Deciphera Pharmaceuticals Inc

F:D05

Earnings Call Transcript 2023-Q2

[Operator]

Good morning, everyone, and welcome to the Deciphera Pharmaceuticals Second Quarter 2023 Financial Results Conference Call. Today's call is being recorded.

At this time, I would like to turn the call over to Jen Larson, Senior Vice President of Finance and Investor Relations. Jen?

[Jennifer Larson, executive]

Thank you, operator. Welcome, and thank you for joining us today to discuss Deciphera's second quarter 2023 financial results. I'm Jen Larson, Senior Vice President of Finance and Investor Relations. With me this morning to discuss the financial results and provide a general corporate update are Steve Hoerter, President and Chief Executive Officer; Dan Martin, Chief Commercial Officer; Matt Sherman, Chief Medical Officer; Margarida Duarte, Head of International; and Tucker Kelly, Chief Financial Officer.

Before we begin, I would like to remind you that any statements we make on this call that are not historical facts are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples include our expectations for our preclinical and clinical programs, our commercialization of QINLOCK and guidance. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we cannot assure you that our expectations will be achieved. Such risks and uncertainties include those set forth in our most recent quarterly report on Form 10-Q as well as our other SEC filings. We assume no obligation to update or revise any forward-looking statements. Following this call, a replay will be available on the company's website, www.deciphera.com.

With that, I will now turn the call over to Steve Hoerter, President and Chief Executive Officer of Deciphera. Steve?

[Steven Hoerter, executive]

Thank you, Jen, and good morning, everyone. Thank you for joining us today as we provide an update from the second quarter, review our financial results and look forward to the rest of the year. We've made tremendous progress so far in 2023, thanks to the exceptional work of our dedicated team at Deciphera. Our commercial business continues to drive strong results, highlighted by a record quarter for QINLOCK, which generated over $38 million in Q2 revenue, an 18% increase over Q2 last year.

We believe that we can significantly grow the QINLOCK brand by expanding the label to include second-line GIST patients with KIT Exon 11 and 17 or 18 mutations, and we are pleased to announce today an important milestone toward that goal. The opening of the first sites for the Phase III INSIGHT study. The compelling results of the exploratory analysis of circulating tumor DNA from the INTRIGUE Phase III study of QINLOCK and second line GIST patients were featured in an encore presentation at the 2023 ASCO Annual Meeting.

These data continue to generate very positive feedback from physicians who are eager to enroll patients in the INSIGHT study, which is designed to serve as the basis for a supplemental new drug application, or sNDA. We are also proud to announce today that we have initiated 2 new combination cohorts for DCC-3116, with encorafenib and cetuximab and with ripretinib.

On today's call, we will share a data update from the 3116 program, including data from both the Phase I single agent escalation and the initial combination escalation cohorts. We're excited to generate additional data from this potential first-in-class program targeting the autophagy pathway. At the American Association of Cancer Research Annual Meeting in April, we presented 8 posters on our early-stage pipeline, including the first disclosure of our new pan-KIT inhibitor, DCC-3009, for which we expect to file an IND in the first half of 2024.

The data we presented at AACR highlighted the sustained productivity of our kinase switch control research engine and its proven ability to generate product candidates with first and best-in-class potential. Now looking ahead, we are moving into an exciting second half of the year as we approach the top line readout for the pivotal Phase III MOTION study of vimseltinib and tenosynovial giant cell tumor and the IND submission for DCC-3084, are potential best-in-class pan-RAF inhibitor.

Now I'd like to take a moment to recognize Dan Flynn, our Founder and Chief Scientific Officer, whose retirement was announced last week. On behalf of the entire Deciphera team, I want to thank him for his vision to found our company almost 2 decades ago and his trailblazing innovations in switch control kinase inhibition, which have brought Deciphera to where it is today. It has been an honor working alongside Dan, and I wish him the very best in his retirement.

We're excited to welcome Dr. Dash Dhanak, as our new Chief Scientific Officer next month. Dash brings an exceptional background as a leader in drug discovery with over 30 years of experience and joins Deciphera from Insight Corporation, where he was most recently Executive Vice President and Chief Scientific Officer. On today's call, Dan Martin, our Chief Commercial Officer, will share insights on the U.S. commercial performance for the second quarter; and Margarida Duarte, our Head of International, will provide an update on QINLOCK's ongoing fourth-line GIST launch in Europe.

Matt Sherman, our Chief Medical Officer, will provide an update on our R&D efforts, including data from the DCC-3116 Phase I/II study. Finally, Tucker Kelly, our Chief Financial Officer, will review the financial results from the second quarter. First, I'll turn the call over to Dan and Margarida to discuss our Q2 commercial performance. Dan?

[Daniel Martin, executive]

Thanks, Steve. Q2 was a record quarter for QINLOCK in the U.S. We achieved launch-to-date highs in terms of net product revenue as well as many of our core brand metrics. U.S. net product revenue was $28.9 million in the second quarter, which represents a 17% increase versus Q1 and a 22% year-over-year increase versus Q2 of 2022. During the quarter, we saw continued momentum in core drivers of demand, including new prescriber growth, new patient acquisition and average duration of therapy.

Together, these factors drove strong volume growth in Q2 as demand bounced back from the seasonality driven the softness we saw in Q1. Additionally, gross net declined slightly in Q2 versus Q1, whereas path increased slightly quarter-over-quarter. Our commercial team continues to execute at a very high level, again, delivering the highest reach frequency and shareholders of any company in this market and maintaining high awareness and positive product perceptions among both academic and physicians.

New prescriber product has continued at a very consistent pace. In Q2, we surpassed 1,000 QINLOCK prescribers launched to date. Our market research and KOL interactions continue to highlight that QINLOCK is firmly entrenched as the clear standard of care in fourth-line GIST. At ASCO in June, we had the opportunity to sit down with many of the leading sarcoma experts from across the country.

GIST KOLs consistently highlighted their positive clinical experience with QINLOCK and the tremendous impact QINLOCK has for their patients. In particular, KOLs highlighted QINLOCK impressive efficacy and tolerability, which they noted is a combination that can be challenging to deliver to patients receiving sunitinib or regorafenib. We remain very pleased with our commercial momentum in the U.S. and look forward to continuing the strong execution in the second half of the year.

We expect to see continued growth in demand balanced with modest increases in path. Consistent with prior years, we expect a path percentage in Q3 and Q4 to be near the high end of our estimated range of 20% to 30%. In addition, we expect to see modestly higher gross to net in Q4 related to the Medicare inflation rebates required by the inflation reduction act.

I will now turn the call over to Margarida Duarte, our Head of International, to discuss the progress of the QINLOCK launch in Europe. Margarida?

[Margarida Duarte, executive]

Thanks, Dan. We remain very excited with the strength of the international business and the launch momentum of QINLOCK in Europe. For the second quarter, international revenue was $8.4 million, up from $7.8 million in the prior year, driven by continued volume growth from the successful entry in Europe and partially offset by a lower monthly price in Germany following the expiration of the free pricing period in 2022 and by timing of orders from distributor markets outside Europe.

QINLOCK continues to be very well received by physicians and patients in Europe based on the high unmet medical need and its unprecedented benefit in fourth-line GIST. In Germany, we continue to see strong demand as we work to unlock a significant opportunity in the more dispersed and fragmented community setting. On the heels of the strong pricing we achieved in Germany, the team continues to work diligently on achieving reimbursement for QINLOCK with authorities in Spain, France, the United Kingdom and elsewhere.

Last quarter, we shared that we expected to launch QINLOCK Italy in the coming months, and today, we are delighted to announce that we are very close to launch. We have successfully finalized the reimbursement negotiation process and are waiting for the publication of the IFO resolution in the official gazette, which is the last step before launch. We look forward to getting QINLOCK in the hands of patients in Italy shortly.

Turning to the rest of the world we are excited that negotiations with the pan-Canadian Pharmaceutical Alliance were successfully completed. The agreement supports the public listing and reimbursement of QINLOCK by provinces in Canada and is a major step in enabling broad access to Canadian patients with fourth-line GIST. QINLOCK is already available in the first provinces and our partner in Canada continues to work with the remaining ones to finalize public reimbursement.

Additionally, we are pleased to have recently received approval for QINLOCK in Singapore. All in all, these are very positive developments, and we expect our international revenue to continue to grow as reimbursement agreements and approvals are achieved around the world alongside the growth from our initial launch markets.

I will now turn the call over to Matt to provide an update on our clinical programs. Matt?

[Matthew Sherman, executive]

Thanks, Margarida. We continue to complement our commercial success with substantial progress across our growing pipeline of clinical and preclinical programs, enabling Deciphera to solidify its position as a leading oncology company. There is excitement at all stages of our pipeline from the upcoming top line results of the Phase III MOTION study to the start of the INSIGHT trial and to the opening of cohorts for DCC-3116.

I'm confident about the prospects we have to apply our discovery, development and commercial capabilities to benefit patients with cancer. First, I'd like to start with our DCC-3116 program. 3116 is designed to be a first-in-class backbone combination agent across a wide range of cancers. As Steve mentioned earlier, we are excited to announce today that we have opened the first site for 2 new 3116 combination cohorts, one encorafenib and cetuximab and the second with ripretinib.

We look forward to continued progress as we work to demonstrate clinical proof of concept for the inhibition of both 12 mediated autophagy to treat cancer. Moving now to discuss updated Phase I/II data from both the single agent escalation and the combination escalation cohorts. At our initial clinical update at ESMO last year, we presented data on the first 18 patients with single-agent dose escalation part of the study. In that selected the striving dose of 3116 of 50 milligrams BID for the initial combination cohorts.

I'll first provide a brief update on the additional data we have generated from the single-agent dose escalation that includes 10 additional patients. In the full 28 patients, single-agent 3116 remain well tolerated at doses from 50 milligrams BID to 300 milligrams BID with no maximum tolerated dose reached. The AE profile was shown to be consistent with prior data disclosed at ESMO 2022. And only 1 dose-limiting toxicity was observed a Grade 3 ALT increase at 100 milligrams BID.

The updated pharmacokinetic profile continued to demonstrate 3116 exposure associated with the anticancer efficacy in preclinical combination studies. The PK profile shows that 3116 exposure increased the doses between 50 and 200 milligrams BID with associated variability. At the dose of 300 milligrams BID 3116 exposure appeared to approach plateau. We continue to see pharmacodynamic effects that were associated with anticancer efficacy in preclinical studies.

At the end of last year, we began evaluating 3116 with 2 MEK inhibitors, trametinib and binimetinib and the KRAS G12C inhibitor sotorasib in patients with advanced solid tumors. As of August 4, 2023, we have enrolled 27 patients in the combination cohorts across a variety of solid tumors. Dose-limiting toxicities were observed at 50 milligrams BID of 3116 in combination with the approved doses of trametinib and binimetinib. Based on these DLTs and the updated PK NPD data from the single-agent dose escalation and the preclinical combination [indiscernible] study with once-daily dosing of 3116, we reduced the dose of 3116 to 50 milligrams QD for both the trametinib and binimetinib combination cohorts.

In the sotorasib cohort, the first dose level of 3116 at 50 milligrams BID and so the Rapp 240 milligrams QD was well tolerated with no DLT observed. We subsequently dose escalated 3116 to 200 milligrams QD and enrollment is ongoing. We expect to have sufficient data in the first half of 2024 to make decisions by opening the next 4 KRAS G12D expansion cohorts after we have completed the dose escalation combinations. We remain excited about opening our 2 new PCC 31 escalation combination cohorts, and we will continue to follow the clinical data to invest in our right expansion combinations to demonstrate clinical proof of concept.

Moving on to vimseltinib in the first quarter, we announced completion of enrollment in the Motion pivotal Phase III study, which we believe will become the second good product from our switch control kinase inhibitor platform. We remain on track to read out top line results for Motion in the fourth quarter. We also expect to present updated efficacy and longer-term safety data from the Phase I/II study in the fourth quarter. We are strongly encouraged by the compelling clinical data we have generated, supporting the potential of vimseltinib to be the standard care treatment for patients with TGCT nonamenable to surgery.

We also opened the first site for Insight, a new pivotal Phase III study of QINLOCK versus sunitinib in second-line GIST patients with KIT mutations in Exons 11 and 17 or 18 and look forward to enrolling the first patients. If positive, we believe the results of the INSIGHT study will support an expanded label for QINLOCK and significantly improved clinical outcomes for patients based on a more precise understanding of the GIST tumors that allow physicians to select the best therapy for their patients.

Lastly, we remain on track to submit an IND for DCC-3084, a potential best-in-class pan-RAF inhibitor in the fourth quarter and another IND for our new pan-KIT inhibitor, DCC-3009 in the first half of 2024.

I will now turn the call over to Tucker Kelly, our Chief Financial Officer, to review the second quarter financial results. Tucker?

[Thomas Kelly, executive]

Thanks, Matt. Total revenue for the second quarter of 2023 was $38.3 million, which includes $37.3 million of net product revenue QINLOCK and $1 million of collaboration revenue, an increase of 18% compared to total revenue of $32.5 million in the second quarter of 2022, including $31.5 million of net product revenue. The $1 million in collaboration revenue this quarter was comprised of product royalty revenue under our agreement with Zai.

Cost of sales were $0.2 million in the second quarter of 2023 compared to cost of sales of $1.8 million for the second quarter of 2022. Cost of product revenue was $100,000 in the second quarter compared to $1 million in the same period last year. In the second quarter, total operating expenses were $90.9 million compared to operating expenses of $74.5 million in the same period in 2022.

Research and development expenses for the second quarter were $58.3 million compared to $44.9 million for the same period last year. Selling, general and administrative expenses for the second quarter of 2023 were $32.6 million compared to $29.6 million for the same period in 2022. We expect quarterly operating expenses in the second half of the year to be consistent with what we saw in the second quarter of 2023. As of June 30, 2023, cash, cash equivalents and marketable securities were $389.4 million, and our cash run rate guidance into 2026 remains unchanged.

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

[Steven Hoerter, executive]

Thanks, Tucker. The first half of 2023 was a strong start to what we expect to be a very significant year for Deciphera. We made significant strides across our commercial business as well as our early and late-stage pipeline. And we are now well positioned to achieve important milestones in the second half of the year. We are excited for the top line readout of the MOTION pivotal Phase III study of vimseltinib in the fourth quarter as this program has the potential to address the significant unmet needs of TGCT patients and become our second approved medicine.

Additionally, we look forward to enrolling the first patient in the INSIGHT pivotal Phase III study of QINLOCK as we seek to change the treatment paradigm for second-line GIST patients with mutations in KIT Exon 11 and 17 or 18, all while we continue to advance our earlier-stage clinical pipeline.

With that, operator, I'd now like to open the call for Q&A.

[Operator]

[Operator Instructions] It comes from the line of Tyler Van Buren with TD Cowen.

[Tyler Van Buren, analyst]

For the registrational MOTION trial reading out next quarter, assuming success, which is likely, how quickly can you file them for TCGT? And as a follow-up or a related question, what specifically should we look forward to from the Phase I/II update expected next quarter relative to what we saw last year?

[Steven Hoerter, executive]

Thanks for the questions. It's Steve. I'll take the first question about the readout and potential timing for filing. And I'll ask Matt to comment on expectation setting for the Phase I/II update. So as we noted on the call, we reiterated our guidance to report out the top line for the Phase III MOTION study in quarter 4 of this year. We're excited to get to that milestone. We think the data we presented so far clearly demonstrate the potential for themselves in it to be best-in-class for the treatment of patients with tenosynovial giant cell tumor.

And so when we get to the report out of the top line in quarter 4, we believe we'll be in a position then to provide an update on potential filing time line. Of course, once we get to the top line report out, we will engage with FDA as we usually do in the ordinary course and have that conversation with them as we prepare for that potential filing. And we're excited about the program, as you know, because there's very nice overlap with the prescriber base for the existing business we have with QINLOCK and GIST. And we think this product has a very high likelihood of being our next commercial product here in the U.S. and outside of the U.S., allowing us to transition to be a multiproduct company. So Matt, do you want to comment on the Phase I/II expectations?

[Matthew Sherman, executive]

Yes. So in regard to the updated data for the Phase I/II study of vimseltinib and TCGT that we plan to present later this year. As you know, a year ago, we presented the data at the ESMO 2022 meeting. And at that time, we were able to put really a very strong objective response rate for both the dose escalation cohorts and cohorts A and B in patients with previously untreated or treated TGCT. So with one follow-up, as we saw previously, patients may respond. So that would be part of the update as well as longer safety information.

And importantly, also, again, looking at the patient reported outcomes and quality out measures that we had measured previously, both pain and for stiffness because those are very important about how patients feel and function. So there will be updated data for those as well.

[Operator]

It comes from the line of Eun Yang with Jefferies.

[Eun Yang, analyst]

So a couple of questions. One is on Phase III INSIGHT trial which just began. According to the clinicaltrials.gov, the primary completion is in February 2026. And this is a 2:1 randomization with the QINLOCK showing 14 months of PFS in Phase II intrigue. So does this time line of some about 18 months, maybe 12 to 18 months enrollment period? And second question is for Tucker. In terms of collaboration revenue for this year, my understanding is that it's going to be around $8 million. And based on the first half of this year run rate, what are the kind of a collaboration partnership revenues that we should be expecting in the second half of this year aside from Zai Lab royalties?

[Steven Hoerter, executive]

Thanks for the 2 questions. I'll take your first question with regard to inside and then Tucker can take your second question. So we were excited, as you heard to announce that we've opened now the first sites for the INSIGHT study and in the conversations we've been having with investigators and with thought leaders, there continues to be really palpable enthusiasm for the study. And for this notion of being able to better understand the genetic profile of patients' tumors in order to guide therapy in GIST.

And as you know, this is, in essence, the first time in GIST that we're able to advance the field in this way. So we're looking forward to getting additional sites open as we begin now screening and then enrollment in the study. As we've noted before, as we get into a cadence of enrollment, we think we'll be in a much better position to provide updates on when we'd expect to get to full enrollment in the study and when we might expect the study to read out.

So I would use the ct.gov listing. I would take that with a pinch of salt for the moment until we really get into enrollment, having more sites open, and we have a better sense of what that cadence of enrollment will be. And as I just said, we'll provide updates along the way so we can share our progress on the study. But we're looking forward to, as I said, opening more sites and remain enthusiastic about what we hear from investigators who are going to be participating in the study.

[Thomas Kelly, executive]

It's Tucker for your second question. So as a reminder, collaboration revenue at the moment exclusively of revenue, we recognized under our collaboration agreement with Zai Labs for QINLOCK, in Greater China. So we recognized so far this year, $1.2 million roughly. The 2 key components historically for collaboration revenue have been product royalties as well as commercial supply revenue. In the first half of this year and particularly in the second quarter, it was really almost exclusively royalty-based revenue. So only a small amount outside of that.

The first quarter was a bit different in that they had been taking a price adjustment based on the NRDL listing, which happened earlier this year. So I think we've got a nice quarter for royalty revenue was just under $1 million for Zai in Q2. And we haven't brought any guidance as to the balance of the year. I think what we'd say is that we would continue to expect royalty revenue to increase over time as they expand the market opportunity in China. And then the commercial supply revenue is more episodic, and we don't provide guidance. But from time to time, in particular quarters, you may see that as well, but the royalty revenues should be the consistent piece.

[Operator]

It comes from the line of Michael Schmidt with Guggenheim.

[Michael Schmidt, analyst]

I had one on DCC-3116. It's interesting, you mentioned these DLTs in the trametinib and binimetinib combination cohorts at 50 milligrams twice a day. Could you talk about that some more? And what were some of DLTs? Do you think this could be mechanism related or perhaps off target? It's just interesting given the single agent dose up to 300 with was tolerated. Just curious if anything else going on in that particular combination.

[Matthew Sherman, executive]

As you know, we've reported some DLTs in the combination cohorts of 3116 with trametinib and binimetinib. And just to go back to the data that we presented initially at ESMO last year and then recently updated today, in the monotherapy cohorts, the doses of 50 milligrams, BID up to 300 milligrams BID of 3116 as a single agent was well tolerated. There's no maximum tolerate dose identified that there's only one dose toxicity identified of asymptomatic reversible ALT elevation in the patient at the 100-milligram BID dose level.

And then in the combination cohorts with both trametinib and binimetinib at the starting dose level of 50 milligrams BID with the standard doses of those agents. We did observe a few DLTs. Interesting, those DLTs have been reported in the labels for both of those single agents, both of those drugs as single agents. So if you look at the warnings and precautions or the most common with regards to trametinib, rash and diarrhea are noted. And certainly for binimetinib cardiac changes and ocular changes are also noted for binimetinib. So those may be related to the single agent of those standard of care drugs.

But of course, in the clinical trial study because the drugs are combined, the attribution is given to the combination. So we proceed with the dose escalation cohorts for both trametinib and binimetinib in addition for sotorasib, and we're also combining sotorasib with 3116, and we've now escalated to 200 milligrams QD in combination with sotorasib. We have not seen any dosing toxicities in that cohort.

[Michael Schmidt, analyst]

So in the MEK inhibitor combination, are you stepping down to 50 QD, but is there opportunity then to escalate after that cohort is completed?

[Matthew Sherman, executive]

Yes. Per protocol, there's opportunities to modify the doses of both 3116 and/or the standard care combination drug. So once we start to complete enrollment in those cohorts and look at all the information, we'll be able to make decisions about the next dose levels that we'll be able to move to in those combination.

[Michael Schmidt, analyst]

And then a question on vimseltinib. Obviously, a lot of focus on the MOTION study, completing that and discussing the data, but just curious how do you think about potential other indications for vimseltinib in the future? Are there other opportunities that you might be interested in pursuing for the [ CSF1R ]?

[Steven Hoerter, executive]

Yes, Michael, thanks for the question. It's Steve. I'm happy to take that. So I think you're familiar with recent reports of CSF1R inhibition in chronic graft versus host disease as an example. So some recent data with an antibody, confirming that the potential role of CSF-1 receptor inhibition in that disease. There have been other reports in the literature about a potential role for inhibitors and treating fibrotic diseases like IPF. So we haven't made any disclosures yet, as you know, about potential additional indications that we might pursue with vimseltinib but we are very actively evaluating additional opportunities for them. And at the right time, we'll have future disclosures with respect to our plans and the opportunity to broaden the role potentially for vimseltinib to treat a variety of diseases. So that's where we stand.

But we're pleased to see how the field continues to evolve. And certainly, with a profile like we've demonstrated already with vimseltinib, being an oral agent and being very potent selective, we think we have a great drug on our hands, which we want to make sure we explore fully.

[Operator]

It comes from the line of Chris Raymond with Piper Sandler.

[Christopher Raymond, analyst]

I've got just 2 questions. Maybe first on QINLOCK. Can you maybe talk about what you're seeing commercially in the second line setting at this point. You had a pretty strong second quarter print. Just kind of curious if you can give any color as to the second line uptake that might be from the NCCN guidelines that may be driving that? And then a question on vimseltinib. I don't think there's any suspense, at least as I talk to investors in terms of meeting the primary endpoint of the MOTION study.

But maybe can you just talk a little bit about what kind of expectations you'd like to set? You've got the dynamic of deepening response rates over time. You've got the 69% at any time point, but this is a 25-week study, which one would argue is likely to skew on the lower end of some of the stuff you guys have shown. So maybe just set expectations, if you will, in terms of what that actual number should be when you see the readout?

[Steven Hoerter, executive]

Thanks, Chris. Thanks for joining us. So I'll ask Dan to take the first question, and Matt can take the second and start before I turn it over to Dan and just say that as we said in the prepared remarks, we're really excited about the performance that we saw in quarter 2 and the strength of the business here in the U.S. and the growth that we saw and of course, our continued launch in Europe and opportunities geographically to expand continues. But Dan, do you want to offer some more color commentary on what we're seeing in the U.S. business?

[Daniel Martin, executive]

Yes, absolutely. Thanks, Steve. Chris, thanks for the question. So extremely pleased with our performance and results in Q2, really a record quarter for QINLOCK in the U.S. Clearly, QINLOCK is entrenched as the standard of care in the fourth-line setting, which we continue to be really pleased with. And importantly, we saw strength across virtually all of our core brand metrics this quarter including new prescriber growth, new patient acquisition and average duration of therapy, among others.

Regarding your question about could there be growth in the off-label setting. First, I'll just note, as we always do, that any second line use is an off-label use that we can't and don't promote. And really, there's sort of 2 elements to this. One is the 1117/18 data that we presented at both the virtual ASCO Plenary as well as the ASCO Annual Meeting in June, where we continue to hear great excitement by KOLs around that data. They call it potentially practice-changing and therefore, real excitement for the INSIGHT study that we've just announced that we've opened.

And then the second component that you touched on is the guidelines piece, which is listing of QINLOCK for patients who may be intolerant of sunitinib. And what we hear from KOLs there really is an appreciation for having another option, albeit some variation prescriber to prescriber in terms of how common it is for them to have a patient that's entitlement of sunitinib. But certainly always appreciate having another option.

So in terms of what those, either of those or both of those dynamics may be having on the business, we think it's still just a bit early to be able to discern what impact, if any, that's having. It's really just a bit early to know certainly something that we'll continue to monitor. And there's no question that overall, we're extremely pleased with the strength and direction of the business.

[Matthew Sherman, executive]

Chris, this is Matt. So in regards to vimseltinib TGCT, as you noted, we're very pleased with the data that we first reported at ESMO last year with really strong objective response rates across all 3 groups of patients from the Phase I dose escalation to the 2 expansion cohorts. And as we noted earlier today, too, we plan to have an update of that data as well later this year.

And importantly, it's not only just the regulatory endpoint for approval at week 25. But as we noted previously and has been previously shown with other agents, with continued treatment, the response rates go up, and that will really be important for how these patients' journeys will progress because as we noted, this is not a malignant disease. So patients have normal life expectancy, even though they suffer from their disease.

So the chronicity of treatment will be really important for these patients' quality of life. With regard to quality of life, importantly as well, too, as we first reported last year. Patient-reported outcomes are really critical to the use of this drug. This was a missing part of the pexidartinib approval because they had a lot of missing data in their evaluations of patients. But we've incorporated the quality of life measures, including pain and stiffness and we reported those last year as well, 2 patients had very meaningful changes in both worst pain as well as in stiffness.

In addition, one of our other endpoints is a range of motion, and this is really important as well, too, if they ask for these diseases, not just how patients survive but importantly how they feel and function. So the quality of life measures and particularly range of motion can be an important secondary endpoint that we will look forward to speaking to in the future.

[Steven Hoerter, executive]

Yes. Just to build on Matt's comment, this is Steve. Chris, good question on expectation setting. When we reported the data last on the Phase I/II at ESMO last year, what we noted was that we saw a week 25 or a 6-month response rate that was at 38%. But yet, as Matt noted, we saw additional responses beyond that time point.

So I think when it comes to how this drug ends up getting commercialized assuming success, it will be based on the totality of the data, including longer-term follow-up, which is very consistent with how Daiichi today markets pexidartinib based on the totality, the PEX data as opposed to solely that week 25 endpoint. But we're really pleased with how the product is performed in the Phase I/II and look forward to reporting up the top line in Q4.

[Matthew Sherman, executive]

And also one more comment on that question as well, too, is the duration of therapy is also very important as we were able to report last year, in the patients that were in the escalation cohorts, we've been on the study for the longest. We had nearly an 18-month duration of therapy for those patients. And with additional follow-up that we expect to report later this year. 2, with longer follow-up for those patients, that duration of therapy number also could we'll report on an updated duration therapy number for the patients.

[Operator]

It comes from the line of Andrew Berens with Leerink Partners.

[Andrew Berens, analyst]

Congrats on the progress, guys. A couple from me. Now that the QINLOCK, the Phase II insight trials opening, can you give us some idea of how long you think it could take to enroll that trial? How many patients do you think you have to screen to identify one with Exon 11 and 17 or 18? And then a question on 309, the Pan-KIT agent. Another Pan-KIT agent has set back before the company got to minimally efficacious dose because of hands and skin reactions, thoughts on that toxicity and how it can be dialed out or avoided. And then just a follow-up on Michael's question. It sounds like 3116 and reactions with mechanism Braftovi maybe PK-related or a metabolic issue that's increasing the levels? Any insights about that?

[Steven Hoerter, executive]

Andy, thanks for joining 3 great questions. So I'll take the first question on Insight and enrollment expectations, and I'll also comment on the 3009 question you had in the setback from the other Pan-KIT inhibitor. Matt, you may want to offer some additional commentary there and then you can take the 3116 question. So first on Insight, Andy, we were excited to announce today that we have the first sites open for the study. As Matt has said, we continue to hear very positive feedback and excitement about enrolling patients on INSIGHT from investigators, also from thought leaders and I think really based on their enthusiasm to finally move GIST treatment into the 21st century and be able to better understand what's driving an individual patient's progression and offer a customized treatment for patients.

So we're really pleased with the reception to the data that we reported from INTRIGUE in the ctDNA analysis and also the excitement and reception to the INSIGHT study itself. As we get the study underway, which we now are and start to see enrollment in the study, we're going to be in a much better position to offer some perspective and color on what we see as the trajectory for enrollment and when we may reach full enrollment in the study. It's really just too early for us to be able to offer meaningful color commentary with respect to that.

But rest assured will provide additional update on future quarterly calls as we see the cadence of enrollment in the INSIGHT study. And then for 3009, as we've disclosed, we expect to file the IND for 3009 in the first half of next year. And you referenced, Andy, a recent setback from a competitor agent despite a lot of sort of promise and expectation that have been created, they unfortunately were unable to reach exposures that were well tolerated, seeing, as you noted, some significant toxicities, namely Palmar-plantar erythrodysesthesia in patients.

So for us, we've now demonstrated, I think, our success in designing inhibitors like ripretinib or QINLOCK. We've applied those same skills to our design and selection of 3009 as our candidate to take forward. And we believe, based on the selectivity profile that we've previously reported at AACR earlier this year, this candidate has an even more selective profile than ripretinib, which is regarded as being very well tolerated. So we're looking forward to getting the IND filed and then getting this drug into patients and understanding the profile in patients. Matt, do you want to comment then on the 3116 question?

[Matthew Sherman, executive]

Thanks. So just to clarify what we were talking about earlier, we did see dose living toxicities with 3116 combination with trametinib and binimetinib. And as I noted, those events have been seen with those other agents alone. So in the clinical trial setting, of course, the relatedness is related to both drugs, both drugs combined. But I know that the DLTs that we noted have been seen either with trametinib or binimetinib alone.

[Andrew Berens, analyst]

Would that suggest that it's a PK issue or a metabolic issue increasing the exposure levels of those drugs?

[Matthew Sherman, executive]

No, not at all. So there was no thought that it might have anything to do with the metabolism of the drug or PK issues. What I was commenting on is that when you see these effects with the combination, it could be due to the single agent alone. If you use that single agent these have reported safety events, adverse events, warning some questions in the label. We don't know. We continue to enroll patients in the cohort really in those cohorts and it's right to the totality of data that will inform us about the overall combinability of 3116 with MEK inhibitors.

But as now, we continue to enroll patients. We're very pleased with the progress that we've had in the trial. So their acid cohort continues to roll as well, too. So we look forward to having an update sometime in the future.

[Operator]

Comes from Brad Canino with Stifel.

[Bradley Canino, analyst]

Two for me. First, any changes in the U.S. inventory you would flag and I guess where are you versus normal levels? And then a question for Tucker on how to think about R&D. You're pretty close to where you were around $60 million a quarter before the optimization following the entry results. So help us understand the puts and takes as you get towards the end of Vimseltinib study, the ramp of insight and you're investing into the pipeline? And should we expect continued increase in spend? And are you likely to exceed the peak spend that we saw in 2021?

[Steven Hoerter, executive]

Thanks for the questions. I'll take the first one on inventory and then Tucker you'd like to take the second one. So Brad, in the quarter, we didn't see inventory as a significant driver of results. So this was principally driven by strong demand growth in the quarter versus first quarter and versus prior year.

[Thomas Kelly, executive]

So Brad, thanks for the question on the R&D expense. So what we said today is we had $91 million of OpEx in the second quarter, $58 million of that was for R&D. And we expect that the balance of the year will be similar in terms of overall total OpEx from what we saw in the second quarter. As you noted, our kind of a high watermark for R&D was back in '21. We had $257 million of R&D expense there based on the results last year, we had $187 million after the restructuring of the portfolio prioritization.

So I don't think we'll get back to that 257 this year, if you kind of again, roll forward our $58 million roughly in the second quarter. And then the balance for '24 and beyond will really just depend on how quickly we can move and success in the pipeline. So we've got a lot of really great things going on in our clinical development area and assuming success, we would continue to prudently invest and in the assets in the right place. So I don't think we're getting back there this year and the balance of that will really depend on the success in the clinic.

[Bradley Canino, analyst]

I appreciate the commentary. Congrats on the quarter.

[Operator]

It comes from the line of Reni Benjamin with JMP Securities.

[Reni Benjamin, analyst]

Congratulations on the quarter. Quick question on Vimseltinib. Can you talk about the remaining steps? Maybe remind us when the last patient was enrolled. When do you think the database might be locked and how long it takes from a database lock to reporting top line results? And can you also remind us, is the filing going to be both in the U.S. and the EU? Will that be filed simultaneously? Or is there more data that's required in the EU?

[Steven Hoerter, executive]

I'm happy to take those 2 questions. So first, with respect to the timing for the readout of the MOTION Phase III study. As you know, we've guided to Q4. We completed enrollment in the study in Q1, which was ahead of schedule. So we're really pleased with the pace of enrollment. And as you know, the primary endpoint is response at 25 weeks or 6 months. And so once all patients get to that time point for evaluation for efficacy, we're then able to do the work that we need to do to block clean the database and then to be able to analyze data and get ready for the report out.

So this is why we've been consistent here in the last couple of quarters and guiding to a Q4 readout for the vimseltinib study. And your question with respect to where we may file, absolutely, of course, in the U.S., it's our intent to file in the U.S. And in Europe, you may recall, there are no approved agents to treat tenosynovial giant cell tumor in Europe. And so our goal would be to file in Europe as close as we can to a U.S. filing.

So as we get to the readout of the top line of the study in Q4, we'll be in a position to provide some better guidance on filing time line and how close we think we could make a U.S. filing and a European filing. But we know there's significant unmet medical need in Europe given no approved agents also, of course, unmet need here in the U.S. And our goal is to get the drug to patients to get assuming success as quickly as we can.

[Reni Benjamin, analyst]

And then just maybe as a follow-up for 3116. Are we on track then to report kind of recommended Phase II doses by the end of the year? And would that be a good point to decisions, especially on maybe the trame and bini combinations? Or do you really feel that you need to…

[Steven Hoerter, executive]

Reni, it's Steve. We lost you there for the last bit of your question. I think your question was about timing for getting to recommended doses for the combinations in the existing cohorts. So as Matt noted, we continue to enroll patients across the trametinib, the bini and the sotorasib cohorts Matt provided, I think, a really full update in terms of what we've seen so far, both from the updated Phase I monotherapy dose escalation data, but also the initial combination dose escalation data.

We also noted in the prepared remarks that we now expect that in the first half of next year, we'll have sufficient data to make decisions around potential expansion cohorts in which we might pursue. And of course, we'll continue to be guided by the data and the science in terms of which expansions we might pursue. Meanwhile, we were also really pleased to announce today that we've now opened the first sites for the new combination dose escalation cohorts.

One of those is with our very ripretinib, as you know. And the second is the result of a clinical supply collaboration agreement with Pfizer for Encorafenib and cetuximab combination. So we were pleased to get those sites open for enrollment for those 2 new cohorts. So we continue to make good progress, and we think we'll be in a position, as I said, in the first half of next year now to make decisions about the potential expansion.

[Operator]

It comes from the line of Peter Lawson with Barclays.

[Shea Feeney, analyst]

This is Shea on for Peter. I just wanted to get a bit of a better sense on the organic growth for U.S. versus ex U.S. Maybe could you speak a little bit more to the volume growth in these 2 components, if there's any one-timers we should be thinking about, such as stocking orders, any pricing benefits?

And just a follow-up on the second line component. I appreciate that it's still early, but is there any metrics you could point to that suggests uptake here or any metrics you look to provide in the near term that might give a little more color on the second line update?

[Steven Hoerter, executive]

It's Steve. Thanks for the great set of questions. So I'll ask Dan to answer your question about the U.S. business and the growth that we saw in Q2 versus Q1 and versus last year. And then Margarida can comment on what we're seeing in the international business.

[Daniel Martin, executive]

Thanks, Steve. Thanks for the questions. In the U.S., the really strong quarter that we had was driven principally by demand volume. So you asked to kind of understand how it breaks down volume versus price. The 22% year-over-year growth that we delivered in the quarter for net revenue was driven largely by growth in demand. And that comes from several sources, average duration of therapy being a really key one that we talked about previously. We continue to feel as though that will continue to gradually increase.

We've said previously that it was about 7 months on average in 2022, and we expect that to gradually grow to 8 to 8.5 months, and we continue to believe that's very achievable. So demand was the primary driver in the U.S. during the quarter.

[Margarida Duarte, executive]

So for international markets, let me start by saying that it's very exciting to continue to see the strength of our launch in the first markets in international and to see all the progress that we are making with regards to market access to unlock new countries, which will allow future launches in Italy and Canada are great recent examples.

So we are going from strength to strength, and we expect our international revenue to continue to grow in the future, keeping in mind that Q3 tends to be historically a softer quarter driven by summer holidays as we saw last year. But overall, QINLOCK is very well positioned for growth, especially as new markets come online, which will be soon the case of Italy.

[Operator]

And ladies and gentlemen, I will conclude the Q&A session now. I turn it back to Steve Hoerter for closing remarks.

[Steven Hoerter, executive]

Thanks everyone for joining us on today's call, and thank you for your continued support. We look forward to keeping you updated on our continued progress here at Deciphera. Hope you have a great rest of your day.

[Operator]

Thank you all for participating in today's program.