Turning Point Therapeutics Inc (TPTX) 2020 Q4 法說會逐字稿

Ladies and gentlemen, thank you for standing by, and welcome to the Turning Point Therapeutics Fourth Quarter 2020 Conference Call. (Operator Instructions) I would now like to hand the conference over to your speaker today, Mr. Jim Mazzola, Head of Investor Relations. Thank you. Sir, please go ahead.

Okay. Thank you. Good afternoon, everyone. Following market close today, we filed our Form 10-K and issued a news release with a summary of our results for the fourth quarter and full year 2020. We also updated our investor presentation, and you may find these documents posted on the Investor pages of tptherapeutics.com.

Leading the call today will be Turning Point's President and Chief Executive Officer, Dr. Athena Countouriotis, who will provide an overview and update of our business results. Athena's remarks will be followed by a review of our financials by our CFO, Yi Larson. We will take questions following our prepared remarks. The 3 of us are in separate locations today, so please bear with us as we manage the call remotely.

Before Athena begins, I want to remind you that during this conference call, we will be making forward-looking statements. The company's actual results may differ materially from those expressed in or indicated by such forward-looking statements. And for a description of risk factors associated with investing in Turning Point Therapeutics, please refer to our recent filings with the Securities and Exchange Commission.

Now let me turn the update over to Athena.

Thank you, Jim, and good afternoon to everyone joining us on today's call. Today, I want to briefly recap our progress in 2020, share a number of updates across our programs and focus on our goals for 2021.

Overall, we continue to make progress in developing our 4 internally-discovered, 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 and investments we have made are all directed towards advancing our vision to be the leader in precision oncology.

Starting with our lead program, repotrectinib in 2020 and January 2021, we reported encouraging preliminary data from our registrational Phase II TRIDENT-1 study. Repotrectinib is a next-generation ROS1 and TRK TKI with greater than 90-fold higher preclinical potency than crizotinib and greater than fiftyfold higher preclinical potency than entrectinib against wild-type ROS1. Repotrectinib has been granted several key regulatory designations, including breakthrough therapy designation in the United States for the treatment of patients with ROS1 positive, TKI-naive metastatic non-small cell lung cancer.

To recap our clinical data updates, which we believe support a potential best-in-class profile. As of a December 31, 2020 data cutoff date, in 15 ROS1 positive TKI-naive advanced non-small cell lung cancer patients who had at least 2 post baseline scans in Phase II portion of the TRIDENT-1 study. The confirmed objective response rate by physician assessment was 93% or 14 of 15 patients with a 95% confidence interval of 68 to 100.

At the time of the data cutoff, the one nonresponder remained on treatment with a 13% tumor reduction. In 22 patients pulled from the Phase I and Phase II portions of TRIDENT-1, the confirmed overall response rate was 91%, with a 95% confidence interval of 71 to 99. For historical reference, both Xalkori and Rozlytrek are approved in this patient population, with confirmed overall response rates of 66% and 67% by Blinded Independent Central Review, respectively.

Equally important is the duration of treatment and in the pool Phase I patient. The duration of treatment ranged from 10.9 to 37.3 months with a median of 30.9 months, which we find encouraging, given it compares favorably to the published data for Xalkori with a median duration of treatment of 22.4 months.

Turning to the preliminary safety profile. As of an October 30, 2020 data cutoff date, in a total of 185 patients in the Phase I and Phase II portions of the study, repotrectinib was generally well tolerated. In addition to the recent update from our ROS1 positive TKI-naive non-cell lung cancer patients within TRIDENT-1, last August in 2020, we reported early encouraging data from multiple other cohorts of the Phase II TRIDENT-1 study in TKI pretreated patients with ROS1 positive non-small cell lung cancer or NTRK positive solid tumors. We look forward to sharing more data from the ongoing TRIDENT-1 study in the second half of this year.

I want to now share an enrollment update. First, we continue to be pleased with enrollment in patients with ROS1 positive TKI-naive non-small cell lung cancer, which is cohort 1 of the current study. In the second quarter, we now anticipate reaching 50 patients pool from the Phase I and Phase II portions and plan to discuss next steps with the FDA during a Type B meeting, which was requested based on our recent Breakthrough Therapy Designation being granted. We hope to be in a position to discuss our path to potential registration following this meeting.

As it relates to the other cohorts of the study, we continue to steadily enroll patients in the TKI-pretreated ROS1 positive and NTRK positive cohorts. And it is our goal to provide an enrollment and clinical data update in other cohorts of the TRIDENT-1 study in the second half of the year.

In addition to our development of repotrectinib in the TRIDENT-1 study, our team continues to make progress towards the planned initiation of the first cohort of our multi-arm TRIDENT-2 combination study in mid-2021. This planned Phase IB/II study in KRAS-mutant solid tumors is based on repotrectinib inhibition of JAK2, SRC and FAK, which is believed to suppress STAT3 and AKT signaling, known mechanisms of oncogenic resistance. We will provide further details of the study design closer to initiation and plan to present additional preclinical data, highlighting repotrectinib's combination potential in KRAS-mutant disease at an upcoming medical conference in the second quarter.

Next in our pipeline is TPX-0022, our MET, SRC and CSF1R inhibitor, currently being studied in our ongoing Phase I SHIELD-1 study in patients with advanced solid tumors harboring genetic alterations in MET. MET-driven cancers represent a heterogeneous population across multiple tumor types, as was reflected in our early clinical data update last October. While there are now 2 therapies approved for MET exon 14 skipping non-small cell lung cancer, we continue to believe we have the potential to expand the development of 022 and focus on MET amplified non-small cell lung cancer, both as a single agent and in combinations as well as GI tumors. Additionally, we believe there is room for improvement in the exon 14 space, given the limited duration of response and safety profile of the 2 approved agents.

As a reminder, our preliminary data update last year showed objective responses across multiple tumor types with a generally well-tolerated safety profile in a heavily pretreated patient population. The Phase I study continues to enroll patients, including those with MET amplification and MET exon 14 skipping alterations. Similar to how we approach the Phase II dose for repotrectinib, we are evaluating multiple doses and schedules for 022 to further characterize the pharmacokinetics, safety and efficacy profile before determining a recommended Phase II dose.

We are currently enrolling patients in the Phase I dose-finding portion of SHIELD-1 with the goal of selecting the recommended Phase II dose in the second quarter. After which, we anticipate proceeding directly into the Phase I dose expansion in multiple patient cohorts. The dose expansion will include select patient populations, including patients who are both TKI-naive or TKI-pretreated.

We have multiple updates anticipated in the second half of this year in our 022 program, including an additional clinical data update from the Phase I dose-finding portion of SHIELD-1, a planned discussion with the FDA to potentially modify the SHIELD-1 study into a registrational Phase I/II design, initiation of the Phase II portion of the study pending FDA feedback, and finally, initiating our combination study with an EGFR targeted therapy.

Lastly, I want to highlight that in January, we signed our second licensing agreement with Zai Lab. Similar to our licensing agreement for repotrectinib, the latest agreement included rights for Zai Lab to develop and commercialize 022 in Greater China. There is a significant unmet need in MET amplified cancer in China, particularly in gastric cancer, where 40% of the world's cases are diagnosed and are often advanced at the time of diagnosis.

Next in our pipeline is our RET inhibitor, TPX-0046. 0046 has demonstrated preclinical potency against wild-type RET and RET solvent front mutations. In the dose-finding portion of our ongoing study, we continue to evaluate multiple doses and schedules to further characterize the pharmacokinetics' safety and efficacy profile. We plan to provide a preliminary data update in the second quarter, which will focus primarily on safety and any early signals of efficacy from initial patients. We anticipate approximately 15 to 20 patients across multiple doses in this data update.

Lastly, in our pipeline is TPX-0131, our fourth drug candidate. Patients with ALK-positive disease comprise approximately 3% to 5% of non-small cell lung cancer, and sales of approved therapies were estimated to be approximately $2 billion globally in 2020. While there are several ALK inhibitors currently approved, we believe TPX-0131 could have great potential initially in TKI-pretreated patients.

Lorbrena is the current standard of care in this setting, yet 0131 is considerably more potent preclinically against many clinically observed resistant mutations, including with sub nanomolar potency against the most common G1202R solvent front mutation, L1196M gatekeeper mutation and multiple compound mutations. TPX-0131 has been designed with a compact macrocyclic structure. And in preclinical in vivo studies, has shown significant brain tissue penetration after repeat oral dosing, supporting its potential to cross the blood-brain barrier in humans. We are excited to have already received approval by the Australian Ethics Committee and plan to submit our IND to the FDA later this month and anticipate initiating our Phase I/II clinical study in the second quarter. We also look forward to presenting additional preclinical data highlighting the profile of 0131 at a medical conference in the second quarter.

Now let me turn the call over to Yi for an update on our financial results.

Thank you, Athena. You will see in our press release and financial tables that operating expenses for the fourth quarter totaled $47.9 million compared to $23.1 million in the fourth quarter of 2019. The $25 million increase was driven by a $17 million increase in R&D expenses and an $8 million increase in G&A expenses. Increased expenses were attributable to the investments we made to develop our pipeline in earlier stage discovery and in personnel.

For 2020, operating expenses totaled $186.8 million compared to $77.7 million in 2019. The $109 million increase was driven by a $55 million increase in R&D expenses and $54 million increase in G&A expenses. Excluding a onetime noncash stock-based compensation charge from the first quarter of 2020, non-GAAP operating expenses increased by $78 million driven by investments made to develop our pipeline in earlier stage discovery and in personnel.

Net cash used during the year totaled $82.8 million. Recall, we recorded $25 million in revenue during the third quarter from the Zai Lab licensing agreement for repotrectinib in Greater China. This revenue partially offset cash used during the year.

Cash, cash equivalents and marketable securities at December 31 totaled $1.1 billion compared to $409.2 million as of December 31, 2019. The increase was driven primarily by net proceeds from our 2 follow-on public stock offerings in May and October of $351.6 million and $433.9 million, respectively, partially offset by cash used in operating activities.

Looking ahead to 2021, we continue to expect expenses will increase during the year as we execute across now 4 pipeline programs, initiate 3 new clinical trials and make investments in our earlier-stage discovery efforts. We continue to project our cash position funds current operations into 2024.

Now I will turn the call back to Athena.

Thank you, Yi. To close, I will summarize our goals for 2021, beginning this month with our anticipated submission of the IND for TPX-0131, our novel ALK inhibitor. We have a busy second quarter expected with anticipated milestones, including reaching enrollment of 50 patients in cohort 1 of the TRIDENT-1 study and discussing next steps towards registration in this population with the FDA. In addition, reporting early interim data for TPX-0046, initiating the TPX-0131 Phase I/II clinical study and multiple pipeline presentations at a medical conference.

Moving on to midyear. We expect to initiate the first cohort of our TRIDENT-2 combination study. And in the second half, we anticipate providing an enrollment and clinical data update in other cohorts of the TRIDENT-1 study, providing a clinical data update from the Phase I portion of the SHIELD-1 study and initiating the Phase II portion of the study, initiating the SHIELD-2 combination study; and finally, outlining our research strategy, including our focused and anticipated time line to development candidates.

With that update, we are now ready to take your questions. Before we do, I want to close by thanking our great and growing Turning Point team for all they accomplished in 2020. We are looking forward to another great year in 2021.

Operator, you may now open the line for questions.

(Operator Instructions) We have your first question from Michael Schmidt of Guggenheim.

Athena, I had one on repotrectinib, but maybe more specifically around the ROS1 market. And maybe I was just wondering if you could maybe share from your experience in rolling a TRIDENT-1 study, what you're seeing at the moment in terms of what percentage of patients is actually receiving an approved ROS1 TKI versus being treatment naive. It seems like your TKI-naive cohort is enrolling pretty quickly here. Just wondering if you could comment on that and then I had a follow-up as well.

Yes. Michael, I'm happy to do so. So our belief is that the ROS1 market remains at approximately 2% of non-small cell lung cancer. And I will say we've gone through with the leadership of our Chief Commercial Officer, a very large market research campaign internally to help prepare us for hopeful potential registration and commercial launch for repotrectinib. And it does appear that at least in the United States that crizotinib is still the standard of care. I think there's been very little change in the annual sales for crizotinib year-over-year. That said, the uptake of Rozlytrek appears to have modestly improved, but I still would say that it's a modest launch at least a year now into its commercial opportunity. That said, as it relates to enrollment for our trial, definitely, we are the most pleased in that our cohort 1 has exceeded our initial projections despite the competition. Obviously, that's in the commercial landscape. So that's why we've been very much focused there. Of course, we've gotten Breakthrough Therapy Designation there, and now moving as quickly as we can to the Type B meeting with the FDA..

Great. And then on TPX-0046, your RET inhibitor, you obviously have activity against solvent front mutations. And I was just wondering if there any other characteristics that could potentially address potentially shortcomings of currently approved RET inhibitors? And how investors should be thinking about the upcoming Phase I update in terms of interpreting the data and then we'll get there?

So as it relates to 046, what we've consistently shown is that it is equally potent to the other 2 molecules based on our preclinical studies in the wild-type setting. And again, as to the point you mentioned on solvent front mutations that 046 is more potent, specifically against certain solvent front mutations. That said, we don't -- we have very limited information as it relates to the prevalence of those mutations. But clearly, we have been enrolling patients to not only our TKI-pretreated, but also have solvent front mutations as well as patients who are TKI naive. The trial has essentially been enrolling for approximately a year on a standard 3 by 3 design. Where we are today is continuing to evaluate additional doses and schedules. We try to guide today to anticipate similar to what we did with the MET program of the mid-teens, and we estimated 15 to 20 patients in the initial update. But we've been consistent in saying that the first update really will focus predominantly on safety as well as any early signals of efficacy across multiple doses.

You have your next question from Paul Choi of Goldman Sachs.

This is Corinne Jenkins on for Paul. As you think about combination studies of repotrectinib in KRAS mutant solid tumors, can you just talk about where you see the clinical hurdle for combination programs in -- especially given there's a lot of development in that area these days?

Yes. Corinne, please say hello to Paul for us. So the first thing I would say is we've been very pleased with the progress we've been making, not only within the combination preclinical datasets that we've been developing around repotrectinib but towards initiation of the trial. We gave a little bit more information today to highlight that this is going to be a multi-arm trial. We will initiate the first cohorts in the middle of this year. Our goal obviously is to submit the IND relatively soon to enable that. And we don't typically give too much guidance as it relates to trial design until our INDs are submitted and ultimately filed. But we do have more data coming at a medical conference in the second quarter, and I'm sure you can anticipate which conference that is to support this. And I think much of the data we've shown so far is in combination with AMG 510 in the G12C setting. We've also shown data with trametinib in the G12C setting. So without trying to forerun too much on what we think the clinical hurdle will be, I think it will be important for us to show you the design as it relates to which combination partner we're using and then we can start talking in terms of what we hope to anticipate showing as it relates to response rate, duration and safety.

Okay. That's fair. And then as you think about the upcoming Type B meeting, could you just talk a little bit about the key questions you'd like to get answered and kind of where you'd like to be exiting that conversation?

Yes. So of course, the Type B meeting is exclusively focused on cohort 1, which is our ROS1 TKI naive population, and that's because this meeting was requested in the context of Breakthrough Therapy Designation. And while it's not a pre-NDA meeting, we do have an extensive briefing document that we'll outline our preliminary clinical pharmacology studies, our CMC plans, our companion diagnostic plans and the patient population. And inevitably, I think the key component here is to try to get some guidance and potentially clarify regulatory path for cohort 1 as it relates to number of patients and/or follow-up.

As you know, we designed the trial to mirror crizotinib and entrectinib, which had essentially 50 patients in their initial applications, and our current guidance is that we will have 50 patients in the second quarter. So there are quite a few questions we hope to get answered. I will say I've been trying to be conservative here in saying that this is the first meeting since having BTD. So it's a preliminary discussion, and you obviously don't have as much until you have the pre-NDA meeting. But I do think any additional information we can receive in terms of regulatory clarity will be very helpful at this point.

Your next question from David Nierengarten of Wedbush Securities.

It's a little bit of a follow-up to the previous one, which is when you think about potential combinations, KRAS and AMG 510 is one, you mentioned trametinib. Kind of maybe if you wanted to elaborate a little bit on your strategy for expanding the reach -- the potential reach here. I mean are you kind of planning to have kind of a multi-pronged approach? Are you just looking at these first 2 and kind of progressing to approval eventually and then looking at additional combinations? I'm just kind of curious as you think about sequencing potential combination studies, kind of what your priorities are and what that might look like over the medium-term of, let's say, a couple of years from now.

Yes David, so let me just start with repotrectinib because, obviously, this is a year where we're going to initiate 2 combination studies. The first to repotrectinib, again, is trying to take advantage of the fact that it also has strong potency against JAK2, SRC and FAK, which, as I mentioned in the prepared remarks, do suppress STAT3 and AKT signaling. So the goal here is in a KRAS pathway to try to hit bypass resistance multiple ways.

What we've shown publicly so far and again, trying not to jump too much of a medical conference that's coming, we have more data coming in our combination strategy. But what we have shown previously is with AMG 510 and G12C setting and trametinib. We do have more data with other G12C inhibitors. We do have more data with other MET inhibitors. And so right now, all we are publicly guiding to is that the initiation of this trial will occur in the middle of 2021, pending FDA filing, and that it will be a multi-arm approach, and how many drugs will be a part of this trial is still to be determined. The trial will initially start in KRAS mutant solid tumors and then potentially narrow down into a non-small cell lung cancer and/or colorectal or pancreatic cancer setting, but that's all still, again, to be determined. And I'm sorry that I can't give too much more, that's just kind of against our standard practice.

That's fine. It's a competitive space, I know.

Your next question from Matt Biegler of Oppenheimer.

I had a question going back to the SHIELD trial eligibility. It's one I get inbounds on. So for MET amplified patients, did you exclude copy number locations, I think, similar to what we've seen in some of capmatinib's recent data?

No. And thanks for the question, Matt. So just as a reminder, thanks for fielding questions, of course. The Phase I SHIELD-1 study essentially is in trial that's open to all MET alterations. And so this, by far, has the majority of patients with non-small cell lung cancer. But as you saw from our update last fall, we've enrolled multiple GI tumors, whether it's gastric cancer, hepatocellular, colorectal. I can tell you, we're continuing to enroll other cancer types, including GYN tumors. And so it's open irrespective of gene copy number for MET amplification. It's open to exon 14 mutations, of course, and then it's also open right now to kinase domain fusions.

As we move towards the recommended Phase II dose, which we're anticipating now will be within the second quarter and move directly into Phase I dose expansion, this is where we'll narrow down the patient population into select cohorts. We may, at that time, change the criteria to have a cutoff, to your point, on gene copy number. We have not made that determination yet. But we will, for sure, decrease the amount of prior chemotherapy.

For the lung cancer MET amplified patients that were enrolled in the initial update that we gave last fall, the median was 3 prior therapies. But again, these patients had more like 4, 5 rounds of prior chemo and/or immunotherapy. So those are the patients that will now potentially be excluded from the expansion. But no is the answer to your question, we did not exclude patients based on gene copy number.

Great. That's really encouraging. Maybe just a quick follow-up, if I may. Just something more on broad strategy here as you think about expanding the pipeline. Do you foresee focusing exclusively on macrocyclic scaffolds in the future? Or are you thinking about being more agnostic to really any type of structure or type of TKI?

Thank you for the follow-up. I think the company, obviously, at this point, is very well-known for our 4 drug candidates that all came off of the initial macrocyclic scaffold. I can tell you, our Chief Scientific Officer, Siegfried, has been not only mining that, but also looking at other opportunities when he is evaluating targets for future development candidates. So right now, I would say that we do plan on continuing to evaluate our current macrocycle scaffolds, but I would also not be surprised if we were to go down a slightly different path. But with the same idea of trying to maintain low molecular weight as well as highly potent potentially best-in-class and/or first-in-class drug candidates.

And congrats on the progress.

You have your next question from Nick Abbott of Wells Fargo.

Thank you very much for a very robust update. Maybe just a quick question on 131. You indicated that this molecule has good brain penetration. And it looks like on corporate deck that you're allowing patients in with asymptomatic brain metastases. Do you think you'll see more of those kinds of patients given the CNS penetration with this molecule and perhaps typical for a Phase I trial?

Well, thanks for the question, Nick, and congratulations for you. I would say one thing. First of all, let me just start. I'm excited about the ALK inhibitor because I think in many ways, it mirrors repotrectinib the most when I look at our pipeline. It is not only very potent in the wild-type setting, and what you see on that corporate deck is somewhere between ten-and thirtyfold more potent than the second-gen TKI, which you would say, alectinib is the standard of care. Equally, we're getting over hundredfold more potents for G1202R. So again, it's a similar story to what you saw with repotrectinib. And again, of course, repotrectinib had CNS penetration.

So I don't know if the patient population will be skewed in that direction. Initially, what you see on the slide, we gave a little bit of information on the trial design is that we will limit down the number of prior TKIs and chemotherapy. This is all up for FDA discussions, though, of course, because the IND has not been submitted. But I don't know specifically which patients we will see in terms of CNS disease or not. I will say that we are hoping to go through dose escalation as quickly as possible. We didn't give too much guidance yet, but the goal is to try to use some type of a single patient dose escalation and go as fast as we can to get to NCD.

Okay. And then maybe just a follow-up on that when you think about the TRIDENT-2 combination study, I mean how potent JAK2 inhibitor is repotrectinib? And part of the question relates to the fact you do see anemia as Grade 3 treatment related to adverse event is that related to JAK2? And then for all of JAK2 and interferon gamma mediated efficacy and that's PD-1 resistance. So is there a concern that it could be potent and interfere perhaps with potential PD-1 combinations?

Yes. First of all, it's a fair question. Let me maybe back step on the anemia component first, and then I can go to the potency. So one thing we've seen with the initial data center, remember, for our safety profile, which we showed in January of 185 patients, about half of that was coming from the Phase I. And remember, of the Phase I, about 1/3 came from heavily pretreated ALK patients. So the majority of patients were -- that had anemia came in not only with some type of baseline low hemoglobin, but also were heavily pretreated ALK patients.

When you look at the in vivo -- excuse me, the in vitro potency data we have for ROS1, of course, we're sub 1 nanomolar. And for JAK2, we're about 1 nanomolar. So it is not as strong as a JAK2 inhibitor, obviously, as it is as a ROS1 inhibitor, but still incredibly potent. So we'll have to see in terms of the translation into the clinic to your point of JAK2 inhibitors being unfortunately prone to anemia.

We have your next question from Zegbeh Jallah of ROTH Capital Market Partner.

The pace have been really good. I wanted to start with repotrectinib. I just kind of wanted to know how much data do you think you'll have at the time of your Type B meeting? I know you talked about having data on 50 patients. But what perhaps be the minimum duration of follow-up at the time of the meeting? And then are we likely to expect an NDA initially on cohort 1 and then the other cohort to follow label expansions?

Zegbeh, thanks for the question. So we're putting the briefing document together now, so I can't give too much information as it relates to the duration of follow-up. What I do feel comfortable saying is the FDA will be seeing slightly more data than what you've seen from World Lung. But again, the follow-up to me is not the more important component, it really is where we are with response rate, confidence interval, duration of response and the overall safety profile. So the totality, the follow-up, of course, will be important as we get closer to NDA submission.

Regarding to your second question, at this point, we can't predict where we will be in terms of what indication will go in first because, to some extent, that will be dictated by the conversation we're going to have with the Type B for frontline. But we are pleased with the way that the other cohorts are enrolling as well. So more to come. Of course, the Type B meeting is in second quarter, and pending minutes, we will give guidance as to the outcome of that call.

And then the next one for me is just about how helpful has Zai been in terms of broad recruitment across TRIDENT-1? And then it does seem, from my perspective, at least that the partnership for 0022 did happen a little bit sooner. So I was just wondering, are they going to be a lot more involved with the clinical development of that program.

My apologies, Zegbeh, it might be the Polycom on my side in the office here. I couldn't hear the first part. I heard the second part as it related to 022. Was there a first part of your question?

Yes. The first part was just about how helpful has Zai been in terms of broad recruitment for TRIDENT-1 so far.

Okay. Understood. Thank you. So Zai Lab reported this morning, and they announced that they will be participating in TRIDENT-1 in the first half. So where I would say that they've been incredibly helpful is not only helping us understand more the market in their region, which obviously, they are the experts, in my opinion, in that region, and getting us prepared to initiate the trial within Greater China. And that's what I can say as it relates to repotrectinib.

You're right in that the 022, I think I heard your second part, you're right in the 022 collaboration was signed earlier in that we had less patient data. But remembering that when we originally signed with Zai Lab, they did have a right of first negotiation for other assets within the pipeline. So it was always my thought that if the MET data was encouraging, especially given the prevalence of gastric cancer within China that, that would be a collaboration that could benefit us both. So I was not surprised in any way that, that one was signed with much less clinical data. And I think if you were to speak to Samantha, I think she would also say, I've been on calls with her recently, that it was also a testament to how she's seen the team deliver. So I don't know if I can predict too much in terms of faster pace of additional collaborations. Of course, we maintain worldwide rights for the other assets in the pipeline.

You have your next question from Silvan Tuerkcan of JPM Securities (sic) [JMP Securities].

Congrats on the quarter. I see that you talked about initiating SHIELD-2, the combination study of TPX-0022 with EGFR in the second half of this year. Could you tell us if this could also become a multi-arm study similar with repotrectinib where -- with TRIDENT-2, where you could actually add a couple more compounds to this? And also, what are your objectives for the EGFR combo in terms of the setting and tumor types you're looking for?

Well, first, thanks for the question. I know you're not at JPM. You're at JMP. So I'm sure that gets unfortunately done quite often. Sorry for you. Unfortunately, it's not our standard practice to give too much in terms of trial design prior to IND submission, and my approach is really until IND filing by the FDA. So I think you're right on track with our thoughts in terms of there are potentials for multiple EGFR inhibitors to whether they're bispecifics or TKIs to include in a MET combination we just haven't given that guidance yet.

And that unfortunately also segues to the second part of your question of whether we'll be using this in patients who have already progressed or frontline, we haven't given that guidance yet. But again, as the study gets closer to initiation and IND clearance, we will give more in terms of the study design.

Great. And then maybe more of a hypothetical question for your KRAS strategy. What do you think is the best way these days to develop KRAS combo? There are multiple companies out there with KRAS, and they have multiple combinations. Would you eventually want to have a firm strategy or partnership? Or do you think it would just be development side by side with multiple KRAS compounds? What do you think is the best strategy?

Well, I would just speak to the data that we have currently, which, of course, is with one of the 2 G12C inhibitors that's what we've shown publicly in the preclinical setting and one commercially available MEK inhibitor. Again, all I can say at this point is that we are already saying now that our trial will be multi armed. So you know that there will be more than just one drug that we're combining repotrectinib with. We're just not saying yet which. I do think that there's lessons to be learned with the SHP2s and others that are currently ahead of us, taking slightly different approach potentially on a different pathway. Of course, we're not targeting SHP2 or targeting JAK2, SRC and FAK. But really much more to say about this trial design once the IND is filed.

We have our last question from Arlin Lee of Canaccord.

Congrats on the progress. I had maybe a follow-up question on your FDA meeting. Considering you -- I think FDA saw less than a dozen patient worth of ROS1 naive patients when they granted the breakthrough designation. And now that you have 50, I'm curious, you talked -- I'm curious what exactly are you guys looking for from their feedback. Is there -- or what gating do you think is to filing. I know you want to be conservative ahead of chatting with them. But is there a durability question, do you think? Do you think you might need additional patients? And are those sites continuing to enroll native patients?

Let me make sure I heard the last part. What was your last part? Arlinda, I'm sorry, you were tailing off something about enrollment.

Yes. Are you continuing to enroll TKI naive patients, a ROS1 TKI naive patients?

Sure. So let me respond to the first part. I mean, first of all, looking at small sample sizes, of course, as each of the data updates have come, hopefully, you've seen specifically from last August, where we only have the 7 patients to the most recent update, a tightening of the confidence interval and specifically the lower bound. And that's important, and so I think that's an important component to bring to the FDA.

But also at the same time, just as a background. Receiving Breakthrough Therapy Designation in December of last year, the FDA asks us to have a Type B meeting within 6 months. And so this is really now the opportunity for us to discuss with the head of the division our overall path, and that includes, as I said, much more than just the number of patients. It's where we are with our clinical pharmacology studies, healthy volunteer studies, DDI studies, hepatic impairment studies, CMC, where we are with our formulations, where we are with our companion diagnostic and, of course, where we are in terms of the patient data. So there is quite a bit to get initial feedback from because remember, at this point, we've had an end of Phase I meeting with the agency, and we had a Type C meeting last August, which was focused more on the pretreated and follow-up and pooling of Phase I and Phase II patients. So this level of conversation that we're going to hopefully have is much more than we've had before. And so it's an important meeting for much more than just the number of patients or duration of response.

As it relates to the key question for NDA timeline, that's important just to really understand is there any difference from the prior guidance, which is the guidance they've given us to date is that approximately 50 patients with a minimum of 12 months of follow-up has the last responder to support standard approval. That's a key question for us to try to understand if there's any difference there as well based on our emerging data. But it's a much bigger meeting than just discussing number of patients, duration of response, et cetera.

Great. That's super helpful. And then on the enrollment of continuing to enroll naive?

Apologies. Yes, I'm sorry, I didn't answer that. That's -- I'm sorry. So we -- I mentioned in January, we had approximately 40 patients. We have guided that in the second quarter, we anticipate we will have 50 patients. And I've also recently said that even after we get to the 50 patients, we will continue to enroll TKI naive patients, especially to help benefit our partner in Zai Lab, who obviously are coming into the trial at a time where we're getting close enrollment completion within cohort 1. So we will, yes, continue to enroll, and that's also important. If you look at all of the precedent with the approved 2 RET inhibitors and the 2 approved MET inhibitors as well as Rozlytrek, all 5 of those approvals, there were more patients and more follow-up that the agency required in the context of their approval letters, and so that will be something we will also mirror.

And speakers, so it would be our last question for this call. Turning back over to Ms. Athena.

Thank you very much, operator. Thank you, everybody, for dialing in today, and of course, for your interest and support of Turning Point Therapeutics. I hope that all of you and your families remain safe and continue to stay well. I was incredibly happy to see many of our employees today in the office. And I will just say personally, I can't wait to hopefully see all of you face-to-face in the near term. Operator, you may now close the call. Thank you very much.

Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you all for joining. You may now disconnect.