Q4 2020 Incyte Corp Earnings Call

Got it.

Greetings and welcome to the Insight Corporation fourth quarter yearend 2020 earnings conference call.

Operator: Greetings, and welcome to the Incyte Corporation 4th Quarter Year-End 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. If anyone should require operator assistance, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Mike Booth, Head of Investor Relations. Please go ahead.

At this time all participants are in a listen only mode.

Anyone should require operator assistance. Please press star zero on your telephone keypad. As a reminder, this conference is being recorded its now my pleasure to turn the call over to Mike Booth head of Investor Relations. Please go ahead.

Thank you Kevin.

Mike Booth: Thank you, Kevin. Good morning, and welcome to Incyte's fourth quarter and full year 2020 earnings conference call on the web. All slides used today are available for download in the Investors section of Incyte.com. I'm joined on the call today by Hervé Barrault.

Good morning, and welcome to insights fourth quarter and full year 2020 earnings conference call on webcast.

The slides used today are available for download on the investors section of insight Dot com.

I'm joined on the call today by <unk>, Barry Steven and Christiana, who will deliver all prepared remarks and by Dash, who will join us for the Q&A session.

Mike Booth: Steven and Christiana, who will deliver our prepared remarks, and Dash, who will join us for the Q&A session. During the question-and-answer session, I asked that you limit yourself to...

During the question and answer session I ask that you limit yourself to one question and if needed one follow up. So this will enable as many of you to ask questions as time allows.

Mike Booth: This will enable as many of you to ask questions as time allows. Before we begin, I'd like to remind you that some of the statements made during our call today are forward-looking statements, including statements regarding our expectations for 2021, including our financial guidance, the commercialization of our products, and our development plans for the compounds in our pipeline, as well as the development plans of our collaboration partners. These forward-looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in We'll now begin the call with Herve.

Before we begin I'd like to remind you that some of the statements made during our call today all forward looking statements, including statements regarding our expectations for 2021.

Including our financial guidance, the commercialization of our products and our development plans for the compounds in our pipeline as well as the development plans of all collaboration partners.

These forward looking statements are subject to a number of risks and uncertainties that may cause our actual results to differ materially including those described in our 10-Q for the quarter ended September 30th 2020 and from time to time in all other SEC documents will now begin the call with all day.

Yeah.

Herve Hoppenot: Thank you, Mike, and good morning, everyone.

Thank you, Mike and good morning, everyone.

So 2020 was a year on from a gross from product commercialized by insights on this is commercialized by our collaboration partner.

Herve Hoppenot: So, 2020 was a year of strong growth for products commercialized by Incyte and those commercialized by our collaboration partners. Total product and royalty revenues grew 18%, fueling continued growth demand for Jaka Fye, which grew 15% year-over-year. And revenue from other hematology and oncology products was up 46% versus the prior year, benefiting from a strong launch of Pemazir and good performance from IQ. The launch of Monjuby is progressing well, as we continue to observe market share gains.

Those are both on product on the royalty revenues grew 18%.

Shoes by continued growth demand from Jakafi, which grew 15% year over year.

On a revenue from it was only a matter of GI oncology product was up 46% versus the price are you benefiting from a strong launch of Timothy on good performance from <unk>.

So launch of months movie is progressing well as we continue to observe market share gains right.

Royalties were up 28% to nearly 400, maybe on Louise circa 23% alumina on Saudi 8% and the launch of that breakdown now contributing to our royalty revenues.

Herve Hoppenot: Royalties were up 28% to nearly $400 million, with Jacavi up 23%, Allumiant up 38%, and the launch of Tabrecta now contributing to our royalty revenue. We also received over $200 million in milestone payments during 2020, resulting in an increase of 24% in total revenues year-over-year. Turning to slide 5.

We also received about 200 million on in milestone payments during 2020, resulting in an increase of 24% in thought all revenues year over year.

Turning to slide five.

In 2020, we presented positive data from several people to try out and submitted seven on a regulatory filing.

Herve Hoppenot: In 2020, we presented positive data from several pivotal trials and submitted seven regulatory filings, and we expect to have decisions on all of these during this year. These decisions include the potential FDA approval of Jakafa in chronic GVHD, retifanlimab in squamous cell anal carcinoma, tafacitamab in DLBCL in Europe, and pemigatinib for cholangiocarcinoma in Japan We are also just a few months away from the potential approval of roxolitinib cream in atopic dermatitis and the expected SNDS submission for vitiligo. I will now pass the call over to Barry for additional details on product performance as well as our commercial preparation for the launch of WorkSolid TINIB.

And we expect to have this season on all of this during this year.

This is all this includes a pause on sort of D. A provider of Jakafi in chronic gvhd Ritchie from the mab in squamous cell anal carcinoma deficit that might have been Bcf a day in Europe, and then we get the need for Cholangiocarcinoma in Japan on Europe, where we all recently obtained deposits you see HMP opinion.

We also have just a few months away from the potential to provide all of Brookfield <unk> cream in atopic dermatitis and your expected NDA submission for vitiligo.

I will now pass the call over to Barry for all this hard to details on first of all months as well as our commercial preparations for the launch of Luxottica day need Crane.

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Barry P. Flannelly: Thank you.

Thank you every day and good morning, everyone Jack.

Barry P. Flannelly: Thank you, Herve, and good morning, everyone. Jackified's performance was excellent in 2020, with revenues growing over $250 million to reach $1,940,000,000. The demand for Jack Fye remains high, with the total number of patients being treated continuing to grow across all three indications. We are also encouraged by the partial recovery of new patient starts in the third and fourth quarters of 2020. For 2021, we expect strong Jackify growth as we reach normalization of oncology visits with a broader availability of COVID-19 vaccines.

Jakafi performance was excellent in 2020 with revenues growing over $250 million to reach $1.940 billion.

The demand for Jakafi remains high with the total number of patients being treated continuing to grow across all three indications.

We are also encouraged by the partial recovery of new patient starts in the third and fourth quarter of 2020.

For 2021, we expect strong jakafi growth as we reach a normalization of oncology visits with a broader availability of COVID-19 vaccines.

The potential approval of Jakafi in steroid refractory chronic gvhd would represent its fourth indication and additional important growth driver.

Barry P. Flannelly: The potential approval of Jack Fye in steroid refactoring chronic GVHD would represent its fourth indication and an additional important growth driver. The range of Jack Fye guidance we have provided today for 2021 of $2,125,000,000 to $2,200,000,000 reflects the ongoing impact of COVID-19, especially in the first half of the year, as well as the expected increase in the gross net adjustment with the largest impact coming in the first quarter. Turning to slide 8.

The range of Jakafi guidance, we have provided today for 'twenty and 'twenty, one $2.125 billion to $2.200 billion reflects the ongoing impact of COVID-19, especially in the first half of the year as well as the expected increase in the gross to net adjustment with the largest.

Impact coming in the first quarter.

Turning to slide eight the launch of <unk> has gone quite well as we have been able to capitalize on our relationships and experience in oncology <unk>.

Barry P. Flannelly: The launch of Pemizer has gone quite well as we have been able to capitalize on our relationships and experience in oncology. Since launch, over 300 physicians have prescribed Temozir. As expected, community-based oncologists are driving adoption, and testing patients for FGFR2 alterations is going smoothly. Given the retail price, we know that appropriate patients are being identified and are being treated with Pemizer, and it is very gratifying to know that we have been able to bring this much-needed therapy to a previously underserved patient population. The launch of Manjubi is progressing well. Sales in the fourth quarter reached $17 million versus $5 million in Q3.

Since launch over 300 physicians have prescribed <unk> as.

As expected community based oncologists are driving adoption.

And testing patients for F. G F. Our two operations is going smoothly.

Given the repo rate, we know that appropriate patients are being identified and are being treated with <unk>.

And it is very gratifying to know that we have been able to bring this much needed therapy to a previously underserved patient population.

The launch of non Judy is progressing well sales.

Sales in the fourth quarter reached $17 million versus $5 million in Q3.

We believe the strong safety and efficacy profile of him on Judy is resonating with physicians.

Barry P. Flannelly: We believe the strong safety and efficacy profile of Monjuby is resonating with physicians, and as expected, we are seeing good utilization in the community setting. Since our Q3 update, the number of accounts purchasing Manjubi has more than doubled to over 400, and we are also seeing good uptake from the vast majority of our top 100 key accounts. According to market research in BMT and eligible diffuse large B-cell lymphoma patients, the Manjubi-Len regimen is the most used treatment in the second-line plus patient population. Turning to slide 10.

And as expected we are seeing good utilization in the community setting.

Since our Q3 update the number of accounts purchasing non juvie has more than doubled to over 400.

And we are also seeing good uptake from the vast majority of our top 100 key accounts. According.

According to market research and BMT ineligible diffuse large b cell lymphoma patients the mine Judy land regimen is the most used treatment in the second line plus patient population.

Turning to slide 10.

We submitted the NDA for retrofitting of cream for atopic dermatitis in December last year, and we expect a regulatory decision mid year.

Barry P. Flannelly: We submitted the NDA for Ruxolitinib cream for atopic dermatitis in December last year, and we expect a regulatory decision mid-year. There are an estimated 21 million atopic dermatitis patients age 12 and above in the United States, of which approximately 5.5 million receive prescription therapy today. The number of prescriptions for the treatment of atopic dermatitis has grown significantly in recent years as new therapies are introduced. However, only approximately 20% of patients report that their atopic dermatitis is controlled with their current treatment.

There are an estimated 21 million atopic dermatitis patients age 12 and above in the United States of which approximately $5 5 million received prescription therapy today.

The number of prescriptions for the treatment of atopic dermatitis has grown significantly in recent years as new therapies are introduced however, only approximately 20% of patients report their atopic dermatitis is controlled with their current treatment highlighting the significant unmet need that currently exist.

Barry P. Flannelly: Highlighting the significant unmet need that currently exists, we expect the initial uptake of ruxolitinib cream to be driven by specialists in medical dermatology and allergies. Our team has identified approximately 11,000 prescribers who collectively account for approximately 80% of total prescriptions written for the treatment of atopic dermatitis in the U.S. Over the past several months, we have been able to recruit an exceptional team with significant experience in successfully launching dermatology products in the United States. We expect a fully recruited field team of 150 FTEs by mid-April, which is optimal to reach these high-volume prescriber I'll now turn the call over to Steven for a clinical update.

We expect the initial uptake of <unk> cream to be driven by specialist in medical dermatology and allergy R.

Our team has identified approximately 11000 high prescribers, who collectively account for approximately 80% of total prescriptions written for the treatment of atopic dermatitis in the U S or.

Over the past several months, we have been able to recruit an exceptional team with significant experience in successfully launching dermatology products in the United States.

We are expected we expect to fully recruited field team of 150 Ftes by mid April which is optimal to reach these high volume prescribers I'll now turn the call over to Steven for a clinical update.

Thanks, Barry and good morning, everyone.

Steven H. Stein: Thanks, Barry, and good morning, everyone. In 2020, we made significant progress across our development pipeline, as shown on slide 12. Some highlights include positive results from our pivotal trials of ruxolitinib in chronic graft-versus-host, Ruxolidum Cream in Atopic Dermatitis, Redifandumab in squamous cell anal carcinoma, and Pastor Klisseb in Non-Hodgkin's Lymphoma, with each study forming the basis for regulatory submissions in their respective indications. We also announced multiple products, including pemmesire and monjuvia in the United States and tuberctin in the United States and Japan and a new indication for lumion in atopic dermatitis in both Europe and Japan.

In 2020, we made significant progress across our development pipeline as shown on slide 12 somehow.

Some highlights include positive results from our pivotal trials of <unk> in chronic graft versus host disease.

<unk> cream in atopic dermatitis.

He found a mab in squamous cell anal carcinoma, and pasta classic in non Hodgkin's lymphomas.

With each study forming the basis for regulatory submissions in their respective indications.

We also announced multiple product approvals, including <unk> in non JV in United States and to break in the United States, and Japan, and a new indication for ILUVIEN in atopic dermatitis in both Europe and Japan.

We also recently announced the positive <unk> opinion for Penni, GAAP NIM, a crucial step towards bringing the first targeted therapy to European patients with Cholangiocarcinoma.

Steven H. Stein: We also recently announced the positive CHMP opinion for Pemigasmin, a crucial step towards bringing the first targeted therapy to European patients with cholangiocarcinoma. As you can see on slide 13, we are expecting multiple regulatory actions during 2021. 7 expected, and six additional submissions during the year.

As you can see on slide 13, we are expecting multiple regulatory actions during 2021 with seven expected approvals and six additional submissions during the year.

<unk> net net we expect an FDA decision for Jackup jakafi in chronic graft versus host disease, and our partner Novartis is expected to submit jackoby on acute and chronic graft versus host disease in both the EU and Japan during the first half of 2021.

Steven H. Stein: For ruxolitinib, we expect an FDA decision for Jackify in chronic graft-versus-host disease, and our partner Novartis is expected to submit Jacobi for acute and chronic graft-versus-host disease and both the EU and Japan during the first half of 2021. In hematology and oncology, we await an EMA decision for taphocytomab in diffuse large B-cell lympho We expect Pemigatnib to receive European approval in cholangiococcinoma, following the recent positive CHMP opinion, and we also have a submission under review in Japan.

Within the hematology and oncology, we await an EMA decision for <unk> diffuse large b cell lymphoma, and then FDA decision already fan of Mab in squamous cell anal carcinoma.

We expect <unk> to receive European approval in Cholangiocarcinoma. Following the recent positive <unk> opinion, and we also have a submission under review in Japan.

Later this year, we plan to submit an NDA for post the close of monotherapy in non Hodgkin's lymphoma based on the pivotal citadel trials.

Steven H. Stein: Later this year, we plan to submit an NDA for parseclusive monotherapy in non-Hodgkin's lymphoma based on the Pivotal Citadel trial. Within dermatology, we expect an FDA decision for ruxolidinib cream in atopic dermatitis in June and will look to submit an SNDA in vitiligo shortly thereafter.

Within dermatology, we expect an FDA decision for <unk> cream in atopic dermatitis in June and will look to submit an NDA in vitiligo. Shortly thereafter, assuming that phase III program in this indication is successful.

Steven H. Stein: Assuming our Phase 3 program in this indication is successful, as you can see, it is shaping to be a very eventful and exciting year ahead for Incyte in terms of clinical development and regulatory action. Slide 14 provides a brief overview of Limba clinical development.

As you can see this shaping to be a very eventful and exciting year ahead for insight in terms of clinical development and regulatory action.

Slide 14 provides a brief overview of the limbic clinical development program.

Once daily <unk> is the furthest along with potential FDA approval before the end of 2022.

Steven H. Stein: Once Daily Ruxolitinib is the furthest along with potential FDA approval before the end of 2022. We have multiple combinations planned and in development, with PR3 kinase delta, BET, or ELK2, which we believe have the potential to significantly improve outcomes for patients living with myelofibrosis. As you can see on the right-hand side, we expect patent protection for many of these novel assets to extend well into the 2030s.

We have multiple combinations planned and in development with PR three kinase Delta bet, all Elk too, which we believe have the potential to significantly improve outcomes for patients living with myelofibrosis.

As you can see on the right hand side, we expect the patent protection for many of these novel assets to extend well into the 20 cities.

Moving to slide 15.

Steven H. Stein: Moving to slide 15. This year, with our partner Morphosis, we intend to initiate two phase three trials. Front Mind is expected to enroll approximately 900 patients, and we'll evaluate the combination of tafacetamib plus lenalidomide and R-CHOP versus R-CHOP alone in first-line diffused large B-cell lymphoma. InMIND is expected to enroll approximately 600 patients and will assess the combination of tapus symptomab plus R-squared versus R-squared in patients with relapsed or refractory follicular or marginal zone lymphoma.

This year with our partner <unk>, we intend to initiate two phase III trials.

Frank mines is expected to enroll approximately 900 patients and all.

All evaluate the combination of <unk>, plus Lenalidomide and R chop versus R. Chop alone in first line diffuse large b cell lymphoma.

In mind is expected to enroll approximately 600 patients and when assessed the combination of Tampa system map, plus all squared versus all squared in patients with relapsed or refractory follicular marginal zone lymphoma.

We also plan on initiating two proof of concept trials in non Hodgkin's lymphoma investigating <unk> in combination with our own peer three kinase Delta inhibitor pasta closer and in combination with Lenalidomide and plan to map, our CD 20, CD three by specific antibody.

Steven H. Stein: We also plan on initiating two proof-of-concept trials in non-Hodgkin's lymphoma, investigating tafacetamab in combination with our own PR3 kinase delta inhibitor paraclysm and in combination with lenalidomide and plamotimab, a CD20-CD3 bispecific antibody. Moving to slide 16.

Moving to slide 16.

We recently announced the acceptance under priority review of the BLA from ready fan demand.

Steven H. Stein: We recently announced the acceptance under priority review of the BLA for Ready Family. The BLA was submitted based on the results from Podium 202. Data from which was shared at the ESMO Congress last year, and the PDUFA date has been set for July 25th. We have also been informed that the FDA expects to convene an advisory committee meeting as part of the review process. This slide also gives me an opportunity to remind you of our development strategy for Rediffandum.

The BLA was submitted based on the results from podium tier two data from which we will share that the ESMO Congress loss share and the Paducah date has been set at July 25th.

We have also been informed that the FDA expects to convene an advisory committee meeting as part of the review process.

The slide also gives me an opportunity to remind you of our development strategy for Red a fan of Mab.

The first part of the strategy is to develop greater fan I mab as monotherapy in certain niche indications, we accelerated approvals all available.

Steven H. Stein: The first part of the strategy is to develop Ritifanamab as monotherapy in certain niche indications where accelerated approvals are available, and other registration-directed trials beyond squamous cell anal carcinoma are ongoing in Merkel cell carcinoma and MSN high endometrial cancer. We also have an ongoing global phase 3 study in London, which of course offers a much more substantial potential opportunity. A key part of our development strategy is related to the utility of having an in-house PD-1 antibody, which gives us the option to run numerous internal clinical combinations with other assets within our immuno-oncology portfolio, including Axelmer and Adenosine 2A, 2B, where there's potential for synergistic activity and enhanced efficacy. With that, I would like to turn the call over to Christiana for the financial update.

And other registration directed trials beyond squamous cell anal carcinoma, all ongoing in Merkel cell carcinoma, MSI high endometrial cancer.

We all seven ongoing global Phase III study in lung cancer, which of course offers a much more substantial potential opportunity.

A key part of our development strategies related to the utility of having an in house PD, one antibody, which gives us the option to on numerous internal clinical combinations with other apps assets within our immuno oncology portfolio, including XOMA and adenosine to a to B, where there is potential for synergistic activity.

And enhanced efficacy.

With that I would like to turn the call over to Kristy on it for the financial update.

Christiana Stamoulis: Thank you, Steven, and good morning everyone. Turning now to our financial results, our fourth quarter results reflect continued strong revenue growth with total product and royalty revenues of $680 million, representing an increase of 17% over the fourth quarter of 2019, and reflecting growth across products commercialized by Incyte and by our partners. Total product and royalty revenues for the quarter are comprised of net product revenues of $517 million for Jaka Fye, $29 million for iKlusik, and $14 million for Pemagine, royalties from Novartis of $87 million for Jacavi and $2 million for Trabrecta, and royalties from Lilly of $31 million for Olum.

Thank you Stephen and good morning, everyone, turning now to our financial results. Our fourth quarter results reflect continued strong revenue growth with bolt on product and royalty revenues of $680 million, representing an increase of 17% over the fourth quarter of 2019 and reflecting growth across <unk>.

<unk> commercialized mine site and by our partners.

Total product and royalty revenues for the quarter on comprised of net product revenues from $517 million for Jakafi $29 million for Iclusig and $14 million flow.

Royalties from Novartis was $87 million from Jakafi and $2 million for top director and royalties from Lilly all $31 million for ILUVIEN.

For the full year 2020, total product and royalty revenues were two point $46 billion an increase.

Christiana Stamoulis: For the full year 2020, total product and royalty revenues were $2.46 billion, an increase of 18% over 2019. Total revenues for 2020 of $2.67 billion increased 24% over 2019, reflecting higher product and royalty revenues and an increase in milestone payments from our collaborative partners for the achievement of development, regulatory, and commercial milestones. Moving on to our operating expenses on a gap basis, ongoing R&D expenses of $380 million for the fourth quarter increased 23% from the prior year period due to our 55% share of the global and U.S.-specific development costs for Tafasit Ahmad and product supply-related costs to support the potential launch in 2021 of Raxolitinib cream as a treatment for atopic dermatitis.

All 418% over 2019.

Total revenues for 2020 of $2.6 billion to $7 billion increased 24% over 2019, reflecting the higher product net royalty revenues and an increase in milestone payments from our collaborative partners for the achievement of development regulatory and commercial milestone.

Moving onto our operating expenses on the GAAP basis ongoing R&D expenses of $380 million for the fourth quarter increased 23% from the prior year period due to our 55% share of the global and U S specific development costs for deficit that mud and product supply.

Related costs to support the potential launch in 2021, all frac, so literally cream as a treatment for atopic dermatitis.

Ongoing R&D expense for the full year 2021 point $24 billion increased by 10% over 2019 also driven by the impact so far 55% share of deficit development costs, and rascality cream product supply related costs.

Christiana Stamoulis: Ongoing R&D expense for the full year 2020 of $1.24 billion, increased by 10% over 2019, also driven by the impact of our 55% share of Tathachitamap development costs and Raxalitinib cream product supply. If a solutive cream is approved, the product supply cost expensed in 2020 will ultimately contribute to a lower cost of goods sold for a period of time subsequent to the product. As a reminder, our total R&D expense of $2.2 billion for the full year 2020 includes the upfront consideration of $805 million for our collaborative agreement with Morphosis and $120 million in expenses related to our purchase of an FDA priority review voucher utilized to accelerate the review of Raxolitinib prim in atopic dermatitis. GNA's expense for the fourth quarter of $167 million increased 23% from the prior year period due to the timing of certain expenses.

If you actually do the cream is approved the product supply cost expense in 2020 will ultimately contribute to lower cost of goods all for a period of time subsequent to the product launch.

As a reminder, at total R&D expense of $2.2 billion for the full year 2020 includes the upfront consideration of all $805 million for all collaborative agreement with Merck forces and $120 million all to expense related to our purchase of an FDA priority review voucher utilized.

All right the review of <unk> cream in atopic dermatitis.

SG&A expense for the fourth quarter, all of a $167 million increased 23% from the prior year period due to the timing of certain expenses.

For the full year 2020, SG&A expense grew 10% compared to 2019, driven by an increase in sales and marketing spend to support the commercialization on the famous here in the U S and to prepare for the potential launch of rux cream in the U S.

Christiana Stamoulis: For the full year 2020, SG&A expense grew 10% compared to 2019, driven by an increase in sales and marketing spend to support the commercialization of Pemazir in the U.S. and to prepare for the potential launch of Rax Cream in the U.S. Our collaboration loss for the quarter was $12 million, which represents our 50% share of the U.S. net commercialization loss for Monjuvi. For the full year 2020, the total collaboration loss was $43 million and was comprised of total net product revenues of $22 million and total operating expenses, including COGS and SG&A expenses of $107 million. Finally, we ended the year with $1.8 billion in cash and marketable assets.

Our collaboration on a loss for the quarter was $12 million, which represents our 50% share of U S. Net commercialization on loss from them on children.

For the full year 2020, the total collaboration on the loss was $43 million in other words.

Price of total net product revenues of $22 million and total operating expenses, including Cogs and SG&A expenses of $107 million.

Finally, we ended the year with $1.8 million in cash and marketable securities.

Looking at the evolution of our P&L also over the past five years, you can see how the growth in all product and royalty revenues has exceeded the growth in both our ongoing R&D expense and G&A expense, leading to increase operating leverage and reflecting our commitment to prudent management of our firm.

Christiana Stamoulis: Looking at the evolution of our PLNL offer over the past five years, you can see how the growth in our product and royalty revenues has exceeded the growth in both our ongoing R&D expenses and SG&A expenses, leading to increased operating leverage and reflecting our commitment to prudent management of our financial resources. Moving on to 2021, I will now discuss the key components of our 2021 guidance on a gap basis. Given the expansion of our commercial portfolio, we are providing 2021 net product revenue guidance for Jaka Fye and as a total for other hematology oncology products.

National resources.

Moving on to 2021, I will now discuss the key components of our 2021 guidance when they got basis.

Given the expansion of our commercial portfolio, we are providing 2021 net product revenue guidance for Jakafi and that's the total for other hematology oncology product.

For Jakafi, we expect net product revenues to be in the range of 2.1 25 to two point $20 billion, which at the midpoint represents approximately 12% growth over 2020, driven by continued growth across all indications.

Christiana Stamoulis: For Jack Fye, we expect net product revenues to be in the range of $2.125 to $2.20 billion, which at the midpoint represents approximately 12% growth over 2020, driven by continued growth across all indications. We expect our gross net adjustment in 2021 to be approximately 18 percent, with the adjustment in the first quarter of the year being higher relative to the previous quarter and subsequent quarter. For other hematology-oncology products, which currently include iClusic in Europe and Pemazir in the U.S., we are expecting total net product revenues to be in the range of $145 to $160 million. However, as in previous years, we're not providing guidance for milestones.

We expect on gross to net on Jasmine in 'twenty to 'twenty, one to be approximately 18% with the adjustment in the first quarter of the year being higher relative to the previous quarter and subsequent quarters.

What other hematology oncology products, which currently include Iclusig in Europe and here in the U S. We are expecting total net product revenues to be in the range of $145 million to $160 million.

As in previous years were not providing guidance for milestone.

All royalty revenues, we are also not providing revenue guidance for any potential on new product launches. During 2021, all four modules in the U S, which was recently launched and which we are commercializing together with our partner more forces.

Herve Hoppenot: All royalties revenue. We are also not providing revenue guidance for any potential new product launches during 2021 or for Monjuvi in the US, which was recently launched and which we are commercializing together with our partner Morphosa. Turning to operating expenses, we expect COGS to range from 6 to 7% of net product revenue. We expect R&D expense to be in the range of $1.35 to $1.39 billion, representing mid-single-digit growth at the midpoint versus 2020, excluding the impact of the MOF forces upfront consideration and the PRV in 2020.

Turning to operating expenses, we expect Cogs to range from 6% to 7% of net product revenues.

We expect R&D expense to be in the range of $1 35 to $1 $39 billion, representing mid single digit growth at the midpoint versus 2020, excluding the impact on them off force is upfront consideration and that the RV in 2020.

Our SG&A expense guidance includes the investment related to the establishment of the new dermatology commercial organization in the U S and the related sales and marketing activities to support the potential launch of approximate net cream for atopic dermatitis.

Herve Hoppenot: Our SG&A expense guidance includes the investment related to the establishment of the new dermatology commercial organization in the U.S. and the related sales and marketing activities to support the potential launch of Raxolitinib cream for atopic dermatitis. The expansion of our sales and marketing activities in Europe to support the potential launches of Pemigatnib for cholangiocarcinoma and afacitamab for DLBCL, and the establishment of a commercial organization in Japan to support the potential launch of penicatinib for cholangiocarcinoma.

The expansion of our sales and marketing activities in Europe to support the potential launch yourself, then you got to need for Cholangiocarcinoma and deficit on mob for they'll be CN and the establishment of our commercial organization in Japan to support the potential launch of spinning out the need for Cholangiocarcinoma.

As a result in 'twenty 'twenty, one we expect GAAP SG&A expense for the year to be in the range of $735 million to $775 million.

Herve Hoppenot: As a result, in 2021, we expect GAAP's GNA expense for the year to be in the range of $735 to $775 million. Excluding the impact of these investments, we expect our SG&A expense for 2021 to remain flat compared to 2020. I will now turn the call back to Herve for further discussions of the year ahead.

Excluding the impact of these investments we expect our SG&A expense for 2021 to remain flat compared to 2020.

I will now turn the call back to wait a day for further discussions on a year ahead.

Thank you Christian.

Herve Hoppenot: Thank you, Christiana.

Herve Hoppenot: Slide 24. Provide a list of the important updates we expect in 2021. This includes pivotal trial results for ROCKSOLID TINIP CREAM in VT-LIGO as well as the approvals for ROCKSOLID TINIP CREAM in Atopic Dermatitis, RETIFAM-LIMAB in SCSE, and JAKA-PHY in Chronic GVHD.

Slide 24 provides a list of important updates we.

In 2021.

These include pivotal trial results for rux cream in vitiligo as well as the approvals for rux cream in atopic dermatitis with you from the Mab in as you see on Jakafi in chronic gvhd.

Herve Hoppenot: So before moving into Q&A, I want to take a minute to let you all know that Mike Booth... will be leaving Incyte at the end of the month, ahead of his planned return to the UK. His role as head of IAAT Incyte will move to Christine Chiou, who joined us in 2019 and who has been working very closely with Mike as part of a planned transition. I want to take this opportunity to thank Mike very much for all of his contributions to Incyte over the past seven years, and we all wish him well in his future endeavors. With that operator, please give your instructions and open the line for Q&A.

So before moving into Q&A I wanted to take a minute to let Jordan knows that Mike Booth will be leaving inside at the end of the month ahead of its planned return to the UK.

Mike's, Florida as head of IR insight, we'll move to Christian <unk>, who joined US in 2019 on who has been working very closely with Mike as part of a planned transition.

I want to take this opportunity to thank Mike for very much.

For all of his contribution to insight all over the past seven years on when we all wish him well in his future endeavor at all.

With that operator, please give your instructions and open the line for Q&A.

Operator: Certainly, we will now be conducting a question and answer session. If you'd like to be placed in the question queue, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key.

Certainly wed all be conducting a question and answer session if you'd like to be placed from the question queue. Please press star one on your telephone keypad all confirmation tone will indicate your line is in the question queue. You May press star two if he'd like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing.

Starkey once again Thats star one to be placed on the question Q1 moment. Please while we poll for questions. Our first question today is coming from the from Pori from Morgan Stanley. Your line is now live.

Vikram Purohit: Once again, that's Star 1 to be placed in the question queue. One moment, please, while we poll for questions. Our first question today is coming from Vikram Purohit from Morgan Stanley. Your line is now live. Great, great, good morning.

Great Great. Good morning, Thanks for taking my question. So I wanted to touch on the dermatology franchise and I had two questions for rux cream.

Steven H. Stein: Thanks for taking my question. So I wanted to touch on the dermatology franchise. And I had two questions for Rook's Cream in advance of the phase three vitiligo data that we're going to be getting over the next couple of months here. So first, could you characterize for us any key differences between the phase two and the phase three patient populations that you're looking at for vitiligo? And second, how should we think about which portion of the vitiligo patient population that Rook's Cream could be most suitable for? How are you thinking about segmenting this patient population? And where do you think Rook's Cream is going to be most valuable?

Advance of the phase III <unk> data there were.

I'm going to be getting over the next couple of months here. So.

So first could you characterize for us any key differences between the phase two and the phase III.

Patient population that Youre looking at for Vitiligo, and then second how should we think about which portion of the vitiligo patient population that rux cream could be most suitable for how are you thinking about segmenting this patient population.

And where do you think rux cream is going to be most valuable.

Vikram Hi, it's Steven I'll take your question in terms of the the question on on the translate ability of the phase III the phase III given the magnitude of the size of the Feight phase to the geography, we conducted it in an eligibility criteria, we actually expect it to be.

Steven H. Stein: Vikram, hi, it's Steven. I'll take your question. In terms of the question on the translatability of the Phase 2 to the Phase 3, you know, given the magnitude of the size of the Phase 2, the geography we conducted it in, and the eligibility criteria, we actually expect there to be no differences in population or in outcome. We expect the results in Phase 3 to be of similar efficacy magnitude to those in Phase 2, and the safety to be the same.

No no differences in population or an outcome, we expect to read in the phase III to be up similar efficacy magnitude to the phase II and the safety to be the same I'll just share the one nuance on the differences we in phase III.

Limit the body surface area of vitiligo patients with deep pigmentation to be up to and including 10%, whereas in the phase two a little more liberal and allowed up to 20%, but that is that is the only difference we expect no other differences in outcome and in read through all of the population.

Steven H. Stein: I'll just show one nuance on the difference is that we in Phase 3 limit the body surface area of vitiligo patients with depigmentation to be up to and including 10%, whereas in Phase 2, we're a little more liberal and allowed up to 20%, but that is the only difference. We expect no other differences in outcome and in read through of the population. In terms of the LIGO itself...

In terms of other lager itself.

It's probably a much more common disease.

Buddy I realize is if you look at the United States.

Steven H. Stein: It's probably a much more common disease than everybody realizes. If you look at the United States, you know, there are several million quote unquote sufferers with vitiligo. Not all of them view it as a disease, and not all of them want treatment. But currently, given the available therapies, about 100 to 150,000 people, we estimate, seek different treatments, including steroids and phototherapy, which is reimbursed as well. They're not very effective in terms of, you know, ameliorating the disease and improving it, and not to the degree we saw in phase two with topical RUX.

There are several million.

Unquote sufferers with vitiligo not all of them are viewed as a disease and not all of them on treatment, but currently given the available therapies about 100 to 150000 people, we estimate six different treatments, including steroids.

Steroids are.

Photo therapy, which is reimbursed as well and not theyre not very effective in terms of.

You know ameliorate the disease on improving it and nothing to the degree we saw in the phase II with topical rux. There's also as you know a large saka social.

Steven H. Stein: There's also, as you know, a large psychosocial component to the condition, with people often depressed from it as well. So we expect it to work in the same population as phase two. It'll include the majority of sufferers with vitiligo, particularly on the face and hands. And that's the label we'll aim for should phase three be as positive as we expect it to be. Thanks.

Component two to the condition with people off all are often depressed from it as well.

So we expect it to work in the same population of the phase II line.

All include the majority of all suffers with little I go, particularly on the face and hands.

And and you know that's the label we will aim for should the phase III EPS positive as we expect it to be.

Steven H. Stein: Got it. Thank you. Thank you. Our next question is coming from Michael Schmidt from Guggenheim. Your line is now live. Hey guys, good morning. Thanks for taking my questions.

Got it thank you.

Thank you. Our next question is coming from Michael Schmidt from Guggenheim. Your line is now live.

Hey, guys. Good morning, Thanks for taking my questions I had a few on the regular day excellent new cream launch coming up here as well.

Michael Schmidt: We had a few on the Roxalidin cream.

Barry P. Flannelly: Thank you all for joining us for the launch coming up here as well. Maybe could you help us understand how far along you are with your launch preparations in AD, especially when it comes to, you know, interactions with payers around pricing and market access? And my follow-up question would be, in context of the recent post-marketing safety data emerging from Celgene, I was wondering how this may potentially affect utilization of oral jack inhibitors more broadly and across indications and how that might position RoxyLipnum Cream and AD in that context.

Could you help us understand how far in are you with your launch prep in in a day.

Especially when it comes to.

Interactions with payers are on pricing and market access.

And my follow up question would be.

Context of the recent post marketing safety data emerging from Sal channel. So I was wondering how you think this may potentially affect.

Utilization of oral JAK inhibitors, more broadly and across indications on how that might position approximate net.

Cream and in that context, thanks, so much.

Barry P. Flannelly: Thanks so much.

Hi, Michael It's Barry I'll take the first part of your question and I'll hand, it over to Steven for the second part of your question.

Barry P. Flannelly: Hi Mike, it's Barry. I'll take the first part of your question, and I'll hand it over to Steven for the second part of your question.

But as far as the preparation goes for lunch, it's going very well we started off at our insight with excellent clinical development team, that's very experienced in dermatology and immunology.

Barry P. Flannelly: As far as the preparation goes for the launch, it's going very well. We started off at Incyte with an excellent clinical development team that is very experienced in dermatology and immunology. We built a medical affairs team in the U.S. that's outstanding and has deep experience in dermatology and immunology. Now we're building out the sales force, and we built out an excellent market access team, again, that has deep experience in immunology and dermatology.

We built our medical affairs team in the U S. That's outstanding and has deep experience in dermatology in immunology.

Now we're building out the sales force and we've built out an excellent market access team again that has deep experience in immunology and dermatology, we have had interactions with payers across the nation with.

Barry P. Flannelly: We have had interactions with payers across the nation, with advisory boards, and we'll begin the process of negotiations with the payers in the very near future. So we think that lunch's preparation is right on schedule. Steven.

With advisory boards, and we'll begin the process of.

Of of negotiations with the payers in the very near future.

We think the launches preparation is right on schedule Steven.

Steven H. Stein: Yeah, Michael, thanks. Thanks for the question. You know, given the Zeljan's non-inferiority data versus TNF therapy, particularly in RA patients, particularly looking at venous thromboembolism, malignancy, and then major adverse cardiac events, you asked a question on the read-through to RUX itself, and then I guess potentially to topical RUX. You know, we've been with RUX on the market since 2011, so we have many, many thousands of years of patient exposure, including with our partner Novartis, as well as long-term follow-up on our clinical trial programs.

Yeah, Michael Thanks, Thanks for the question given the Xeljanz non inferiority data look.

As a TNF therapy, particularly in <unk> patients, particularly looking at venous thromboembolism malignancy in major adverse cardiac events. You you asked a question on the read through to Rux itself, and then I guess potentially too topical rux.

We've been with rocks on the market since 2011, so we have many many thousand years of patient exposure, including with our partner Novartis as well as long term follow up on the on our clinical trial programs. So let me just talk a little bit about the clinical trial programs. If you look at the comfort data.

Steven H. Stein: So let me just talk a little bit about the clinical trial programs. If you look at the comfort data in MF, now with, you know, five years of follow-up in those studies, there's been no signal for any of those events that are worrying in that particular exposure. In polycythema vera, the response studies, which is a prothrombotic disease, also now have, you know, five years of published follow-up, and we've looked across the board at thromboembolic events, cardiac events, and malignancies there.

In in MF.

Now with.

Five years of follow up on those studies, there's been no signal for any of those events at all worrying in that particular exposure.

Polycythemia Vera the response studies that is a pro thrombotic disease also now have five years of published follow up and we've looked across the board at thromboembolic events cardiac events of malignancies, there and in fact on the treated arms.

Steven H. Stein: And in fact, on the treated arms, the rates are lower in both the primary treated arm and the crossover arm versus the best available therapy arms there. So it's in keeping as well with our market experience that we're not seeing a signal for any of those events, as we are asked to on a yearly basis by regulatory authorities.

The rates are lower.

In both the primary treated on the crossover arm versus the best available therapy arm. There. So it isn't keeping us well with our market experience, we've not seen a signal for any of those events as we ought to on a yearly basis by by regulatory authorities and just to remind you you know rux cream has no warnings on black.

Steven H. Stein: And just to remind you, you know, RUX Cream has no warnings or black boxes for any of those. Topical RUX itself, as we have shown in two published papers now, one in AD and one in vitiligo, shows that the bioavailability of the cream is about 4 to 7% of that applied, on average about 5%. And those are two published papers, one in AD and one in vitiligo. Thus, the effect of oral exposure there is very small and not at pharmacologically relevant concentrations. So given the parent compound itself not having an issue, RUX cream having that sort of bioavailability, and our safety from those clinical programs, we don't expect any read-through there at the moment. Great, thank you.

Fox for any of these.

Topical topical rux itself as we have and to publish papers now I'm wanting a D and one in vitiligo share.

And that the bioavailability of the cream is about a 4% to 7% of that applied on average about about 5% so and in those other two published papers one in India.

They didn't want even lager and thus.

The effective.

Our all exposure there is very small and not at pharmacologically relevant concentrations. So given you know the parent compound itself not having an issue rux cream, having that sort of bioavailability and now all our.

Safety from those clinical programs, we don't expect any read through there at the moment.

Great. Thank you.

Reni John Benjamin: Thank you. Our next question today is coming from Corey Kazma from J.P. Morgan. Your line is now live. Hey, good morning, guys.

Thank you. Our next question today is coming from core CASM all from Jpmorgan. Your line is now live.

Hey, good morning, guys. Thanks for taking my question I'll stick with the same line of questioning here on on Rux cream and Barry wanted to follow up with a bond your comments on the pending launch for a D and just given everything you've said so far what do you see as the key impediments and this kind of market introduction and how should we be thinking about the heavy lifting.

Barry P. Flannelly: Thanks for taking my question. I'll stick with the same line of questioning here on RUX Cream. Barry wanted to follow up with your comments on the pending launch for AD. And just, you know, given everything you've said so far, what do you see as the key impediments to this kind of market introduction? And how should we be thinking about the heavy lifting required here versus perhaps some of that potentially low-hanging fruit you could relatively quickly capture, given the data, the mode of administration, and the number of patients who just aren't benefiting from existing meds? Thank you.

Third here versus perhaps some of that potentially low hanging fruit you could relatively quickly capture given the the day to the motive administration and the number of patients who just aren't benefit benefiting from existing beds. Thank you.

Hi, Corey well you know as far as impediments go I don't really see very many impediments. We've actually we think we're really in a very good situation.

Barry P. Flannelly: Hi Corey. Well, you know, as far as impediments go, I don't really see very many impediments. We're actually in a very good situation. You know, we think we can really help patients with mild to moderate eczema, atopic dermatitis, from steroids all the way up to Dupixent, and biologics. So we think that there is a broad range of patients who will be very happy to use a cream like Rux cream as opposed to using systemic therapy that may, in fact, suppress their immune system in general.

We think we really can help patients with mild to moderate.

Eczema atopic dermatitis.

From steroids, all the way up to depicts into biologics. So we think that there is a broad range of patients who will be very happy to use a cream like rux cream.

As opposed to using systemic therapy that may in fact.

Suppress their immune system in general.

Barry P. Flannelly: So we're very excited about it. We know that when talking to dermatologists across the country, when they look at the data from TRU-AD1 and TRU-AD2, they're very excited. They've never seen anything like this that is a targeted therapy that's topical and has biologic-like activity. So we think that the safety and efficacy we've demonstrated so far in TRU-AD1 and TRU-AD2 are going to help the uptake and patients throughout the United States.

So we.

We're very excited about it we know that.

In talking to dermatologists across the country.

On that when they look at the data.

From Troy do you want on a true 82, theyre very excited they've never seen anything like this that has.

Targeted that as a targeted therapy that is topical that has biologic like activities. So we think that the safety and efficacy we demonstrated so far and true a day one into a day two.

Is going to help the uptake and Ah patients throughout the United States.

Barry P. Flannelly: Great, thank you very much. Thank you, and this question is coming from Srikripa Devarakonda from Truist. Your line is now live. Hey guys, thank you so much for taking my questions. Staying on Rox Cream, I was...

Great. Thank you very much.

Thank you. The next question is coming from <unk> totaled from Chris Your line is all lives.

Hey, guys. Thank you so much for taking my question.

Staying on rux.

Cream I was wondering what sort of conversations have you had around the NDA.

Srikripa Devarakonda: I was wondering what sort of conversations you had around the NDA that you found with the FDA following your submissions?

What you find with the FDA following year submissions have you had any further conversation and also can you talk about your strategy for rux cream in pediatric populations can we expect it to be similar between atopic derm and vitiligo.

Steven H. Stein: Have you had any further conversations? And also, can you talk about your...

Steven H. Stein: Another strategy for Rux cream in pediatric populations. Can we expect it to be similar between atopic derm and vitiligo? Thank you.

Steven H. Stein: Kripa, hi, it's Steven. Thanks for your question. You know, we don't talk in detail about any ongoing conversations with regulatory authorities, but I will tell you, as we've said publicly, the submission went in successfully in December. We utilized a priority review voucher that will give us a six month review, and we expect action in the middle of the year on that. Given that it's now, you know, early February, it's still early days for that submission and review, and it's going exactly as expected.

<unk>.

Crippa Hi, it's Steven Thanks for the.

Your question.

We don't talk in detail about any ongoing conversations with regulatory authorities, but I will tell you as we've said publicly the submission went in successfully in December we utilized a priority review voucher that will give us a six month review and we expect an action in the middle of the year on.

Net.

Given that it's now in our early February it's still early days.

All of that submission and review and it's going exactly as expected its in 12 years and above the true <unk> studies, which covers the majority of the population Barry was talking about with with atopic dermatitis. However, there is a population that is younger than it does also have the.

Steven H. Stein: It's in 12 years and above, the TrueAD studies, which cover, you know, the majority of the population Barry was talking about with atopic dermatitis. However, there is a population that is younger that does also have atopic dermatitis, and we have an commitment to continue to study that. We have to do more safety enabling work in the pediatric population to enable those studies to look, for example, whether there is any bone effect, et cetera, as you look at young ages.

The topic dermatitis, and we have a commitment to continue to study that we have to do more safety, enabling work in the pediatric.

Eric population to enable those studies to look for example is is there any bone effect et cetera. As you look at young ages and we've gone through those hurdles successfully and we will determine this calendar year.

Steven H. Stein: And we've got through those hurdles successfully, and we'll determine this calendar year, you know, given that Phase 2 is successfully completed, what sort of Phase 3s we'll be conducting in conjunction with regulatory authorities to address that population of two years and above and conduct those studies. And we'll let you know as soon as we have those studies in place. But it's going well.

Given that the phase two is successfully completed.

So the phase III will be conducted in conjunction with regulatory authorities to address that population two years and above and conduct those studies and we'll let you know as soon as we have those studies in place, but it's going well.

Great. Thank you.

Brian Corey Abrahams: Great, thank you. Thank you. Our next question today is from Brian Abrahams from RBC Capital Markets. Your line is now active. Hey guys, thanks so much for taking my question. First off, I just want to thank Mike for all his help throughout the years and wish him well in his next endeavors and offer congratulations to Christine. Maybe shifting gears to Manjuvi, I'm curious if you could talk a little bit more about how that's being used in the real world, in particular, where it fits in relative to CAR-T, and what you may look towards to further the reach in academic settings, where I would imagine cell therapy and investigational treatments like biospecifics are more available, in addition to the community setting, and how important that's going to be to continue the Thanks.

Thank you. Our next question today is coming from Brian Abrams from RBC capital markets. Your line is now live.

Hey, guys. Thanks, so much for taking my question first off I just want to thank Mike for all his help throughout the years and wish him well on his next endeavor and offer congratulations to Christine maybe shifting gears to <unk> I'm curious if you could talk a little bit more about how that's being used in the real world in particular, where it's fitting in relative to car T and what you mean.

Look towards to further the reach in academic settings, where I would imagine cell therapy, an investigational treatments like bi specifics are more available. In addition to the community setting how important that's going to be to continue the current uptake momentum. Thanks.

Sure Brian well.

Barry P. Flannelly: Sure, Brian. Well, the uptake of Monjuvi, like I said, is going very well in the second line plus patient population. You know, like any new therapy that launches, you end up starting in later line therapies, third and fourth line therapies, for example, and we continue to try to move patients, and try to move physicians up into the second line setting because we think that's where patients will benefit the most.

The uptake on my Juvie like I said is going very well in the second our second line plus patient population.

Any new therapy that launches.

End up starting in later line therapies third and fourth line therapy for example, and we continue to.

Tried to move patients tried to move positions up into the second line setting because we think that's where the patients will.

Benefit the most you know our uptake at launch was mostly in the academic centers and we do follow the academic centers that actually have car T therapies available to them and we're actually doing very well Ah patients who are referred to academic centers for car T therapy, sometimes get there and they're actually not eligible for <unk>.

Barry P. Flannelly: You know, our uptake at launch was mostly in academic centers, and we do follow the academic centers that actually have CAR T therapies available to them, and we're actually doing very well. However, patients who are referred to academic centers for CAR T therapy sometimes get there, and they're actually not eligible for CAR T therapy, so then they need another therapy to choose from. As we progressed with our launch, more and more community oncologists are taking up Monjuvi, and that's surpassing the number of patients who are being treated in the academic center, but we still have, you know, some of the largest centers in the country that are using this regimen of Monjuvi and Len.

T therapy. So then they need another therapy.

<unk> therapeutics to choose.

Choose as we progressed with our launch.

More and more of the community oncologists are taking up our mind UV and that's surpassing number of patients.

Who are being treated in the academic center, but we still have.

Some of the largest centers in the country that are using this regimen on juvie and land as far as bi specifics go we don't know that that's a problem necessarily yet.

Barry P. Flannelly: And in fact, we think that the safety and efficacy profile of Manjubi will match up very well to any of the new therapies that might be coming next year. As far as the CAR T therapies go, again, you know, physicians will choose their patient population based upon their ability to tolerate the side effects of the CAR T therapies. So generally, it might be younger patients who are healthy that they might select for those therapies. But again, that's only a limited number of centers around the country. So we think that Manjubi has a long way to go before treating patients with diffusible RGB cellulose.

And in fact, we think that the safety and efficacy profile of mine Judy.

We will match up very well to any of the new therapies that might be coming next year as far as the car T therapies go again.

Physicians will choose their patient population based upon their ability to tolerate the side effects of the car T therapy, So generally might be younger patients who are healthy.

Select for those therapies, but again, that's a limited number of centers around the country. So we think that on Judy has a long way to go.

With treating patients with diffuse large b cell lymphoma.

Barry P. Flannelly: That's really helpful, Conor. Thanks, Barry. Thank you. Our next question is coming from Tyler Van Buren on behalf of Piper Sandler. Your line is now live.

That's really helpful color. Thanks Barry.

Thank you. Our next question is coming from Tyler Van Buren from Piper Sandler Your line is in that line.

Hey, guys. Good morning, Thanks for taking the question just set up another one on Judy you talked about the successful launch on the uptake in the academic and community settings and market share gains. So curious to hear your latest thoughts on if you believe on jewelry it could be $1 billion product in the existing indications or if you need the front line.

Tyler Van Buren: Hey guys, good morning. Thanks for taking the time to answer the question. I just had another one on Juvie. You talked about the successful launch and the uptake in academic community settings and market share gain. I'm so curious to hear your latest thoughts and if you believe Monjuvie could be a billion-dollar product in the existing indication or if you need the front mind and in mind studies to be successful. And I noticed that BeMind wasn't mentioned in the presentation and barely mentioned in the press release. So I was just curious to hear if that was like a deliberate deprioritization of what's going on there.

In line studies to be successful and I noticed that the mine wasn't mentioned in the presentation and barely mentioned in the press release, So just curious.

That was like a deliberate de prioritization on what's going on there.

So Tyler I'll just take the first part of your question I hand, it over to Steven about B mind, but.

What we said.

Barry P. Flannelly: So, Tyler, I'll just take the first part of your question and hand it over to Steven about BeMind, but, you know, what we said several times in the past is that in the current indication, Montjuvi could reach $500 to $750 million. And, you know, we'll, as we continue to develop more combinations and move up to the frontline setting, and that's $500 to $750 million in the U.S. So, anyway, that's where we're at, and I'll hand it over to Steven for BeMind.

Several times in the past is that in the current indication I'm on.

Judy could reach 500 to 750.

<unk> million dollars and.

Well as we continue to.

<unk> developed a more combinations and move up to frontline setting and that's 500 to 750 in the U S by the way.

So so anyway, that's where we're at and I'll have them at all Steven if you're being on it.

So that's the world I mean, if you.

Look at the worldwide sales for majority in solo on lines year, it'd be Seattle, assuming it's 500 to show interest in the U S. It would be around 1 billion or north of that for the world.

Steven H. Stein: Just a word, if you look at the worldwide sales for Montjuc in second line DLBCL, assuming it's 500 to 750 in the US, it would be around a billion or north of that for the world.

Carter Hi, it's Steven in terms of your question on B mind, It's just that it's an ongoing study there are no changes to it and there are no news updates.

Very relevant study its comparing to Bendamustine rituximab, which is a regimen used in that particular setting and studying the utility then all of a CD 19 anybody in deficit of map. There. We hopefully will have data on that study if the event tracking as expected in 2022, but not just that it doesn't nothing new to <unk>.

Steven H. Stein: Tyler, hi, it's Steven. In terms of your question on B-Mind, it's just that it's an ongoing study, there are no changes to it, and there are no news updates. It's a very relevant study, it compares Bendomastine Rituximab, which is a regimen used in that particular setting, and studies the utility then of a CD19 antibody in Taplacetamab there. We hopefully will have data on that study if the events track as expected in 2022, but just that it had nothing new to say.

Port.

Great. Thanks, so much.

Thank you. Our next question today is coming from other Youll see a young from Cantor Fitzgerald. Your line is that lives.

Hey, guys. Thanks for taking my question also congrats on being great at all.

All of that they're in the biotech world.

Tyler Van Buren: Great, thanks so much. Thank you. Our next question today is coming from Alethea Young from Cantor Fitzgerald. Your line is now live.

And that's on track.

I did want to ask two questions. One just about your thoughts on the European economies with the approval of TG Therapeutics yesterday, and how do you think about positioning in that market after them.

Reni John Benjamin: Hey guys, thanks for taking my question and, also, Mike, congrats on being one of the greatest IRs out there in the biotech field and keeping us in check. I did want to ask two questions. One, just about your thoughts on your PI3 kinase with the approval of TG Therapeutics yesterday, and how do you think about positioning in that market after them? And then also, I just wanted to get kind of your perspective on the adenosine axis of the CD73 PD1 combination. Is that something that you would use in non-small cell as a potential option, or how do you think about non-small cell combinations with your PD1 thing?

And then also I just wanted to get from your perspective on the adenosine access other 73 PD. One combination is that something that you would use in non small cell.

On the potential option or how do you think about like non small cell combinations with PD one thing.

Alicia Hi, it's Steven Thanks for the question.

I think the umbrella, let's say of approval from TG Therapeutics is good for patients. Obviously, we all believers in the P. S. Three kinase Delta class, we think it has somewhat of a on.

Unfair overhang from idealists of years ago, and that many have now addressed many of the untoward side effects.

Steven H. Stein: Alethea, hi, it's Steven. Thanks for the question. You know, I think the umbrellas of approval from TG Therapeutics are good for patients. Obviously, you know, we are believers in the PR3 kinase delta class. We think it has, you know, somewhat of an unfair overhang from idealistic years ago, and that many have now addressed many of the untoward side effects. So, you know, we view that as a positive outcome.

We view that as a positive outcome it doesn't in any way impact our plans in terms of where are we going with the citadel studies in the filings this year hopefully in follicular marginal and mantle cell lymphoma. If you look on the face of it you know with with many many caveats on cross trial comparisons, but all independently reviewed activity.

<unk> in all of those indications follicular marginal and mantle cell is higher than net reported with drugs like umbrella stuff again with lots of caveats. So we are very encouraged by the efficacy we've seen with past the close up and obviously you are proceeding with our plans tolerability is important as well.

Steven H. Stein: It doesn't, in any way, impact our plans in terms of where we go with the Citadel studies and the filings this year, hopefully in follicular, marginal, and mantle cell lymphoma. If you look at the face of it, you know, with many, many caveats on cross-trial comparisons, but our independently reviewed activity in all those indications, follicular, marginal, and mantle cell, is higher than that reported with drugs like umbrellas, again, with lots of caveats.

And obviously you know we looked at their label and they just continuations versus hours et cetera, and we again think the Clos has been somewhat unfairly burdened by by prior products Ah We lock all at all both efficacy and safety profile and we see again to be repetitive no impact in terms of switching you know too.

Steven H. Stein: So, we're very encouraged by the efficacy we've seen with parseclysib and obviously are proceeding with our plans. Tolerability is important as well, and obviously, you know, we looked at their label and their discontinuations versus ours, etc., and we again, you know, think the class has been somewhat unfairly burdened by prior products. We like both our efficacy and safety profile, and we see, again, no impact. In terms of switching, you know, to earlier programs, you spoke about adenosine and adenosine-targeted compounds.

Earlier programs you spoke about.

<unk> and the adenosine targeted compounds, we have one in the clinic already a small molecule <unk> inhibitor, that's open and enrolling and we announced at Jpmorgan. We also said you know we'll be following very shortly with the CD 73 antibody.

<unk> inhibits adenosine production higher up in the pathway and other they showed any.

Kitchen at the two together at least in a preclinical model on a synergistic. We also feel that that this is potentially an area, where you may require triplet therapy and you'll have to add checkpoint on top of other PD. One it's too early to say you know way, where these will be going in terms of histology lung would always be.

Steven H. Stein: We have one in the clinic already, a small molecule A2A and A2B inhibitor that's open and enrolling that we announced at J.P. Morgan. We also said, you know, we'll be following very shortly with a CD73 antibody that'll inhibit adenosine production higher up in the pathway, and Herve showed in his... The two together, at least in a preclinical model, are synergistic. We also feel that this is potentially an area where you may require triplet therapy, and you'll have to add a checkpoint on top of it, PD-1.

Of interest, particularly in lung patients that don't respond to current Io therapies.

So that will remain of interest I'll just remind you also that both the adenosine program in the CD 73 antibody all in house programs and we're very very proud of them.

Thank you. All next question today is coming from Casino model from Bank of America. Your line is now.

Steven H. Stein: It's too early to say where these will be going in terms of histology, but lung would always be of interest, particularly in lung patients that don't respond to current IO therapies. So that will remain of interest. I'll just remind you also that both the adenosine program and the CD73 antibody are in-house programs, and we are very proud of that.

Lives.

Hi, good morning, Thanks for taking my question.

As you approach the rux cream launch I, just wanted to get a little bit more color on how youre thinking about how the gross margin for rux cream, let's start with atopic derm might differ from the gross margins that you see for Jakafi and then other quick follow up.

Tazeen Ahmad: Thank you. Our next question today is coming from Tazeen Ahmad from Bank of America. Your line is now live. Hi, good morning. Thanks for taking my questions. As you approach the RUX Cream launch, I just wanted to get a little bit more color on how you're thinking about the growth margin for RUX Cream. Let's start with a topic that might differ from the growth margins that you see for Jackify, and then have a quick follow-up.

So in English.

Yeah, not in terms of as they.

The Cogs for our for.

[noise] rux cream the guidance that we provided on books or the 6% to 7%.

That's all reflect a rux cream I swell in the near term as we indicated we have been I'm dealing on the supply of API for rux cream and that would result in the Cogs being lower as we and we use up the supply that we have already.

Christiana Stamoulis: So in terms of the cogs for RACSCREAM, the guidance that we provided on COGS, the 6 to 7 percent, does reflect RACSCREAM as well. In the near term, as we indicated, we have been dealing with the supply of API for RACSCREAM, and that would result in COGS being lower as we use up the supply that we have already expensed in 2020, and which was reflected under R&D.

Expense in 2020.

And that which was reflected on the R&D.

Okay. So would you expect that once you have a second indication that that Cogs, but continue to improve.

So the Cogs that we had the Cogs benefit from that.

Christiana Stamoulis: Okay, so would you expect that once you have a second indication, that COGS would continue to improve?

API that we have already expense will take place over a period of time, starting with the launch and then obviously all go back to more normalized levels. So we're all asking if we use what has already been expense it would be reflected in lower Cogs.

Tazeen Ahmad: So the COGS benefit from the API that we have already expensed will take place over a period of time, starting with the launch, and then obviously will go back to more normalized levels. So as we use what has already been expensed, it will be reflected in lower COGS.

Barry P. Flannelly: Okay, and then as it relates to how physicians are viewing Rux cream now, just kind of based on, you can't officially market it, but how do you think they understand the difference between Rux cream and Eucrisa and where the benefits of Rux cream might be?

Okay, and then as it relates to how physicians are viewing rux cream now just kind of based on you can officially marketed but.

How are you thinking they understand the difference between rux cream, and Cressa and where the benefits of rux cream might be.

Hi, Tien tsin, it's Barry I'll try to handle that.

Barry P. Flannelly: Hi Tanzines, Barry, I'll try to handle that. Well, the I think, as I said before, that the positions we've spoken to, and there are many across the country, all the dermatologists see the TrueAid 1 and TrueAid 2 data as really unique. They really like using topical therapy, and they see this as the most effective topical therapy that they've seen. Ever.

Well, the I think as I said before that the.

Physicians, we've spoken to and there's many across the.

The country all the dermatologist.

The true a D. One entry way day two data.

It's really something unique they really like dermatologist really like using topical therapy and they see this as the most effective topical therapy that they've seen ever so.

Barry P. Flannelly: So, you know, Eucrisa had some disadvantages. When it launched, certainly, it actually burns on application and doesn't seem to be that effective. The side effect profile is pretty good, but I think physicians and dermatologists have turned away from it, and they're very excited about what they see so far from Ruxcreme.

Chris I had some disadvantages to it when it launched certainly.

It actually burns on application and it doesn't seem to be that effective.

Side effect profile is pretty good, but I think physicians dermatologist have turned away from it and they're very excited about what they see so far from rux cream.

And so there is it does get approved do you think.

Barry P. Flannelly: And so Barry, if it does get approved, do you think that it would have a steep uptick, or do you think there still would need to be some physician education initially?

That it would have a steep uptake or do you think theres still would need to based on physician education other Shelly.

Barry P. Flannelly: Well, there's always physician education that's necessary as well as perhaps patient education, but we think that the uptake is going to go very well.

Well, there's all these physician education, that's necessary as well as perhaps patient education, but we think that the uptake is going to be go very well.

Salveen Richter: Okay, thank you. Thank you. The next question is coming from Salveen Richter from Goldman Sachs. Your line is now live.

Okay. Thank you.

Thank you. The next question is coming from Celgene Richter from Goldman Sachs. Your line is now live.

Good evening, Thanks for taking my question.

Steven H. Stein: Good morning, thanks for taking my questions. Could you remind us where the QD formulation for the Jackify study stands from the Limber Initiative? And then, Herve, if you could just give us your kind of updated thoughts on business development strategy as you look to 2021 and beyond. Thank you.

Could you remind us where the QD formulation of Jakafi study spans from the number of initiatives and then on our vape you could just give us your kind of updated thoughts on on business development strategy as you look to 2021 and beyond thank you.

Herve Hoppenot: Salveen, hi, it's Steven. I'll start.

Sylvian Hi, it's Steven I'll start.

The once daily formulation of Rex in lithium continues to go well the bio availability and bioequivalence work is being completed.

Steven H. Stein: The once-daily formulation of ruxolitin continues to go well, and the bioavailability and bioequivalence work are being completed. We're now in stability, and we need 12 months of stability to complete to then put the submission in. We would expect a 10-month review from that, and thus expect approval before the end of 2022 if everything goes smoothly. We are within everything expected in terms of the strict guidance required for BABE, so we're hopeful this will be a successful submission.

As we know in stability and we need 12 months of stability to complete to then put the submission in we would expect a 10 month review from that and thus expect an approval before the end of 2022, if everything goes smoothly.

We are within you know everything expected in terms of the strict guidance required on B a b. So we are hopeful this will be a successful submission.

Herve Hoppenot: Regarding BD, in fact, looking at what we did this year, in 2020, last year, is a good way maybe to see what we are, how we are approaching the BD strategies. We had a deal like Morphosis that was very complementary to our portfolio. You can see we have combinations that we are doing now with Partaclizib.

From a fundamental regarding regarding BD in fact.

Looking at what we did this year in the in 2020 plus year is a good way of maybe two to see what we are with how we are approaching what would be the biggest strategies. We we had a deal like this where it was very complementary with our portfolio you can see we have combinations as well.

All doing though is perfect because it.

Herve Hoppenot: There are a lot of synergies on the commercial side, both in Europe and in the US. So if there are opportunities looking like that, I think it will certainly be interesting to us to continue to grow our revenue line and to diversify. So that would be one aspect. We also did a technology deal with a company called Selencos, and that was about myelofibrosis.

All of a lot of synergies on the commercial side.

In Europe on the.

And in the U S. So if there are opportunities.

Looking like like that I think it will certainly be.

<unk> to us to continue to grow our revenue line and to diversify so that would be one the one aspect. We also did the a.

Technology deal with a company called <unk> and.

That was about myelofibrosis. So you can imagine on so that we are looking at opportunities that would be adding to our internal portfolio.

Herve Hoppenot: So you can imagine that we are looking at opportunities that we'll be adding to our internal portfolio as part of the Limber program. And in general, the way we are thinking about it is if there are products that could be available, that would fit with our hematology and oncology portfolios, that would be the priority. And if there were opportunities that were also providing additional revenue to our dermatology team in the U.S., it could be something that we looked at, but mostly on the different timelines, as we will be launching first atopic dermatitis this year and then vitiligo next year, so there is no urgency to add to that in the short term.

Zimbra program on.

I mean as you know all of the way we all we are thinking about it is if the products.

Well that could be available that would be fitting with our hematology oncology portfolio that would be the priority on.

But if there were opportunities that are also providing additional revenue.

Revenue to our dermatology team in the U S. It could be all sorts of things that we look but mostly.

On the on the different timelines as we will be launching for atopic dermatitis. This year on the July go next.

Next year, so there's no urgency to add to that in the short term. So I would say in the short term and metallurgy oncology, maybe over a longer period of time, we could be looking at.

Herve Hoppenot: In the short term, hematology, oncology, maybe over a longer period of time, we could be looking at immunodermatology, and the type of assets we are looking at are products that will be launched between 2023 and 2026.

No other dermatology.

On the type of Oh as I said, we are looking up all products that we'd be launching between the 'twenty to 'twenty three 'twenty 'twenty six.

Herve Hoppenot: Thank you, the next question today is coming from Mara Goldstein from Izuho. Your line is now live. Yes, thanks so much for taking the question.

Thank you.

Thank you. Your next question today is coming from Mara Goldstein from Mizuho. Your line is now live.

Yes. Thanks, so much for taking the question just a follow up perhaps on rux cream and just trying to understand a little bit around the dynamics of launches is most of them until derm products are associated with some type of support couponing program and the like and so on I'm curious as to what your thoughts are on that and all.

Mara Goldstein: Just a follow-up, perhaps on Rux cream, and just trying to understand a little bit about the dynamics of launches, as most derm products are associated with some type of support, couponing program, and the like. And so I'm, I'm curious as to what your thoughts are on that. And also, one of the areas that the company hasn't touched on in a while is Jackify in PV and some of the efforts before COVID to enhance that patient population. So I'm wondering if you could touch on that as well.

One other areas that the company hasn't touched on on Awhile is jakafi in PV on some of the average pre COVID-19 to enhance that patient population I'm wondering if you could touch on that as well.

Barry P. Flannelly: Sure Mara, I'll try to answer both of those on RUX Cream and then on Jackify in PV. So, you know, we have plans in place, just like many products that you see, particularly in dermatology, but, you know, throughout the United States for newly launched products, where we're going to ensure that when a dermatologist, when a physician prescribes RUX Cream, that it's as easy as possible for the patient So, that begins first with market access, working with PBMs and payers to make sure that there are as few restrictions as possible, as few prior approvals as possible, and then once we get to the pharmacy counter, to be able to help patients with their co-pays and deductibles through, as you say, a couponing program or other ways for us to manage that.

Yeah.

Sure My all I'll try to answer both of those on Rux cream and then on Jakafi in PV. So.

We have plans in place just like many products that you see particularly in dermatology, but throughout the United States for newly launched products.

Where we're going to ensure that when a dermatologist.

Dermatologists, when a physician prescribes rux cream that it's as easy as possible for the patient to obtain it.

So that begins first with market access working with Pbms and payers.

To make sure that there's a few restrictions as possible SKU prior approvals as possible and then once we get to the pharmacy counter to be able to help the patients with their copays and deductibles through as you say it couponing program or other ways for us to manage that.

Barry P. Flannelly: As far as Jackify goes, Jackify in PV, Jackify continues to grow in PV faster than it does in MF, and even though MF continues to grow, the total number of patients continues to grow. I suppose our biggest activity that we're doing in PV is first talking about the long-term follow-up of the response studies, which are very, very important. Over time, the data just continued to get more impressive and look better, but we also had our disease awareness campaigns around polycythemia vera and the number of patients who are suffering because of the symptoms that they undergo when they get PV.

As far as Jakafi goes you know Jakafi continues to Jakafi in PV goes Jakafi continues to grow on T D.

Faster than it does in MF and even though MFS continues to grow the total number of patients continues to grow I suppose our biggest activity that we're doing in PV well first talking about the long term follow up of the response studies, which are very very important over time. The data just continue to get more.

And look better but also we had our we had our disease awareness campaigns around.

Around polycythemia, Vera and the number of patients.

Who are suffering because of the symptoms that they undergo when theyre getting PV. So we're very encouraged about the future of Jakafi and polycythemia Vera.

Barry P. Flannelly: So we're very encouraged about the future of Jackify and polycythemia vera, as well as our other indications, but as you indicated, there is a pressing need for those patients to make sure that they have the most effective therapy to take care of their symptoms and their hematocrit.

As well as our other other indications, but as you indicated it's a pressing need for those patients to make sure that they have.

Most effective therapy to take care of their.

Their symptoms and their adequate.

Barry P. Flannelly: Thank you.

Marc Frahm: Thank you. The next question is coming from Marc Frahm from Cameron & Company. Your line is now live. Thanks for taking my questions, and let me offer my congratulations also to Mike on his next step in his career. Maybe Barry, with a bit of LIGO and your comments and Steven's comments, there certainly are people who do get reimbursed today for off-label use of various products, but we also hear from consultants that a number of plans, you know, consider this to be a cosmetic indication.

Okay. Thank you.

Thank you. Our next question is coming from work from from Cowen and company. Your line is all lives.

Hi, yes, thanks for taking my questions and let me offer my congratulations also to make the next step in his career.

Maybe Barry with.

Little I go in your comments on Steven's comments on yes, there certainly are people, who do get reimbursed today.

Yeah, the off label use of various products.

But we also hear from consultants on a number of plans.

Consider this to be a cosmetic indication I guess.

Marc Frahm: I guess, Barry, what's your sense as to what percent of the relevant population, you know, already has this kind of coverage and is recognized by their plan as a true medical and a reimbursable condition? And then kind of what efforts do you need to do between now and launch to grow that number?

Your centers take on what percent of the relevant population you know already has this covered and recognized by their plan as a as a true medical and a reimbursable condition and then kind of what efforts do you need to do between now and launch.

Barry P. Flannelly: Well, I'm not sure I can tell you what number are currently covered for therapies because there aren't very many. Stephen talked about phototherapy. That's one way.

Grow that number.

Well I'm not sure I can tell you what number are currently covered for therapies, because there arent very many therapies Steven talked about photo therapy.

That's one way.

Barry P. Flannelly: You know, other topical therapies may or may not be reimbursed, but I think it's, you know, Stephen talked about the millions of patients in the United States, somewhere between 2 and 4 million patients that have the LIGO, but maybe only 150 to 200,000 patients are seeking therapy. And that's because, in fact, there aren't very many effective therapies. We do have to continue to educate both payers, but I don't think we really have to educate dermatologists very much.

Other topical therapies may or may not be reimbursed, but I think it's.

Steven talked about the you know the millions of patients in the United States somewhere between two and 4 million patients that have the legal but maybe only 150 to 200000 patients are seeking therapy and that's because in fact, there aren't very many effective therapies. We do have to continue to educate both pairs I don't think we really.

Have to educate dermatologists very much dermatologists know that this is an autoimmune disease that drastically impacts patients' lives.

Barry P. Flannelly: Dermatologists know that this is an autoimmune disease that drastically impacts patients' lives. So having a therapy like Rux Cream for vitiligo, we think, can greatly enhance the quality of life for those patients, and it's essential for us to educate payers that this is not a cosmetic issue, that it is an autoimmune disease, and that the responsible thing is actually to pay for it.

So having a therapy like rux cream for vitiligo, we think can greatly enhance the quality of life for those patients and it's essential upon us to educate payers that this is not a.

A cosmetic issue than it is in autoimmune disease and that.

The responsible thing is actually to pay for it.

Barry P. Flannelly: Are there any kind of similar launches that have happened historically that you'd point to that have kind of faced the same type of dynamic?

Are there similar launches have happened historically that you'd do.

That all kind of face the same type of dynamic.

Yeah.

Well.

That comes to mind. So I'm, you know I think theres lots of disease.

Barry P. Flannelly: Well, that comes to mind. So, you know, I think there are lots of diseases that we come across that haven't had, you know, payers wanting to pick them up. You know, you might even say eczema, for example, when older products were launched; they might have thought that this was something that was not important. But, in fact, you know, it impacts patients' lives very much, where they don't want to go out of the house and where, you know, they're suffering, not just itching and staying awake at night, but, of course, even bleeding and infections.

Diseases that we.

We come across that Havent had.

Payers wanting to to pick it up you know you might even say eczema on for example, when a new older products. We're launching they might've thought that this is something that's not important but in fact.

It impacts patients' lives very much where they don't want to go out of the house and where are they are suffering.

Not just itching and staying awake at night, but of course, even leading and infections. So that's one example, I'm sure. There's many other examples where education of payers and prescribers is very important and we think that is the July go, but we think that we can manage to overcome that hurdle.

Barry P. Flannelly: So that's one example. I'm sure there are many other examples where education of payers and prescribers is very important. And we think that is a bit of a ligo, but we think that we can manage to overcome that hurdle.

Barry P. Flannelly: Great, thank you. Thank you. The next question is coming from Evan Sigerman from Credit Suisse. Your line is now live. Hi all, thank you for taking my question. I just want a quick shout out to Mike for everything over the past couple of years. You will be missed. So I wanted to ask about the Limber program, you know, while it might be early, can you characterize kind of maybe some demand or feedback you've gotten on the QD RUCS option among both physicians and patients? And what do physicians really want to see from this QD formulation in terms of efficacy to potentially switch patients from the current Jacobi?

Okay, great. Thank you.

Yeah.

Thank you next question is coming from Evan Siegel moving from Credit Suisse. Your line is now live.

Thank you for taking my question I, just want a quick shout out to Mike for everything over the past couple of years, you will be missed so I wanted to ask on the limber program, while it might be early can you characterize kind of maybe some demand or feedback you've gotten on the QD Judy rocks option, among both physicians and patients and physicians really want to.

See from this QD formulation in terms of efficacy to potentially switch patients from the current on Jakafi.

Evan Sigerman: Okay, Evan, hi, thank you. It's Steven.

Okay, Evan Hi, Thank you, it's Steven I'll I'll start others may want to add comments.

Steven H. Stein: I'll start; others may want to add comments. You know, the LIMBA program itself is an umbrella program; there are numerous pillars. The formulation work was one of the pillars. Obviously, you know, once daily has potential compliance improvement over twice daily, although in oncology, you know, people tend to do very well with twice daily. But that was one of the efforts behind it for those people who would potentially benefit from that. Additionally, you know, it does give us very important optionality on fixed dose combinations should we develop, you know, for example, PR3 Delta or BET or L2 as a once daily, it could lend itself to being combined with a once daily Ruxolitinib in one FTC.

You know the limber program itself as an umbrella program as numerous pillars. The formulation work was one of the pillars are obviously you know once daily has potential compliance improvement over twice daily although in oncology you know people tend to do very well with twice daily but that was.

One of the efforts behind it for those people, who would potentially benefit from that additionally.

It does give us down the line very important optionality on on fixed dose combinations should we developed for example, PR three delta or pay it all out to as a once daily it could lend itself to be combined with the once daily Rux Loopnet and one FTC so that that would be really really important from that.

Steven H. Stein: So that would be really, really important from the point of view of that. You know, after we pursue the 505B route through bioavailability and bioequivalence, there may be slight differences in the clinical profile of the once daily. For example, just by its very nature, from a pharmacokinetic point of view, it'll have a lower peak, a lower C max. If that is one of the causes of anemia from the drug, which we think it is, it may tend to have a lower rate of anemia with the once daily, which would be of benefit in patients because that's one of the reasons they discontinue and then, you know, allow patients to stay on the drug longer.

After we pursued a five or five be route through bioavailability and bioequivalence finished the stability fall and hopefully have it approved at the end of 'twenty 'twenty two we could look at things.

It may be slight differences in the clinical profile of the once daily for example, just by its very nature from a pharmacokinetic point of view it'll have a lower peak lowest C. Max if and if that is one of the causes of anemia from the drag which we think it is it may tend to have a lower rate of anemia.

With the once daily which would be a benefit in MF patients because that's one of the reasons. They just continue and then allow patients to stay on drug longer and then you know as a direct result, actually enhance efficacy as well. So there are lots of aspects to the program at step wise, it's about getting approval first which may lend itself.

Steven H. Stein: And they, you know, as a direct result, actually enhance efficacy as well. So there are lots of aspects to the program. It's stepwise. It's about getting approval first, which may lend itself to compliance, optionality on fixed dose combinations, and potentially an upside to ameliorating anemia.

All to compliance.

Optionality on fixed dose combinations and potentially an upside on ameliorate in anemia.

Steven H. Stein: Thanks. Excellent. Thank you. Thank you.

Yeah.

Excellent. Thank you.

Thank you ladies and gentlemen, we have time for two more questions. Our next question is coming from Ren Benjamin from JMP Securities. Your line is now live.

Ren Benjamin: Ladies and gentlemen, we have time for two more questions. Our next question is from Ren Benjamin from J&P Securities. Your line is now live. Hey, good morning, guys. Thanks for taking the questions. Congratulations on an amazing quarter, great guidance, and congratulations, Mike, as well. Maybe just starting off the Limber program, you know, this is probably for Steven, can you just talk a little bit about these two Phase III trials that are ongoing, maybe the timing as to when we might see readouts and how the optimal dosing was determined for both Ruxin and Parcyclofib?

Hey, good morning, guys. Thanks for taking the questions congratulations on an amazing quarter, great guidance and congrats Mike as well.

Maybe just starting off the Limber program. You know this is probably for Steven can you just talk a little bit about you know these two phase III trials that are ongoing maybe the timing as to when we might see readouts and how the optimal dosing.

Whats determined.

For both rux in past cycles.

And maybe just as a follow up already mentioned selling costs I'm just kind of curious what was the rationale to to lead to this collaboration is there an unmet need that this collaboration seeks to address or is it more just trying to find a best response rate and in.

N M P N and M P S.

Yeah, Ren it's Steven Thanks for your question. So again back to the Limber program. We just spoke about in a prior question about the first pillar around formulation work. The second pillar is around you know important combination work with combinations that either enhance efficacy or enhance safety like the L. Two.

Ren Benjamin: And maybe just as a follow-up, Herve mentioned Stollenkos. I'm just kind of curious, you know, what was the rationale that led to this collaboration? Is there an unmet need that this collaboration seeks to address, or is it more just, you know, trying to find the best Response Rate in MPNs.

<unk> or both because youre ameliorate anemia without too and you can stay on rocks. The Delta program that you alluded to has two very important phase III is that all open sites initiations on going now one is a sub optimal setting for patients who have had.

Steven H. Stein: Yeah, Ren, it's Steven. Thanks for your question. So, you know, again, back to the Limba program, we just spoke about in the prior question about the first pillar around formulation work. The second pillar is around important combination work with combinations that either enhance efficacy or enhance safety, like the L2 or both, because you know, you're ameliorating anemia with L2 and you can stay on rocks. The Delta program that you alluded to has two very important phase and site initiations ongoing.

Had at least three months of our excellent net but have not had an adequate response in terms of spleen or symptom control and other than in a randomized to rux plus delta in that setting <unk> delta versus rux alone.

The dosing as because you asked a question specifically is forex itself, obviously, we know optimal dosing and how to titrate based on on on potential safety issues like thrombocytopenia. The Delta dosing came from proof of concept work, we did in prior patients who had.

Inadequate responses to long term rocks and that's how we determine that the five milligram was active there as well as had a terrible profile and that's what we're using in both the sub optimal study on the first line study, which are now open and Sox initiations on going.

Steven H. Stein: In terms of selling costs, it's a completely new mechanism of action. There are some enticing small clinical anecdotes. It's umbilical cord-derived regulatory T-cells that they have a way to enrich for CXCR4, which are then regulatory T-cells that would then hone in on the bone marrow. And they've shown in a small number of patients who are heavily pretreated, some enticing data of clinical response, drop in allele burden, and maybe even some fibrosis improvement. It's very early in the morning.

In terms of selling costs.

A completely new mechanism of action, it's Tyson small clinical anecdotes its umbilical cord derived regulatory T cells.

They have a way to enrich for <unk> for which all then regulatory T cells that would then hone to the bone marrow.

And they've shown in a small number of patients who are heavily pretreated some enticing data of clinical response.

Drop in allele burden and maybe even some fibrosis improvement it's very early we like the way the deal is structured because we go in with a small upfront we finance the proof of concept work and then we have the option to take it up and we really we really you know it's exciting it's an off the shelf umbilical cord.

Steven H. Stein: We like the way the deal's structured because we go in with a small upfront, we finance the proof of concept work, and then we have the option to take it up. And we really, you know, it's exciting. It's an off-the-shelf umbilical cord with a completely new MOA. So those are the drivers behind that.

With a completely new MMA. So that's the drivers behind that one.

Steven H. Stein: Thanks for taking the questions. Thank you. Our final question today is coming from Jay Olson from Oppenheimer. Your line is now live. Oh, hey, thanks for asking me that.

Thanks, Thanks for taking the questions.

Thank you. Our final question today is coming from Jay Olson from Oppenheimer. Your line is now live.

Oh, Hey, thanks for taking the question and thanks to Mike Booth for all his help over the years, maybe just to continue on the theme of your Limber program I. Appreciate the progress there and I was wondering if you could provide any details on your bet inhibitor and what level of incremental benefit for the combination of.

Jay Olson: Thanks for taking the question and thanks to Mike Booth for all his help over the years. Maybe just to continue on the theme of your Limber program; I appreciate the progress there, and I was wondering if you could provide any details.

Bet inhibitor, plus rux versus rux alone would be clinically meaningful on SVR 35, and TSS. Thank you.

Steven H. Stein: That inhibitor plus RUX versus RUX alone would be clinically meaningful in SVR35 and TSS. Thank you.

Steven H. Stein: Hey Jay, it's Steven. Thanks for the question. So just a reminder, this is not a new compound. It's a compound we had in the clinic years ago and dosed more than 100 patients in a very solid tumor mind frame. At the time, we were trying to drive MYC inhibition with our BET inhibitor. And we treated, you know, as I said, north of 100 patients; we had adequate inhibition, but we had a lot of on target toxicity in terms of thrombocytopenia.

Yeah, Jay it's Steven Thanks for the question. So just to remind that this is not a new compound. It's a compound we had in the clinic years ago that we dosed more than 100 patients in a very solid tumor.

Line frame at the time, we were trying to drive <unk> inhibition with.

With our bet inhibitor and we treat it as I said north of 100 patients we had adequate inhibition, but we had a lot of untargeted toxicity in terms of thrombocytopenia and not much efficacy in solid tumors. So we put that program ourselves on hold on the shelf so to speak and then obviously they.

Steven H. Stein: And not much efficacy in solid tumors. So we put that program on hold or on the shelf, so to speak. And then obviously, you know, the externally, the field involved, CPI 610 showed data, there's monotherapy in MF patients in the second line setting, and then in combination with RUCs in the first line setting, that we think has an interest in signals. So we reinvigorated our program. It's up in an open now for enrollment.

External either field evolved CPR 610 showed data as monotherapy in <unk>.

<unk> patients in second line setting and then in combination with rux in the first line setting that we think is an interesting signals. So we reinvigorated our program it's.

It's up in an open now for enrollment and the idea is this calendar year in the first half hopefully COVID-19 behaves, but it's to get monotherapy safety and then in the second half of this year and get the combination safety with rux with our own bet inhibitor.

Steven H. Stein: And the idea is, this calendar year, in the first half, hopefully COVID behaves, but to get monotherapy safety. And then, in the second half of this year, get combination safety with RUCs and our own BET inhibitor. And then potentially, you know, go ahead with pivotal studies. But you ask, how does it differentiate? So we were able, with external data, to model a completely different dosing scheme from our prior one; we had about one third to one quarter of the dose we were in the clinic before.

And then potentially you know go ahead with with pivotal studies you asked how does it differentiate so we were able with the external data to model a completely different dosing scheme from a prior one we added about one.

One third to one quarter of the dose we are in the clinic before we've looked at the external environment and we think that'll we've the therapeutic ratio in terms of effect because we know it's effective in MF without one day, the preclinical as well and then not have unacceptable rates of thrombocytopenia, but it's not a different bedroom.

Steven H. Stein: We've looked at the external environment, and we think that'll affect the therapeutic ratio in terms of effect, because we know it's effective in MF, with our own data, preclinically as well, and then not have, you know, unacceptable rates of thrombocytopenia. But it's not a different BET inhibitor in any way in terms of targeting otherwise. And then we'll make, you know, bigger decisions once we have the safety data at the end of this calendar year. Thanks.

EBITDA in any way in terms of targeting otherwise.

And then and then we'll make bigger decisions once we have the safety data at the end of this calendar year.

Mike Booth: Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to Mike for any further closing comments. Thanks, Kevin. And, also, thank you all for your time today, for your questions, and also, of course.

Thank you we reached end of our question and answer session I would like to turn the floor back over to Mike for any further or closing comments.

Thanks, Kevin. Thank you will feel time today for your questions and also of course for your kind words.

Mike Booth: Also, of course, for your kind words. It will be in excellent hands with Christina, I'm sure.

It'll be in excellent hands with Christina I'm sure and on both of US are available for the rest of the day for any follow up questions, but for now. Thank you all very much and goodbye.

Operator: And both of us are available for the rest of the day for any follow-up questions. But for now, thank you all very much and goodbye. Thank you. This does conclude today's teleconference and webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.

Thank you that does conclude today's teleconference and webcast you may disconnect. Your line at this time and have a wonderful day, we thank you for your participation today.