Q2 2021 Deciphera Pharmaceuticals Inc Earnings Call

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Operator: Good afternoon, everyone, and welcome to DeCypher Pharmaceuticals' Second Quarter, 2021 Financial Results Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Jen Robertson, Vice President of Investor Relations. Jen...

Good afternoon, everyone and welcome to decipher.

Pharmaceuticals second quarter 2021 financial results Conference call. Today's call is being recorded at this time I would like to turn the call over to Jen Robinson, Vice President of Investor Relations Jim.

Jennifer Larson: Thank you, Operator. Welcome, and thank you for joining us today to discuss DeCypher's second quarter 2021 financial results. I'm Jen Robinson, Vice President of Investor Relations at DeCypherra. With me this afternoon to discuss the financial results and provide a general corporate update are Steve Herder, President and Chief Executive Officer, Dan Martin, Chief Commercial Officer, Matt Sherman, Chief Medical Officer, 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 or forward-looking statements reflecting the current beliefs and expectations of management may be made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Thank you operator, welcome and thank you for joining us today to discuss the side for a second quarter 2021 financial results I'm, Jen Robinson, Vice President Investor.

Patients at the size of that with me. This afternoon to discuss the financial results and provide a general corporate update are Steve harder President and Chief Executive Officer, Dan Martin Chief Commercial Officer, Matt Sherman, Chief Medical Officer, 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.

Jennifer Larson: Examples of forward-looking statements may include our expectations for our pre-clinical and clinical programs, our commercialization of Kimlock, and 2021 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 corollary report on Form 10Q, as well as in our other SEC filings. We assume no obligation to update or revise any forward-looking statements.

Examples of forward looking statements made during this conference call include our expectations for our preclinical and clinical programs and commercialization of <unk> and 'twenty 'twenty..1 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.

The forward looking statements and we cannot assure you that our expectations will be achieved.

Such risks and uncertainties include those set forth and our most recent quarterly report on form 10-Q, as well as our other SEC filings, we assume no obligation to update or revise any forward looking statements. Following this call a replay will be made available on the company's website Ww dot display for dot com with that I will now turn the call over to Steve.

Steven L. Hoerter: Following this call, a reply will be made available on the company's website, www.decipher.com. With that, I will now turn the call over to Steve Herder, President and Chief Executive Officer of Deciphera.

President and Chief Executive Officer of the SIFI Steve.

Steven L. Hoerter: Thank you, Jen. During the first half of 2021, we continue to execute on our strategic priorities across the company, positioning us for a catalyst-rich second half of the year that will set the stage for the company's next phase of growth. As our chief commercial officer Dan Martin will outline on today's call, our U.S. commercial organization has rapidly established Kinlock as the standard of care in fourth line GIST, which has created a strong foundation for our future expansion into the second line setting.

Thank you John during the first half of 2021, we continued to execute on our strategic priorities across the company positioning us for a catalyst rich the second half of the year that will set the stage for the company's next phase of growth.

As our Chief commercial Officer, Dan Martin will outlined on today's call are U S. Commercial organization has rapidly established kinlaw as the standard of care and fourth line Gist, which has created a strong foundation for our future expansion into the second line setting.

Steven L. Hoerter: In addition, we continue to publish key data updates from Kinloch studies, which underscore the broad clinical benefit Disbest in Class Medicine provides for GIST. Outside of the United States, we are making excellent progress with launches now underway in China and Hong Kong.

In addition, we continue to publish key data updates from Kinloch studies, which underscore the broad clinical benefit this best in class of Medicine provides and Jess.

Outside of the United States, we are making excellent progress with launch is now underway in China, and Hong Kong and.

Steven L. Hoerter: As a reminder, an estimated 30,000 new patients are diagnosed with GIST in China each year, and we look forward to supporting our partner, Zy Lab, as they launch Kinlock in this important territory. In Europe, where our marketing authorization application is under review, we are building out an experienced commercial organization that is preparing for the expected approval by the European Medicines Agency in the fourth quarter of this year. This focus team will be well positioned to quickly deliver Kenilock to patients in early launch markets once EMA approval is secured.

As a reminder, and estimated 30000 new patients are diagnosed with just in China, each year, and we look forward to supporting our partner XI lab as they launch can lock in this important territory.

And Europe, where our marketing authorization application is under review, we are building out and experienced commercial organization that is preparing for the expected approval by the European Medicines agency and the fourth quarter of this year.

And this focus team will be well positioned to quickly deliver Ken lots of patients and early launch markets. Once the EMA approval is secured.

Steven L. Hoerter: Our next priority for Kinlock is moving this medicine into earlier lines of therapy for GIST. We have seen the significant difference Kenlock has been able to make in the lives of patients with fourth-line gist and are eager to bring that life-changing impact to patients in earlier lines of treatment. We continue to expect to announce top-line results from the ongoing Phase 3 Intrigue study in second-line GIST in the fourth quarter of this year.

Our next priority for Ken losses, moving this medicine into earlier lines of therapy for Jess.

We have seen the significant difference can lock has been able to make and the lives of patients with fourth line gist and are eager to bring that life changing impact to patients and earlier lines of treatment.

We continue to expect to announce top line results from the ongoing phase III intrigue study and second line Gist and the fourth quarter of this year.

Steven L. Hoerter: In addition to Ken Locke, we remain focused on advancing our growing pipeline of novel kinase inhibitors. In June, we treated the first patient in our phase one study of DCC 3116. This phase one study is investigating the safety and tolerability of our first in-class switch control, an ulk-kinase inhibitor, first as monotherapy in patients with solid tumors expressing a mutant raz or rap gene, and then in combination with a mech inhibitor.

In addition to Ken lock, we remain focused on advancing our growing pipeline of novel kinase inhibitors and June we treated the first patient and our phase 1 study of DCC 31.16.

This phase 1 study is investigating the safety and Tolerability of our first in class switch control all kinase inhibitor first as monotherapy in patients with solid tumors expressing and mutant Ras RAF Jane and then in combination with the mechanism.

Steven L. Hoerter: We believe we have a leading position in the development of regulators of autophagy for cancer, an approach that holds tremendous potential to help a very large group of patients. As Matt Sherman, our chief medical officer, will discuss in more detail, we were pleased to announce today an exclusive licensing agreement with Sprint Bioscience for a research stage program targeting VPS 34, another important kinase in the autophagy pathway. This research program is complementary to DCC 3116 and builds on our expertise in the science of regulating autophagy in cancer.

We believe we have a leading position and the developments of regulators of Autophagy for cancer and approach that holds tremendous potential to help of very large group of patients.

As Matt Sherman, our Chief Medical Officer, who will discuss in more detail. We were pleased to announce today and exclusive licensing agreement with sprint and Bioscience for a research stage program targeting Vps 30 for another important kinase and the Autophagy pathway.

This research program is complementary to <unk> 31, 2016, and builds on our expertise and the science for regulating autophagy and cancer.

Steven L. Hoerter: We are also pleased with the progress we are making with our later stage clinical development programs. At the upcoming ESMO Congress, we look forward to presenting new data from the Phase 1-2 study of Vimseltonib in patients with tenisinovial giant cell tumor, as well as data from the platinum-resistant ovarian cancer cohort from the Phase 1B2 study of ribastinid in combination with Pachlactin

We are also pleased with the progress we are making with our later stage clinical development programs at the upcoming ESMO Congress, we look forward to presenting new data from the phase 1 and 2 study of them Sultanate of inpatients with tennis and OBL giant cell tumor.

In addition to data from the platinum resistant ovarian cancer cohort from the phase <unk> study of <unk> and combination with Paclitaxel.

Daniel C. Martin: We plan to finalize pivotal development studies for both programs in the second half of the year. I'll now turn the call over to Dan Martin, our chief commercial officer, to discuss the U.S. Kenlock commercial results from Q2, Dan. Thank you, Steve.

We plan to finalize pivotal development studies for both programs and the second half of the year.

I'll now turn the call over to Dan Martin, Our Chief commercial officer to discuss the U S can lock commercial results from Q2, Dan.

Thank you Steve in Q2, the commercial team continued to execute against our core launch objectives. Since our approval in May of last year, we've established <unk> as the clear standard of care and our initial fourth line indication and of rapidly penetrated the fourth line market opportunity.

Daniel C. Martin: In Q2, the commercial team continued to execute against our core launch objective. Since our approval in May of last year, we have established Kinlock as the clear standard of care in our initial fourth-line indication and have rapidly penetrated the fourth-line market opportunities. Importantly, we have also built broad clinical experience of positive product perceptions among both academic and community prescribers in advance of our planned launch into the significantly larger second-line opportunity.

Importantly, we have also built broad clinical experience of positive product perceptions, among both academic and community just prescribers and advance of our planned launch into the significantly larger second line opportunity.

Daniel C. Martin: In Q2, we achieved 22 million in total net product revenue globally, including 20.7 million in the U.S. Kinlock performance metrics remain extremely positive as we continue to capitalize on the opportunity for Kinlock to provide significant clinical benefit in the fourth line settings. Despite lingering physician access challenges created by the pandemic, our sales and marketing teams continue to achieve high levels of prescriber reach and share a voice. Kenlock awareness and familiarity among targeted just treaters remain extremely high.

And Q2, we achieved 22 million and total net product revenue globally, including $20.7 million and the U S.

Kinloch performance metrics remain extremely positive as we continue to capitalize on the opportunity for kinloss to provide significant clinical benefit and the fourth line setting.

Fight lingering physician access challenges created by the pandemic, our sales and marketing teams continue to achieve high levels prescriber reach and share of voice.

Kind of like awareness and familiarity among targeted gist treaters remain extremely high and.

Daniel C. Martin: And prescribers from both academic and community settings continue to cite strong Kinlox performance across all key product adjuncts. In Q2, we continue to expand our prescriber footprint. Since launch, over 450 physicians representing more than 400 institutions have prescribed Kinlox. As expected, while academic physicians made up the majority of our earliest adopters, most of our new prescriber growth is now coming from community sites.

And prescribers from both academic and community settings continue the site strong kinlaw performance across all key product attributes.

In Q2, we continued to expand our prescriber footprint since launch over 450 physicians representing more than 400 institutions have prescribed kinlaw.

As expected while academic physicians made up the majority of our earliest adopters most of our new prescriber growth is now coming from the community setting.

Daniel C. Martin: We are pleased with our progress within community practices, not only as it relates to our current fourth line launch but also as it relates to our planned second line launch, as we expect community prescribers to play an even larger role in earlier lines of therapy. Overall, we believe our success to date across both academic and community settings reflects Kinlux's highly differentiated clinical profile and proven patient benefit, as well as its historically difficult to treat disease. Regarding duration of therapy, the real-world persistency that we see for patients who have received Kinloat continues to be similar to what we saw in the Invictus study, consistent with our pre-launch expectations.

We are pleased with our progress within the community practices not only as it relates to our current force line launch, but also as it relates to our planned second line launch as we expect community prescribers to play an even larger role and earlier lines of therapy.

Overall, we believe our success to date across both academic and community settings reflects <unk> highly differentiated clinical profile and proven patient benefit and this historically difficult to treat disease.

Regarding duration of therapy, the real world Persistency that we see for patients who have received kinlaw continues to be similar to what we saw and the Invictus study.

And with our prelaunch expectations.

Daniel C. Martin: As we have shared previously, we expect the average time on therapy to eventually be longer than the median, based on experience from our clinical trials in which some patients remained on therapy for extended periods. We continue to monitor the impact that the COVID pandemic is having in oncology broadly and in just specifically. Recent data from IQVAS show that the pandemic's negative impact on diagnosis visits has persisted into 2021. Acuvia now estimates that this has reduced total oncology prescriptions by 21% through the first half of the year.

As we have shared previously we expect the average time on therapy to eventually be longer than the median based on experience from our clinical trials and which some patients remained on therapy for extended periods and.

We continue to monitor the impact that the Covid pandemic is having and oncology broadly and and just specifically <unk>.

Recent data from accuse me of shell.

Pandemic has negative impact on diagnosis of visits has persisted into 2021.

Excuse me and now estimates that this has negatively impacted total oncology prescriptions by 21% through the first half of the year.

Daniel C. Martin: Regarding just patient volume, claims data continue to show an approximate 10% decline in new patient starts in earlier lines of therapy over the past year. Assessing the impact of COVID is challenging, particularly given that we lack a pre-pandemic baseline for comparison.

And just patient volume claims of the continued to show an approximate 10% decline and new patient starts and earlier lines of therapy over the past year.

Assessing the impact of Covid is challenging, particularly given that we lack of pre pandemic baseline for comparison. However, taken together. These data suggest that COVID-19 may be having an impact on the volume of gist patients progressing the fourth line treatment.

Daniel C. Martin: However, taken together, these data suggest that COVID may be having an impact on the volume of just patients progressing to fourth-line treatment. One of our core objectives is to optimize patient access to Kinlo. And we were very pleased to see excellent payer coverage continue during the quarter with policies aligned to our FDA label. Regarding the percentage of patients receiving free drugs under our patient assistance program, or PAP, we saw an increased trend in Q2 versus prior quarters.

1 of our core objectives is to optimize patient access to Kinloch and we were very pleased to see excellent payer coverage continued during the quarter with policies aligned to our FDA label.

Regarding the percentage of patients receiving free drug under our patient assistance program or Pap, we saw an increased trend in Q2 versus prior quarters for the quarter. The type of percentage was at the high end of our estimated range of 20% to 30%.

Daniel C. Martin: For the quarter, the PAP percentage was at the high end of our estimated range of 20 to 30%. This trend appears to be driven by increased patient affordability challenges that result from the Medicare Part D drug benefit design. It's important to keep in mind that Medicare patients who receive free drugs under a company's patient assistance program must remain within that program through the end of the calendar year.

And just trying to appear to be driven by increased patient affordability challenges that result from the Medicare part D drug benefit design and it's.

And it's important to keep in mind that Medicare patients, who receive free drug under a company is patient assistance program must remain within that program through the end of the calendar year, therefore, although projecting pap and future quarters is challenging we expect to see higher pap levels persist in Q3, and Q4 potentially exceeding our estimated.

Matthew L. Sherman: Therefore, although projecting PAP in future quarters is challenging, we expect to see higher PAP levels persist in Q3 and Q4, potentially exceeding our estimated range. As we look ahead, preparations are underway for our planned second-line launch pending FDA approval. We are extremely optimistic about the significant potential for Kinlock in the second-line setting, driven by a larger estimated patient population and anticipated longer duration of therapy. Our enthusiasm regarding Kinlox's potential to positively impact a broader population of just patients is widely shared by just treaters, underscoring the recognized need for an improved second-line treatment. In market research, leading thought leaders and community oncologists have consistently shared their desire to use Kinlock in the second line, pending FDA approval.

Range.

As we look ahead preparations are underway for our planned second line launch pending FDA approval. We are extremely optimistic about the significant potential for kinloch and the second line setting driven by a larger estimated patient population and anticipated longer duration of therapy.

And our enthusiasm regarding kinlaw ex potential to positively impact the broader population of patients is widely shared by just treaters underscoring the recognized need for and improve second line treatment option and <unk>.

Market research, just thought leaders and community oncologists have consistently share their desire to use Kim lock and the second line pending FDA approval.

Matthew L. Sherman: To date, Kinlock has had a profound impact on the treatment of patients with GIST, and we believe the success we have seen in our initial fourth-line indication provides a strong foundation for Kinlock in the future. We look forward to building on that foundation and to helping even more patients with GIST by expanding into the second line setting, pending positive data from intrigue later this year and subsequent approval. I will now turn the call over to Matt to discuss the progress of our clinical programs. Matt?

To date Kinloch has had a profound impact on the treatment of patients with gist and we believe the success, we have seen and our initial fourth line indication provides a strong foundation for Kinloch and the future. We look forward to building on that foundation and to help even more patients of ingest by expanding into the second line setting pending positive data from <unk>.

For this year and subsequent approval I will now turn the call over to Matt to discuss the progress of our clinical programs Matt.

Matthew L. Sherman: Thank you, Dan. This quarter was marked by impressive progress expanding our pipeline of exciting novel kinase inhibitors. I'd like to start today by discussing our newest policy program, DCC-3116, which we believe to be a first-in-class oak kinase inhibitor in development for the treatment of mutant, RAS, and RAS cancer. In June, we achieved an important milestone, enrolling the first patient in the Phase 1, First in Human Studies. DCC-3116 is designed to inhibit autophagy, an important process in which recycling components fails to generate Phatophagy is often upregulated in cancer cells through the stress advantage caused by anti-cancer treatment.

Thank you Dan this quarter was marked by impressive progress expanding our pipeline of exciting novel kinase inhibitors.

And I'd like to start today by discussing our newest clinical program DCC 31, 16, which we believed to be of first in class <unk> kinase inhibitor and developments of the treatment of Ras.

And <unk> and Ras cancers.

And Julie achieved an important milestone dosing the first patient receipts 1 first in human study.

DCC 31, 16 is designed to inhibit autophagy and important process in which sales recycled conforms to generate energy.

The conference is often up regulated and cancer cells to the stress of the damage caused by the airplane cancer treatments.

Matthew L. Sherman: DCC-3116 is designed to suppress atopathy by inhibiting the oak kinase, the initiating factor in the autopsyche path. The clinical development plan for DCC 3116 will focus on documented RAS and RAF cancer mutations, which utilize autophagy for tumor growth and survival. Assuming positive results in the dose escalation phase, expansion cohorts in combination with Tremetnib, a commercially available MEC inhibitor, are currently planned in multiple tumor treatments. We're continuing to explore other combination partners for DCC 3116 preclinically, and we expect to evaluate it in combination with other inhibitors of the RAS, NAP, and Kinesis signaling pathways beyond MAP.

PTC 31, 16, this designed to suppress the top G by inhibiting the <unk> the.

And the initiatives factor and your top 2 pathway the.

And the clinical development plan for DCC through 2016, we will focus and documented Ras and <unk> cancer mutations would utilize the constitute the tumor growth and survival.

The assuming positive results and the dose escalation phase expansion cohorts and combination with permitting and commercially available net inhibitor for currently planned multiple tumor types.

We're continuing to explore other combination partners for DCC 31, 16, pre clinically and we expect to evaluated in combination with other inhibitors of the Ras map kinase signaling pathway beyond net.

Matthew L. Sherman: Our research team has generated additional exciting preclinical data with DCC-3116 in combination with approved, targeted oncology agents and multiple tumor types, demonstrating the potentially broad applicability of targeting metopoies through OPE in addition. We look forward to sharing some important work at an upcoming medical meeting. Our enthusiasm for the potential of autophagy as an important targetable pathway in oncology does not end with DCC-3116.

Our research team has generated additional exciting preclinical data with DCC through 2016, and combination with approved targeted oncology agents in multiple tumor types and demonstrating potentially broad applicability the targeting the top of the Gs who in addition.

We look forward to serving some important work with and upcoming medical meeting.

Our enthusiasm for the potential of the cough and she is an important target will pathway and oncology is not and with DCC 31.16.

Matthew L. Sherman: As Steve mentioned, we in-licensed the exclusive rights to a research stage program targeting VPS 34. The VPS 34 program complements our robust internal research programs and growing pipeline and enhances our efforts to explore the potential of regulating ontophagy and cancer. Together, the Pfeiffer's ALC and DPS 34 programs represent a comprehensive approach to addressing the clinical role of autophagy in cancer, with the potential to benefit a very large number of patients. Moving on to our other programs, we were excited to present data from both the Kim Locke and Repd Ascent Clinical Studies at this year's ASCO annual meeting.

Steve mentioned, we in licensed the exclusive rights to of research stage programs targeting Vps 30 for.

The bps 30 per program complements of our robust internal research programs and growing pipeline and enhances our efforts to explore the potential for regulating on concentrate and cancer.

Together, the pressures and EPS.

For the 4 programs represents a comprehensive approach to addressing the critical role of the competency and cancer with the potential to demonstrate a very large number of patients.

Moving onto our other programs, we were excited spruce and data from both of the Kim Wellington and ripped out of the clinical studies and this year's ask of annual meeting.

Matthew L. Sherman: For Kinlock, we presented an exploratory analysis of our unfitist phase three studies showing that dose escalation with Kinlock, 150 milligrams BID acid progression and 150 milligrams QD can offer substantial additional clinical benefit with a tolerable safety profile. These data were published in the peer-reviewed journal, The Oncologist, just last week. As the body of data supporting Kinloch's efficacy and safety continues to grow, we are pleased with its potential to offer clinically meaningful benefit for just patients and multiple settings of the disease.

For <unk>, we presented and exploratory analysis from Orange.

This phase III study showing the dose escalation for 10 lakh 150 milligrams PID ask the progression of 150 milligrams QD can offer substantial additional clinical benefit with a tolerable safety profile of.

These data were published in the peer reviewed journal the oncologists just last week.

The body of data supporting 2 months for efficacy and safety continues to grow we are pleased with the potential to offer a clinically meaningful benefit so just patients and multiple settings of the disease.

Matthew L. Sherman: For the ongoing intrigue phase three study comparing Kinlock Q submit and patients with second-line gist, we remain optimistic that the top-line data expected in the fourth quarter of this year will demonstrate significant clinical benefit for these patients. We believe that the exceptional results of the Invitous Phase 3 study, showing a median PFS of 6.3 months with fourth line plus just patients receiving Kinlock, as well as the phase one data, strongly support the likelihood of 6-fast in the intrigue.

For the ongoing and treat phase III study comparing similar to submit <unk> and patients with the second line Gist, we remain optimistic of the top line data expected in the fourth quarter. This year will demonstrate significant clinical benefit for these patients. We believe that the exceptional results of the Invictus phase III study showing a median PFS of $6.3.

The months of sports and line plus just patients receiving 10 months as well as the phase 1 data strongly support the likelihood of success and the increase.

Matthew L. Sherman: For the fourth quarter, we are excited to initiate a phase 1BQ study of Kinlock in combination with Binim Metinip, a commercially available neck inhibitor, to address one of the potential resistance mechanisms in post-Matinib chip patients. As we stated before, the goal of this new study is to see whether we can deepen and prolong initial responses by combining broad kidney inhibition with pinlock with inhibition of the MAP kinase pathway using a MEC inhibitor for patients with post-Matinib resistance.

Planned for the fourth quarter, we are excited to initiate the phase <unk> study of Kinloch and combination with many net net a commercially available neck and difficult to address 1 of the potential resistance mechanisms and post the mountain of just.

As we stated before the goal of this new study is to see whether we can deepen and prolonged initial responses by combining rudkin and ambition with Kumar within the addition of the map kinase pathway using a mechanism for their for patients with post Imatinib chips.

Matthew L. Sherman: We've also been studying Rabafinip, our selective TIE2 inhibitor, in two phase 1B2 studies utilizing a Simon two-stage design in combination with Paco-Taxil and in combination with Carboplatin. For the Carbo-Platin study, we presented preliminary data from the dose escalation phoesas as no last year, and have been evaluating the combination in three tumor-specific expansion cohorts While we have seen additional clinical activity in the carboplatin expansion and a tolerable safety profile, we have not seen the level of clinical activity that we believe is necessary to continue development at this time and have decided to focus our resources on the redactyl-tacyl combination.

We've also been studying the definite for selective tie 2 inhibitor and 2 phase 1 the 2 studies utilizing a Simon 2 stage design and combination with Paclitaxel income and as with Carboplatin and for.

For the Carboplatin and study we presented preliminary data from the dose escalation phase of the ESMO last year and have been evaluating the combination of 3 tumor specific expansion cohorts.

While we have seen additional clinical activity and the carboplatin and expansion and a tolerable safety profile, we have not seen the level of clinical activity of the we believe is necessary to continue development of this time and have decided to focus our resources for a desk.

For example combination.

Matthew L. Sherman: We continue to generate informative data in the Pacotaxil study, and we look forward to sharing updated data from the Platinum Resistant ovarian cancer cohort at the Esmo Congress in September. The data will include updated safety and efficacy data on the full cohort of patients in the second stage, including progression-free survival, which we believe is the key indicator of clinical activity and is difficult to treat in the patient population. Based on the published literature, single-age impactalactin and platinum-resistant ovarian cancer is expected to be approximately three to four months.

We continued to generate and forms of data and the Paclitaxel study and we look forward to sharing updated data from the platinum resistant ovarian cancer cohort at the ESMO Congress in September the.

Data will include updated safety and efficacy data on the full cohort of patients and the second stage, including progression free survival, which we believe is the key indicator of clinical activity and this difficult to treat patient population base.

Based on the published literature single agent Paclitaxel in platinum resistant ovarian cancer is expected to be approximately 3 to 4 months. We look forward to presenting these updated results of ESMO next month.

Matthew L. Sherman: We look forward to presenting these updated results at ESMO next month. We plan to finalize pivotal development plans for robustening the combination with Paco-Taxin in the second half of this year. Finally, we are excited to share updated data for Zim Sultanate, which we believe is the best in class inhibitor of CSF1R for the treatment of Tenozoin-Sinobio Giant Soul Tumor, at this year's ESMO Congress in September, along with guidance on our pivotal development plans for this program.

We plan to finalize the pivotal development plans for divestment of the combination with Paclitaxel and the second half of this year.

Finally, we are excited to share updated data for themselves and which we believe to be the best in class inhibitors and discipline are for the treatment of tenants and the OBL giant cell tumor and this year's ESMO Congress in September along with guidance on the pivotal development plans for this program.

Thomas Patrick Kelly: At ESMO, we expect to present updated safety and efficacy data from the ongoing phase one-two study in the approximately 50 TGCT patients. We look forward to the continued progress of these programs, each of which has the potential to make a meaningful difference in the lives of patients and fulfill current medical needs. I will now turn the call over to Tucker Kelly, our chief financial officer, to review the financial results. Thanks, Matt.

And Theres no we expect present updated safety and efficacy data from the ongoing phase <unk> study and the approximately 50 <unk> patients.

We look forward to the continued progress of these programs each of which has the potential to make a meaningful difference and the lives of patients and fulfill current unmet medical needs.

And I will now turn the call over to Chuck and Kelly, Our Chief Financial Officer to review the financial results Tucker.

Thanks, Matt.

It would be the highlights of our second quarter financial results.

Revenue for the second quarter was $23.6 million, which includes $22 million and net product revenue of Kinloch net product revenues for the second quarter of 2021 includes U S sales of <unk> of $20.7 million and ex U S sales of Kinloch of $1.3 million.

Thomas Patrick Kelly: I'd like to share the highlights from our second quarter financials. Total revenue for the second quarter was 23.6 million, which includes 22 million in net product revenue with Kinloch. Net product revenues for the second quarter of 2021 include U.S. sales of Kinlock of 20.7 million and ex-US sales of Kinlock of 1.30. The growth to net adjustment in the second quarter was significantly lower than our annualized estimate, at 15%, and we expect to be more in line with our 15% estimate in future quarters.

The gross to net adjustment and the second quarter was significantly lower annualized estimate of 15% and we expect it to be more in line with our 15% estimate in future quarters collab.

Collaboration revenue of the quarter was $1.5 million, which includes commercial supply and royalty revenue under argument was eyelab for greater China.

Cost of sales for the 3 months ended June 30 of 2021 was $1.3 million, which included 400000 and cost of net product revenue for kinlaw product sales and 900000 and cost of collaboration.

As we've said previously and we expect the cost of net product sales and the U S. We made immaterial for at least this year and would not expect net cost of sales to be significant until the initial prelaunch inventories depleted and additional inventories manufactured and sold.

Thomas Patrick Kelly: Collaboration revenue in a quarter was $1.5 million, which included commercial supply and royalty revenue. Under our argument, ILAB was for greater. Cost of sales for the three months into June 30th, 2021, was $1.30 million, which included $400,000 in cost of net product revenue for Kinlox and $900,000 in cost of collaboration.

Total operating expenses were $94.1 million and in the second quarter of 2021 compared to total operating expenses of 76 million and the same periods of 2020.

Research and development expenses, and the second quarter was $60 million compared to $46.1 million and the same period and 2020.

Selling general and administrative expenses and the second quarter were $32.8 million compared to $29.9 million in the same period and 2020.

Thomas Patrick Kelly: As we have said previously, we expect the cost of net product sales in the U.S. will remain immaterial through at least this year, and we would not expect the cost of sales to be significant until the initial pre-launch inventory is depleted, and additional inventory is manufactured and sold. Total operating expenses were $94.1 million in the second quarter of 2021, compared to total operating expenses of $76 million in the same period in 2020. Research and Development expenses in the second quarter were $60 million compared to $46.1 million in the same period in 2020. Selling general and administrative expenses in the second quarter were $32.8 million compared to 29.9 million in the same period in 2020.

We continue to expect that our operating expenses will increase modest and this year as we invest and the development of our clinical pipeline execute on the commercialization of can lock and the U S and prepare for potential commercial launch in Europe.

We ended the second quarter, and a strong financial position and remain well capitalized with cash cash equivalents in marketable securities of approximately $451 million, which we expect will be sufficient to fund our operations into the first half of 2023 with that I'll now turn the call back over to Steve.

Thank you Tucker, we continue to make important progress across our strategic priorities in 2021, while our focus has been on established and Ken lock as the standard of care and fourth line gist around the World. We are excited as we prepare to report the top line results from the intrigue study and Q4 of this year. If successful. These study results will enable filings around the world.

World and dramatically expand the potential for Ken locked the benefit patients with just our progress and this most recent quarter has demonstrated the strength of our pipeline and beyond Kinlaw. We have successfully initiated the phase 1 study of DCC 3116, and we look forward to sharing new data and finalizing pivotal development plans for them Sultanate of and robust and it later this year.

Steven L. Hoerter: We continue to expect that our operating expenses will increase modestly this year as we invest in the development of our clinical pipeline, execute on the commercialization of Kinlock in the U.S., and prepare for potential commercial launch in Europe. We ended the second quarter in a strong financial position and remain well capitalized with cash, cash equivalence, and marketable securities of approximately $451 million, which we expect will be sufficient to fund our operations into the first half of 2023. With that, I'll now turn the call back over to State. Thank you, Tucker.

Operator, I'd now like to open the call for Q&A.

And thank you.

And as a reminder, we just ask that you limit yourself, the 2 or 3 questions and then get back into queue. As a reminder to ask the question you'll need the press star 1 on your telephone to Joel Your question press. The pound key please standby will be compile the Q&A roster and our first question comes from.

Steven L. Hoerter: We continue to make important progress across our strategic priorities in 2021. While our focus has been on establishing Kenlock as the standard of care and fourth-line GIST around the world, we are excited as we prepare to report the top-line results from the intrigue study in Q4 of this year. If successful, these study results will enable filings around the world and dramatically expand the potential for Kenlock to benefit patients with GIST. Our progress in this most recent quarter has demonstrated the strength of our pipeline beyond Kenlock.

Jessica Fye from Jpmorgan. Your line is now open.

Hi, This is Daniel for Jessica Fye, Thanks for taking our question and your prepared remark you have described the impact of Covid on new patient starts as well as from free drug use do you of any new insight and whether Covid has an impact on the duration of therapy and how that makes you kind of evolved over the last year and into second half first half of 2021.

That's my first question.

Steven L. Hoerter: We have successfully initiated the phase one study of DCC 3116, and we look forward to sharing new data and finalizing pivotal development plans for Vimseltenib and Rabastinib later this year. Operator, I'd now like to open the call for Q&A. And thank you.

The question is the addressable fourth line market seems smaller than we had previously anticipated as we approach and treat the data read out and think about the second line opportunity. What gives you the confidence at the St will not be true for the second line of opportunity.

And last question is maybe can you set the stage for us for the phase 1 the phase won't be flash to steady of for back to net in platinum resistant ovarian cancer settings.

Operator: And as a reminder, we just asked that you limit yourself to two or three questions, then get back into Q. As a reminder, to ask a question, you'll need to press Star 1 on your telephone. To draw your question, press the pound key.

In terms of what we can see and patient number wise for a lot of number of scans. Thanks.

Operator: Please stand by. We'll be compiling the Q&A roster, and our first question comes from Jessica 5, from J.P. Morgan. Your line is now open. Hi, this is Daniel from Jessica Fai.

Great Daniel Steve. Thanks, Thanks for all the questions. So I will try and take these somewhat of an order maybe what I'll do first is.

Jessica Fye: Thanks for taking your question. In your prepared remarks, you described the impact of COVID on new patient starts as well as free drug use. Do you have any new insight on whether COVID has an impact on duration of therapy and how that matrix has evolved over the last year and into the first half of 2021? That's my first question.

Your second question, which relates to the performance and the fourth line and then I'll ask Dan to talk a little bit about the COVID-19 impact to the extent of you could add some additional color and then I'll ask Matt to take the platinum resistant ovarian cancer cohort questions of the data that's coming up here next month at ESMO, which we're excited about.

So first with respect to your question on the fourth line opportunity I think I'll just start by reiterating what I said and Dan says and the prepared remarks, which is that we're really pleased with the launch performance and the U S to date and how this sets the stage as you pointed out for the second line and shrink study, which is due to readout and quarter 4 so we think.

Jessica Fye: The second question is the addressable market for the live market seems smaller than we had previously anticipated. As we approach intrigue data readout, think about that. About the second line opportunity, what gives you the confidence that the same will not be true for the second line opportunity? And last question, maybe you can set the stage for us for the phase 1B slash 2 study of Rabastinup in platinum-resistant ovarian cancer settings in terms of what we can see patient number wise, as well as number of scans? Thanks. Great. Daniel, and Steve.

Having established the drug as the standard of care and the fourth line indication with largely with the community Docs now as Dan outlined in his prepared remarks with a large fraction of the new prescribers coming from the community really sets the stage now for us to move and so the second line of with the readout of the intrigue study later this year and then filings that wood.

Steven L. Hoerter: Thanks for all the questions. We'll try and take these somewhat in order. Maybe what I'll do first is take your second question, which relates to performance on the fourth line. And then I'll ask Dan to talk a little bit about the COVID impact to the extent that you can add some additional color. And then I'll ask Matt to take the platinum-resistant ovarian cancer cohort question, data that's coming up here next month at Esmo, which we're excited about.

Flow from that I think with respect to the demand of dynamics that we see and the fourth line the underlying drivers of demand and this fourth line indication.

And the same as we talked about on the quarter 1 call. So.

And we noted on that call that the the next big leg up and growth. We thought was going to be coming from the second line indication and Thats really driven by 2 factors..1 is just the larger number of patients that we see and the second line and as you know we estimate the treatment eligible number of patients and the second line and the U S of being at about 2000 patients and the second driver and the second 1 we believe.

Steven L. Hoerter: So first, with respect to your question on the fourth-line opportunity, I think I'll just start by reiterating what I said and Dan said in the prepared remarks, which is that we're really pleased with the launch performance in the U.S. to date and how this sets the stage, as you pointed out, for the second-line intrigue study, which is due to be read out in quarter four. So we think having established the drug as the standard of care and this fourth-line indication, largely with community docs now, as Dan outlined in his prepared remarks, with a large fraction.

And it's going to be related to duration of treatment.

So those of the 2 factors that really to look to as we think about the second line opportunity per.

Ending the and treat readout, Dan would you like to take the the Covid question and the mattresses of reminder of the platinum resistant ovarian cancer cohort question for asthma.

Steven L. Hoerter: of new prescribers coming from the community really sets the stage now for us to move into the second line with the readout of the intrigue study later this year and then filings that would flow from that. I think with respect to the demand dynamics that we see in the fourth line, the underlying drivers of demand for this fourth line indication remain the same as we talked about on the quarter one call. So, you know, we noted on that call that the next big leg up in growth we thought was going to be coming from the second line indication. And that's really driven by two factors.

Yeah, absolutely. Thanks for the question Daniel So just to clarify we did note that we continue to track the <unk>.

Impact of Covid and try to assess what impact, it's having on oncology broadly and and.

Just specifically.

And what I, what I mentioned just to make sure I'm clarifying is that some of the data that we look at points to potential impact to new.

The new patient starts and earlier lines of therapy over the last year of approximately 10%.

Thank you asked about path, we haven't spoken specifically to COVID-19 impact on Pap.

Steven L. Hoerter: One is just the larger number of patients that we see in the second line. And as you know, we estimate the treatment-eligible number of patients in the second line in the U.S. It being at about 2,000 patients. And the second driver in the second line, we believe, is going to be related to duration of treatment. So those are the two factors really to look at as we think about the second line opportunity pending the intrigue readout. Dan, would you like to take the COVID question and then Matt, this is a reminder of the platinum-resistant advanced cancer cohort question for ESMO? Yeah, absolutely.

Pat was increased in Q2, as we talked about at the high end of our range and because of the way path works, where patients, who and where that program and have to remain in the program and for the balance of the calendar year, we expect that our higher levels of patent may persist into Q3, and the Q4 potentially above the.

The estimated range that we provided.

But didn't.

And tie that into the Covid specifically.

And then lastly are are we able to discern any impact of COVID-19 on duration and the short answer to that is no. We have not and we continue to be really pleased with.

Daniel C. Martin: Thanks for the questions. So just to clarify, we did note that we continue to track the impact of COVID and try to assess what impact it's having on the ecosystem broad. And what I mentioned, just to make sure I'm clarifying, is that, you know, some of the data that we look at points to potential impact to new patient starts in earlier lines of therapy over the last year of approximately 10%. I think you asked about PAP.

The persistency that we're seeing and patients who've received cannot for launch as we've noted.

And it's developed as we expected and it looks a lot like what we saw and the Invictus study.

Yeah.

Yes.

And hi, Daniel This is Matt let me pick up the question about the rig thousands of data and Clinton resistant ovarian cancer and we plan to update next month as the meeting and as you remember it was the year ago that we present with the first part of the 2 stage Simon design and the expansion cohort for platinum resistant ovarian cancer.

Daniel C. Martin: We haven't spoken specifically about COVID's impact on PAP. PAP was increased in Q2, as we talked about at the high end of our range. And because of the way PAP works, where patients who enter that program have to remain in the program for the balance of the calendar year, we expect that higher levels of PAP may persist into Q3 and, and Q4, potentially above the estimated range that we've provided, but I didn't, I didn't tie that to COVID, you know, specifically. And then lastly, are we able to discern any impact of COVID on duration? And the short answer to that is no, we have not.

At the.

As the meeting 1 year ago and at that time, we had 24 evaluable patients and we reported 9 of the 20 for having a response for an objective response rate of 38%.

And that was early and the studies. So we now have completed full enrollment in the ex.

Spansion cohort and we have 33 evaluable patients and now not only on update on the objective response rate, but we'll also be able to provide the progression free survival and this cohort of patients. So we look forward to providing that data next.

The next month.

Thank you very much.

And thank you and our next question comes from Chris Raymond from Piper Sandler. Your line is now open.

Hey, thanks.

Daniel C. Martin: We continue to be really pleased. The persistency that we're seeing in patients who received Canlock from launch, as we noted, it's developed as we expect, a lot like what we saw on, And Hi, Daniel. This is Matt. Let me pick up the question about the rate base of data and platinum-resistant ovarian cancer that we plan to update at next month's ESMO meeting. As you remember, it was a year ago that we presented the first part of the two-stage Simon Design in the expansion cohort for platinum-resistant ovarian cancer at the ESMO meeting one year ago.

I wanted to just explore and maybe.

What I think I heard from Dan to the last question.

E D.

And I think you'd mentioned the last quarter. The fourth line Gist was already well penetrated.

And conferred no quarter on quarter growth.

The U S growth is my math goes it looks like it was 7% on the revenue line.

And I think I heard you say there was some patient starts and earlier lines of therapy. So maybe just can you just clarify is that what's driving the growth there or is there some other and.

I think I also heard you guys talk about the gross to net benefit can you maybe break out what what's driving that growth of its if it's not increased penetration and fourth line.

And then the second question is on the intra patient dose escalation data at <unk> and.

Daniel C. Martin: And at that time, we had 24 valuable patients, and we reported nine of the 24 having a response for an objective response rate of 38%. And that was early in the study, so we now have completed full enrollment in the expansion cohort, and we have 33 valuable patients. And now, not only an update on the objective response rate, but we'll also be able to provide progression-pre-survival data in this cohort of patients. So we look forward to providing that data next month. Thank you very much. And thank you. And our next question comes from Chris Raymond.

And the last time, we did of check which was pre <unk>, we didn't really see any indication of docs doing that maybe can you just broadly talk about how if youre seeing any anecdotal use and.

Employment of that is the data of resonating with the auction interest sort of any color sort of on that data you can provide.

<unk>.

The question Sidney Thanks, Thanks for the question Dan would you like to take both of the Chris's question Sir.

Yes, sure absolutely thanks, Chris and I appreciate the question so.

With respect to the performance and the 7% quarter over quarter.

And when we think about the.

The story for this quarter, we think about it in terms of demand and and then.

Christopher Joseph Raymond: from Chris Raymond on behalf of Piper Sandler. Your line is now open.

The things that impact Pap and gross to net and that's how we tried to sort of lay out.

Christopher Joseph Raymond: Hey, thanks. I wanted to just explore maybe what I think I heard from Dan on the last question. You know, Dan, I think you mentioned last quarter that the fourth line gist was already well penetrated, which I think inferred, you know, no quarter on quarter growth. Uh, the U.S. growth, as my math goes, it looks like it was 7% on the revenue line. Um, And I think I heard you say there were some patient starts in earlier lines of therapy.

The story of the quarter as it relates to demand.

Things are basically unchanged.

Changed consistent with what we've communicated previously which is that.

All of our data sources continue to suggest that <unk> is highly penetrated in the fourth line opportunity and.

Because of this higher share and that's why we've said as you noted that we expect the opportunity for demand growth to be limited.

Until our planned second line launch.

Christopher Joseph Raymond: So maybe can you just clarify, is that what's driving the growth there, or is there some other... Yeah, and I think I also heard you guys talk about a gross-to-net benefit. Can you maybe break out what's driving that growth if it's not increased penetration in fourth line? And then the second question is on the intrapatient dose escalation data at ASCO. You know, last time we did a check, which was pre-ASCO, we didn't really see any indication that doctors were doing that.

Did benefit quarter over quarter from lower gross to net as Tucker mentioned.

That was a component as well and then importantly, and the Pap piece, we saw particularly as we exited the quarter.

But of the increase and that Pat percentage, and we attribute that to the Medicare part D drug benefit design and how patients know that they are in that program and the need to stay in that program and how the program works.

And that's why we spoke to expecting potentially higher.

Christopher Joseph Raymond: Maybe can you just broadly talk about how, if you're seeing, you know, any anecdotal use, employment of that, is the data responding with docs, sort of any color, you know, sort of on that data you could provide? Thanks.

Tap and Q Q3, and Q4 as.

As well so I think those of the major pressure Oaks.

And then for IPD and.

The good question. So as Matt said, we're really pleased that we continue to grow the.

Sort of the.

The pace of data for kind of like broadly, but you are right. So far as we've said on prior calls we have not seen.

Daniel C. Martin: Hey, Chris, and Steve, thanks for the questions. Dan, would you like to take both of Chris's questions there? Yeah, absolutely. Thanks, Chris.

A lot of use of IPD, we see some.

And by the way and as always I should mention that we don't promote this data.

Daniel C. Martin: Appreciate the question. With respect to the performance and the 7% quarter over quarter, you know, when we think about the story for this quarter, we think about it in terms of demand and then, you know, things that impact PAP and gross to net. And that's how we tried to sort of lay out the story of the quarter. As it relates to demand, you know, things are generally unchanged, consistent with what we've communicated previously, which is that, you know, all of our data sources continue to suggest that Kinlock is, you know, highly penetrated in the fourth line opportunity.

Given that it's a it's an off label regimen and so we do see some payer coverage currently is a bit inconsistent.

And some claims get paid for some don't.

And so it is rather.

Minimal at this time.

So pretty consistent with what it sounds like Youre seeing and your survey.

And if I can ask a follow up on that and.

You guys did take a.

The almost 5% price increase I think.

Before the quarter began and it was there some impact from that that we should be thinking about as we model.

Yes of course, so that's why we did take a 4.9% price increase as of July 1. So that's the price increase that we've taken which is really in line with what we've seen with other oral on clinics.

Daniel C. Martin: And because of this higher share, that's why we've said, as you noted, that we expect the opportunity for demand growth to be limited until our planned second-line launch. We did benefit quarter over quarter from lower gross to net, as Tucker mentioned. That was a component as well.

As Dan just outlined there of variety of different factors of course, the contribute to overall performance and Dan just spoke to a couple of them that we thought and wanted to highlight for for quarter, 2 but there are a whole variety of factors, including price the play into the balance of the year. Okay. Thanks.

Daniel C. Martin: And then importantly, the PAP piece, we saw, particularly as we exited the quarter, a bit of an increase in that PAP percentage, and we attribute that to the Medicare Part D drug benefit design and how patients, now that they're in that program, they need to stay in that program. That's how the program works. And that's why we spoke to expect potentially higher PAP in Q3 and Q4 as well. So I think those are the major brush strokes.

And thank you and our next question comes from you and Yeung from Jefferies. Your line is now open.

Thank you so based on the steel based on your comments.

Daniel C. Martin: And then for IPDE, it's a good question. So, as Matt said, we're really pleased that, you know, we continue to grow the sort of base of data for Kinlock. But you're right, you know, so far, as we've said on prior calls, we have not seen a lot of use of IPDE. We see some. By the way, as always, I should mention that we don't promote this data, given that it's an off-label regimen.

And the clinical data that we've assigned to day.

Do you think it to fair to say that in the U S and leased the second line gist opportunity would that be about 4 times greater than fourth line.

And.

The question is for Matt.

Can you just sort of into the trial.

Daniel C. Martin: And so we do see some. Payer coverage is currently a bit inconsistent. Some claims get paid for, some don't. And so it is rather, you know, minimal at this time. So, you know, pretty consistent with what it sounds like you're seeing in your survey.

You guys are allowing.

So 10 does the reduction in the event of the toxic effects.

Can you comment on what percentage of of patients, So 10 and growth.

Christopher Joseph Raymond: If I can ask a follow-up on that, you guys did take an almost 5% price increase, I think, before the quarter began. Was there some impact from that that we should be thinking about as we model? Yeah, correct.

Uh huh.

Does the reduction and how.

And may compare to Pfizer.

The study for Syn 10, and second line and the last question is the Tucker.

Steven L. Hoerter: Yeah, Chris, and Steve, that's right. We did take a 4.9% price increase as of July 1st. So that's the price increase that we've taken, which is really in line with what we've seen with other oral oncoletics. And as Dan says that line, there are a variety of different factors, of course, that contribute to overall performance. Dan just spoke to a couple of them that we thought we wanted to highlight for quarter two. But there are a whole variety of factors, including price, that play into the balance of the year. And thank you, and our next question comes from

Are you planning to at some point are you planning to break out.

Revenue from the lab from the collaborative revenues. Thank you.

By you and Steve Thanks for the question so before I turn it over to Matt and then Tucker of let me let me take your first question and it really is just to reiterate what I said.

So the question from Daniel earlier, and the call earlier in the Q&A, which is the way we think about the second line opportunity relative to the fourth line opportunity is really driven by those 2 factors that we've talked about very consistently 1 is about the epidemiology. So the number of patients that we see and the second line and we believe there of about 2000, new patients that are treatment eligible and the U S. Each year.

Eun Kyung Yang: comes from you and Yang, Jeffries. Your line is now open.

Eun Kyung Yang: Thank you. So based on Steve, based on your comment, and the clinical data that we've seen to date, do you think it's fair to say that in the U.S., at least, the second-line gist opportunity would be about four times greater than the fourth line? And the second question is for Matt. So in the phase three intrigue trial, you guys are allowing Sutton a dose of reduction in the event of toxic effects. So can you comment on what percent of a patient's on the Sutton group?

And then the second component of that is really going to be about duration of the duration of treatment and how long patients are staying on therapy. We think those are going to be the 2 biggest.

<unk> differences and drivers relative to the fourth line opportunity.

And that would you'd like to take the question about and tree.

Sure.

And snapped so yes, we have an ongoing phase III study comparing the recruitment of Kim of too soon.

And the second line setting and this head to head comparison and as you know we fully enrolled the study as of the end of last year. We are we remain blinded to the data and so none of them to the treatment of something but to how patients have done on the study in terms of dose reductions or the modifications per treatment arm. So once we have the.

Eun Kyung Yang: I had dose reduction and how it may compare to Pfizer's Phase 3 study for Surtenant Second Line. And the last question is for Tucker. Are you planning to, at some point, are you planning to break out royalty revenue from Zyla from the collaborative revenues? Thank you. Hi, Unit, Steve.

The top line results, which we are planning to have this fourth quarter of this year, we will be able to make those comparisons compared to the indication the labeled indications of sunitinib and that setting.

Steven L. Hoerter: Thanks for the question. So before I turn it over to Matt and then Tucker, let me take your first question. And it really is just to reiterate what I said to the question from Daniel earlier in the call during the Q&A, which is the way that we think about the second line opportunity relative to the fourth line opportunity is really driven by those two factors that we've talked about very consistently.

Great and.

It's tough for all the answer your last question on the collaboration revenue at the moment, we don't have any.

The intention to breakout of the various components of collaboration revenue, which include the clinical and commercial supply that we have with the XI as well as now here in Q2, and the initial royalty payments and then and other quarters, we had milestone payments. So it's all at the moment related to the XI collaboration, but we haven't broken out the various components other than the.

Steven L. Hoerter: One is about the epidemiology, so the number of patients that we see in the second line. And we believe there are about 2,000 new patients that are treatment-eligible in the U.S. each year. And then the second component of that is really going to be about duration, duration of treatment, and how long patients are staying on therapy. We think those are going to be the two biggest differences in drivers relative to the fourth line opportunity. Matt, would you like to take the question about Intrigue? Sure. How are you doing in MAP?

Times, where we have a large milestone payment.

This quarter does include the commercial supply and initial royalty payments.

Thank you.

And thank you and our next question comes from Michael Schmidt from Guggenheim Securities. Your line is now open.

Hey, good afternoon, everybody. This is Charles Xu on for Michael and I guess, 1 commercial question first of all of shipped off to the pipeline, but how much line of sight do you have.

Matthew L. Sherman: So, yes, you know, we have our ongoing phase three study comparing reprintantant to Cynit in the second line setting in this head-to-head comparison. As you know, we fully enrolled this study as of the end of last year. We remain blinded to the data, so not only to the treatment assignment but to how patients did on the study in terms of those reductions or other modifications per treatment arm.

And 2 the number of second line patients currently present at the accounts, where you have of commercial presence off of your fourth line label and given the overlap and your experience thus far and fourth line I guess, how should we think about the potential launch trajectory and market opportunity assuming intriguing of successful. Thanks.

Thomas Patrick Kelly: So once we have the top line results, which we are to have in the fourth quarter this year, we'll be able to make those comparisons compared to the indication, the labeled indication of students in that setting. Great, and it's Tucker. I'll answer your last question on the collaboration revenues. At the moment, we don't have any intention to break out the various components of collaboration revenue, which include the clinical or commercial supply that we have with Zai as well as now here in Q2, the initial royalty payments, and then in other quarters we've had milestone payments.

And thanks, Charles that's a great question, Dan would you like to take that.

Absolutely and thanks for the question. So we've been really I've been really pleased with our ability to reach.

Treating of Gist treaters, despite the ongoing challenges of the pandemic it's tough.

And trying to pandemic of course, but the team really did a great job.

And pivoting just prior to launch and and finding ways to leverage both remote virtual but also in person interactions when possible.

And as a result of that we've been able to reach the vast majority of our targets.

Thomas Patrick Kelly: So it's all related to the ZI collaboration, but we haven't broken out the various components other than at times where we have, say, a large milestone payment. But this quarter does include both commercial supply and initial role.

And those targets arent just current fourth line treaters.

Target Gist treaters broadly.

Because of its hard to know, which 1 is going to have a fourth line.

Ah patient and when and so we've reached.

Thomas Patrick Kelly: And thank you. And our next question comes from Michael Smith, from Guggenheimer Securities. Your line is now open.

Quite a number of gist treaters we.

We do also work too.

Michael Werner Schmidt: Hey, good afternoon, everybody. This is Charles Zhu on for Michael. I guess the one commercial question first before I shift over to the pipeline, but how much line of sight do you have into the number of second-line patients currently present at the accounts where you have a commercial presence off of your fourth line label? And given the overlap in your experience thus far and with fourth line, I guess how should we think about potential launch trajectory and market opportunity, assuming intrigue is successful? Thanks, Charles. It's a great question. Dan, would you like to take this?

The 2 identify and be mindful of where.

Patients in earlier lines are out there so that when they do progressed the fourth line.

We're able to capitalize so we feel like we've got a really good feel for the just market now being out there as long as we have and.

And then we think it sets a great for a second line launch, but 1 of the things that we're really excited about is the progress we've made and the community setting.

And noted in my prepared remarks.

And that the majority of our new prescribers are now coming from the community.

And we think Thats ex.

Right because they are likely to play an even larger role when.

And when we get the second line. So we think the.

Daniel C. Martin: Yeah, absolutely. Thanks for the questions. So we've been really, I've been really pleased with our ability to reach, treating, you know, just treaters despite the ongoing challenge. Drugs and a pandemic, of course, but the team really did a great job, pivoting just prior to launch and finding ways to leverage both remote, you know, virtual, but also in-person interactions when possible. And as a result of that, we've been able to reach the vast majority of our targets.

The progress we've had and the fourth line.

And then has been great and right in line with our expectations and.

And.

And we've got a nice foundation set for a successful second line launch pending approval.

Makes sense and then maybe of 1 for Matt I think or so looking at our top of Judy I know Theres a lot of literature out there that describes the knowhow autophagy can play a role and the knee.

Immunization and addition to it.

Net net 10 minutes of alongside the rest of the rest and that the pathway I guess, how would you characterize your interest on that front in terms of clinical study and are there any sort of particular I guess the valuable biomarkers that could indicate and increase the tumor reliance on autophagy 2 of beat the immune system.

Daniel C. Martin: And, you know, those targets aren't just current fourth-line treaters. We target just treaters broadly because it's hard to know which one is going to have a fourth-line patient and when. So we've reached quite a number of just-treaters.

Daniel C. Martin: We do also work to identify and be mindful of where, you know, patients in earlier lines are out there so that when they do progress to fourth-line, we're able to capitalize. So we have a – we feel like we've got a really good feel for the just market now being out there for as long as we have. And then we think it sets up great for a second-line launch.

Yeah, Charles list of Great question and that 1 in Chicago.

Yes, Hi, Charles So yes. Thanks for the question, it's really interesting and I can spend a minute talking about some of the newer findings of both the role and Autophagy.

Surveillance.

Daniel C. Martin: One of the things we're really excited about is the progress we've made in the community setting. I've noted in my prepared remark that the majority of our new prescribers are now coming from the community. And we think that's great because they're likely to play an even larger role when we get the second line. So we think, you know, the progress we've had on the fourth line has been great and right in line with our expectations. And, you know, we've got a nice foundation set for a successful second line. Makes sense. And maybe one for Matt, I think.

The first we're very excited about the initiation of our phase 1 study of 31.16 of our old kinase inhibitors that we announced last month to have the first in human.

For the underway now and.

And we'll be progressing with the single Egypt for safety of 316, followed by combination initially targeting combination with <unk>.

Mutant Ras and Ras cancers of targeting the map kinase pathway for the initial combination study.

I think you referred to and your question and some recent published data is also very exciting the showing the subset of non small cell lung cancer patients who have the commutation of a Ras mutation plus the okay. The 1 mutation occurs and about 20% of non small cell lung cancer patients. They are hardly resistance of PD, 1 PD lone checkpoint blocker.

Matthew L. Sherman: So, looking at autophagy, there's a lot of literature out there that describes, you know, how autophagy can play a role in meaning immune evasion. In addition to, you know, its met mechanism alongside the RAFMECA pathway. I guess, how would you characterize your interest on that front in terms of clinical study? And are there any sort of particular, I guess, valuable biomarkers that could indicate it?

So and comparisons to the 30% of our greater response rates.

The PD 1 agents to provide some non small cell lung cancer patients if they could mute.

Matthew L. Sherman: and increased a tumor reliance on autophagy to a vaguely system. Yeah, Charles, it's a great question, Matt. Why don't you go ahead, please? Yeah, hi, Charles.

Carey the.

The KD, 1 mutation as well the have listened and timber sort of response rate.

The study of recently published showing back and inhibiting the <unk> in the tumor cells of the population.

Matthew L. Sherman: So, yeah, thanks for the question. It's really interesting, and I can spend a minute talking about some of the newer findings about both the role in autophagy and immune surveillance. You know, first, we're very excited about the initiation of our phase one study of 3116, our alkyness inhibitor that we announced last month to have the first in human study underway now. And we'll be progressing with a single agent for safety of 3116, followed by combination, initially targeting combination with, mutant rass and raff cancer.

And can restore immune responsiveness and allow for responsiveness to checkpoint inhibitors, such as the PD 1 PDL 1 pathway so that provides potential.

Opportunities for us and the future and.

Terms of combination studies.

Got it thanks for taking the questions.

And thank you and our next question comes from Robyn <unk> from <unk>.

True Securities. Your line is now open.

Hey, guys. Thank you so much for taking my question just the scrip on for Robyn.

I have the question about the ex U S expansion opportunities.

And fourth line and eventually and second line Gist I know your EMA approval is still on track for fourth quarter and you talked about.

Matthew L. Sherman: So targeting the nap kinase pathway for the initial combination study. What I think you referred to in your question is some recent published data. It's also very exciting to show that in a subset of non-small cell lung cancer patients, you have a co-mutation of a RAS mutation plus the LKB1 mutation. This occurs in about 20% of non-small cell lung cancer patients.

Launched in China, and Hong Kong.

The first.

Can we can you talk to us about any potential impact of COVID-19 on the commercial non commercial preparedness and EU, especially given how different the situation seems to be amongst the different countries and then looking beyond regions, where you either have approval or where you expect to privilege.

Matthew L. Sherman: They are highly resistant to PD1, PDL1 checkpoint blockade. So in comparison to the 30% or greater response rate that PD1 agents can provide to not small lung cancer patients. If they co-mutate or carry the LKB1 mutation as well, they have less than 10% response. The study of Ruisian published showing that by inhibiting the old kinase in tumor cells in that population, it can restore immunosponses and allow for responsiveness to checkpoint inhibitors such as PD1, PDO1 pathway.

Any color on expansion strategy.

The geographies, where you think it would be easy to penetrate and would be meaningful markets.

Thank you.

Yes, thanks for all of that Steve. Thanks for the Great question about our progress outside of the U S. So let me, let me try and address the questions that you posed.

Matthew L. Sherman: So that provides potential opportunities for us in the future in terms of combination studies. Thanks for taking the time to answer the question. And thank you. And our next question comes from Robin Karnaskis, from Choose Securities. Your line is now open. Hey, guys, thank you so much for taking my question. This is Crippa on for Robin.

First as you as you'll know we of course have the approval and the U S. The approval in Canada as well as Australia and now we've added to that the XI approval and their territory and.

And greater China, and in China, and Hong Kong, specifically, and we expect that we will see additional territories come on line additional approvals that will come both from the XI territory and also as you noted from outside of the XI territory, specifically, our EU approval, which we expect and quarter 4 of this year. So we've made really good progress in terms of starting to build our organization.

Robin Karnaskis: I had a question about the ex-US expansion opportunities, both in the fourth line and eventually in the second line, just so you know, EMA approval is still on track for the fourth quarter, and you talked about the launch in China and Hong Kong. First, can you talk to us about any potential impact of COVID on commercial launch and commercial preparedness in the EU, especially given how different the situation seems to be amongst the different countries. And then looking beyond regions where you either have approval or where you expect approval, any color on the expansion strategy? Are there other geographies where you think it would be easy to penetrate and would be meaningful markets? Thank you.

And in Europe to address the opportunity there.

And our focus is as I've mentioned before on prior calls it really on the early access markets. So as you may know certain markets, we have the opportunity to price freely and others. It requires of negotiation on price and on the reimbursement and.

Steven L. Hoerter: Yeah, thanks for the great question about our progress outside of the U.S. So, let me try and address the questions that you have posed. You know, first, as you'll know, we of course have the approval in the U.S., the approval in Canada as well as Australia, and now we've added to that the Zai approval and their territory in Greater China, China and Hong Kong specifically. And we expect that we will see additional territories come online, additional approvals that will come both from the Zai territory and also, as you noted, from outside of the Zide Territory, specifically our EU approval, which we expect in quarter four of this year.

And so as a result of market access can take some time, particularly in southern Europe, where it can take substantially longer and some cases, and we're making very good progress that only and attracting the right talent and building the team, but also getting the work done as we prepare for the potential approval in Europe at the end of this year and then we'll build and.

And the relevant territories across the U as we get market access so that we're very much be a staged approach to both the builds as well as for the launch as we get market access and of the opportunity to to deliver on revenue.

Steven L. Hoerter: So we've made really good progress in terms of starting to build our organization in Europe to address the opportunity there. And our focus is, as I've mentioned before, on prior calls, really on the early access markets. So, as you may know, in certain markets, we have the opportunity to price freely in others. It requires a negotiation on price and on reimbursement. And so, as a result, market access can take some time, particularly in southern Europe, where it can take substantially longer in some cases.

So with respect to expansion strategy. There really are 2 key areas of expansion strategy for Ken lock and the first day as we've talked about previously is about moving the drug and to an earlier line of treatment. That's the basis for the intrigue study, which we've spent a lot of time talking about and the second is you addressed is about geographic expansion. So our focus as a company.

Steven L. Hoerter: But we're making very good progress not only in attracting the right talent, building the team, but also getting the work done as we prepare for that potential approval in Europe at the end of this year. And then we'll build in relevant territories across the EU as we get market access. So that will very much be a staged approach to both the build as well as to the launch as we get market access and have the opportunity to deliver on revenue.

And in addition to of course of the U S launch here for fourth line and looking to the second line launch is really about Europe and that really is where our focus is so we're trying to go where the largest market opportunity is to try to capture that ourselves and other territories as we've already demonstrated and Australia, and Canada will work through distributors to access those markets.

Steven L. Hoerter: So with respect to expansion strategy, there really are two key areas of expansion strategy for Ken Locke. And the first, as we've talked about previously, is about moving the drug into an earlier line of treatment. That's the basis for the intrigue study, which we've spent a lot of time talking about. And the second, as you mentioned, is about geographic expansion. So our focus, as a company, in addition to, of course, the U.S. launch here for the fourth line and looking to the second line launch, is really about Europe.

<unk>.

Alright. Thank you very much if I can ask 1 more question and this has more to do with no.

As you tweak the multiple of patients now have a couple of quarters.

Not sure how much of analysis youre doing it by the mutational background of.

Patients that are being treated as it can lock is that comparable to the Invictus trial are you seeing any differences.

And the mutational background of responders in particular.

Steven L. Hoerter: And that really is where our focus is. So we're trying to go where the biggest market opportunity is to try to capture that ourselves in other territories. As we've already demonstrated in Australia and in Canada, we'll work through distributors to access those markets. Great, thank you very much.

Yes, so it's sort.

Really good question and Unfortunately, we don't have good access to that sort of data from from patients who are being treated and a commercial setting what we would expect based on the size of the Invictus study and where we enroll those patients and get the commercial experience is consistent with what we saw in the Invictus, where we should.

Steven L. Hoerter: If I can ask one more question. This has to do with, you know, as you've treated multiple patients now, you've had a couple of quarters. Not sure how much analysis you're doing about the mutational background of patients that are being treated with Kinloch. Is it comparable to the Invictus trial? Are you seeing any differences?

So a very broad activity of the drug irrespective of mutational background, but I think dan's comments earlier about persistency and duration of treatment tracking pretty closely to invictus and that is something we have access to I think that suggests to us that and the real world setting that we're seeing a very similar patient populations of what we treated and invictus and the drug.

Steven L. Hoerter: in the mutation background of responders in particular. Yeah, so it's a really good question, and unfortunately, we don't have good access to that sort of data from patients who were being treated in a commercial setting. What we would expect, based on the thighs of the Invictus study and where we enrolled those patients, is that the commercial experience will be consistent with what we saw in Invictus, where we saw a very broad activity of the drug, irrespective of mutational background.

It's behaving very similarly.

Great. Thank you for lunch.

And thank you and our next question comes from Ren Benjamin from JMP Securities. Your line is now open.

Steven L. Hoerter: And I think Dan's comments earlier about persistency and duration of treatment tracking pretty closely to Invictus. That is something we have access to. I think that suggests to us that in the real world setting, we are seeing a very similar patient population to what we treated in Invictus, and the drug is behaving very similarly.

Hey, good afternoon, guys. Thanks for taking the questions I.

And I guess, maybe just with the robust and the program you mentioned, you're not moving forward with Carboplatin them.

And I'll cover flat and can you talk a little bit about what led to that decision was it more on the efficacy side more on the safety side and and as we think about sort of the new data that we're going to get our updated data we're going to get at ESMO.

Unknown Caller: Hey, good afternoon, guys. Thanks for taking the questions. I guess maybe just with the Rabastin program. You mentioned you're not moving forward with Carboplatin. Can you talk a little bit about, you know, what led to that decision? Was it more on the efficacy side, more on the safety side? And as we think about, you know, sort of the new data that we're going to get or updated data we're going to get at ESMO,

Given that it's only whatever it is 7.7 more patients and what we've seen before maybe 9 more patients and what we've seen before is it fair is it fair to say that you have a pretty good ideas for the efficacy and safety here and there likely is the path forward or will you be going through the same sort of decision, making process as to whether or not.

Unknown Caller: The same sort of decision-making process as to whether or not you want to move that program.

Unknown Caller: Yeah, thanks, Ren, for the question about the Rabassan program. And as I noted, we're excited to share the data from the PROC cohort coming up here next month at ESMO. Matt, would you like to address the question that Wren asked with respect to Carbo versus Pactyl and the safety profile of the drug relative activity? Sure, so, Hi, Rand, it's math.

Do you want to move that program forward.

Yes, Thanks, Ron for the question about the reverse and the program and as I noted we're excited to share of the data from the cohort coming up here next month at ESMO and that would you like to address the question that Ryan asked with respect to cover Carbo vs Paclitaxel and <unk> and the safety profile of the drug relative to activity.

Sure. So I ran the snaps so yeah just to go back for it as you know we're about some sort of potent and selective inhibitor of the <unk> kinase and <unk>.

Matthew L. Sherman: So, yeah, just to go back, so, you know, we're about some sarpotent and selective inhibitor of the TIE2 kinase, and TIE2 is expressed on endothelial cells as well as endrogenic macrophages, and inhibition of TIE2 can block those macrophages as well as tumor angiogenesis. We did preclinical studies a while back, and we noticed that Paco-Taxil in these tumor models could promote angiogenesis and increase the number of TIE2 expressing macrophages within the tumor cells. So that's the basis for using radarsin in combination with Paco-Taxil and showing that we could have this amputin response.

<unk>, 2 is expressed and endothelial cells and.

As well as the energetic macrophages and inhibition of tied to can block goes.

Macrophages as well as the tumor angiogenesis, we did preclinical studies.

Oil back and we push we noticed the paclitaxel and these tumor models could promote angiogenesis and increase the number of trying to express and macrophages within the tumor cells. So that from the basis for using reverse and become an issue with paclitaxel and showed that we could have the simply of tumor response.

We move that forward into the phase into the.

Matthew L. Sherman: We moved that forward into the combination in phase one to trial. In addition, because carboplatin is also a very common backbone therapy and oncology drug, we decided to extend that observation into a clinical trial in combination with carboplatin. But as we announced today, the activity we saw there, while the combination was safe, and we did see activity in these cohorts of patients, it did not meet the level of evidence for us to proceed with further development, and we discontinued carboplatin.

Combination phase 1.2 trial in addition, because of Carboplatin and <unk>.

So a very common backbone therapy in oncology, we decided to extend the observations and to a clinical trial in combination with carboplatin, but as we announced today the activity. We saw the while the combination was safe and well just see activity and these cohorts of patients.

And did not meet the level of evidence for us to proceed and.

And to further development and would discontinue the carboplatin and trial.

Matthew L. Sherman: trial. In regard to what we plan to present at ESMO next month, as I said earlier, we have a full enrollment of the extension cohort of the platinum-resistant ovarian cancer patients, and not only updating the objective response rate, but looking at the progression-free survival for these patients, not that they've been on for quite an extended period of time, will be very informative to inform us moving forward in this indication. And as we think about the finalization of the pivotal programs at the end of this year, how should we be thinking about the time as to when those pivotal programs should start? Would you need to meet with the FDA ahead of that for the regulatory buy-in of

So what we plan to present the ESMO next month as I said earlier, we have the full enrollment of the extension cohort of the.

The platinum resistant ovarian cancer patients and the annuity updating the objective response rate.

Looking at the progression free survival for these patients now that they've been on for quite a mixed and period of time will be very informative to some form of.

Moving forward.

And the communication.

And as we think about the finalization of the pivotal programs.

At the end of this year, how should we be thinking about the timing.

As the windows pivotal programs might initiate and would you need to meet with the FDA ahead of that for some for the regulatory by end of of.

Steven L. Hoerter: the structure of the Pivis Programs, of course.

Steven L. Hoerter: Hi Ren and Steve. It's a really good question. So I think there are really two pieces of information for us to consider moving into a pivotal study. One, as we've just talked about, is getting the data presented and evaluating the data and understanding how the drug performs and the relevant indication. And you're exactly right.

The structure of the pivotal programs before starting.

And I ran and see the it's a really good question. So I think there are really 2 pieces of information for us to consider moving into the pivotal study 1 as we just talked about is getting the data presented and evaluating the data and understanding of the drug performs and the relevant education and Youre exactly right and the second is to make sure that we have good regulatory input as we think about the.

Steven L. Hoerter: The second is to make sure that we have good regulatory input as we think about the potential design of a pivotal study for the program. So those would be the two key steps. So we're looking forward to getting the data out there, as Matt referenced, coming up next month, and then we'll be in a position, as we've noted here in the second half, to start to talk about what a pivotal program could look like.

And the potential design of a pivotal study for the program. So those would be the 2 key steps. So we're looking forward to getting the data out there as Matt referenced coming up next month, and then moving in a position as we've noted here and the second half to start to talk about what the pivotal program could look like.

Steven L. Hoerter: And then a final question for the new asset, VPS34. Can you talk a little bit about, I guess, you know, what the overlap, biological overlap might be, or how molecules at one point may find themselves biologically. And separately, did you guys utilize the switch control, Chinese inhibitor platform that you have, try to find drugs that might target PPS 34, or was this sort of something different?

Got it and then a final question for the new asset Vps 30 for.

Can you talk a little bit about.

Is there.

And what the overlap of biological overlap might be with oak.

Or how.

The 2 molecules.

At 1 point maybe.

By themselves and a combination study if that works biologically and I guess separately did you guys utilize the switch control kind of kinase inhibitor platform that that you have.

Steven L. Hoerter: Yeah, thanks for the question, so let me start off, and then I'll turn it over to Matt just to talk about the two ways that we're targeting autophagy and how they're differentiated. But first, let me just say that we're really excited to announce today the licensing of this research stage program targeting VPS 34 from Sprint. And this really builds upon not only our interest but also our expertise in targeting this pathway for the potential treatment of cancer. And as you referenced, we have a first-in-class.

Just to try to find drugs that might target GPS 30 for ore.

It was the sort of something that came out of the out of the blue or from your own BD development pathways.

Yes. Thanks for the question of and so let me start off and then I'll turn it over it and that just to talk about the 2 ways that we're targeting autophagy and how they are differentiated but the first let me just say that we're really excited to announce today of the licensing of this research stage program targeting Vps 34 from sprint and.

Steven L. Hoerter: Yeah, thanks for the question, so let me start off, and then I'll turn it over to Matt just to talk about the two ways that we're targeting autophagy and how they're differentiated. But first, let me just say that we're really excited to announce today the licensing of this research stage program targeting VPS 34 from Sprint. And this really builds upon not only our interests but also our expertise in targeting this pathway for the potential treatment of cancer.

And Thats really builds upon not only our interest but also our expertise and targeting this pathway for the potential treatment of cancer and as you referenced we have a first in class program targeting Olk, which we're excited now to have that phase 1 study underway and to the actively enrolling patients and as we.

As we have been evaluating the pathway and looking for potential additional targets to pursue vps 30 for certainly was was a target of debt.

Steven L. Hoerter: And as you referenced, we have a first-in-class program targeted, and we're excited now to have that phase one study underway and to be actively enrolling patients. And as we, you know, have been evaluating the pathway, looking for potential additional targets to pursue, VPS 34 certainly was a target that we've been tracking. And so we're excited to have brought a program in that would substantially advance the internal work that we might otherwise do.

We've been tracking and so we're excited too broad of program in which would advance the substantially and the internal work can be made of otherwise done the Matt why don't you talk a little bit if you're worried about the the difference between targeting bulk versus EPS 34.

Okay.

Yeah.

Yes.

Yeah.

Hey, Steve did I lose you.

Yeah.

You guys didn't have.

No idea of Hi, Rob.

Steven L. Hoerter: But Matt, why don't you talk a little bit, if you would, about the difference between targeting ilk versus VPS? 34. Thank you. Steve, did I lose? No, I think, um, Matt, we're having a hard time hearing you. Okay, can I continue? Yes, sorry. Yes, if you can start from the beginning. I'm not sure how far back. I would start from the beginning, and, Ren, thank you for your question.

Matt we're having hard time hearing you.

Oh.

Yes.

Okay.

And I continue.

Yes, Sir yes, and he can certainly I'm not sure of it.

I would start from the beginning and Ryan. Thank you for your question. So is all commercial with EPS of <unk> 34, correct.

Matthew L. Sherman: Correct, and I didn't hear anything. It, like, completely cut off.

Correct, and I and I didn't hear anything like completely cut off Matt I'm sorry.

Matthew L. Sherman: Okay, no, I'm sorry, can you hear me now, Ren? Yes, totally. Okay, so let me just go back and add my excitement about the VPS 34 opportunity that we recently in-licensed from Sprint Bioscience. And as Steve was saying, you know, this will allow us to develop a leadership position in the use of treatment of cancer with autophagy inhibitors. While we've indicated before that the old kinase is the initiating factor for autophagy, VPS-34 works at a different node, which is involved in endosomal circular trafficking of cargo within these autophagosomes for regenerating energy. This regenerating of energy that becomes, you know, a survival mechanism for tumor cells under stress or treatment with anti-cancer therapy.

Okay, and I am sorry can you hear me now.

Yes totally.

Okay.

Yes, So let me just go back and add my excitement about the Vps 30 per opportunity that we recently and licensed from sprint Bioscience.

And as Steve was saying this will allow us to build the leadership position.

The use of the treatment of cancer with the top of the exhibitors.

Well, we've indicated before that the <unk> of the initiating factor for a top of G. Cps 30 for it works out of different new who's involved and the sone the circular trafficking of recycling and cargo within these and within these autophagosome for regenerating energy usage revenue.

Free cash.

Generating of energy that becomes survival mechanism for the tumor cells under stress of the treatment with anti cancer.

Matthew L. Sherman: And I was also noting that recently published work by a group in Luxembourg's Health along with the Carol Lindskit Institute showed that VPS 34 inhibition could restore immune-cold tumors to inflamed tumors with increases in chemokines in tumor T-cells and killer and K-cells sensitizing these tumors to check-going addition with PD1 and PDL-1 blockers. So, you know, taken together, this really can provide a great opportunity for patients who otherwise have tumors that are not responsive to checkpoint blockade.

Therapy and it was not.

Noting that the recently published work.

Bye.

The group and the Luxembourg, and the suite of health, along with the Karolinska Institute and I'm sure.

<unk> the bps 30 for ambition could restore immune cold tumors to inflame tumors with increases and chemo kinds and tumor.

T cells and killer NK cells.

Sensitized and these tumors, particularly the ambition with PD 1 PD 1 blockers. So taken together this really can provide.

The great opportunity for patients, who otherwise have tumors that are non responsive to checkpoint blockade.

Matthew L. Sherman: Got it. Thank you guys very much for taking the questions.

Got it. Thank you guys for very much for taking the questions.

Peter Richard Lawson: Thank you, and our next question comes from Peter Lawson from Barclay. Your line is now open. Hi, thanks for taking the questions. Just on phase three intrigue and four Q, just the level of detail that we're seeing in that, release of data, and

Thank you and our next question comes from Peter Lawson from Barclays. Your line is now open.

Hi, Thanks for taking the questions just just on the phase III and trade and for Q, just the level of detail that we see in the.

The release of data revenue.

Peter Richard Lawson: Do we get any kind of subgroup analysis and just thoughts on how the

And do we get kind of subgroup analysis and just the thoughts on the panel the.

Steven L. Hoerter: thoughts on how the control on them could be behaved. Hi, Peter, it's Steve.

Controlling out of it could be.

Paving.

And that theater and Steve. Thanks. Thanks for the question. So in terms of what you expect from the top line I think probably the best guidance as to think about what we previously presented.

Steven L. Hoerter: Thanks for the question. So in terms of what you expect from the top line, you know, I think probably the best guidance is to think about what we previously presented as the top line from the Invictus study when we reported that out. So I imagine it will be a relatively fulsome top line providing the key information to investors about the study. I wouldn't expect at that readout of the top line, however, to have subgroup analyses and a deeper analysis that would likely take some time.

Presented as top line from the Invictus study when we reported that out so I imagine will be of relatively fulsome topline the providing the key information to investors about the study wouldn't expect at that readout of top line. However to have subgroup analyses and of deeper analysis that would likely take some time. So I think that's the best way to think about what to expect.

Steven L. Hoerter: So I think that's the best way to think about what to expect from the top line results. In terms of the study itself, we're really pleased with the fact that we've, of course, gotten to full enrollment last year. The study conduct has been great, and we're looking forward to getting the top line report out. As you know, we're blinded to the studies, so we don't have visibility into how things are progressing arm by arm.

<unk> from top line results in terms of the study itself. We're really pleased with the fact that we use of course gotten the full enrollment last year. The study conduct has been great and we're looking forward to get into the top line report out as you know we're blinded to the study. So we don't have visibility to how things are progressing arm by arm, we know of an aggregate of course.

Steven L. Hoerter: We know in aggregate, of course, how events are accumulating, which is how we're able to provide guidance on when the study may report out. But as I said, we don't have any other color because we don't have any additional insight into specifics in the study given that we are blind. And then, just as you

And how events are accumulating which is how we're able to provide guidance on when the study may report out, but as I said, we don't have any other color because we don't have any additional insight into specifics on the study given that we are blinded.

Thank you and then just as we think of that ESMO.

Steven L. Hoerter: If we think about ESMO for Rabastin, what's the bar for you?

Estimated.

Barry and what's the what's the bar for you to move forward.

Steven L. Hoerter: for you to move forward with the Yeah, so I think, as Matt mentioned in his prepared remarks, and Matt, feel free to amplify that if you'd like. You know, we would expect that single agent Paco-Taxil would deliver a progression-free survival in this patient population of somewhere in the order of three to four months. So we haven't been guided to a specific bar, Peter, but I think what we would need to see is something that's substantially different from what we would expect to see with single-agent Pac-Latylactyl. Thank you. And then just the final question, just on

Yes, So I think as Matt mentioned in his prepared remarks, and Matt feel free to amplify that if you'd like we would expect the single agent Paclitaxel will deliver a progression free survival in this patient population of somewhere in the order of 3 to 4 months. So.

So we haven't guided to a specific borrower Peter but I think what we would need to see is something thats substantially different from what we would expect to see with single agent Paclitaxel.

Perfect. Thank you and then just final question just some of the P. GCT at ESMO kind of.

Peter Richard Lawson: Just on PGCT, ESMO, kind of what you really expect to see at the level of detail around that initial efficacy date?

Or should we expect to see and the level of detail around that.

Initial efficacy data.

Matthew L. Sherman: Sure, Matt, would you like to provide some additional detail on what you expect there? I know you covered some of this, and I think, in your prepared remarks. Sure, no, thanks, and thanks Peter for the question.

Sure Matt would you like to provide some additional detail on what you expect there I know you kind of some of this and I think of your prepared remarks.

Sure. Thanks, and thanks, Peter for the question. So as you noted and absorb.

Matthew L. Sherman: So, you know, as we noted, Fulton is our selective and potent inhibitor of the CSF1 receptor and is now in development for treatment of patients with TGCT. And we've had very rapid enrollment into the phase one study. So, just as a reminder, the study was designed with both an escalation phase and two expansion cohorts. The first expansion cohort was in treatment aid patients, and the second one was in increasingly treated patients. So now we have fully enrolled the expansion cohort with 32 TGCT patients, as well as fully enrolled the treatment in the youth patient cohort with 40 patients, and we'll be able to report upscu data on the approximately 50 patients from both the escalation and the expansion phases at the ESMETA meeting next month. And just as a note, these 50 patients is more than double the 22 patients that we were able to report on at CECOS last year.

And the as our selective and potent inhibitor of the CSF 1 receptor and.

And now in development for certain of the patients with <unk>.

And we've had very rapid enrollment into the phase 1.2 studies so for.

And just as a reminder of the study was designed with doesn't the escalation phase 2 expansion cohorts the.

First the expansion cohort and treatment nave patients and the second 1 and previously treated patients.

So now we fully enrolled the extension cohort with 32, <unk> patients as well as fully enrolling the treatment and patient cohort with 40 patients and we will be able to report and let's keep data from the person and 50 patients from both the escalation and the expansion phases at the ESMO meeting next month and just as note. The sub 50 patients has more than doubled.

The 22 patients that we were able to report on Etsy to us last year.

Matthew L. Sherman: And thank you. And our next question comes from our Linda Lee from Cannacord. Your line is now open.

Perfect. Thank you so much.

And thank you.

And our next question comes from Arlinda Lee from Canaccord. Your line is now open.

Unknown Executive: Great, thanks for taking my questions. I had a couple, sorry. So on the Sulton in a bit of ESMO, the 50 patients are going to include both CSF1 naive and experienced, and then can you maybe clarify a little bit on the interest second line? You mentioned that you have just the aggregate information at this point. Can you maybe talk about what proportion of patients do you think have the Exxon 1314 mutation and then maybe what your assumptions are for efficacy. I think, with student being in the five and a half to seven month expectations, I'm wondering what your assumptions are. Thank you. Yeah, Deir Linda, it's Steve.

Great. Thanks for taking my questions I had a couple of key sorry, so on.

And Sultan and at ESMO the <unk>.

The patients are going to include both the CSF, 1 nave and experienced and then can you maybe clarify a little bit of it.

The interest.

The second line you mentioned that you have.

Just the aggregate information at this point can you maybe talk about.

What the question of patients do you think have exon 13 fortune mutation and then maybe what.

And your assumptions are for.

Efficacy I think.

Even with.

And with <unk> being in the 5.5 to 7 months of expectations I'm wondering what your assumption part. Thank you.

Yes, the higher Linda it's Steve So let me take the second part of your question and then I'll ask Matt just to address the himself and the questions. So first with respect to intrigue and we are blinded to the study. So we don't have visibility to things such as the mutation status for profile of the patients that are being enrolled in the study and that isn't something that we have visibility to.

Steven L. Hoerter: So let me take the second part of your question, and then I'll ask Matt just to address the Thimeltin question. So first, with respect to intrigue, we are blinded to the study, so we don't have visibility to things such as mutation status or profile of the patients that are being enrolled in the study. That isn't something that we have visibility to.

Steven L. Hoerter: And with respect to our assumptions about how repressive may perform in the study, it's really driven by what we've seen in the phase one study. With repretinib, we saw an impressive PFS rate in the cohort of second-line patients. And in terms of what to expect from Sutent in that same study, we anchor, of course, to what's in the label for Sutent, which is about five and a half months.

And with respect to our assumptions about how were pregnant may perform and the study it's really driven by what we've what we've seen and the phase 1 study with the with Rhopressa and <unk>, we saw and impressive PFS rate and the cohort of second line patients and in terms of of what you expect from Sutent and that same study and we are.

Of course of what's in the label for <unk>, which was about 5.5 months. So we've we expect the 2 time with perform and the 6 month range in terms of PFS.

Steven L. Hoerter: So we expect that Sutton would perform at the six-month rate in terms of PFS. So that's how we think about the efficacy part of the story potentially coming from Intriged. Matt, would you like to take the VEMSeltin question with respect to ESMO? Sure, so just go back.

And so that's how we think about the the efficacy part of the story potentially coming from and tree.

Would you like to take the themselves and a question with respect of asthma.

Sure. So just to go back to the for the escalation phase of the study we did not limit it to treatment of these patients so as the mix of growth.

Matthew L. Sherman: So for the escalation phase of the study, we did not limit it to treatment-manufactured patients. So it was a mix of both treatment, basically treated patients with the CSF-1 inhibitor, or treatment-iniev patients. And that's the 32-patient cohort that will be able to report on poor efficacy. In addition to that, we enrolled a treatment-naive cohort of 40 patients.

The treatment previously treated patients for the CSF Oner inhibitor.

Or treatment naive patients and that's the 32 patient cohort that we will be able to report on tour of efficacy in addition to that.

We enrolled the treatment naive cohort of 40 patients and that will also be part of the efficacy of valuable data set that will present the ESMO the <unk>.

Matthew L. Sherman: And that will also be part of the EPSA valuable data set that will present to ESMO. The previously treated patients cohort is still enrolling, and we may have an update on enrollment, but no, EFSI at this time, from that reputation. Okay, great. Thank you very much. And thank you for that question. I'm showing no further questions. I would now like to turn the call back over to Steve Horder, President and CEO, for closing remarks.

Treatment and.

The previously treated patients.

And still enrolling and the.

And we may have an update and enrollment but no efficacy at this time from that group of patients.

Okay, great. Thanks very much.

Okay.

And thank you for that question.

I'm showing no further questions I would now like to turn the call back over to Steve of order President and CEO for closing remarks.

Matthew L. Sherman: Great, thank you. Thank you everybody for joining us on today's call, and thank you for your continued interest and support of DeCyp. We'll look forward to keeping you updated on our continuing progress to the balance of 2021. I hope you all have a great evening. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Great. Thank you thanks, everybody for joining us on today's call and thank you for your continued interest and support of the cycle. We look forward to keeping you updated on our continuing progress for the balance of 2021 Hope you all have a great evening. Thank you.

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

Okay.

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And.

And then.

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