Turning Point Therapeutics, Inc.
Q1 2020 Earnings Call Transcript

Published: 12 May 2020

[Operator:]

Ladies and gentlemen, thank you for standing by, and welcome to the Turning Point Therapeutics' First Quarter 2020 Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation there will be a question-and-answer session. I would now like to hand the conference to your speaker today, Jim Mazzola. Please go ahead, sir.

[Jim Mazzola:]

Good afternoon, everyone. Following market close today, we filed our Form 10-Question, and issued a news release with a summary of our results for the first quarter of 2020. We also updated our investor presentation. 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 today. Before I begin I want to acknowledge how incredibly challenging this past quarter was for so many in our society, and especially thank each and every one of the dedicated healthcare providers who have made so many sacrifices these past few months for the health and wellbeing of patients worldwide. Despite the challenges, we have remained focused on our goals to bring meaningful therapies to patients in need, while navigating the rapidly evolving situation with COVID-19. I am incredibly proud of the progress our team made during the quarter, and pleased to now provide an update on the quarter, and our response to the pandemic. For anyone new to our story, at Turning Point we have internally discovered and developed our wholly owned pipeline of next-generation tyrosine kinase inhibitors that target numerous genetic drivers of cancer. Today, we have four active development programs with the potential to address up to 15% of the targeted therapy opportunity in advanced non-small-cell lung cancer if each of our drug candidates are utilized as single agents, starting with repotrectinib, and specifically the TRIDENT-1 Phase 1 study. In the first quarter, we remained pleased with the rate of global site activations, with approximately 50% of our sites now activated across 11 countries. This includes the majority of our U.S. sites and key sites in Europe and the Asia-Pacific region.

[Yi Larson:]

Thank you, Athena. You will see in our press release and financial tables that operating expenses for the first quarter were $62.6 million, and included one-time non-cash stock-based compensation expense of $31.4 million associated with modifications to the vesting of existing stock option grants as a part of the transition agreement of the company's scientific founder. Excluding this one-time item, non-GAAP operating expenses in the first quarter totaled $31.2 million, compared to GAAP operating expenses of $14.1 million in Q1 of 2019 and $23.1 million in the fourth quarter of 2019. Primary drivers of the year-over-year increase were investments made to develop repotrectinib and the rest of our pipeline, including the headcount we have added. Reported operating expenses included a total of $38.4 million in non-cash stock-based compensation expenses, primarily comprised of the $31.4 million one-time items. We continue to expect expenses in 2020 will increase as we execute across four clinical trials for a three clinical stage assets and make investments to develop our health program and earlier stage discovery efforts. Net cash use during the first quarter was $28.4 million and our cash, cash equivalents and marketable securities at March 31st were $380.8 million. We project our cash position will fund current operations into 2022. With that brief update, I will turn it back to Athena.

[Athena Countouriotis:]

Thank you, Yi. To close, I will summarize our goals for the year, which are advancing enrollment in each of our clinical trials. The extent of the COVID-19 impacts on our clinical trial enrollment and data collection will depend on the duration of the pandemic. This is a clear area focus for our team, presenting a preclinical update for TPX-0046 at the virtual ASCO meeting on May 29, presenting our preclinical repotrectinib combination data, and our preclinical data for TPX-0131 at the virtual AACR meeting in late June, providing an update of early interim data from initial patients in the TRIDENT-1 Phase 2 study during the second-half of the year, potentially in the third quarter. We anticipate this update will include preliminary efficacy and safety data from approximately 30 to 40 patients across multiple Phase 2 cohorts, including registration and exploratory cohorts, providing interim data from initial patients treated with TPX-0022 during the second-half of the year, and advancing TPX-0131 towards IND submission, which we anticipate in early 2021.

[Operator:]

Thank you. Our first question comes from Paul Choi with Goldman Sachs. Your line is now open.

[Corinne Jenkins:]

Hi, this is Corinne Jenkins on for Paul. I was wondering if there's anything you'd point out on the label approved last week, and whether you see any potential impact to the ongoing enrollment in your study of 0046 with the availability of an approved product ?

[Athena Countouriotis:]

Hi, Corinne, thank you for the questions. I hope everything's okay with you and your family. Last week was a busy week, obviously with two approvals in the targeted oncology space. I think we all anticipated the approval of capmatinib orrepotrectinib you've outlined. I think I've consistently always said that I think it's a very good drug. I think those that may have detected changes as it relates to duration of response and/or warnings and precaution information, I'll leave that debate to them, but we've always been focused on how our drug differentiates. I think one of the ways, it clearly differentiates is also its selectivity as it relates to SRC and potentially to the safety components that we do not hit the VEGF3 and specifically VEGFR2, so there may be areas that we can differentiate versus the warnings and precaution labeling. As it relates to the impact, one of the things that we were incredibly pleased with through the first quarter, as well as moving into the second quarter, is how our Phase 1 studies have progressed. I think that's a testament to not only again the way that our molecules hopefully differentiate, which goes beyond just 046, but also that we have a global setting for our MET inhibitor and for that Phase 1 study, and also multiple sites for the RET program that you're asking about. So, an overall impact for the future is hard to predict, I think, equally as we've outlined from the duration of the pandemic, but so far we've been very pleased with enrollment for not only the RET program but our other Phase 1 studies, which include the MET.

[Corinne Jenkins:]

Great, thank you. And then I would imagine that conferences, like the ASCO and AACR time for you to connect with KOLs that become involved in clinical trials, and I was just wondering if you could talk about how you're kind of maintaining some of those touch points given the shifts to a lot of virtual engagements?

[Athena Countouriotis:]

One of the things I would say is many of the KOLs have also unfortunately been adapting to the new environment and have been at home much more than they would have normally been, and so, I've been just as much online with some of the KOLs who might have been more focused on clinic in the more recent past. So I really don't believe that any engagement has changed, at least from my perspective or, obviously, Mohammad, our CMO, has been incredibly engaged across all of our four ongoing programs. I think to your point, that you're right; it's unfortunate that we don't get the face-to-face for many of the major medical conferences. But I don't think in any way that it deters or distracts us as it relates to trying to connect with our key investigators as it relates to new drugs that are approved or obviously our ongoing studies.

[Corinne Jenkins:]

Great, that makes sense. Thank you so much.

[Operator:]

Thank you. Our next question comes from Jim Birchenough with Wells Fargo. Your line is now open.

[Jim Birchenough:]

Yes, hi, guys. Thanks for all the detail, and congrats on the progress through the difficult environment. I guess first just on TRIDENT-1, going from 100 to 120 sites. Is that just to offset the impact of COVID-19 or is there anything in terms of screening for ROS1 and NTRK+ patients that you're seeing different than you'd assumed previously?

[Athena Countouriotis:]

Thanks for the question, Jim. Same comment I made to Corinne, hope everything is okay for you and your family. First, I would say that we were making the decision to evaluate additional countries throughout the conduct of the trial just looking back. Of course, I'd given a lot of detail through our Phase 1 updates in the context of our fast track designation that was granted today. So I appreciate that's all new data, but to try to remind folks, our Phase 1 study was really seven sits, two countries, and so the Phase 2 is just such a much more global scale program, and we've been evaluating over time what additional countries we may or may not bring into the trial. So, going from a 100 to 120 actually included additional sites at the prior countries that we had selected, as well as some new countries that we've selected as we've learned more through outreach to KOLs in those areas, as well as outreach with our CRO, but just to the point that you're making, that I think trying to mitigate any potential impact down the road, we're obviously saying today that we've seen some delay as it relates to site initiations for the Phase 2. So adding additional sites hopefully will help mitigate that if we can going further.

[Jim Birchenough:]

And then Athena, just looking ahead to what may be an update in third quarter, but certainly second-half for TRIDENT-1. Can you give us a sense is it still Cohort 2/3, where we'd expect the preponderance of patients? And then just wondering if, to the extent you've had such as strong CNS response, have you enrolled patients that could confirm that activity? And maybe just to set expectations around what would you expect if it is Cohort 2/3 what would be your expectations on this number of patients in terms of responses we should look for.

[Athena Countouriotis:]

Sure. So what we've outlined today and what we said at the beginning of the year was, right now in Q2 we give you more guidance as it relates to what to expect in the second-half. And what we've tried to outline is, again, one of the things we said in the prepared remarks is that we're monitoring overall study conduct and data collection, and what I mean by that is, as you know, many sponsors have had to allow greater flexibility right now as it relates to patients potentially having local labs and/or local CT scans collected. It's now in our shop to get that data out of the local institution into the treating centers, and then inevitably into our database. So what we've said today is that we're potentially going to provide the second-half update in third quarter. But we do still have to watch where we are with data collection. And so, I can't fully answer whether it'll be cohorts 2/3. What we've said today is that it will be multiple Phase 2 cohorts. And at the same time, to the question you've asked about CNS disease, it's too early for me to assess how much data I have collected in patients that have had intracranial disease. When I look at kind of how I should think about the data coming in the second-half, it's really probably more to the point I made earlier about the difference between the Phase 1 study, two-country versus now where we have 11 activated countries. Over half of those countries have now enrolled patients. And so it's clearly a much more global trial, which to some may think that that would add more variability. And so, we want to look at an early number of patients to be able to assess, not only a change from two countries to a much more global scale, but also as a reminder our Phase 2 dose is a regiment that allows titration after two weeks of 160 milligrams daily. You can go and double the dose to twice daily. And that we didn't explore in Phase 1, we explored it after a shorter period after seven days. So my assessment when I think about the data, again to the point you've made, which is a relatively small dataset. We're looking at approximately 30 to 40 patients, which is consistent, we always said early initial patient. I really just want to see the data obviously utilizing our Phase 2 dose in a much more global scale trial.

[Jim Birchenough:]

Well, thanks again for all that detail. And be safe, thanks so much.

[Athena Countouriotis:]

Thank you, Jim.

[Operator:]

Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is now open.

[Michael Schmidt:]

Hey, thanks for taking my questions, AND Athena, thanks for the detailed update today. It looks the, based on what you said, that the PFS in the frontline treatment one patient cohort seems to mature really nicely. Good to hear that. Just curious if you could also share any updates on potential treatment discontinuations from the Phase 1 study as you start taking a look at it .

[Athena Countouriotis:]

Yes, thank you for highlighting that, Michael. One of the things we clearly wanted to highlight, of course, we taped our prepared remarks. And so, we've received obviously very recently the fast track designation approval. And so, with that we provided an update to the FDA not only utilizing the July 2019 data cutoff, but also additional information that we've received utilizing physician assessment data. SO we've not looked at a formal blinded, independent central review analysis since the July updated from last year. Having said that, what you pointed out, I think there's two points I would point out. Previously we had said that the maturity of the duration of response was not yet there. And so that we had estimated that there was a high likelihood, that 65% of it being at least 18 months. Today, we've now said the at median has been met, and the median is 23.1 months, which again if you're trying to do a historical comparison remembering crizotinib's duration of response is just over 18 months. I think for progression-free survival, at 24.6 months, again it compares historically to both the approved agents, which are essentially at 19 months. So a delta, we were looking at five-and-a-half plus months. So we're very pleased with the update as it relates to the Phase 1. All we've additionally commented on today is that all of the seven patients remain on treatment, and we gave the extension since, what we gave in January, as to where our patients are, with now multiple patients out over two-and-a-half years on drug, and only one patient that was in a previous response that has now subsequently progressed. So that's what we gave in terms of the update as it relates to discontinuations.

[Michael Schmidt:]

Makes sense, thanks. And then obviously hard to predict at the moment and re-acknowledging the additional sites that you're activating, but any additional color on when you think you might be able to complete enrolling the first registrational cohort, and how we should think about potential filing timelines?

[Athena Countouriotis:]

No, it's a very fair question. And we've consistently said is that we would give more guidance as it relates to the timeline, so we have not yet given the timeline for the Phase 2 study, yet we would do that as we got closer to full site activation. Today, we've clearly said that we've made progress within the first quarter, with now over 50% of our sites activated, but we've seen a little bit of a delay moving into Q2. So it's a little hard to predict right now when we'll hit 100% site activation. But I do still believe that we'll be in a better position to provide you a timeline potentially for trial completion once we have all of our sites activated and can truly assess the enrollment curve. So it's a question I can't fully answer today.

[Michael Schmidt:]

Thank you. And then very nice to see the FDA approval reasonably often Novartis MET inhibitor capmatinib and with a very broad label including frontline based in a very small study. I'm just wondering how you think about that in terms of read through the program and potential longer-term plan with regards to path to market and how we should think about that as well as through the efficacy bar maybe that Novartis sort of has said at this point.

[Athena Countouriotis:]

Sure. Yes. Last week as I said before was it was a busy week for precision oncology and I think for those that don't see the map, unfortunately their lung cancer still remains the cancer that unfortunately has the highest rate of death, and it's actually higher than when you add breast colon and pancreatic altogether. So, any advancements within the lung cancer space to me are incredibly positive, so two approvals last week was a big win for the field. I think to the point that you're making the data we've consistently seen is that there are ways we still believe we can differentiate as it relates to potentially prolonging duration of response with that benchmark of about 12 months in the truly treatment naive patient population. Again, I think there were some that might've been surprised by some of the data as it related to the safety profile. And so for us, again, we will be interested when we do provide the update for our MET program, which we've said will still be within the second half. It will predominantly be a safety update. And of course we've always known that there is a high rate of peripheral edema with that asset. So I think those are the ways when we look at their label, we still have the same belief and conviction we had before as potentially how we could differentiate. And then to your point, I think you're correct, in the fact that it was a relatively small sample size that led to both of the indications.

[Michael Schmidt:]

Well, great. Thanks, Athena, and appreciate the update.

[Athena Countouriotis:]

Thanks very much, Michael. I hope everything's going okay for you.

[Operator:]

Thank you. Our next question comes from Robert Burns with H.C. Wainwright. You line is now open.

[Robert Burns:]

Hi. Thanks for taking my questions and congrats in the quarter and all the phenomenal progress turning point is making. Most of my questions have been answered already, but I just one, one follow-up. So as we think about the development of all these assets, looking further on down the road and taking into consideration the higher propensity for off target resistance mechanisms and later generation TKI inhibitors, are you considering combining these with additional agents, for example, an SHP2 inhibitor, later on in the development pathway? Thank you.

[Athena Countouriotis:]

Yes, sure, very good question. So I think, there was a question earlier as it relates to medical conferences and KOL engagement. I think it's important for us to highlight that we do have at least between the two conferences, ASCO, there'll be predominantly a preclinical update as it relates to our RET program, but AACR at the end of June will really be the first place where we start to show our combination strategy. We've talked about this for quite a while now. We've continued to work on it. We've built our team to evaluate multiple ways that we can combine at least our lead asset repotrectinib, but we're fully aware that there is another investigational RET inhibitor that's now being combined with any EGFR inhibitor. So I think to your point, while we are looking at our entire pipeline and combine inability with other targeted therapies, whether it's TKIs or others, but just something that we haven't necessarily shown publicly, but again, ACR abstracts will be coming out very soon and then subsequently obviously the presentation.

[Robert Burns:]

Awesome, thank you.

[Athena Countouriotis:]

Thanks very much, Rob.

[Operator:]

Thank you. Our next question comes from Jim Birchenough with Wells Fargo. Your line is now open.

[Jim Birchenough:]

Yes. Hi guys. Thanks for taking the follow-up. Just maybe a broader question, as you think about the profile Athena of your drugs, where you're hitting the wild type mutation and the solvent front mutations, are there good categories that you can point to where that becomes the preferred frontline approaches? Is Tagrisso Tarceva in lung cancer an example, or just want to get a sense of as we start to think about what's going to be the dominant frontline agent over time and things like non-small-cell lung cancer, if there's some precedent for something that hits wild-type and prominent resistance mutations. Thanks.

[Athena Countouriotis:]

Yes, sure. Jim. I think Tagrisso is a very good example, of course, one that started in and then moved clearly to the front line based on its potency, I think one of the reasons and I know we've been asked repeatedly and so I hope today's update will be perceived positively as the Phase 1 update for TKI-naive patients showing now the DOR of close to two years at 23 months and showing median PFS of over two years where the competitors are at 19 months, I still think again is the strongest data set that we have to show why we believe repotrectinib is the best-in-class agent, and clearly that's the drug that hits wild type as well as the only currently that has activity in the clinic against solvent-front mutations. So when we think about other benchmarks out there, we often use the example that you've outlined in Tagrisso. Sometimes we'll also look at Al Kansa given the fact that it started in a different setting and now is really become the frontline agent for ALK-positive non-small cell lung cancer, but I think it's a very fair point to think of how we think each of our molecules not only differentiate for treatment resistance, but also can be best-in-class.

[Jim Birchenough:]

Great. Well, thanks for taking the follow-up.

[Athena Countouriotis:]

Thanks, Jim.

[Operator:]

Thank you. Our next question comes from Zegbeh Jallah with ROTH Capital Partners. Your line is now open.

[Zegbeh Jallah:]

I just wanted to ask a quick question about any regional differences in the enrollment for TRIDENT and then kind of get a sense of how that may overlap with sites where you're seeing more of an impact of COVID-19?

[Athena Countouriotis:]

Yes, thank you for the question. So first, I think it's as it relates to the Phase 1 versus the Phase 2. Let me just say from the Phase 1 component, it was two countries, so United States and South Korea, the largest enroller within the Phase 1 was here within the United States at Sloan Kettering, our Phase 2, we've not given any guidance as it relates to periodic enrollment or where enrollment is coming, but what I did say today is we have 11 activated countries now and over half of them have enrolled patients within the Phase 2. So I haven't given you specifically the countries, but I have at least given you information to say that it is a broad base of where enrollment has already started within the Phase 2 study. So that's the best way that I could answer the question as it relates to enrolment as of today.

[Zegbeh Jallah:]

That's helpful, thanks. And then another follow-up here, just wanted to also get a sense of how many scans, what the median treatment duration will likely be for the data update that might happen in 3Q for TRIDENT Phase 2?

[Athena Countouriotis:]

That's something that we're currently evaluating now, given the fact that we have multiple patients who have data that is still being collected from local institutions. So I would be able to give you any further guidance as to whether patients will have more than one or two post baseline scans in the context of what the update will be, because it will also be dependent on when the update will be, whether it will be in Q3 or later in the second-half.

[Zegbeh Jallah:]

Got it. Thanks, Athena.

[Athena Countouriotis:]

Of course, thanks for the questions.

[Operator:]

Thank you. Our next question comes from Arlinda Lee with Canaccord. Your line is now open.

[Arlinda Lee:]

Hi, guys. Thanks for taking my questions. I had maybe I was looking for maybe additional color on some of the data sets that we might be expecting towards the end of the year. You mentioned that you were looking for 30 to 40-ish patients in exploratory and registration arm. I was curious since the trial started late last year, or sorry, middle of last year again. Are those patients then going to largely not be impacted by COVID? And then I was curious about if you're, if you anticipate any issues from requiring biopsies fresh versus maybe archival and whether there's any change to the workup of these patients during this time? Thank you.

[Athena Countouriotis:]

Yes, thanks. Thanks for the questions, Arlinda. We actually had previously guided and have outlined it again in some of our documents that currently for enrollment patients can come in with local testing. So, there is no current requirement for a fresh biopsy of course, unless the patient is a naive patient who's just recently been diagnosed. So the biopsy components hopefully is not a barrier for patients that are coming through within the trial. The impact as it relates to the data analysis again, it will be partially based on the last question as to where we're with current stand and where the patients were in their treatment paradigm, before we will be able to answer your question. So, I can't answer entirely whether any of the patients that will potentially be in the dataset will have had scans during this time, more than likely they would have, but again, the question I think you're asking is patients that we had enrolled, your timeline was correct, the studies enrolled started in July of last year, but only early patients versus more recent patients. Again, why we are looking at overall contact and data collection, it's a question that's hard to answer right now.

[Arlinda Lee:]

Okay, thank you.

[Athena Countouriotis:]

Okay.

[Operator:]

Thank you. I'm not showing any further questions at this time. I would now like to turn the call back over to Athena Countouriotis for closing remarks.

[Athena Countouriotis:]

Well, thank you again everybody for dialing in. I really appreciate the time, and obviously your interest and support in Turning Point Therapeutics. Given the company is under the stay-at-home directive, I know many of our employees are at home, and so, I thank you for everything that you have been doing, you know that. I hope you and your families stay well during all of these unprecedented times. And operator, you may now close the call. Thank you.

[Operator:]

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