Deciphera Pharmaceuticals, Inc. (DCPH) Q4 2022 Earnings Call Transcript

Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) Q4 2022 Earnings Conference Call February 7, 2023 8:00 AM ET

Company Participants

Jen Larson – Senior Vice President-Finance and Investor Relations

Steve Hoerter – President and Chief Executive Officer

Dan Martin – Chief Commercial Officer

Matt Sherman – Chief Medical Officer

Margarida Duarte – Head-International

Tucker Kelly – Chief Financial Officer

Conference Call Participants

Daniel Wolle – JPMorgan

Paul Jeng – Guggenheim

Tyler Van Buren – Cowen

Eun Yang – Jefferies

Nicole Gabreski – Piper Sandler

Brad Canino – Stifel

Peter Lawson – Barclays

Operator

Good morning, everyone, and welcome to Deciphera Pharmaceuticals Fourth Quarter and Full Year 2022 Financial Results 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. [Operator Instructions] Please be advised that today’s conference is being recorded.

I would now like to hand the conference over to your speaker today, Jen Larson, Senior Vice President of Finance and Investor Relations. Please go ahead.

Jen Larson

Thank you, operator. Welcome, and thank you for joining us today to discuss Deciphera’s fourth quarter and full year 2022 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 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 reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements made during this conference call include our expectations for our preclinical and clinical programs, our commercialization of QINLOCK and 2023 guidance.

Forward-looking statements made on this call 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 annual report on Form 10-K 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?

Steve Hoerter

Thank you, and good morning, everyone. Thank you for joining us today as we provide an update from the fourth quarter and full year 2022, review our financial results and provide additional context on our strategic outlook and planned corporate milestones for 2023. 2022 was a year of exceptional execution for Deciphera. Global QINLOCK product revenue grew 44% compared to 2021, driven by very strong performance in the U.S. as well as launches outside of the U.S. QINLOCK is now approved for fourth-line gastrointestinal stromal tumor, or GIST, in 12 jurisdictions around the world.

Last month, we outlined our key strategic priorities for the year, which will enable Deciphera to continue its evolution towards being a fully integrated company with multiple approved medicines and capabilities ranging from international commercialization to early-stage discovery, all powered by our proprietary switch-control kinase inhibitor platform. These priorities include expanding the market potential for QINLOCK into earlier lines of GIST by initiating the INSIGHT Pivotal Phase 3 Study of QINLOCK versus Sunitinib in second-line GIST patients with mutations in KIT Exon 11 and 17/18 in the second half of 2023. If successful, we believe the INSIGHT study has the potential to change practice in second-line KIT driven GIST and to double the U.S. revenues for QINLOCK.

We were very pleased that the circulating tumor DNA, or ctDNA data, from our Phase 3 INTRIGUE study of QINLOCK in second-line GIST was selected for presentation at the ASCO Plenary Series Session a few weeks ago. Matt Sherman, our Chief Medical Officer, will review the data later in the call and outline our plans for the new Phase 3 INSIGHT study. As we begin enrollment in the new Phase 3 INSIGHT study for QINLOCK, we also expect to readout another pivotal trial, the Phase 3 MOTION study of vimseltinib, our highly selective switch-control kinase inhibitor of CSF1 receptor in patients with tenosynovial giant cell tumor, or TGCT, in the fourth quarter of this year. We have been very pleased with the pace of enrollment and are excited to announce today that we now expect to complete enrollment in the MOTION study in the first quarter and report top-line data in Q4 of this year.

For DCC-3116, our first-in-class inhibitor of the ULK1/2 kinases designed to inhibit autophagy, we expect to present updated data from the single-agent dose escalation portion of the Phase 1/2 study and initial combination data in the second half of 2023. Finally, we were very pleased to announce a clinical trial collaboration and supply agreement with Pfizer for a new combination dose escalation study of DCC-3116 and encorafenib and cetuximab in colorectal cancer that we plan to initiate in the second half of this year. We look forward to presenting the preclinical data supporting this new combination cohort in the first half of this year, along with additional new preclinical data for DCC-3116.

We continue to complement these commercial and clinical stage advancements with investment in our research pipeline. Our discovery platform continues to drive new growth opportunities with potential first-in-class or best-in-class precision oncology agents, including DCC-3084, our newly nominated pan-RAF clinical development candidate for which we expect to present preclinical data in the first half of this year and to file an investigational new drug application in the second half of the year. DCC-3084 was discovered using the same proprietary switch-control kinase inhibitor platform that has brought us QINLOCK, vimseltinib and 3116, and we look forward to quickly advancing this program to the clinic.

In addition, we plan to debut a new development candidate from our proprietary discovery engine in the coming months as well as preclinical data from other research programs our team has been working on. Matt Sherman, our Chief Medical Officer, will provide more detail about upcoming milestones for our pipeline programs on today’s call. Dan Martin, our Chief Commercial Officer, will then share insights on the U.S. commercial performance for the quarter and Margarida Duarte, our Head of International, will provide an update on QINLOCK’s ongoing fourth line launch in Europe, which has sustained its strong momentum throughout 2022. We’ll end with Tucker Kelly, our Chief Financial Officer, who will review highlights from the fourth quarter and full year 2022 financial results and the recent highly successful follow-on equity offering that will allow us to continue to execute on our goals.

First, I’ll turn the call over to Matt Sherman to provide an update on our R&D efforts. Matt?

Matt Sherman

Thanks, Steve. We are thrilled with the progress we have made across our clinical and preclinical pipeline in 2022 and already in the first few weeks of this year. As Steve mentioned, it was our privilege to present additional ctDNA data from the INTRIGUE Phase 3 study at QINLOCK at the ASCO Plenary Session last month, which we believe represents a potential practice-changing event in the treatment of second line KIT-driven GIST. The results strongly support our planned INSIGHT study and the potential to expand QINLOCK’s label which, if approved, will allow physicians for the first time to optimize treatment for patients in the second-line setting based on the mutational profile to improve outcomes over the current standard of care.

In the ctDNA analysis for patients with KIT Exon 11 and 17/18 mutations, QINLOCK showed a striking benefit compared to sunitinib across all efficacy measures, beginning with a 44% confirmed objective response rate with all patients on QINLOCK achieving either a partial response or stable disease. In contrast, there were no objective responses in the sunitinib arm. Similarly, QINLOCK demonstrated a greatly improved PFS with a median of 14.2 months compared to only 1.5 months for sunitinib. In fact, half of the patients receiving sunitinib had progressed or died by their first restaging scan at six weeks. This resulted in a hazard ratio of 0.22, meaning that treatment with QINLOCK resulted in a 78% reduction in the risk of disease progression or death.

We also saw a strong trend for overall survival in favor of QINLOCK in the subgroup of patients. The OS results are based on an updated data cut as of September 2022 and showed that the QINLOCK arm still had not reached the median while patients randomized to sunitinib had an overall survival of 17.5 months. This resulted in a hazard ratio of 0.34 or a 66% reduction in the risk of death. And the landmark analysis showed that the number of patients alive at 30 months on QINLOCK was estimated to be nearly twice that of patients randomized to sunitinib. QINLOCK was generally well tolerated and the subgroups’ safety and tolerability profile was consistent with the primary analysis of the INTRIGUE study.

For patients with mutations in KIT Exon 11 and 17/18, fewer patients in the QINLOCK arm experienced grade 3, 4 treatment-emergent adverse events compared to sunitinib. Based on the INTRIGUE ctDNA data and regulatory input, we plan to initiate INSIGHT, a new pivotal Phase 3 study of QINLOCK versus sunitinib in this group of second-line GIST patients. If positive, we believe the results of the INSIGHT study will support as an expanded label for QINLOCK in select second-line GIST patients and transform how physicians treat these patients.

Moving from one pivotal Phase 3 program to another, I now want to talk about vimseltinib, which we believe will become the second approved product from our proprietary switch-control kinase inhibitor platform. We are strongly encouraged by the compelling clinical data we have generated to date supporting the potential of vimseltinib to be the standard of care treatment for patients with TGCT non-amenable to surgery. We began enrolling patients in the Phase 3 MOTION study in early 2022, and I’m very pleased to announce today that we now anticipate completing enrollment this quarter, enabling us to readout the top-line results in the fourth quarter of this year. We also expect to present updated data from the Phase 1/2 study of vimseltinib in the second half of this year that will focus on longer-term safety and efficacy and provide additional support for the clinical and commercial opportunity for vimseltinib.

Turning now to DCC-3116. We were excited to announce our first clinical trial collaboration and supply agreement for the program a few weeks ago. Under the agreement, Pfizer will supply encorafenib at no cost as part of the new dose escalation combination evaluating 3116 with encorafenib and cetuximab in patients with colorectal cancer. Additionally, we plan to present updated data from the single-agent dose escalation cohorts and initial data from the combination dose escalation cohorts of the Phase 1/2 study and initiate one and more expansion cohorts in the second half of this year in combination with the MEK inhibitors, trametinib or binimetinib or the KRASG12C inhibitor sotorasib.

We remain optimistic about the potential for DCC-3116 to broadly impact the treatment of cancer as a first-in-class autophagy inhibitor based on the strong preclinical in vitro and in vivo data we have generated showing additive or synergistic activity in combination with multiple agents targeting the RTK, RAS and MAP kinase pathways.

Finally, the next program slated to enter the clinic is DCC-3084, our pan-RAF inhibitor for which we expect to submit an IND in the second half of this year. We plan on presenting in vitro and in vivo data in the coming months demonstrating its preclinical profile as a potent and selective inhibitor of BRAF/CRAF-kinases with optimized pharmaceutical properties for potential development in both single agent and combination opportunities, as well as data from additional undisclosed research programs and look forward to the expected nomination of our newest development candidate.

I’ll now turn the call over to Dan Martin, our Chief Commercial Officer, to provide an update on the U.S. commercial efforts. Dan?

Dan Martin

Thanks, Matt. In 2022, we continued to execute on our commercial goals for QINLOCK in the U.S., further reinforcing its status as the clear standard of care in fourth-line GIST, irrespective of mutational profile while continuing to expand our prescriber footprint. U.S. net product revenue was 25.6 million in Q4. And for the full year 2022, QINLOCK sales grew to 97.2 million, representing an increase of about 20% over 2021.

Approximately half of this growth came from increased demand volume with the remainder coming from net price growth and a lower percentage of patients receiving free drug under our patient assistance program or PAP. The higher demand volume seen in 2022 was driven principally by an increasing average duration of therapy as the real world persistency curve continues to mature and more fully reflects the impact of patients who received prolonged clinical benefit from QINLOCK. Specifically, we estimate that the average duration of therapy in 2022 grew to approximately seven months. We expect the average duration of therapy to continue to increase gradually over time and could ultimately reach as high as eight to eight and a half months.

As expected, the percentage of patients receiving free drug under our PAP program increased in the fourth quarter versus the prior quarter. Consistent with what we saw in Q4 of 2021, the PAP percentage was slightly above the high end of our estimated annual range of 20% to 30%. This PAP seasonality is common and is driven by patient affordability challenges that tend to increase as the year progresses due to the Medicare Part D drug benefit design.

The development and approval of QINLOCK for fourth-line GIST addressed a major unmet medical need and fundamentally changed the treatment paradigm in advanced GIST. Based on the compelling data from the ctDNA analysis of INTRIGUE, we are eager to start the INSIGHT study and we believe to prove for this new indication, QINLOCK has a potential to advance the GIST treatment paradigm yet again. This time in the second-line setting based on mutational profile, we believe that if we are successful in expanding the label with a second line KIT exon 11 plus 17 or 18 indication that it would double the QINLOCK peak revenue potential to 350 million to 400 million in the U.S. alone.

Turning to vimseltinib. With the readout of the Phase 3 MOTION study fast approaching, the commercial team continues to prepare for a potential approval and launch. We remain highly encouraged by the market opportunity in TGCT where we have estimated a total adjustable market of $850 million in the U.S. With a potentially best-in-class product profile, we believe vimseltinib is uniquely positioned to address the high unmet medical need within TGCT and given the approximately 90% overlap among GIST and TGCT prescribers. We believe vimseltinib will be an excellent addition to our commercial business and that QINLOCK and vimseltinib together have the potential to generate in excess of $1 billion in global peak revenue.

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

Margarida Duarte

Thanks, Dan. We are very proud of the strengths and sustained momentum of QINLOCK’s European market entry. 2022 was a key year that solved very successful execution in two critical markets. Our launch in Germany and the post-approval paid access program in France. It was also a year in which we made significant progress towards market access in other major European markets. With the submission of the reimbursement application to NICE for access in England and in Wales and to AIFA for access in Italy. And the initiation of the market access process in Spain.

For the full year 2022, international net product sales were 28.3 million, up significantly from 5.9 million in 2021. These strong results reflect QINLOCK’s best-in-class clinical profile in fourth-line GIST and the significant unmet need. And I’m very proud of the team’s super execution of our launch strategy that enabled such exceptional performance.

Our fourth quarter international net product revenue of 7.3 million was driven primarily by continued growth in demand in Germany and in France. However, net product revenue for the fourth quarter did include a one-time reserve for QINLOCK’s product sales in Germany. It would change in Germany law effective as of November 2022, shortening the free pricing period retroactively to six months from 12 months.

In Germany, our team is in the last stages of the price negotiations. And although we are not yet in a position to disclose the details, we remain confident that our final negotiated price will reflect the high value that QINLOCK brings to patients and payers in Germany. We also continue to advance our access discussions with NICE as well as with the authorities in Italy and Spain and look forward to sharing update on future calls.

Turning to rest of the world. We were pleased to see that the National Reimbursement Drug List released by China’s National Healthcare Security Administration was recently updated to include QINLOCK, which will provide access to QINLOCK for many more patients in China for our partner Zai Lab. In 2022, we recognized 8.5 million in collaboration revenue and our agreement with Zai and look forward to their continued strong commercial execution in Greater China.

In addition, we are excited to announce that we recently received approvals for QINLOCK in New Zealand, Israel, and Macau, increasing the number of jurisdictions around the world to 12 in which QINLOCK is approved for fourth-line GIST.

I will not turn the call over to Tucker Kelly, our Chief Financial Officer, to review the fourth quarter and full year financial results and recent financing. Tucker?

Tucker Kelly

Thanks, Margarida. Total revenue for the fourth quarter was 36.3 million, which included 32.9 million in net product revenue QINLOCK and 3.4 million in collaboration revenue. With a full year, total revenue grew 39% to 134 million including net product sales of 125.5 million in collaboration revenue of 8.5 million.

Cost of sales in the fourth quarter was 3.2 million, including 0.7 million in cost of net product revenue and 2.5 million in cost of collaboration revenue. For the full year, cost of sales was 8.8 million, including 2.7 million in cost of net product revenue and 6.1 million in cost of collaboration revenue.

In 2021, total cost of sales was 2.9 million of which 1.6 million was cost of collaboration revenue, and 1.3 million was cost of net product revenue. In the third quarter of 2022, we completed the sale of zero cost inventories that had been expensed as R&D prior to FDA approval in 2020.

In Q4, total operating expenses were 83.5 million compared to operating expenses of 112.6 million in the same period in 2021. For the full year 2022, total operating expenses were 316.8 million, a decrease of approximately 20% compared to operating expenses of 396.2 million in 2021.

Research and development expenses in the fourth quarter of 2022 were 48.1 million compared to 74.9 million for the same period in 2021. In 2022, R&D expenses were 187.8 million compared to 257 million in 2021.

Selling, general, and administrative expenses in the fourth quarter were 32.2 million compared to 37.2 million in Q4 of 2021. For the full year, SG&A was 120.2 million compared to 136.3 million in 2021.

We ended the year with cash, cash equivalents and marketable securities of approximately 339 million. In January of this year, we raised an additional 134.7 million in net proceeds through a very successful public offering that further strengthened our financial position and extended our cash runway into 2026. The strong support we received from both existing and new investors in the offering will allow us to increase shareholder value as we strive to become a company with multiple approved products.

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

Steve Hoerter

Thank you, Tucker. The outstanding progress we’ve made at Deciphera over the past year, along with our plan 2023 milestones puts us firmly on the path to becoming a company with multiple approved products around the world. As we near enrollment completion and prepare to announce top line results from our Phase 3 MOTION study, we look forward to also initiating our Phase 3 INSIGHT study later this year. We are proud to leverage our proprietary switch-control kinase inhibitor platform and deep pipeline to make a difference for people living with cancer.

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

Question-and-Answer Session

Operator

[Operator Instructions] Our first question comes from Daniel Wolle with JPMorgan. Your line is now open.

Daniel Wolle

Good morning everyone. Thank you for taking my question. Just a couple of questions. First, for INSIGHT, with the idea of combining QINLOCK with – considered for the pivotal trial. Second, you’re able to refine the timeline for enrollment completion for MOTION from first half 2023 to 1Q 2023? What can you attribute this acceleration to? And then for DCC-3116, while results from the dose escalation combination study are not expected until second half, what should investors expect with initial data? And specifically, should there be an expectation for antitumor activity? Thank you.

Steve Hoerter

Yes, hi. Good morning, Daniel. Thanks for joining and thanks for the three questions. So let me take those in order. First, you broke up on the first part of your question with respect to INSIGHT. I believe it was related to a combination. Can you just repeat that for me? Operator…

Daniel Wolle

Yes.

Steve Hoerter

Go ahead.

Daniel Wolle

Sure. I guess the question was, was the idea of combining QINLOCK would considered as one arm of the pivotal study?

Steve Hoerter

I see. Okay. Thanks for that question. So I’ll take the question on INSIGHT and on MOTION, then ask Matt just to speak to 3116 and expectations here in the second half for the combination dose escalation data. So first, Daniel, with respect to INSIGHT, the data that we presented at the ASCO Plenary Series Session just last month and we, of course, disclosed at the beginning of the year, we view as being very, very clear, very compelling in terms of the activity of QINLOCK in this group of patients relative to Sutent. So no, as a result, we did not consider adding a third arm to the study looking at a combination because we don’t believe that a combination with Sutent in particular, would add additional activity in the selected group of patients.

With respect to MOTION, we were very pleased as we announced today that we’ll be reaching full enrollment in the MOTION study in quarter one instead of quarter, the first half of this year, still reporting out in quarter four of this year. And the enrollment in the study, as we’ve been telegraphing over the course of the last six to nine months, we’ve been really pleased with the pace of enrollment how enthusiastic investigators and patients are to enroll in the study. And it’s really that enthusiasm and the pace of enrollment that allowed us to enroll the study faster than we previously anticipated and is going to allow us to get to full enrollment here in this first quarter. So we look forward to reporting out the study in quarter four of this year. Matt, do you want to speak to the 3116 question?

Matt Sherman

Yes, hi. Daniel, it’s Matt. So yes, in regards to the 3116 program, as you know, at ESMO last year, we were able to present the monotherapy dose escalation data and we’re very pleased with the results showing that we had good dose proportional PK, that we had a very good safety profile and also we’re able to inhibit the target of autophagy in patients treated with 3116. So as we announced earlier as well, taking that forward in the combination escalation cohorts with 2 MEK inhibitors, binimetinib and trametinib, as well as the KRASG12C inhibitor sotorasib. So as we’ve announced, we’ll expect to have an update on the combination cohorts in the second half of this year and our expectation there will be to continue to show the PK as well as the safety profile of the drug. And in terms of efficacy, certainly, it is designed as dose escalation in small cohorts of patients, but, of course, if there is a signal of efficacy, we’d be very pleased to have that information for updating in the second half later this year.

Daniel Wolle

Okay. Got it. One last question. With multiple KRAS inhibitors in development actually and on the market as you continue development of 3116, is there an opportunity for you to select the best fit partner as you advance into late-stage development?

Steve Hoerter

Yes. Thanks for the question, Daniel, with respect to KRASG12C inhibitors. And you’re right there are a variety of agents now, two approved in the U.S. And what we’re – as we’ve reported previously, the effect that we see with 3116 addressing autophagy is an escape when used in combination with the KRASG12C inhibitor is not specific to an individual KRASG12C inhibitor. It’s certainly a class effect. It’s a mechanistic effect that we see. So we’ve seen that and reported that preclinically, both with sotorasib, but also with at adagrasib. So there would be an opportunity going forward for us to consider additional KRASG12C combinations as we think about the ideal partner for a potential 3116 KRASG12C inhibitor combination.

Daniel Wolle

Great, thank you very much.

Operator

Please stand by for our next question. Our next question comes from Michael Schmidt with Guggenheim. Your line is now open.

Paul Jeng

Hi, good morning. Thanks for taking our question. This is Paul on for Michael. One from us on recruitment for the INSIGHT study. So your analysis sort of suggests that only a portion of GIST patients have detectable KIT mutations through ctDNA and there is some discussion at the ASCO Plenary about just as a relatively low ctDNA shedding cancer. So I just wanted to get your expectations on the speed of recruitment of patients for this target mutation population at INSIGHT once that study kicks off later this year and whether you anticipate any sort of challenges in that aspect? And then secondly, on 3116, maybe just provide some color on what drove your decision to combine with encorafenib and cetuximab and where you see that potential for the combination in colorectal cancer? Thank you.

Steve Hoerter

Yes, hi. Good morning, Paul. It’s Steve. So I’ll take the INSIGHT question that you posed and then ask Matt to speak to the 3116, encorafenib and cetuximab combination. So first, with respect to INSIGHT and enrollment in that study, we’ve now demonstrated very clearly the capability to enroll these large randomized studies in GIST globally. So we have a clear capability in terms of getting these studies up and running and enrolling them rapidly. With respect to patients with the specific mutation that we’ll be looking for patients who don’t shed ctDNA, this is a very similar fraction in GIST versus other solid tumors. So we don’t see that as being a differentiating factor.

And with a simple blood-based diagnostic with a rapid turnaround time of 5 to 10 days, we don’t see that as being a barrier at all. In fact, we see it as being an advantage to enrolling in the study. And then lastly, I would just offer that what we continue to hear from investigators and from thought leaders is a considerable amount of enthusiasm given the data that’s now been reported at ASCO for the potential of QINLOCK in the selected group of patients, and I think that’s going to serve as a real tailwind in terms of not only getting sites up and running, but also getting patients enrolled on study. Matt?

Matt Sherman

Yes. Hi, Paul. It’s Matt. So yes, in regards to our plan to initiate a cohort of 3116 in combination with encorafenib and cetuximab, we’re obviously very excited overall with the preclinical data we’ve generated to date showing that we can inhibit multiple nodes along the RTK, RAS and MAP kinase pathway in combination with 3116 and show an additive or even a synergistic combination effect on tumor killing. So as we’ve initiated a number of these combination cohorts now looking at the unmet medical need in treating advanced-stage colorectal cancer and while cetuximab and encorafenib have activities demonstrated in the BEACON study a number of years ago, that was somewhat limited activity with an objective response rate of approximately 20% and the PFS of about 4 months. So they’re showing a lot of headroom for improvement in treating these patients and recognizing this might be a huge opportunity for 3116 and colorectal cancer.

Paul Jeng

Got it. Very helpful. Thanks so much.

Operator

Please stand by for our next question. Our next question comes from Tyler Van Buren with Cowen. Your line is now open.

Tyler Van Buren

Great, thank you. Good morning guys. I had a couple for you. The first is can you help us understand what the magnitude of the one-time reserve for QINLOCK sales in Germany was and elaborate more on your expectations for the cadence of ex-U.S. sales throughout the year? And the second is for vim in TGCT, you’ve presented an extensive claims analysis, but what other data points give you confidence in this market, given that patients are so diffused throughout the country and not necessarily concentrated in centers of excellence?

Steve Hoerter

Yes, good morning, Tyler. Thanks for the set of questions. I’ll ask Tucker to comment first on the reserve in Germany. Margarida, perhaps you can then comment on what you see as the cadence in terms of the commercial business across Europe. And then, Dan, why don’t you take the final question with respect to vimseltinib claims analysis and the confidence we have and the size of the opportunity. Tucker?

Tucker Kelly

Sure, Tyler. So we haven’t quantified the amount of the reserve in Germany that we took in the fourth quarter. But just to remind folks, what happened is that the German authorities in November changed the law. It used to be that you had a 12-month period of free pricing and that got shortened to six months effective retroactively based on the law change in November. So in the fourth quarter, we took a reserve based on the net sales that we had booked at our free pricing price in the third quarter. And then in the fourth quarter, the sales in Germany were booked at an estimate because we’re still not at our final price in Germany, but an estimate of where we think we may end up with the German authorities on pricing. So we haven’t quantified it, but it certainly was a larger number in the quarter that we wanted to make sure people understood that as they looked at the quarter-over-quarter change in international product sales.

Margarida Duarte

Okay. I will take the second one. Thanks, Tyler, for the question. So I would say that the cadence for the rest of the year in Europe will come from two key strategic drivers. The first one is to continue to successfully drive price and reimbursement in the countries where we don’t have yet access, so that we can launch in new markets in the future; And the second one, I would say, is to continue to successfully execute on our launch strategy and continue to raise awareness to drive demand and to expand the prescriber base. And I would also offer to and – say that I’m extremely pleased with the success that we are seeing so far and with the strong demand that we continue to see.

Dan Martin

And Tyler, this is Dan Martin. I’ll take your question on what gives us confidence in the TGCT market. I think what gives us confidence is several factors. First, you mentioned the claims analysis that we’ve presented on. That was just a component of our overall analysis of the opportunity. We actually conducted a couple of different methodologies, all of which gave very similar answers. We conducted a more typical sort of literature-based epi build up and totally separately, we conducted the claims analysis, and both resulted in a really similar findings in terms of the overall patient journey for TGCT as well as the size of the addressable opportunity.

We – as it relates to the claims data, the 1,300 to 1,400 patients that we have noted as being the incident Rx-treated patients in the U.S. in this data set, we’ve always viewed that as really a floor of the opportunity and one that gives us real confidence because this is an analysis that doesn’t provide indicators of patients, it actually sees the patients. And so we can see these patients being treated in the data, which gives us great confidence. Lastly, I would just note that one of the things that we get asked is our view of sort of products used in the space and market share, and we’ve presented the findings from the claims database there as well showing that only about 15% of the patients received pexidartinib in this data set. And that enables us to sort of triangulate or crosswalk back to the opportunity that we’ve laid out. So across multiple different views of the market we land in very similar places which gives us great confidence that the opportunity is there.

Lastly, I’ll just note that diffuse markets with patients being spread between both academic and community settings as a bit of a specialty of ours. We’ve developed real capability and being successful in that space because that’s very much the description of GIST. GIST is very similar in that way. And frankly, one more point is that we know that the overlap between GIST and TGCT is really high. So for all these reasons, we have great confidence that the market is there and that we’re uniquely positioned to be successful.

Tyler Van Buren

Thank you very much.

Operator

Please stand by for our next question. Our next question comes from Eun Yang with Jefferies. Your line is now open.

Eun Yang

Thank you. I have actually a few questions. First, you mentioned that in 2022, the treatment duration for QINLOCK was 7 months and expect that to increase to 8.5 months. What’s driving the increase in the treatment of duration? And do you expect to achieve 8 to 8.5 months of this year? Second question is on the NCCN guidelines. I don’t know, it’s something – I understand it is something that we cannot predict. But you have submitted your data for second-line INTRIGUE data. But in light of the subgroup analysis in Exon 11, 17 and 18 patient population, do you expect the NCCN decision could be on that subgroup? Thank you.

Steve Hoerter

Yes. Hi, good morning. Eun. Thanks for the great questions. So I’ll take the second question first with respect to NCCN, and then I’ll ask Dan to cover off on the treatment duration for QINLOCK that we see in the real-world experience in the U.S. market. So first for NCCN, you’re exactly right, Eun. It’s not something that we can predict in terms of whether the NCCN is going to update the guidelines when that might occur or what might be reflected in the guideline update. We were excited to present the data from the subgroup as part of the ASCO Plenary Series Session just last month, very compelling data in this group of patients with QINLOCK. So we’re excited about that. I think the field is very excited about it as you will have seen from the presentation and the discussion at the ASCO session at the end of January. And so we await as you do any potential updates to the guidelines, difficult for us to predict in what shape or form or timing that might be in. So we’ll stay tuned for that and see if there are any updates. Dan?

Dan Martin

Yes. Thanks, Eun, for the question regarding average duration of therapy. It’s a really important dynamic that was key in driving the really solid growth that we saw year-over-year. As I noted in my remarks – prepared remarks, we demonstrated about 20% growth year-over-year with 97 million in the U.S. in 2022. And that was driven by a number of factors, but importantly by volume growth. And the volume growth was driven principally by this increasing average duration of therapy that we see. And the driver for that is really just a maturing of the real world persistency curve, or said another way maturing of the real world sort of prevalent treated pool that now more fully reflects patients who have had extended and prolonged benefit from QINLOCK which just pulls the average duration of therapy up now beyond the median PFS that we saw in the INVICTUS study.

And that’s really important because we expect that to continue to be a gradual growth driver over time. We had noted – we expect that could potentially reach eight to eight and a half months, and there’s a number of proof points for that which I could certainly go into, but we feel confident that ultimately eight to eight and a half month average duration of therapy is very achievable. However, we have noted that’s a gradual phenomenon. That’s a gradual trend that we will expect to see develop over time. So it’s hard to predict exactly what timetable that will develop in, but that’s why we underscored, we see that as a peak average duration of therapy. And we don’t expect that to be something that changes dramatically quarter-to-quarter, so likely something that we will share additional color on sort of as warranted over time.

Eun Yang

Thank you. Can I ask you some follow-up questions?

Steve Hoerter

Please do Eun. Go ahead.

Eun Yang

Yes. So a question on the INSIGHT trial. So based on the sub-group analysis that you’ve done from the INTRIGUE. It looks like you may need to screen about 400 patients to 500 patients. So question number one is how long do you think it would take to enroll about 54 patients? And secondly, in the currently in practice, is this a mutational analysis after imatinib done routinely? Thank you.

Steve Hoerter

Yes, Eun. Thanks for the two questions. Good questions. So I’ll take both of those. So first with respect to the INSIGHT study, you’re right. Our sites will need to screen patients for eligibility for enrollment in this study. We – from our experience with INTRIGUE, which we ran as a large global study, multiple sites, we have the capability of course, and have demonstrated the capability to run these large studies to open multiple sites and to find patients for enrollment.

At the site level of course, we know that physicians will be using an easy liquid diagnostics or a liquid biopsy where they simply draw blood and there’s a five to 10 day turnaround time to identify patients. And furthermore, sites will know generally the primary mutation status for their patients already from their time of diagnosis. So we would expect that physicians would really be interested in looking at their primary exon 11 patients, of course, and understanding what their secondary mutation profile as they consider them for enrollment in the study.

So we have a lot of confidence based on our demonstrated capabilities in this area of running these sorts of studies. And we’re looking forward to getting INSIGHT up and running at the end of this year. Now with respect to practice within the U.S. or globally even there isn’t a need – hasn’t been a need up until now for physicians to consider looking at the emergence of secondary mutations post imatinib treatment. But what we know from other analogs, whether it’s looking at lung cancer or other solid tumors, is that these sorts of liquid biopsies, these blood-based diagnostics see very good adoption.

As I noted, these are easy to run. It’s simply a tube of blood that’s sent off to a lab with a five to 10 day turnaround time. So we don’t expect, especially given the nature of the data that we’ve now presented with QINLOCK in this group of patients. We don’t expect adoption of a diagnostic to be a barrier to use at all. In fact, we think there’ll be a considerable amount of enthusiasm among physicians and patients to understand what their secondary mutation status is. So they’ll know whether QINLOCK could be an option for them in the second-line setting.

Eun Yang

Thank you.

Operator

Please stand by for our next question. Our next question comes from Chris Raymond with Piper Sandler. Your line is now open.

Nicole Gabreski

Thanks and good morning. This is Nicole Gabreski on for Chris. Thanks for taking the questions. Maybe just two from us. One, just in terms of using ctDNA as a potential companion diagnostic for patient identification. I guess, can you talk about how that would be integrated if the subset analysis data is included early in NCCN guidelines maybe versus if you get regulatory approval in the second line KIT exon 11, 17, 18 setting. Are there any differences just in the setup? I guess we’re trying to understand if it’s important to have a cleared or approved companion diagnostic in the setting?

And then maybe second just around vimseltinib, going back to your ESMO presentation last year, I know that you guys were highlighting that responses deep and over time, but ORR at the 25-week time point for vimseltinib match the pexidartinib label. And we understand that the safety profile will be the key differentiator, allowing patients to stay on therapy longer. But I guess how will that be effectively captured within the Phase 3 MOTION study and how does that translate into a potential label?

Steve Hoerter

Good questions, Nicole. Thanks for those. So let me take first the ctDNA question. And then I’ll ask Matt just to comment on the MOTION study and the data we’ve presented last year at ESMO and touched on the data we’re collecting as part of MOTION that would then inform a label and the profile of the drug in a commercial setting upon a potential approval. But first for the ctDNA data in just today, and I think your question Nicole was in the present day environment, even absent of regulatory approval for QINLOCK and this patient population, what could physicians do in practice? We know that of course, these source of blood-based panels are already available. So from companies like Foundation Medicine, Guardant Health and the like. And so physicians today, if they were so inclined, could draw a tube of blood and send it off to Foundation or to Guardant for analysis.

And these panels today will pick up the secondary mutations seen in just patients and report back on that. So physicians, if they so chose – to do so, they could run that analysis and then make treatment decisions which would be off-label today. So this isn’t something that we can or would promote to. But physicians could then make treatment decisions and they would have to work with the patient’s insurance provider to obtain coverage for that off-label use. But I guess my point is just that these diagnostics are available today for physicians who are interested in understanding the secondary mutation status for their patients. Matt, do you want to comment then on vimseltinib in MOTION?

Matt Sherman

Yes, good morning, Nicole. So, yes, as you know for the 25-week endpoint in the vimseltinib, TGCT study, we had a 38% response rate, which was similar to what was reported for the ENLIVEN, pexidartinib [ph] study and then they’re labeled. But also as we also know, these patients continue on therapy for longer than six months and can have a response beyond that. And we reported for the Phase 1 dose escalation cohorts who were on study the longest a 69% overall response rate in the TGCT patients in the Phase 1/2 study.

And in terms of a label, it’s also you can – it’s also noted that ENLIVEN’s label or pexidartinib label based ENLIVEN study also shows their overall response rate in the open label portion of the study. And that’s 61% in the current label for pexidartinib. So we could expect that our label for vimseltinib may contain some longer-term follow up and a higher overall response rate.

Nicole Gabreski

Great. Thanks.

Operator

Please stand by for our next question. Our next question comes from Brad Canino with Stifel. Your line is now open.

Brad Canino

Good morning and thank you. Steve, maybe a follow-up on your previous comments. I guess I want to know, based on the KOL and physician feedback to the subgroup analysis, do you expect the material enough proportion of practices to adopt a second line ctDNA guided treatment paradigm in the next few years to impact QINLOCK sales?

And then a second question with the top line readout for vimseltinib slated for 4Q. When you think about the degree of data that you would include in the package to the FDA is successful, can you add any comments about how long you expect it to take to reach an NDA filing? Thank you.

Steve Hoerter

Yes, thanks, Brad. Two good questions. So with respect to expectations around taking the data that we’ve presented at ASCO and that being translated or changing practice today it’s an uncertainty. So of course we can’t promote to that use. We don’t have extensive market research that tells us whether physicians will adopt the use of the drug on an off-label basis. What we’ve seen so far in our experience is that use has been for QINLOCK has been generally within our approved label. So we’ll continue to monitor and understand how physicians, if they choose to change practice, how that practice changes over time. But we don’t have any information at the moment with respect to what changes might occur. Clearly having a label in the second line setting in this patient population is what will ultimately allow us to drive share and drive utilization. And that is one of the reasons that we’ve decided to conduct the INSIGHT study and seek a label in the second line is to be able to promote to that use upon approval.

Your second question, I think Brad was related to vimseltinib and our announcement this morning that we expect to complete enrollment in the first quarter of this year and read out the study in Q4. And your question was around the timing for a potential NDA. So it’s really premature for us to share our thoughts around what the timing could be for an NDA post top line readout. What I can say is that our team has demonstrated with – certainly with QINLOCK and our fourth line label, our ability to quickly move from topline data readout to get a filing in. This will be no different. And when we have a readout of the study of the topline results, I’m sure we’ll be in a position of that time to offer some additional color around what the timing could be for a potential filing in the U.S. and filings outside of the U.S.

Operator

[Operator Instructions] Our next question comes from Peter Lawson with Barclays. Your line is now open.

Peter Lawson

Great. Thank you. Thanks for taking my questions. Just from NCCN guidelines for GIST, are you looking to gain guideline inclusion for exon 11, 17, 18?

Steve Hoerter

Yes. Thanks for the question, Peter with respect to NCCN. So we’re going to continue to monitor what NCCN decides to do with respect to any guideline update, and that will guide our decision about any future submissions of data. So that’s the approach that we plan on taking with respect to NCCN going forward.

Peter Lawson

Got you. Does – I mean, does the exon 11, 17, 18 data plus various other mutations, doesn’t that make the NCCN guideline changes the second line will come as [ph] difficult for them to make that judgment call?

Steve Hoerter

Yes, I think what we’ve learned Peter from the analysis is that there’s a level of complexity and nuance I think to the data. I mean, certainly the 11, 17, 18 population, the result is very clear in terms of QINLOCK – the benefit of QINLOCK versus sunitinib. And we have this group of patients in whom ctDNA is not detectable where we see on the forest plot. The hazard ratio for PFS is virtually in the center of that forest plot. So I think it’s unclear at the moment what NCCN might choose to do. We know that physicians generally are interested in having more options available to treat their patients. We don’t think that this situation with just is any different. So we would expect that will be of interest to physicians on the panel as they think about providing options to patients going forward.

Peter Lawson

Got you. Thank you. And then just on China, just kind of the size of the opportunity how we should think about pricing and kind of how you think it could help revenues over the next couple of years, whether it’s 2023 or 2024?

Steve Hoerter

Sure. Margarida, would you like to address the China opportunity and Zai disclosures?

Margarida Duarte

Absolutely. Thank you. Thanks for the question, Peter. So we review this listing very positively as it’ll increase affordability and access for Chinese patients moving forward. So we do expect this to be a key contributor of volume growth over time how quickly that happens we do not have a lot of details yet. But all in all, we view these extremely positively.

Peter Lawson

Got you. Thank you so much.

Steve Hoerter

Thank you, Peter.

Operator

I show no further questions at this time. I would now like to turn the conference back to Steve Hoerter for closing remarks.

Steve Hoerter

Great. Thank you, Michelle. Thanks to all of you for joining us on today’s call. Thank you for your continued support of the work that we’re doing here at Deciphera. We look forward to keeping you updated on our progress for the balance of this year, and hope you have a great rest of your day.

Operator

This concludes today’s conference call. Thank you for participating. You may now disconnect.