Turning Point Therapeutics, Inc.
Q1 2021 Earnings Call Transcript

Published: 8 May 2021

[Operator:]

Thank you all for standing by, and welcome to the Turning Point Therapeutics First Quarter 2021 Conference Call. All lines have been placed in listen-only mode until the question-and-answer session of today's conference. I'll now hand the call over to your host, Jim Mazzola. Sir, you may begin.

[Jim Mazzola:]

Okay. Thank you, Jessie, and good afternoon, everyone. Following market close today, we filed our Form 10-Q issued an 8-K and issued a news release with a summary of our results for the first quarter of 2021. We also updated our investor presentation and you may find these documents posted on the Investor pages of tptherapeutics.com.

[Athena Countouriotis:]

Thank you, Jim, and good afternoon to everyone joining us on today's call. For anyone new to our story, just 2 years ago, Turning Point had approximately 50 employees, has just completed our initial public offering and had one clinical stage assets in one ongoing Phase 1 study. Now two years later, we have approximately 170 employees. We are advancing four clinical stage assets with our lead asset repotrectinib with five regulatory designations, including Breakthrough Therapy designation, and this year we plan to start our 6th and 7th clinical study of our drug candidates. I'm so proud of the tremendous progress our growing team has continued to make as we work to accomplish the many important milestones we have outlined for 2021. Overall, we continue to advance our four clinical stage next generation tyrosine kinase inhibitors that target genetic drivers of cancer. In addition, we are investing in a discovery engine, with the goal of establishing a pipeline for long-term growth. The progress in investments we have made are all directed towards advancing our vision to be the leader in precision oncology. I will start with our lead program repotrectinib which is a next-generation, ROS1 and TRK TKI with greater than 94 higher preclinical potency than crizotinib and greater than 54 higher preclinical potent, Entrectinib against wildtype ROS1. Repotrectinib is currently being studied in our ongoing registrational Phase 2 portion of TRIDENT-1 in patients with ROS1 positive advanced non-small cell lung cancer and NTRK positive advanced solid tumors.

[Operator:]

Our first question is from the line of Michael Schmidt of Guggenheim Securities. Your line is now open.

[Charles Zhu:]

This is Charles Zhu on for Michael Schmidt. Thanks for taking the questions and congrats on the quarter, especially with the feedback from the FDA. Regarding that meeting and the potential registration path forward for and ROS1 of lung cancer. Correct me if I'm wrong this actually sounds very similar to the old guidance from the early pre-Rozlytrek days, which is great. I am wondering, how we should think about the potential efficacy benchmark so given Rozlytrek's recent updates? And what types of scenarios might be FDA request something like a 12-month follow-up or perhaps a randomized study? Thanks.

[Athena Countouriotis:]

Yes, sure. First of all, Charles thanks for the questions and the comment. And so let me start with we agree with you, and thank you for the congratulations comment. We do believe that feedback is positive. That said, the feedback was specifically that we should come back and request a meeting to discuss the top line data based on blinded independent central review as you know we've not unblinded that data yet. Specifically for the Cohort one patient population with a minimum of 6 months of follow-up, since the last response.

[Charles Zhu:]

Got it. Makes sense and very helpful. I was also kind of wondering if you could help us in a level set expectations for the TPX-0022 update later this year relative to what was presented to the last year at the Plenary. I guess as a related follow-up, given the diversity of MET alterations and potential ranges of copy number of amplification, you could provide some of your thoughts around potentially refining this population and expansion cohorts going forward? Thanks.

[Athena Countouriotis:]

Sure. So as I said during the prepared remarks, we have three clinical trial updates we will give in the second half of the year. You're alluding to one from the SHIELD-1 study, which is our MET program. That study still remains in the dose finding portion. If you remember when we presented in the Plenary session last fall, we had data at multiple cohorts, 40 milligrams, 80 milligrams and 120 milligrams. We have subsequently also done additional titration cohorts going from lower doses to higher doses, or QD to BID dosing. So that information is what we're currently collecting. We anticipate that the update in the second half of the year will be coming from this dose finding portion. We don't have an estimate yet on the number of patients, and we've not done a dataset cut for this analysis yet. But that said, it will be a heterogeneous population to the point that you made this will still be advanced solid tumor patients with MET alterations. And we have not refined down the gene copy number for MET amplification yet to your point. It is something we may consider in the future as we move into dose expansion. But we haven't done that yet during the dose finding portion.

[Operator:]

Next question is from the line of Paul Choi of Goldman Sachs. Your line is now open.

[Paul Choi:]

Maybe just starting with a follow-up on the MET question. Have you provided anymore or gotten any more clarity on how you're thinking about which EGFR combination you're focus on and which tumor types? And just as you kick off the Phase 1b portion of SHIELD-2 there, just what and how you'll communicate to the market on that?

[Athena Countouriotis:]

Yes, I'm happy too. So we have discussed that it would be focusing within non-small cell lung cancer likely. The EGFR combination partner, though, we have not yet discussed. And so that could be either an approved agent or utilizing an investigational agent through a collaboration. So that's the additional guidance we haven't provided, but remaining on track to initiate that trial in the second half of the year.

[Paul Choi:]

Okay, thanks for that, Athena. And then maybe circling back to TRIDENT-1, and ahead of your planned FDA discussion early next year. Just with regard to sort of completion and telegraphing to the market. Just the results from that front-line cohorts. Any specific medical meetings that might provide a forum for that, or just how are you thinking about that? Thank you very much.

[Athena Countouriotis:]

Yes, I mean, so as I said to Charles, a moment ago we're pleased with the FDA feedback. Of course, we are remaining on track to complete this cohort this quarter, and then further the FDA feedback, in addition to where we are with enrollment completion we're looking at the first quarter of next year for the timing for that meeting. It would likely be our standard practice to discuss the results with the FDA first. And then to submit the dataset to a future medical forum. We have not yet determined which forum that would be though, but obviously in 2022.

[Operator:]

Next question is from the line of Matt Biegler of Oppenheimer. Your line is now open.

[Matt Biegler:]

Congrats on the regulatory update. It seems like duration of follow-up is still somewhat of a wildcard here. But have you gotten any sense from your recent Type B about the size of the safety database that the FDA would want to consider for approval?

[Athena Countouriotis:]

Yes, I mean first of all, interesting in that the way the duration of follow-up conversation has gone with the agency. Historically, if you go back, of course, they discussed with us a minimum of 12 months of follow-up to support approval. And then that was the precedent that was used for ROS1/TRK. As you know, this is a unique asset in the sense that it received Breakthrough Therapy Designation in an indication where there are already two approved agents. And so with that led to this Type B meeting, and we're encouraged by the fact that the agency wants to review the dataset with us with less follow up. So what I can't say yet is will that dataset support registration, and that of course will be data dependent, and we've never looked at the blinded independent central review data from the Phase 2, but it is encouraging that the agency is willing to discuss with us, less follow up than the prior guidance. So with that said, I mean that's kind of the first way I would address it. From a safety database perspective, we have general benchmarks from Mohammad's history of taking drugs to market from my history of taking drugs to market from our ongoing conversations with the agency. And the way we built the TRIDENT-1 study of course, supporting safety not only just from the Phase 2, but also the Phase 1. We believe that we'll have a sufficient number of patients to support a safety profile. Now the exact numbers as to how many patients would be needed that would be discussed during the review.

[Matt Biegler:]

That makes sense. Maybe I can just follow up with a quick one on labeling and timelines. I appreciate the focus is obviously on ROS1. But any guidance, or when you might be in a position to guide on when you might be able to discuss like label expansion opportunities for the NTRK tumors?

[Athena Countouriotis:]

So, as you know, we have two cohorts within the TRIDENT-1 study now, right to the naive cohort as well as the pretreated cohort, we've already received Fast Track designation for that track pre-treated cohorts. We are now going to share our first data from our ongoing pediatric study that is enrolling TRK patients. So there will be more information coming not only to turn the study, but also we talked about that we plan on doing a clinical data update in the second half of the year as it relates to the TRIDENT-1 study. I think to your specific question, when will TRK go into the label with our first indication is based on ROS1. I can't predict that yet. Of course that will also be data dependent, and in discussion with the agency. But clearly, we've been having ongoing discussions with the agency because we've already received Fast Track.

[Operator:]

Next question is from the line of Zegbeh Jallah of ROTH Capital Partners. Your line is now open.

[Zegbeh Jallah:]

Thanks for the very nice update. Just have a couple of different questions. Yes, I think the first Athena, is about the Type B meeting. I think had mentioned perhaps discussion with the FDA, progress with your companion diagnostics. I was just wondering if you had any update on that? And then how that factored into your timeline?

[Athena Countouriotis:]

Yes. Thank you. And it's interesting Zegbeh I just, real as you probably have more difficulty with pronunciation of your name then I do. And I obviously always have issues. So I feel for you there. The feedback only go back to the conversations we've had with the agency over the last few years. And we had previously disclosed that we submitted for an investigational device exemption with CDRH and that was cleared, and that's kind of a standard first step as it relates to companion diagnostic development. We have already identified our partner for companion diagnostic development and we've been using our clinical trial assay in the study for prospective testing. So we've been doing quite a bit of work as it relates to the companion diagnostic. The discussion with the agency was really just in line with where we are today and what we need to do to support potential labeling in the future. And so that's what I would share as of now, but again we've had ongoing discussion with the agency and specifically the CDRH group.

[Zegbeh Jallah:]

And then on, for the TRIDENT-2 study, I'm just wondering if you're going to be enriching for specific tumor types. And are you planning to pursue some kind of label as you're thinking about dividing study?

[Athena Countouriotis:]

The TRIDENT 2 study, and so where we're starting right now is obviously with trametinib in G12D advanced solid tumors and we've said that this is a multi-cohort or multi-arm trial. So there may be other KRAS-driven indications are obviously others outside of G12D. You know, we've already done data with AMG510, and so whether we would add G12C arm in the future is something that we just haven't disclosed yet. But for right now, the focus is on initiating the trial. We're very happy that the IND cleared in combination so far with trametinib.

[Zegbeh Jallah:]

Thanks. And then just the last one here, regarding the pediatric CARE study. Just thinking about our model base, just want to know in terms of patient identification, is it similar to that policy? Are there any nuances that we should take into account?

[Athena Countouriotis:]

So, the one thing I would say about the pediatric trial remembering that this is still relatively rare indication. But unfortunately for many children that are diagnosed year with NTRK driven tumors, out driven tumors or even very rare ROS1 fiber sarcomas we have had a heterogeneous group that has enrolled. And so we're encouraged to share the first initial data from that study. And that's all we're ready to say today. But that will come in the second half of the year.

[Operator:]

Next question is from the line of Silvan Turkcan of JMP Securities. Your line is now open.

[Silvan Turkcan:]

Thank you for taking my questions, and congrats on all the progress and the Type B meeting. I have a question maybe big picture about your KRAS and the specific KRAS G12D strategy in the phase of that has some preclinical and KRAS G12D inhibitors. How can we think about the data that we may get? And what could be the strategy going forward with you then maybe switch partnering with those specific inhibitors, or would there always be a MET inhibitor, or a triplet or, how would that look like?

[Athena Countouriotis:]

Thank you first of all for the questions, Silvan. At this point given the IND just cleared, and we're looking forward to initiation of the trial, I think it's a little early to say where we'd be going in the future if we stay on the doublet, stay with a MEK inhibitor, or go to a triple TKI regimen. But I will say that our preclinical data that we've shown consistently over the last year and a half at multiple medical conferences, supports the rationale based on the synergistic effect to combine the two agents. And so that's where we're going to start the strongest depth of the dataset is MG12D and so that is where we're focusing first, and then again as we add more arms, hopefully to this trial you'll see where we're additionally going to go with potentially other doublets.

[Silvan Turkcan:]

And with respect to the MET inhibition to be - 022. There will be Phase 2 dose, if I understood correctly in the second quarter. Will you communicate that or will we find out and you do update in the second half of the year?

[Athena Countouriotis:]

We've talked about that. I mean we are evaluating obviously knowing that we want to define the dose this quarter. So we're evaluating where we are with pharmacokinetics, as well as ongoing safety. And this is an area where Mohammad's team is incredibly focused. The likely scenario is, we'll move right into dose expansion cohorts as we've outlined in the prepared remarks. And then potentially discuss our recommended Phase 2 dose on our next quarterly call.

[Operator:]

Last question is from the line of Arlinda Lee of Canaccord. Your line is now open.

[Arlinda Lee:]

Congrats on the regulatory discussions. I have a couple of questions. One on the TRIDENT-2 combination. You just announced that IND has been cleared for the first combination. Can you talk about what constitutes an interesting combination for you, or additional combinations? And how many of these might you undertake?

[Athena Countouriotis:]

First of all thank you, Arlinda for the comments about the regulatory discussions. As it relates to TRIDENT-2 at this point, we're focused on initiating the trial with trametinib. That's the design that went to the agency to support IND clearance. Future cohorts again without saying too much as you've seen, we've shown data with two MEK inhibitors, both trametinib as well as their Verastem-6766 agents and then we've also showed data with AMG510. We have publicly said that we've also compiled more data with other G12C inhibitors. I will say this is one of the strengths of Siegfried and his entire group that has been growing tremendously on the translational front, as well as Cancer Biology front, really looking at the science to dictate where we should go in these combinations. And so to some extent, I would just say how we are going to determine where we go next will absolutely based on the preclinical data. And at this point, Arlinda that's probably all I'll say until we start moving the trial towards patient dosing and then adding additional cohorts.

[Jim Mazzola:]

Thanks, operator. Any other questions?

[Operator:]

No further questions.

[Athena Countouriotis:]

Okay. Well, first of all, thank you again for everybody who dialed in today for your interest and support of our team and for Turning Point Therapeutics as a whole. I hope you and your families continue to stay well. And operator, you may now close the call. Thank you very much.

[Operator:]

And that concludes today's conference. Thank you all for participating. You may now disconnect.