Greetings, and welcome to the Insight Fourth Quarter And Year End 2019 Earnings Conference Call. At this time all participants are in a listen only mode. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It is now my pleasure introduce your host, Mike Booth, Head of Investor Relations for Insight.
Please go ahead, sir.
Thank you, Kevin. Good morning, and welcome to Insight's fourth quarter full year 2019 earnings conference call and webcast. The slides used today are available for download on the Investors section of insight.com. I am joined on the call today by Herve, Barry, Steven, and Cristiana, who will deliver our prepared remarks, and by Dash who will join us for the Q and A session. During the question and Before we begin, I'd like to remind you that some of the statements made during the call today are forward looking statements.
Including statements regarding our expectations for 2020 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 our 10 Q for the quarter ended September 30, 2019, and from time to time in our other SEC documents. It is also important to note that our recently announced collaboration with MorphoSys for the global development and commercialization of tafasitumab is subject to clearance by antitrust authorities.
And therefore, any statements we may make about the collaboration and tafasitumab are conditioned on such clearance. We'll now begin the call with Herve.
So 2019 was another year marked by strong commercial performance, including surpassing EUR 2,000,000,000 in annual revenue for the first time. In addition, we continued to advance our R and D portfolio and make progress towards our strategic goal of diversification and growth. During the year, we achieved 13 of the 15 key goals we laid out this time successful launch of Jakafi in steroid refractory acute GvHD. Whilst the results of the Gravitas-three zero one trial of itacitinib was disappointing, We announced positive results of the phase 3, reached 2 trial. We submitted the NDA for Pemigatinib based on strong updated data and we are very pleased to recently report positive top line Phase III results from Rockstream in atopic dermatitis.
In addition to our internal portfolio, we continue Our recent collaboration with MorphoSys for Tafasitamab represent a strong fit with our portfolio, and we expect to be able to capitalize on our commercial expertise in the We had another year of robust top line growth. Product and royalty revenues grew 22% year over year, with growth coming from all four sources. Jakafi was up 21%, Jakavi Royalties, up 16% iclusic up 13% and aluminum royalties doubled to $80,000,000. Slide 5 shows the revenue momentum over the last several years. Product and royalty revenues have more than tripled since 2015.
Jakafi with a 4 year CAGR of 29 percent remains a significant revenue driver and non Jakafi revenues have shown over 50% compounded growth over same period. 2 new molecules, both of which were discovered at Insight are currently under priority review at the FDA, And these are highlighted on Slide 6, both have breakthrough therapy designation from the FDA. The benefit for Pemigatinib is made SOLIRES and we expect the FDA decision on Novartis application for the approval of CAPENTINib in around 6 months' time. The Catmatini economics to Insight include royalties in the range of 12% to 14% on global net sales by Novartis and over 500,000,000 in potential milestones. Tafasitama from our recently announced collaboration with MorphoSys is a third molecule currently under FDA review.
We see CD19 inhibition with an Fc engineered antibody as a unique mechanism of action that is fundamental to the treatment of Citamab can become a very important part of our oncology portfolio and provides both a near term opportunity through the potential launch in DLBCL where the BLA was submitted late last year and the MAA is expected to be submitted mid this year as well as significant potential upside in the medium to longer term. Tafasitamax fits very well with our current commercial hematology footprint and therefore enable us to capitalize our significant commercial capabilities in US and Europe. Turning now to the key development and commercial priorities for 2020. We have the 3 potential new products approval this year that I have already mentioned, and we also expect to submit the NDA for ROCStream. In atopic dermatitis before the end of the year.
We also expect to continue the momentum within our Limber program, with the initiation of the 1st pivotal combination development trial as well as important data from the once a day formulation of ruxolitinib. On the commercial side, we will work to drive continued Jakafi growth in all three indications while also ensuring that we are ready to pursue successful launches of Pemigatinib and Tafasitamab. I will now pass to Barry for more detail on both 2019 Jakafi performance as well as our commercial preparations for Permian and Tafar.
Thank you, Herve, and good morning, everyone. In the fourth quarter of 2019, Jakafi grew 23 percent year over year to $466,000,000, Patient demand continued to drive the uptake of Jakafi and growth was strong across all three indications. Jakapai has grown consistently in total patients treated and net sales for each of the past several years, fueled by growth across all indications. The 2020 net product revenue guidance we provided for Jakafi today reflects a continuation of this growth in patients and in top line sales to a range of $1,880,000,000 to 1 $950,000,000. Slide 11 also highlights the key priorities for our U.
S. Team this year. These priorities include continuing the growth of total where we recently launched a strong traction since the launch in the steroid refractory acute setting. In the presidential symposium at the EBMT meeting next month and to the results of Reach 3 in the second half of this year. Reach III is the randomized Phase III trial of Jakafi versus best available therapy in steroid refractory chronic GBHD.
In addition, we are also planning for the potential launches of both tafasitumab and pemigatinib. We expect to be able I'll turn the call over to Steven for our clinical updates.
Thanks, Barry, and good morning, everyone. At the beginning of 2019, we had laid out a list of key R and D goals for the year, and I'm pleased to say that we achieved most of what we set out to do. While the recent results of Gravitas 301 was disappointing, we were able to report multiple successes last year. Some highlights include the positive top line result reported for the randomized reach to trial of ruxolitinib in steroid refractory acute Graft versus host disease. The submission of an NDA for pemigatinib in cholangiocarcinoma and the initiation of pivotal trials for ruxolitinib cream in both atopic dermatitis and Vitiligo We recently announced that the first of 2 Phase III trials evaluating ruxolitinib cream in atopic dermatitis met its primary endpoint, and I'll cover this on the next slide.
We were pleased to announce that our pivotal phase 3 TRUDE AD2 study achieved its primary endpoint of proportional patients with an IGA treatment success following 8 weeks of therapy. This is the first of 2 identical pivotal trials, and we expect the results of TRU 81 later in the first quarter. In terms of study design, TRU 82 recruited approximately 600 patients with mild to moderate atopic dermatitis. Inclusion criteria included an age range of twelve to seventy five years of age, an IGA score of 2 to 3 and a percentage body surface area affected of 3% to 20%. Patients were randomized 2 to 2 to 1 to 0.75 Percent Rux Cream BID, 1.5% Rux cream BID and a vehicle cream, respectively.
And were on therapy for 8 weeks, at which point, all eligible patients could either switch to or continue on 0.75% or 1.5% RACS cream BID for the long term safety extension period. In the phase TRU-eighty two study and for both doses, the efficacy data as measured in the primary and secondary endpoints as well as the safety profile are consistent with previous data from our phase 2 program, which as a reminder, were presented at EADV in 2018 and have since been published in manuscript form studies, long term safety data are being collected, and we continue to expect to submit the NDA for ruxolitinib cream in Q4 of this calendar year. I wanted to take this With morphosys, we intend to pursue development in both relapsedrefractory and frontline diffuse large B cell lymphoma. As well as in relapsedrefractory CLL and other non Hodgkin's lymphomas. For relapsedrefractory diffuse large B cell lymphoma, L MIND was the basis for the BLA submission seeking approval of the combination of tafasitinmab plus lenalidomide.
The B MIND Phase III studies also underway, assessing TAFSA versus rituximab, both on top of Bendamustine. The futility analysis for B MIND was passed in late 2019 and primary completion is estimated for 2022. TAPA has also been evaluated in frontline diffuse large B cell lymphoma. The safety portion of the first mine study is expected to be completed as it relates to relapsedrefractory CLL and other non Hodgkin's lymphomas based on some promising data of TAVA in combination with a PR3 kinase delta inhibitor in the Kosmos trial, we expect to initiate a trial of TAPA plus our own PR3 kinase delta inhibitor, parsiclib in 2020. Moving on to our lumber project on Slide 16, which is our initiative focused on expanding our leadership within MPNs beyond ruxolitinib.
Later this year, we expect initial bioavailability and bioequivalence data for once a day ruxolitinib, which is an important step towards a potential launch in 2022. We expect to begin proof of concept combination trials of ruxolitinib with both our bet and L2 inhibitors during this year, and we also plan to initiate a pivotal trial combining ruxolitinib with parsiclib in myelofibrosis patients with a suboptimal response to ruxolitinib monotherapy based on encouraging proof of concept data. This initiation would mark the 1st pivotal trial within the Lumber program. With that, I would like to turn the call over to Cristiano for the financial update it.
Thank you, Steven, and good morning, everyone. The financial update this morning will include GAAP and non GAAP numbers. For a full reconciliation of GAAP to non GAAP, please refer to Slides 2526 in the backup section of the deck and to the press release we issued this morning. Our 4th quarter results reflect continued strong revenue growth across all product with total product and royalty revenues of $579,000,000, representing an increase of 24% over the fourth quarter of 2018. This is comprised of $466,000,000 in Jakafi, and $24,000,000 in Iclusics net product revenues, $65,000,000 in Jakavi royalties from Novartis and $24,000,000 in Olumiant royalties from Lilly.
Our total cost and expenses for the quarter on a non GAAP basis of $434,000,000 increased by 10% from the prior year quarter. Expenses was well below the growth rate in product and royalty revenues. Ongoing R and D expense for the quarter was $282,000,000 a non GAAP basis, representing a 3% increase from the prior year quarter. This was primarily due to our existing pipeline programs progressing to later stages of development and was partially offset by our election to end additional co funding of development of baricitinipu with Lilly. SG and A expense for the quarter was $123,000,000 on a non GAAP basis, representing a 27% increase over the prior year quarter.
This was primarily due to an increase in the commercialization efforts related to Jakafi Looking at full year 2019 results, total products and royalty revenues of $2,080,000,000 grew 22%, while total cost and expenses stayed relatively flat at $1,550,000,000 on a non GAAP basis. As a result, non GAAP operating income increased by 88% from $325,000,000 in 2018 to $610,000,000 in 2019. Looking at the trend from 2015 through 2019, The growth in our products and royalty revenues has exceeded the growth in both our ongoing R and D expense and SG and A expense on a non GAAP basis leading to higher operating leverage and reflecting our commitment Moving on to 2020, I will now discuss the key components of our 2020 guidance. Please note that the guidance we provide today does not include the financial impact of our recently announced collaboration with MorphoSys, which has not yet closed. And also excludes the impact of any additional potential future strategic transactions.
For the full year 2020, on both a GAAP non GAAP basis, we expect net product revenue for Jakafi to be in the range of $1,080,000,000 to $1,950,000,000 driven by continued growth across all indications. For Iclusig, we expect net product revenue to be in the range of 100 to 105 $1,000,000. As in previous years, we will not be providing guidance for milestone or royalty revenues. We expect our gross to net adjustment for 2020 to be approximately 16% for Jakafi with the adjustment in the first quarter of the year being higher relative to both the previous quarter and subsequent quarters. We expect GAAP R and D expense to be in the range of $1,210,000,000 to $1,280,000,000 and non GAAP R and D expense to range from 1.08 to one $15,000,000,000.
The increase compared to 2019 is primarily driven by our existing pipeline program progressing to later stages of development. We expect the GAAP SG and A expense to be in the range of 505 $5,000,000 and non GAAP SG and A expense to range from $447,000,000 to $477,000,000. The increase compared to 2019 is primarily driven by efforts to support the expansion of our commercial portfolio investment in infrastructure to support the continued growth of the business. Both in the case of R&D And SG And A, the non GAAP expense guidance excludes estimated stock based compensation expense. I will now turn the call back to Herve for further discussion of the year ahead.
Thank you, Christiana. So 2019 was a strong year in term of business performance and pipeline progression. And as you can see on Slide 23, 2020 is shaping up to be another busy and important year for insights. In my opening remarks, I laid out our key priorities for the year, and here we have highlighted the 5 key regulatory updates that we expect, which are the FDA decision on pemigatinib, tafasitamab, and CAPmatinib, the MAA submission of Tafar and the NDA submission of ROC screen. We also look forward providing numerous other data announcement as the year progresses.
Operators that concludes our prepared remarks and please give you instruction and open the call for Q And A.
Certainly. We'll now be conducting a question and answer session. Session. Our first question today coming from Brian Abrahams from RBC. Your line is now live.
Hey guys, thanks very much for taking my question. And congrats on the continued commercial performance and on the true 82 results. On topical rux, I was wondering if you could talk about your expectations for whether there might be ultimately a boxed warning on the label with respect to class safety. What, if any, impact that you think that might have on dermatologists views and take of the agent ultimately. And I guess along those lines, any type of work that you have done or expect to do over the course of the program, to fully characterize systemic exposure and maybe the relative importance of that as you think about a future label there and adoption?
Thanks.
Brian, it's Steven. Thank you for your question. The data that we've already presented both at EADV and then published in a paper in JACI shows the safety profile to date for our topical rec cream. Obviously, what you referenced in terms of boxed warning has to date largely applied to compounds that give you substantial systemic exposure. And what we've already published, we have little to no systemic exposure.
We have a very clean safety profile. So given all of the above, we don't think that we're going to be in that territory of having a boxed warning. Obviously, ultimately, it's up to the FDA and not to us. But again, given the little to no systemic exposure seen to date, the very clean safety profile, we don't expect that. And then we'll update safety as this year goes along with more long term data.
But that's our expectation currently.
Thank you. Our next question is coming from Mark Frum from Cowen and Company. Your line is now live.
Hey, guys. Thanks for taking my questions. It's for Ervein and Cristiano. Just with the MorphoSys deal unit assuming this closes, you'll have about 3 products probably launching the next year and a half or so. So I'm just wondering kind of appetite for continued M and A?
And should we expect that you might do more larger deals like the MorphoSys deal for late stage assets or think you're kind of done on that end of the pipeline and we should really be more focused on kind of smaller earlier stage deals going forward?
Hi, Mark. Thank you for the question. So in terms of the BD strategy, it hasn't really changed from what it was before the Morpho deal. We are continuing to look at the external assets to complement or supplement our internal activity And the focus is similar to what it was before looking at programs that could help diversify and continue to grow revenue, programs that allow us to capitalize on our existing capabilities in oncology, hem, NPNs, of course, and, more on the bolt on type of, transactions versus, larger deals. And, when you look from a capacity point of view, we ended the year with 2.1 $1,000,000,000 of cash on the balance sheet.
The pro form a for the MorphoSys transaction is $1,200,000,000. So we still have capacity to continue to look for those bolt on type of transactions.
Thank you. Our next question is coming from Tyler Van Buren from Piper Sandler.
Are the true AD results in the press release. There's one line which appears pretty deliberate, and was repeated in the press release this morning where you state that the overall efficacy and safety profile of ruxolitinib cream is consistent with previous data. So and I know you guys can't can't speak about the data, but I guess just with respect to that statement, could you say that consistent with the effect size compared to vehicle as we think about it relative to prior data. And then just As a quick follow-up, just can you talk about the potential conferences that you guys might present data at? And I'm assuming that you would wait for the results from TRU-eighty one as well.
Got it. Yes, it's Steven. Thanks for your question. Question first. The TRU Eighty one results will come sometime this quarter.
And obviously, we are awaiting them and we expect them to be in line with 382. And then again, with the proof of concept data, what we're trying to communicate as much as we can without actually giving the actual results because we have to protect future meetings when we want to present the data as possible is that directionally and quantitatively, the active arms, the 0.75% and 1.5% were in line with the primary and secondary efficacy endpoints seen in the phase 2 data. And the vehicle was as well. Which was very encouraging. So when we went from 150 patient proof of concept study to a 600 patient Phase III in TRU82, We are seeing the same quantitative results in terms of the primary and secondary efficacy as well as the safety.
And that's as much as we can say to try and protect both presentation and a future manuscript, which we hope to be able to do soon.
You. Our next question is coming from Cory Kasimov from JP Morgan. Your line is now live.
Hey, good morning guys. Thanks for taking the question. I wanted to ask on Jakafi, just regard to your 2020 guidance, looks like it implies growth of, I think, is 12% to 16%. Can you just qualitatively discuss how much of this is coming from GVHD versus the longer term indications of MF and PV? And then also can you just comment on what happened with the Jakafi set study in ET saw in the press release that recruitment was discontinued.
So curious what happened on that front. Thank you.
Hey, Corey, this is Barry. I'll let Stephen handle the reset study. But, as far as the growth goes, we're very encouraged by the approval and launch in acute steroid refractory GvHD for Jakafi that continues to now add a significant portion to the overall net sales, but myelofibrosis continues to be the largest portion of our net sales while TV, total percentage of patients, continues to increase at a faster rate than MF but those 2 indications MF and PV will drive the indications. Obviously, we've talked before, whether it's acute GVHD or chronic GvHD. The total population in the United States in the steroid refractory setting is about some patients.
And obviously, you know that it's a much larger patient population. So MS and PV will continue to drive the growth towards $3,000,000,000 ultimate but GVHD is now a significant contributor to that. Steven?
Sorry, in terms of the RESET study, so that's looking at ruxolitinib in essential thrombocythemia. The study design was a little bit complicated because of the composite endpoint. So the endpoint that was required in negotiation with the regulatory agencies was to obtain control of blood counts in terms of both the white blood cell count and the platelet count together. And not an event endpoint, lung thrombosis. So what was required in terms of eligibility was patients coming on who had, either intolerance or progressed on hydroxyurea had a white blood cell count above 11,000 and had no prior exposure to Negrilite because the study was randomized against the Negrilite.
And trying that for more than a year, in fact, longer, unable to enroll sufficient number of patients in a timely manner. We looked at various amendments to try and get around this, but ultimately because of that composite endpoint, we couldn't do that in terms of either the white count or prior nebulide. So the current thinking is to change to a publication strategy, finish up the study and publish it, but we'll it'll not be of, registration quality in terms of its size.
Okay. Thank you. Appreciate it.
Thank you. Our next question is coming from Vikram Pravet from Morgan Stanley. Your line is now live.
Good morning. Thanks for taking my question. So I had a question on your commercialization plans for Rux Cream. So you previously noted that you're still thinking through your options when it comes to whether you'd like to pursue commercialization independently to find a partner for Europe. And I just wanted to see if your thinking here has evolved or changed at all based on the first set of phase 3 data you saw based on the recent readout?
So the recent avenue here, so the recent readout is obviously, you know, improving our optimism regarding the the chance of getting regulatory approval in the U. S, whereas you know, we have, decided to go by ourselves. Regarding the rest of the world, as I said previously, things have not changed. I mean, we would be there's a high probability we'll have a partnership regarding Asia. And in Europe, we are still in the sense of looking at what options we have either going alone, licensing out completely or some form of a partnership and each of the 3 option is still open or regarding Europe.
Okay, understood. Thanks.
Thank you. Our next question is coming from Evan Seagerman from Credit Suisse. Your line is now live.
Hi, all. Thank you for taking my question. Congrats on the progress. So I noticed in the press release, there was some updates on the Lotus trial in ulcerative colitis and osteoparaciclib and Sjogren's disease. Can you help me understand why the UC trial was discontinued what you saw on the data from the Sjogren trial not to warrant continuation?
Sure, Evan, that's Steven. Thanks for your question. In terms of the low dose itacitinib in inflammatory bowel diseases, particularly ulcerative colitis, Again, it was around operational dynamics in the competitive space. So we were unable to enroll in a sufficient numbers of patients to keep progressing the study, as well as given the competitive space with other compounds with similar mechanisms being way ahead, We elected at the end of last year to no longer pursue that program. In terms of sjogren's, again, a difficult medical condition in terms of measuring endpoints, and getting sufficient spread versus standard of care or even placebo, we're not seeing enough of the activity to warrant going forward into a full registration program.
It was a proof of concept study. And in our opinion, we didn't get to the proof of concept we wanted to pursue reg situation further there. Across inflammation and autoimmunity, one of the beauties of the program is we have this pipeline of targeted therapy agents, immuno oncology agents, all of which were primarily in the beginning developed for either hematology or oncology indications. But because of their mechanism of action, either in terms of JAK inhibition or B cell inhibition with Delta inhibitors, they lend themselves to conditions in the inflamed autoimmune setting, where those mechanisms are important. So we have the ability to conduct multiple proof of concept studies very efficiently and then make decisions to go forward or not.
And in those two instances, it didn't meet our own internal expectations to pursue registration programs.
All right. Thank you for the color.
Thank you. Our next question is coming from Jay Olson from Oppenheimer. Your line is now live.
Hey, thanks for taking the question and congratulations on the financial performance in 2019. You delivered impressive non GAAP operating margin growth last year. And since you're now investing in multiple new product launches over the next year or 2, do you expect to continue growing operating margins at the same rate? And where do you see them going longer term? And then maybe if I could just ask a follow-up question on QD Jakafi.
Do you expect any clinical benefits versus BID Jakafi? And if so, would those benefits appear in the label?
Hi, Grace. Cristiano, let me take the the part on, on the margins. As you can see, both in the case of 2019 and with the guidance that we provided for 2020, we are looking to continue to invest in supporting our portfolio both on the R and D and commercial side, but the growth on the expense front is lower than that of the top line, which is what we had indicated in the past. And as you can see, we are in line with what we had said. We'll continue to invest in our activities and in the company on the R and D front as we have discussed in the past, we will be looking to invest based on the quality of the programs.
And if data supports moving programs into development and later stages of development will continue to do that. But, the trend that we see is continuing to have growth
Jane, in terms of your question, for the 1 stay formulation, so the work with that is progressing very well, the intent is to follow a 505b route in terms of 1st obtaining, you know, sufficient bio availability in terms of PK of the different strength. And then moving on to prove those individual different once day strength meet the bio equivalence in terms of the ratios on the FDA guidance, each of the strengths you match in it up with. So there's no in the beginning, it's not built around clinical differentiation, if you will. It's built around BA be route to obtain approval in that 2022 timeframe. We do know from a publication in 2011 with a single one daily strength, the 25 milligram XR strength, not surprisingly, the PK profile was flatter.
So there was less of a Cmax. Which we think is related with these products. That'll need to be proven, down the pike once we've, finished the Wednesday formulation work once you've taken it through the BABE route and gotten approved, then we could potentially do clinically differentiating work to see if there is a flatter profile with all the strengths and ultimately less anemia and then make that claim and get it in a label. So it's a very stepwise approach.
Great. Thank you very much.
If I may add on the QD, the strategy around the QD, that there is obviously this practical aspect of QD. There is this potential clinical benefits, maybe on anemia we just discussed, and there is the ability to combine with other mechanisms that have a once a day regimen. So this project by itself has a lot of potential positive consequences on the management of the lifecycle of Jakafi.
That's super helpful. Thank you.
Thank you. Our next question is coming from Salveen Richter from Goldman Sachs. Your line is now live. Great.
Thanks for taking our questions. This is Andrea on for Salveen. The first one, as you look to the upcoming launch for Pemegatinib and cholangiocarcinoma. Can you talk a little bit more about how you've approached building out a solid tumor sales force and the efforts that might be needed for patient or physician education to improve the disease awareness as well as the need for diagnostic screening. And then I have a follow-up.
Sure, Andrea. This is Barry. First, we're actually launching, in cholangiocarcinoma and his patients population that has FGFR2 fusions or rearrangements. We're already educating, providing, healthcare professionals getting them ready to in fact always test cholangiocarcinoma patients for various mutations, alterations, and so forth. So those educational efforts are ongoing now.
In terms of FTEs that we put in the field, we do have a few more FTEs in the field, but the way it works in the United States, we have now, 147 representatives across the United States and they call on, community oncologists and academic centers across the nation, even though there's people who are specific to heme and solid tumor, most of the community oncologists offices throughout the United States treat both. And certainly geographically, we hit all of the centers So we will have a dedicated team that's specifically trained on solid tumors and particularly, pemigatinib and cholangiocarcinoma. And of course, the need for NGS testing or diagnostic testing, to remind all of these healthcare professionals that are treating these patients. But in fact, we have, oncology clinical nurse educators who are providing educational services. We have medical science liaisons that are all trained.
So each of the teams have already been trained and we have ongoing training for the sales force. So we think we're in solid shape and we're going to continue to, educate all healthcare professionals about the need for diagnostic testing to best help these patients.
Got it. Thanks, Barry. Maybe just another one for you then on the morphosis potential launch. Just what additional add to the infrastructure is needed there? And where do you see points of synergies or components that can be leveraged from your existing network?
Well, Andrea, as you know, until we close, we can't really plan together with our future partners at MorphoSys. So we've been thinking about this a lot. And independently, we been planning about what we actually need, but the ability to guide. Now on the other hand, We certainly have a great deal of experience in heme malignancies, certainly here in Wilmington, Delaware and throughout the United States. So we're very confident that we know the space, the lymphoma space very well.
We just have to take time, wait a couple of more weeks to get together and sit down with our partners. I'm more focused about the real details that we have that we can do.
Got it. Thank you so much.
Thank you. Our next question is coming from Alethia Young from Cantor Fitzgerald. Your line is now live.
Hey guys, thanks for taking my questions and congrats on progress. 1, can you just talk a little bit about the status of the SIVL program and, when we could expect data there? And then, you know, basically kind of your thoughts and your increased conviction. And I saw some data obviously from paraciclib and ruxolitinib, but just maybe talk a little bit about your increased conviction in that combo and then also the other kind of combos in the Limber program as well. Thank you.
Alethia, it's Steven. Thanks for the question. So the Citadel program has 3 components in terms of B cell malignancies. There's a follicular lymphoma study 203, citadel, a marginal zone lymphoma study 204 and then a mantle cell lymphoma study 205. Essentially, we've completed recruitment across all those studies.
There may be just a few patients left on one to be done. And now we're in the follow-up phase. As we presented this data multiple times because they open label single arm studies. We're very encouraged by the high activity of particlissive across these B cell malignancies. And now it's really a wait for the duration of response data.
And then they all could be potentially accelerated approval routes in the United States given the designs of the study. And we may have to then go on and do confirmatory studies as well. So we'll get the bulk of all of that data with the long follow-up through this calendar year and then look at potential submissions across the board, but we're very encouraged by that program and what we've done with it. In terms of the mild fibrosis combinations, as we announced in our prepared remarks, the most advanced is the RUX plus PR3 Delta combination. We also presented that data a number of times We now have the updated data set, looking at the experiments we did in terms of weekly versus daily dosing.
And we're most encouraged by the daily dosing arm of the proof of concept study. And that's why we'll be going forward this year in a pivotal registration route with that combination. We still have to work out the details with regulatory agencies, but the likely population as we said in our prepared remarks are patients who have been on rux probably for approximately 3 months, but don't have a sufficient response and are then randomized to RUX Plus PR3 Delta versus RUX alone in some sort of registration fashion with sufficient numbers. And given the effect we seen from the addition of Delta in that population to date where we saw further spend volume response, particularly with the daily arm, as well as symptom response, obviously, we're encouraged by going forward to a pivotal program there. In terms of the rest of the Lumber program, it's also a big year as we announced at JP Morgan.
We're beginning and we've resurrected our pet program. Based on the external environment and what's happening with bet inhibitors in my fibrosis. So we're a go with our own bet inhibitor this year. We'll do the monotherapy safety work and go as quickly as we can to combination with rux there. And then our L2 program as well, which is targeted around alleviate in the anemia through a hepcidin mechanism in combination with this year.
And then we'll get further proof of concept data for RUX plus perm innovation. So, obviously, an extremely important development program to us given the importance of rocks and milder proliferative neoplasms in general and an active year in terms of, initiating the pivotal study, getting further proof of concept study and starting 2 new mechanisms.
Thank
Our next question is coming from Mara Goldstein from Mizuho. Your line is now live. Great.
Thank you very much for taking the question. Just to circle back on the previous question and the ruxplusplusplusclicid, and myelofibrosis, can you characterize what that proof of concept was? And, and also what is considered an insufficient response to RUX in the clinical trial, but also in clinical practice today?
Hey, Maura, thanks for your question. It's a good question, because as you look across, not only us, but everybody else doing studies in this arena. You have to be very careful of doing cross study comparisons and make sure that you're actually doing apple to apple comparisons, particularly in terms of how people define the population they study in terms of the amount of prior RUXA exposure, what constituted either refractory or disease that's progressing and how much was allowed. And then was RUX actually discontinued versus was it continued. And the reason I mentioned the latter is just to be clear is that if you discontinue rux and then allow patients to a rebound, if you will, in terms of the spleen and symptoms, just reintroducing rugs again.
You'll see quite a substantial effect and And we've documented that before and published that. So you have to be very, very careful of the populations you're looking at. Our proof of concept work from a definition point of view with Rux plus PR3 Delta was defined as patients should be on at least 6 months of ruxolitinib for at least 2 months of stable dosing And then we're showing insufficient response, in terms of spleen or symptoms and then allowed, to come on to the combination without discontinuing rugs. With that, we showed a further detriment in terms of spleen volume reduction that was better with daily dosing rather than weekly dosing. If you're asking the exact quantitative excursion in terms of spleen volume response, that's a good question.
In the frontline setting, obviously given our own approval in the setting, we have now established the endpoint of spleen volume reduction of 35 percent or greater done through a measurement like MRI, for example, which is not subjective, as the probable endpoint that regulators will use going forward as well as validated symptom scores. In the latter line settings, one could argue that that may be too high a bar to get to and maybe 20% or more improvement in spin volume reduction with concurrence symptom improvement may get you across the finish line or other endpoints like transfusion independence. But that's sort of where the field is right now. I think for the moment, 1st line studies will still require clean volume response as a primary endpoint with symptoms as a secondary endpoint. And we've established with our own label what that bar is.
With the comfort studies, and that's what people will have to use going forward. In the other settings, there may be somewhat more creative endpoints you could do as long as you prove to regulators and patients that you're actually getting clinical benefit.
Thank you. Our next question is coming from Christopher Marai from Nomura Instinet. Your line is now live.
Hey, good morning and thanks for taking the question. I'm wondering if you could elaborate a little bit on the vehicle for moments in true AD that you saw. Just being cognizant that the Eucrisa Phase III saw some variability in that vehicle performance. How do you feel, I guess, given that type of variability about the chance for success of TRU-eighty one? And maybe if you could just remind us of some of your powering assumptions around that.
Thank you.
Yes, Chris, it's Steven. So if you look at the at the atopic dermatitis renamed in general. There are some vehicles that on their own without, quote unquote, active ingredient will have a response rate because of the amoliant effect of different vehicles that will then result in an improvement in the underlying condition. Our vehicle is cream based, just like our actual active product. And you saw in the proof of concept 150 patient study, our vehicle response rate was 10% or less percentage points.
Just to give you by way of comparison a number, but not to make a direct comparison, UCRISA in their registration studies had to use an ointment based vehicle because of their constitution of their active product. And their ointment based vehicle response rate was north of 20%. So we don't expect and that's why, you know, earlier when we spoke, we said our results are consistent with our proof of concept data to date directionally and quantitatively. We expect the same vehicle cream response rate in our 381 and 382 studies that we saw in our proof of concept work. And that's where we stand right now.
Obviously, we want to share this with you as soon as we can in an appropriate meeting.
Thank you. I appreciate that. And just one last one on OXO guidance. How much GBHD acute or chronic is sort of in those numbers. Thanks.
I'm sorry. Could you repeat the question? I didn't hear the question.
Oh, and Cat, just on in terms of your RUX guidance for the year, how much of that, if any, accounts for use in GvHD? Thank you.
Well, we were hoping for a particular number of page I think I said before that there's 3000 patients totals for refractory GvHD acute GvHD is about 1500 patients We think we were approaching about 1000 patients. It's hard to actually for GvHD because the drug oftentimes is given in the hospital and we don't get detail as you do when you get a prescription on the outside. So GvHD is an important part of the guidance for this year. But, overwhelmingly, it's the continued growth in myelofibrosis, which is really going very well. And the continued growth in for patients with polycythemia vera, again, which is continuing to go going very well, but, Jakafi in acute steroid refractory GvHD, is becoming one of the most used, if not the most used drug other than steroids in treatment of these patients.
Thank you.
Thank you. We reached
the end of our question and answer session. I'd like to turn the floor back over for any further or closing comments.
Thank you, and thank you all for your time today and for your questions. So we look forward to seeing you at upcoming investor and medical conferences. But for now, we thank you again for your participation to the call today. Thank you, and goodbye.
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