for closing remarks.

Thank you. Thanks all for joining the call. Please reach out to us, if you have any additional questions. Look forward to seeing many of you at ASCO, and have a good evening.

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program. You may now disconnect. Everyone, have a great day.