Q4 2023 Deciphera Pharmaceuticals Inc Earnings Call

Participants

Jen Larson; SVP, Finance and IR; Deciphera Pharmaceuticals

Steven Hoerter; Independent Director; Deciphera Pharmaceuticals LLC

Matthew Sherman; Independent Director; Deciphera Pharmaceuticals Inc

Dan Martin

Margarida Duarte

Tucker Kelly

Jessica Fye; Analyst; JP Morgan

Tyler Van Buren

Eun Yang; Analyst; Jefferies

Michael Schmidt; Analyst; Guggenheim Securities

Chris Raymond; Analyst; Piper

Andrew Berens; Analyst; Leerink Partners

Brad Berning; Analyst; Stifel

Reni Benjamin; Analyst; Citizens

Peter Lawson; Analyst; Barclays Investment Bank

Presentation

Operator

Good morning, everyone, and welcome to Deciphera Pharmaceuticals Fourth Quarter and Full Year 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 Larson

Yes, thank you, operator. Welcome and thank you for joining us today to discuss Deciphera Fourth Quarter and Full Year 2023 financial results, and Jim Johnson, 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 Herda, President and Chief Executive Officer, Matt Sherman, Chief Medical Officer, Dan Martin, Chief Commercial Officer, migrated to our day, 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 Caremark 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 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 Hunter, President and Chief Executive Officer of Deciphera.

Steven Hoerter

Steve, this is Joe. Good morning, everyone, and thank you for joining us today as we provide an update from the fourth quarter and full year 2023, review our financial results and discuss our strategic outlook and planned corporate milestones for 2020 for 2023 was a year of significant progress toward our goal of becoming a self-sustaining company with multiple approved medicines. Continued strong catalog growth in the US and internationally drove record annual revenue, demonstrating the global capabilities of our commercial organization with a highly successful Phase three study in TGCT., we expect themselves to be our second approved medicine. We believe that at peak can lock into the Sultanate will be able to generate over $1 billion in global revenue with a long IP runway for both products. We are actively pursuing label expansion opportunities to create further value for patients and for our shareholders.
Beyond these late-stage programs, we continue to strategically invest in key earlier-stage programs to help build a sustainable pipeline of potential new medicines to improve the lives of people with cancer. Last month, we outlined our key strategic priorities for 2024. We expect 2024 to be a year of continued growth in catalog sales, driven by strong demand both in the US and internationally. Meanwhile, our clinical team is working towards our goal of expanding can locks label based on the ongoing Phase three INSIGHT study in second-line GIST patients with mutations in KIT Exon 11 and 17 or 18, which has the potential to double peak sales a few weeks ago, we were thrilled to announce the publication in Nature Medicine of the exceptional results from the CTDNA. analysis from the INTRIGUE study in second-line patients with mutations in KIT Exon 11 and 17 or 18 showing that Ken lock provided significant progression-free and overall survival benefit compared to the current standard of care. Sunitinib publication in one of the world's leading medical journals highlights the clinical importance of this compelling data and serve as a strong validation for the ongoing INSIGHT study.
In addition to the Nature Medicine publication, we also recently presented the final overall survival results from the INTRIGUE study at the ASCOGI. Symposium, which showed that the overall survival rate was similar for both Ken Locke and sunitinib and the treatment with Ken Locke continued to show a favorable safety profile compared to treatment with sunitinib. We believe that these results demonstrate the strong clinical activity of can log in the second line GIST patient population studied in entry for himself in a building upon the exciting positive results of the motion Phase three study in patients with Tennessee NOVA giant cell tumor. We remain on track to submit the NDA to the FDA in the second quarter of this year and an MAA to the EMA in the third quarter of this year with the potential approval of themselves and at Incyte, we are also exploring potential indication expansion opportunities, including our plan to initiate a Phase two proof of concept study of themselves in it for the treatment of chronic graft versus host disease or CGVHD. in the fourth quarter of 2024. In addition, we're making focused investments in our earlier stage pipeline, which we expect will fuel our future growth for our Ultra inhibitor DCC. 31 16. Our goal is to select a recommended Phase two dose later this year and move to our first expansion cohort for DCC. 30 84, our pan Raf inhibitor. We expect to initiate a Phase one study in the first half of this year.
Finally, for DCC. three zero zero nine, our new pan KIT inhibitor. We expect to submit an IND with the FDA in the first half of this year and initiate a Phase one study in the second half of 2024. We remain well capitalized with 352 million in cash at the end of the year and a cash runway into the second half of 2026.
I'll now pass the call to Matt Sherman, our Chief Medical Officer, who will provide more detail on our development pipeline.
Dan Martin, our Chief Commercial Officer, will then share insights on the US commercial performance and outlook for the year ahead, Margarita to our today, our Head of International will provide an update on the progress of the ongoing Kinross launch in Europe for fourth-line GIST and its continued strong momentum.
We'll end with Tucker Kelly, our Chief Financial Officer, who will review highlights from the fourth quarter and full year 2023 financial results. Matt?

Matthew Sherman

Thanks, Steve. Together with our commercial success, we continue to make great strides with our development pipeline that we believe will provide continued growth for Deciphera over the coming years.
First, I'd like to start with our recent Caremark updates. As Steve mentioned, in January, we presented the final overall survival results from INTRIGUE Phase three study at the SCOGI. conference. As you may recall, in the TREAT trial, 400, 53 patients with second-line GIST were randomized one to one to receive can lock or submitting them.
The final analysis included 18 months of additional follow-up data from the data cut in March 2023, median overall survival in the intent-to-treat population was very similar with Kim like at 35.5 months versus sunitinib at 31.5 months, resulting in a hazard ratio of 0.86 long-term safety profile was consistent with the primary analysis showing fewer patients with Grade three four T. East and a lower rate of treatment discontinuations due to AEs with Camlog versus sunitinib. We also looked at whether treatment in the second line with Camelot versus submit had any differential impact on clinical outcomes at the third line treatment irrespective of treatment with Kim like in the second line, the results show that the patient outcomes in the third line with similar median PFS on the next line of therapy was 7.7 months. We can lock versus 7.4 months for sunitinib. These final results when treat demonstrate that Kimberly-Clark for similar efficacy versus at it in the second line, GIST population studied inventory, the Nature Medicine publication last month was another major achievement for Deciphera, showcasing the potentially practice changing results from an exploratory CTDNA. analysis from INTRIGUE in one of the world's leading medical journals in second-line GIST patients with KIT Exon 11 and 1718 mutations treatment with Ken lock resulted in the 78% reduction in the risk of disease progression and a 66% reduction in the risk of death compared to sunitinib. Median PFS was 14.2 months for the Caremark patients compared to only 1.5 months for the student and the patients, median overall survival for Caremark was not reached versus 17.5 months versus Internet cannot showed an objective response rate of 44% compared to 0% for commitments together, the data represents a striking clinical benefit to these second-line GIST patients when treated with chemo. We're excited about our INSIGHT pivotal Phase three study in the same patient population is now actively enrolling patients. If positive, we believe the results of the Insight study will support an expanded label for Chemlogics and significantly improve clinical outcomes for patients based on the precise understanding of the GIST tumors, we are also working hard to get our second potential approved medicine to patients as quickly as possible. We remain on track to submit an NDA for themselves and for patients with TGCT in the second quarter of 2024 and in MA. in the third quarter of 2020. For these filings so supported by the outstanding success of the Phase three motion study, which achieved its primary endpoint of our and we 25 as well as all six key secondary endpoints in a disease such as TGCT. The secondary endpoints are critical measures of clinical benefit. These outcomes of how patients feel and function play an incredibly important role in treatment decisions as well as for patients interested in starting and staying on drug therapy. TGCT. can be a difficult chronic condition associated with severe pain, swelling, stiffness and loss of mobility. All of these can severely limit patients' daily activities and quality of life, including their ability to continue to work of function independently without an effective treatment of TGCT. diagnosis can have a profound impact on their ability to lead a normal active and healthy life. And we look forward to making this important medicine available to these patients as quickly as possible. We plan to present results from the motion study at a major medical meeting in the second quarter of 2024, as well as updated results from the ongoing Phase one two study in the second half of this year. Cipher remains committed to ensuring that the full therapeutic potential of medicine and product candidates are explored to that end, we plan to initiate a Phase two proof of concept studies themselves admit and chronic GVHD based on its potential as a best-in-class CSF1 receptor inhibitor, chronic GVHD at six 30% to 50% of allogeneic hematopoietic stem cell transplant recipients with an estimated 14,000 prevalent patients in the US. There is a significant unmet medical need in this setting with 50% of patients being refractory to treating with steroids and an overall desire to move towards combination therapy. Inhibiting CSF1 receptor expressing pro-inflammatory and Pro fibrotic macrophages has been clinically validated for patients with GVHD based on the recent pivotal study with an antibody targeting the CSF-1 receptor as an oral agent themselves, and it may offer a best-in-class CSF1 receptor option as a single agent or in combination with other oral therapies. We expect to initiate a proof-of-concept study by the end of this year, putting us on a path to potentially expand the utility of incentive for patients in the future.
Beyond Caremark and consultative, we remain very excited about the potential for our clinical and research pipeline to fuel to Cipher's growth.
As Steve mentioned, earlier, we expect to select a recommended Phase two dose for DCC 3,001 16 and 2024 to move into our first expansion cohort. We also expect to initiate a Phase one study for DCC. three D 84 in the first half of 2024. Finally, we expect to submit an IND for DCC three series or in line with the FDA in the first half of 2024 and initiate a Phase one study in the second half of 2024.
I will now turn the call over to Dan Martin to discuss our U.S. commercial updates. Dan?

Dan Martin

Thanks, Mark. 2023 was a very successful year for Caremark in the U.S. with net product revenue growing to 121.5 million, a 25% increase over 2022. In the fourth quarter, U.S. net product revenue was $35.3 million, a 38% increase over Q4 2022. These record results were driven by strong demand in our core Portland visits, increasing average duration of therapy and contribution from on promoted earlier line use in Q4. The percentage of total demand that was fulfilled through our patient assistance program or PAP was at the high end of our 20% to 30% expected range and gross-to-net was between 15% and 20%. Looking at 2023 as a whole, consistent with prior years path was between 20% and 30%, and we expect the PAT percentage to be similar in 2024. Gross to net in 2023 was between 15% and 20%, and we expect it to be in a similar range in 2024. As a result of the Medicare inflation rebates required by the inflation Reduction Act, we expect continued can lock revenue growth in 2024, driven by its position as the standard of care in fourth-line GIST potential on promoted off-label use in earlier lines of therapy based on physician decision as well as increasing average duration of therapy. Further, we expect quarterly revenues this year to follow a similar pattern to what we have seen in prior years, including Q1 seasonality. Consistent with industry dynamics, we remain confident in the strength of our business and the potential for another record year for Kinross in 2020.
For now, I will turn to the exciting opportunity we see in TGCT. with consulting and our potential second approved medicine. Based on our analysis of U.S. claims data, we believe the total addressable market for TGCT. in the US is approximately 700 million based on the estimated 1,400 treatment incident. Patients who are diagnosed receive systemic therapy and have recently engaged with an oncologist if US opportunity does not include the estimated 9,000 prevalent patients seen by oncologists or the estimated 1,300 treatment incident patients seen by surgeons. We believe there is a comparable number of patients in the five largest European markets where there are no approved treatments. We recently have provided additional insight into the treatment landscape for these 1,400 treatment incident patients in the U.S. that has increased our confidence in the market opportunity and in our commercial team's ability to reach these patients, given our deep experience and just based on our claims analysis, we believe there is a 70% to 80% overlap in the prescriber base for GIST and TGCT. and that we are uniquely positioned to drive awareness and use in both the academic and community settings. We have tested a blinded product profile of insulting them versus pexidartinib, which is approved in the US, but not Europe and versus amendment, which is commonly used off label to manage patients with TGCT. The results from the qualitative market research show that consultant and it's rated the highest across the key measures of efficacy and tolerability that physicians tell us they view as most important when selecting the TKI. to treat their TGCT patients. In the same market research study, 100% of physicians surveyed selected themselves in their profile as their preferred agent for managing patients with TGCT. We are working diligently on prelaunch activities as we prepare to leverage our strong commercial capabilities to launch themselves in that rapidly upon approval.
I will now turn the call over to Margarida Duarte, our Head of International to discuss the progress of the Kinderhook launch in Europe. Margarita.

Margarida Duarte

Thanks. Then we are very enthusiastic about the notable achievements we made in 2023 in our international business, delivering strong results that accounted for more than 25% of the Cipher's total revenue while laying the foundation for future growth. In 2023, kilowatt generated $37.5 million in international net product revenue, up 33% from 2022 as well as $4.3 million in collaboration revenue from our partner, Zai Lab in Greater China. For the fourth quarter of 2023, international net product revenue increased 56% from the fourth quarter of last year to $11.4 million. And collaboration revenue was an additional $1.6 million. Last year was a milestone year for Europe with growth across the entirety of the business, Stonepath outcomes, significant progress in market access in multiple countries and the launch in Italy, which is off to an excellent start the initial strong results we are seeing in Italy are a testament to the high unmet medical need. The exceptional KOL advocacy and the remarkable full integration rating granted to came locked by the Italian authorities, the highest for a non disease, which has significantly accelerated the launch in the many Italian regions.
Our recent entry in Italy is a good example of the type of opportunity that remains to be unlocked in Europe and underscores the importance of geographic expansion to overall growth in the business.
Last month, we announced a new distribution agreement with Genesis pharma for Central and Eastern Europe, expanded geographic reach of came up to 14 European Union countries with a combined population of 118 million people. Caremark has already received regulatory approval in all of these countries under the EMA umbrella, which will significantly accelerate the time to commercialization for Central and Eastern Europe.
We are also excited to announce that we have submitted some pricing and reimbursement in the Netherlands and continued with the price negotiations in Spain, France and Switzerland.
Our key growth drivers for 2024 include a continued focus on geographic expansion and opened new markets to drive successful launches. We are very pleased by the strength of our execution, and we expect our international revenues to continue to grow as reimbursement agreements and approvals are achieved alongside the growth from our initial launch months, positioning Timok to reach more patients around the world.
Touching on himself, a palpable excitement in Europe surrounding the outstanding Phase three motion data, we believe the number of patients is comparable to the US in the five largest European markets and the unmet need is higher. If there are no approved treatments. We are working hard towards our first initial engagements with HTA agencies earlier this year, and I look forward to the NDA submission in the third quarter and preparing for the commercial.
I will now turn the call over to Tucker Kelly, our Chief Financial Officer. We'll review the fourth quarter and full year financial results.

Tucker Kelly

Thanks, Margarita. Total revenue for the fourth quarter was $48.3 million, which included $46.7 million in net product revenue KinderHawk and $1.6 million in collaboration revenue for the full year, total revenue grew 22% to $163.4 million, including net product sales of $159.1 million in collaboration revenue of $4.3 million. Cost of sales in the fourth quarter was $1.8 million, which includes 900,000 in cost of product sales compared to cost of product sales of 700,000 for the fourth quarter of 2022. For the full year, cost of sales were $3.7 million including $2 million in cost of product sales compared to cost of sales of $8.7 million in 22, including product cost of product sales of $2.7 million. As a reminder, the third quarter of 2022, we completed the sales of zero cost inventory of KinderHawk that had been expensed as R&D prior to FDA approval in 2020.
Research and development expenses for the fourth quarter of 2023 were $58.6 million compared to $48.1 million for the fourth quarter of 2022 and $234.1 million for the full year compared to $187.8 million in 2022.
Selling, general and administrative expenses in the fourth quarter were $39.1 million compared to $32.2 million in the fourth quarter of 2022 for the full year, SG&A was $136.5 million compared to $120.2 million in 2022. We ended the year with cash, cash equivalents and marketable securities of approximately $352.9 billion. In January, we announced we had extended our cash runway guidance into the second half of 2026, which remains unchanged.
With that, I'll now turn the call back over to Steve.

Steven Hoerter

Thanks, Tucker. We're very excited for 2024 as we continue to drive commercial growth with Ken Locke seek regulatory approval for consultative in TGCT. and advance our clinical pipeline, including our plans to develop themselves in IT in GDHG. building off our momentum in 2023. We're pleased by our late-stage clinical execution and global commercial excellence as we continue our evolution into a self-sustaining company with multiple approved medicines.
With that, operator, I'd now like to open the call for Q&A.

Question and Answer Session

Operator

Thank you. As a reminder, to ask a question, please press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one. Again, One moment for questions. Our first question comes from Jessica Fye with JP Morgan and you may proceed.

Jessica Fye

Hey, guys, good morning. Thanks for taking my questions. Two from me. First, what's the latest you're hearing about doctors are turning to Ken Locke for second line, just in promoted real-world use. Is this happening mainly with Kemrock experienced treaters who are otherwise using it for fourth line? Or are you seeing any pickup of new prescribers as a result of that type of use? And second and appreciate the details on Consultronics. Can you just frame a little bit more how you think about the shape of that launch ramp? Thank you.

Steven Hoerter

I'd just say good morning, it's Steve. Thanks for the two questions. I'll ask Dan to take both of those questions. The one with respect to on promoted off-label use of can lock in the second line based on physician decision and then the expected ramp for a potential themselves that launch here in the US that?
Yes.

Jessica Fye

Thank you, Jess, for the questions. And good morning on. So as it relates to your question about Ken Locke, as we've noted, it is challenging to measure exactly what and where we're seeing in terms of the contribution of earlier line use the data sources for us to be able to do that just aren't great. And we do believe that it's been a mix of existing and new prescribers. So we really think that it's something that reflects a broad appreciation for the role of ripretinib for patients across lines of therapy in GIST, of course, I always want to underscore that that's an on promoted use. So of course, we're not out there promoting that on. It needs to happen spontaneously based on physician decision.
With respect to your second question, on the launch ramp and the shape of the ramp, we'll have the opportunity to get into more details about launch strategy and expectations as we draw closer to a potential approval but what we're focused on right now is a significant unmet need that we know exist in the space where patients were suffering from the significant morbidity of TGCT and what physicians keep telling us that there's a real opportunity to improve upon the existing therapies. So we look forward to continuing to work really hard to be ready to launch consultant nib as rapidly as possible, pending approval. Thank you.

Operator

Thank you. One moment for questions. Tyler Van Buren, Steve Cohen. .

Tyler Van Buren

Hey, guys, good morning. Congrats on the progress during the quarter. Can you guys discuss what else needs to be done to have the themselves and then filing ready for submission next quarter? And related to that was your confidence that you will not see a REMS program or a black-box warning upon approval?

Steven Hoerter

And Tyler, it's Steve. Good morning. Thanks for the question. So first, we remain very much on track for the filing of the NDA for themselves and it here in Q2 coming up and then the MAA to the EMA in Q three. So it's really just the usual and customary activities as we prepare for that filing that we are engaged and we remain very confident in the profile of themselves.
And then based on the motion data as you know, the study achieved the primary endpoint and all six key secondary endpoints also demonstrated that the drug is well tolerated in this patient population. So we believe we have a very clean and well-characterized safety profile with the drug and continue to have the expectation that we would. There's no reason to expect a REMS program or a black black box warning for that potentially fatal hepatotoxicity that is seen with pexidartinib and is believed to be an off-target effect. So we remain on track for the filings, and we're excited to bring our potential next approved medicines forward to patients.

Operator

Thank you. One moment for questions. Our next question comes from Eun Yang with Jefferies. You may proceed.

Eun Yang

Thank you. Show a chemo access second line off-label use is that largely driven by patients who are intolerant to So 10 or patients who leave it is an 1178 mutation.

Steven Hoerter

Thank you and good morning, this is Steve. I'll ask Dan to take the question on the off-label use that we're seeing and earlier line based on physician decision there. Yes. Hi, Hugh, and good morning and thanks for the question. So we believe that the two significant events that occurred last year on our what's behind the contribution that we've seen from earlier line use on promoted earlier-line use. So there was the, as you noted, the NCCN listing for patients who are intolerant of suite and second line as well as the really exceptional data that was presented and now recently published in Nature Medicine showing the dramatic treatment benefit that ripretinib can offer patients with C. Exon 11, 17, 18 mutation. We think that both of those certainly have increased the noise level on again, I always score this is something we don't promote, but just through that national dissemination of this information, the presentation, the publication, you'll certainly have raise the noise level. So it's hard to discern on which which patient which bottle is being driven by which of those factors. But we think that both are reflective of real interest in opportunities to use ripretinib in patients with GIST and of course, on.
Yes, we think that it's important to note the level of energy that we see around the Incyte study and the excitement that we have for a potential approved indication pending a positive study.

Eun Yang

You and I have one question for Tucker and so OpEx in 4Q, sequentially, R&D is down slightly but SG&A is up. So could you could you give us some guidance of how OpEx level would be in 2024 as well as the collaboration revenue line? Thank you. Sure.

Steven Hoerter

So on the OpEx side was a little higher sequentially. You mentioned in SG&A, there's some one-off items and end-of-year items that we think are more exceptional. So we wouldn't expect to have that be the run rate going forward or For SG&A, we will have some kind of second half of the year expenses as we prepare for the launch of self in IT as well.
And in terms of collaboration revenue, as we've always said, that's composed really of a couple of components. One is the royalty revenue that we get from our collaboration side. And then secondly, there's often supply revenue. The supply revenue is much more episodic system quarters. We have in some quarters, we don't and there was some supply revenues.
You'll see in the cost of goods line for the collaboration revenue this quarter, and that's difficult to predict. So I think we're always trying to guide people to focus on the and expectation for the royalty revenue and the upside in quarters where we do have supply revenue coming.
Thank you.

Operator

Michael Schmidt, Guggenheim Securities. You may proceed.

Michael Schmidt

I had one on Minnesota nerve ends of your plans in GBHD. and how do you think about potential differentiation of Incyte than urban GVHD from some of the antibodies like axatilimab? And can you comment about the possible design of your planned Phase two study you know that B and axatilamab naive patients, will you include pretreated patients? How do you think about that space?

Steven Hoerter

Yes, good morning. It's Steve. I'm happy to take the question. So first, we're excited about the potential to expand themselves in urban, its utility beyond TGCT. and into a new potential indication and chronic GVHD. And certainly one of the factors that enables us to do that.
In addition to the strong data we have now in TGCT. is the very long IP runway that we have for themselves in a with a composition of matter patent that takes us to 2034 plus PTE., which we believe takes us to the end of the decade. And that doesn't include secondary patents for consultants. So ample opportunity for us to make additional investments in them to take it into additional indications where we'll have the opportunity to benefit patients. So in terms of the landscape of GVHD and how we see differentiation at this early stage.
First, I would just comment that certainly the target CSF1 receptor is now clinically validated in this disease, which is which is very important. So it's a derisked mechanism. NGDHG., we believe the data that we've generated in Tennessee, no real giant cell tumor demonstrates that we have a very potent and selective inhibitor against the target and in a disease where the current backbone of treatment is all oral regimens, we believe that an oral agent like themselves can have an oral CSF1 receptor inhibitor could play an important role as an add-on therapy in addition to monotherapy in later lines. But as an add-on therapy to current standard of care, whether that be a Jack inhibitor or whether that be on a drug like ReSure rock as an example. So we haven't yet disclosed full details of our clinical development strategy in GBHG., I'm sure we'll have incremental additional disclosures over time, particularly once we get the Phase two study stood up at the end of this year, but we're excited about the potential now to expand and the places where them can benefit patients.

Operator

Chris Raymond with Piper Sandler.

Chris Raymond

Just another question, I guess on themselves in the US and this is on the on the adjuvant opportunity. I know this has come up in the past, but what do you guys see as sort of the go no-go points to running a study in the adjuvant setting as you guys even note in your market landscape slide, that's a pretty sizable opportunity. Just any sort of plan there that you guys can articulate? And then maybe a second part of that question is, is there an opportunity or a chance that you get a broad label that could be potentially and inclusive of the adjuvant setting?

Steven Hoerter

Thanks. Yes, Chris, it's Steve. Thanks for the two questions. Really good questions. So of course, excited about the data from motion, which will give us this initial label antenna Snowfield giant cell tumor. As you'll remember, the patient population that we treated in the motions study is patients who are not amenable to surgery. So it's too early for me to comment on what ultimately FDA will decide as the indication statement or the label for themself and INTBTT., but we too have heard also from investigators interest in exploring a role of an inhibitor like themselves in other lines or earlier lines of treatment for Tennessee, no real giant cell tumor. So recall, this is a disease that and particularly in the localized form of the disease is often curable through surgery alone, so we'd probably be speaking about a patient population that would not be amenable to surgery, but potentially could be made amenable to surgery with adjuvant or neoadjuvant treatments. So again, too early for us to comment on any specific plans. But certainly with the evidence that we have now in the patient population that we've studied, it's very clear. We have strong activity in this disease with consultants have been there may be opportunity for us to pursue whether label-enabling studies or non label-enabling studies to further characterize the potential of themselves. And that did benefit patients here.

Operator

Andrew Berens with Leerink Partners.

Andrew Berens

Hi, this is Ken on for Andy and thanks for taking the question. Actually, you guys, I think have been saying that the average duration for Coinmach in the fourth-line setting starting to come to believe about seven months now increasing and potentially at the in half. But wondering if you can give any color on the penetration in the fourth-line Palm, where that could be greater than that. Thanks for that.

Steven Hoerter

Thanks for the question, Daniel. I'll take that. Sure, absolutely. So yes, you had mentioned about the average duration of therapy. In fact, we think that's a really important dynamic to our continued growth as we think about 2024. As we look to the continued strength in our fourth-line opportunity, we look to a continuing increasing average duration of therapy. And as we've noted in earlier questions, contribution from promoted earlier-line use. So as we think about the opportunity for 2024, we're looking forward to another potential record year in the US for for Kellogg as it relates to penetration in the fourth-line setting, as we've said in the past. But we feel as though we've done a really good job penetrating that opportunity and that it's a pretty highly penetrated opportunity as a result of not only a really strong drug, high unmet need. And you know, our ability to execute over the last number of years.

Operator

Brad Berning with Stifel.

Brad Berning

Morning and thank you. Have a question from me on the incentive. Wondering how many doses you plan to use in the proof-of-concept study in chronic GVHD? And I'm asking in light of the inverse dose response noted for the antibody and the working hypothesis there around allowing for some degree of macrophage function recovery.

Steven Hoerter

Yes, thanks for the question, Brad. Matt, would you like to take that on GTH Sure.

Matthew Sherman

Good morning, Brad. Yes, this is Matt. So yes, so what you're referring to is the pivotal second stone with Texas otilimab in GVHD, where they tested three dose levels in different schedules as well to what they did demonstrate an inverse dose response where some of the lower doses and more efficacy for much of the problem behind us that may be more unique to antibiotic because we know the antibody inhibition of the CSL. receptor has led to a much more prolonged prolonged on-target effect. And it's been difficult in other indications to develop those antibodies clinically. So as Steve said earlier, you know, we're excited about moving forward with our proof of concept study in the second half of this year in GVHD. We haven't yet given the details of the of the study. But as we are closer to the initiation of study, we certainly will be speaking. So we've designed that study and we expect to achieve.

Operator

Reni Benjamin with Citizen's GMP.

Reni Benjamin

Thanks for taking the questions and congratulations on the progress. And maybe just to start off, Steve, can you give us any sort of color on on the inside study and how that's progressing? Have you have you kind of hit all the trial sites? Are they all kind of open? Or do you are you still ramping that up? Any sort of color as to how that's progressing because that seems to be key in terms of unlocking the second line just opportunity.
And then just as a follow-up with himself and if you're filing the NDA and EMA any chance that we could get and sort of a priority review or is that is the base case scenario standard review and both in the U.S. as well as Europe and how long does it take in Europe just to get the decision?

Steven Hoerter

Yes, Irina, Steve, very good morning and thanks for the great questions. So first support insight. I know as you're aware, Dan, I should first note that we publish the results from the analysis of intrigue in Nature Medicine last month. So really exciting to see the data in such a top-tier journal and the noise that done that analysis has generated both with the presentations at Asco and now with the publication in Nature, medicine has been a real tailwind in terms of building enthusiasm for the ongoing INSIGHT study.
So we continue to make really good progress in getting sites open and actively screening and enrolling patients in that study and the enthusiasm from investigators is really palpable. I think they're really excited not only about the data that's been published and presented so far from the analysis of INTRIGUE, but just also the potential to be part of advancing how second-line GIST is treated based on insights into a patient's tumor using circulating tumor DNA. So drawing a simple tube of blood in order to understand a secondary mutation status. That is an aim or goal.
I think that the field and thought leaders in the field are really excited about and their participation in the Insight study. We believe will help us to achieve that goal of demonstrating prospectively this outsized benefit can lock versus sunitinib in this selected patient population. So we continue to be moving forward very much on schedule and on track with the INSIGHT study. And we'll have further updates, I'm sure over the coming quarters on our progress with that specific study in second-line GIST patients, your second question was related to themselves and it and what our expectations are in terms of regulatory review and timing.
And your specific question was with respect to whether we may enjoy priority review with the application. So it's too soon for us to comment on that. And certainly the FDA will make that determination as to whether or not the application qualifies for priority review. As you may remember, the ENLIVEN study and the application to pexidartinib was reviewed by FDA with priority review status. So that certainly is the precedent, if you will, in this disease. So we're looking forward to our ongoing and continued productive dialogue with the FDA as we prepare to file here in the second quarter. And we'll, of course, make appropriate disclosures at the right time in terms of whether that is a priority review or a regular review at the FDA's discretion.
And then in terms of the European review process that as you may remember, is a lengthier process. So we would expect that and that will take potentially longer than the FDA review. But as we get into our further dialogue with the EMA, we may be able to better forecast, say, a time line as to when we might expect action on the application once it gets filed now. But we remain super excited about the profile of the drug. The motion data are very clear and compelling, and we're looking forward to delivering our second potential approved medicine to patients.

Reni Benjamin

Right. And then if I can just have a follow-up regarding consulting and what it could ultimately are involved in prelaunch activities. Is this something that we should just be in just given the overlap?
I think that Dan mentioned in the call, is this something that could just be as easy as kind of dropping it into the bag of sales and they're sort of off and running? Are there significant prelaunch activities that need to be conducted given given this market? Yes.

Steven Hoerter

I'll ask Dan to comment on the prelaunch activities, but you're right, Randy, we believe there is 70% to 80% overlap in terms of the prescriber base. So a really meaningful opportunity, both in the U.S. as well as in Europe for meaningful synergy with our existing commercial organization. Can you comment further on the prelaunch activities?

Dan Martin

Yes, absolutely. Thanks, Ryan, for the question on. So we think that investment in market development or pre prelaunch activities is really important on our focus will be on disease education, largely to make sure that all potential treaters of TGCT. on are fairly educated on the on the outcome and TGCTI.s and the burden that these patients deal with this is a really debilitating disease. And it's something that isn't a lethal disease, of course, but it is one that can be very locally aggressive and really have a significant impact on how patients feel and function. And we want to really paint that patient picture, bring that to life raise that awareness on.
So certainly that coupled with our med affairs organization and data from our studies, all of this will be part of making sure that prior to launch physicians appropriately so know the information that they need. And then as Steve mentioned, at launch, yes, we think there's tremendous synergy and we think we're really uniquely positioned to take advantage of both the opportunity and just with Caremark and the opportunities you see to themselves.

Operator

(Operator Instructions) Peter Lawson with Barclays.

Peter Lawson

Thank you so much for taking the questions. I guess to firstly, just on the seasonality and how we should think about that for the U.S. versus ex U.S. We have investors model out 2020 for revenues and then just moving into GVHD, just your thoughts on differentiation as well around safety and potentially efficacy versus an antibody and the ability to combined with other regimens in that GBHD. space?

Steven Hoerter

Yes, Peter, thanks for the two questions. So I'll ask Dan and Margarita to comment on expectations for the year broadly in 2024 and our expectation of the usual seasonality patterns. And then I'll ask Matt to take your second question with respect to themselves in ED and GVHD. Daniel, I'll go first. Sure, absolutely.

Dan Martin

Hi, Peter. Good morning, thanks for the question on. So as we noted on the call, we feel really excited and pleased with the progress that we've made in the I'll speak to the US specifically in the fourth quarter, delivering $35.3 million in revenue and net product revenue, which was a 38% year over year increase for the full year 2023, $121.5 million, which was a 25% year over year increase. So we feel really pleased with that. And as we look to 2024. We think some of the core drivers of our recent success will continue to be the core drivers of what we expect to be another record year for Kinross specifically on strengthen our core business, increasing average duration of therapy. And then as noted earlier, contribution from on promoted earlier line use on.
So when we take a step back and look at the year as a whole. Those are sort of the themes and the reason for our excitement as we think about just the quarter-to-quarter pattern on we wanted to note that we would expect a patterns similar to past years, which reflects some seasonality dynamics specifically as it relates to Q1 on very common in the industry to see a strong quarterly buying pattern at the end of the year that can potentially impact Q1 as well as some early in the year, sort of post holiday demand, seasonality or demand softness and of course, the other factor that we've noted in the past and would expect this year to also play out true to form is the pack dynamic, which we typically see a lower percentage in the early part of the year with a gradual increase throughout the year.
So those are some of the moving parts that we that we wanted to note on Margarita your So regarding ex U.S., I mean, let me start by saying that we are delighted with the launch. How is it going? It's going under strong revenue growth from last quarter, which was driven by strong performance in existing markets, but also the contribution from the launch in Italy. So I would say that as we continue to successfully advance our price and reimbursement and launch in new markets. We expect expecting love to continue to grow in international. It is always difficult to predict when new markets will open different, the different reimbursement processes and different time lines in each market. But assuming we get there, I expect this to happen more toward the second part of 2024.
So another thing to note is that while we expect future growth, we cannot exclude quarter over quarter variability. So we have seen this in the past, and we may see this again in the future. So I would say all in all, geographic expansion is a key focus for us in 2024. Caremark is well positioned for growth and the recent deal with Genesys for Central and Eastern Europe is also a good example of the type of transactions that you can expect from us in the future.
Great.

Steven Hoerter

Thanks, Margarita. Mads, you want to take those themselves? And the question.

Margarida Duarte

Yes. So hi, Peter Jensen regards, of course, Belgium's ultimate and TGC. comes and preferences, host disease and our ability to be able to differentiate this and we do remain very excited about our plan to initiate our proof-of-concept study in the second half of this year. And also, we have a very large database of safety based on consultant and TGCTI. both from the motion Phase three studies was from the Phase one two study. And GVHD is a chronic disease and particularly with the skin and joint involvement, there can be severe limitations of patients, so will facilitate and the antibody therapy would have to be given intravenously every two weeks. So for chronic disease such as GvHD. That's a pretty significant burden on patients. So one of the major features of using consultants as an oral agent will be to combine with other oral therapies. As you know, the standard of care now consists primarily of oral agents, whether it's subject to kinase inhibitor portion of our two inhibitor, and I'll come back on steroids as well, too. And so our ability to differentiate from the antibodies is pretty pretty significant within that is our Phase two study.

Peter Lawson

But just thinking is there any way from, I guess, preclinical data to see any differentiation from an oral drug versus a an antibody, if you think that could drive differences in efficacy or durability of safety?

Matthew Sherman

I think most of the preclinical data just speaks to the role of the macrophage in the Pro fibrotic manifestations of the disease. And that's particularly important in several organs, as I mentioned, particularly the skin because these patients with a pretty severe sporadic skin lesions and even joint contractions and also particularly the ones as well too. And progress we will own roughly that weather. Indonesia was strongly not satisfied current arrangements with four GVHD. So the role of macrophages in macrophages in those particular markets and could really be a benefit for for consulting in this disease.
Thanks, Mike.

Operator

Thank you. I would now like to turn the call back over to Steve Hoerter for any closing remarks.

Steven Hoerter

Thank you all for joining us on today's call, and thanks for your support. We look forward to keeping you updated on our continued progress here at Deciphera during the course of the year. Hope you had a great day.

Operator

Thank you for your participation. You may now disconnect.