Greetings. Welcome to TG Therapeutics' Second Quarter 2021 Earnings Call and Business Update. At this time, all participants are in listen-only mode. A question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero from your telephone keypad. Please note this conference is being recorded. At this time, I'll now turn the conference over to Jenna Bosco, Senior Vice President of Corporate Communications. Jenna, you may now begin.
Thank you. Welcome, everyone, and thanks for joining us this morning. I'm Jenna Bosco, and with me today to discuss the second quarter 2021 financial results and provide a business update are Michael Weiss, our Chairman and Chief Executive Officer, Adam Waldman, our Chief Commercialization Officer, and Sean Power, our Chief Financial Officer. Following our safe harbor statement, Mike will provide an overview of our recent corporate developments, as well as an update on our current pivotal programs and remaining key goals for 2021. Adam will then provide an update on our commercialization efforts, and Sean will provide a brief overview of our financial results before turning the call over to the operator to begin the Q&A session.
Before we begin, I'd like to remind everyone that we will be making forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include statements about our anticipated future operating and financial performance, including sales performance, projected regulatory milestones, clinical development plans, and expectations for our marketed and pipeline products. TG cautions that these forward-looking statements are subject to risks that may cause our actual results to differ materially from those indicated.
Factors that may affect TG Therapeutics' operations include various risk factors that can be found in our SEC filings, including our most recent reports on Forms 10-K and 10-Q. In addition, any forward-looking statements made on this call represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. This conference call is being recorded for audio rebroadcast on TG's website, www.tgtherapeutics.com, where it will be available for the next 30 days. All participants on this call will be on a listen-only mode. Now, I would like to turn the call over to Michael Weiss, our CEO.
Great. Thank you, Jenna, and thanks, everyone, for joining us today. During the first half of 2021, we hope that our long-term goals and vision for TG have really come into focus for investors. With the first phase of our multi-phase strategy now complete with the accelerated approval of UKONIQ, the first and only dual inhibitor of PI3K-delta and CK1-epsilon for the treatment of relapsed or refractory marginal zone lymphoma and follicular lymphoma. We are very proud of these accelerated approvals for patients who have failed prior therapies and have limited treatment options. We estimate approximately 8,000 patients each year will be seeking treatment in our approved MZL and follicular indications, which we see as an excellent starting point for our commercial efforts.
Building on the momentum from our UKONIQ launch, we have submitted and received a PDUFA target goal date of March 25, 2022, for a BLA application requesting approval of the combination of UKONIQ plus ublituximab, our novel glyco-engineered anti-CD20 monoclonal antibody, the combination of which we refer to as U2, for the treatment of patients with chronic lymphocytic leukemia. We have also submitted a supplemental new drug application, sNDA, for UKONIQ for the same indication and have received the same PDUFA date for the sNDA. We are excited about the potential to bring our novel U2 combination to CLL patients, especially those who have failed or who are not good candidates for current standards of care. CLL is a significantly larger patient population than marginal zone and follicular. We currently estimate that approximately 30,000-40,000 patients will be seeking a new treatment each year in a proposed CLL indication.
Not only is CLL multifold larger patient population than marginal zone and follicular, but we would expect the median duration of treatment to be longer in CLL as well. One other important factor to note is that we believe about 85% of our target prescribers for marginal zone and follicular lymphoma are the same prescribers that we will be targeting for chronic lymphocytic leukemia. The significant efforts our team has made in building relationships for the marginal zone and follicular launch should translate nicely into our potential CLL launch. Next up in our multi-phased approach is the largest patient population we will be addressing, which is patients with the relapsing forms of MS, with ublituximab as a single agent. We are targeting a submission of a BLA for MS this quarter and hope to receive a target PDUFA date in the third quarter of next year.
We believe our Phase III data supports an attractive treatment option for patients with the relapsing forms of MS. Entering MS will also raise our commercial profile significantly, as we expect to participate as one of only 3 anti-CD20 monoclonal antibodies in what has been projected to become a $10 billion-$15 billion per year market just for anti-CD20 monoclonal antibodies in the treatment of MS. While the core focus will be on the regulatory and then commercial execution of these first three opportunities, especially the larger market opportunities in CLL and MS. We will continue to seek to enhance our hematology oncology franchise by broadening the potential U2 label to new indications, such as in marginal zone and follicular lymphoma, and also into new combination uses of U2 in CLL, for example, in combination with venetoclax and our very own TG-1701.
The ability to combine with standard of care agents in CLL, we hope will bring better outcomes to patients and should also broaden the potential penetration of U2 in CLL. On the MS side, we will seek to build on ublituximab, potentially in other autoinflammatory diseases, as well as seek to build additional programs in MS. With that, let me provide some recent highlights related to our initial commercial launch efforts with UKONIQ and our key regulatory efforts and development programs. First, let me just remind everyone and restate that in February, the FDA granted accelerated approval of UKONIQ for the treatment of adult patients with a relapsed or refractory marginal zone lymphoma who have received at least 1 prior anti-CD20 based regimen, and for adult patients with a relapsed or refractory follicular lymphoma who have received at least three prior lines of systemic therapy.
This approval was based primarily on the results from the UNITY-NHL trial, which were recently published in the Journal of Clinical Oncology. On the commercial side, UKONIQ became commercially available a few weeks following approval. Overall, I can say we're extremely pleased with the performance of the commercialization efforts to date. Launching during a global pandemic is no easy task. Under the circumstances, the team has done a really nice job in engaging target prescribers, both commercially and educationally, under the leadership of our Chief Commercialization Officer, Adam Waldman. Adam will join us shortly to discuss some launch metrics and give some high-level qualitative assessments of the launch thus far. I don't want to steal his thunder. Again, from where I sit, the launch is going well and believe it's positioning us for future success with the potential approval of U2 for CLL early next year.
Speaking of which, as noted above, the BLA and sNDA for U2 and CLL have both been granted a PDUFA target goal date of March 25th, 2022. For the MS program, we were pleased in the second quarter to be able to present the positive results from our ULTIMATE I and II phase III trials evaluating ublituximab in relapsing forms of MS at two major conferences, the American Academy of Neurology Annual Meeting and the European Academy of Neurology Annual Meeting. As mentioned during our last call, both studies met their primary endpoint, with ublituximab treatment demonstrating a statistically significant reduction in annualized relapse rate, referred to as ARR, with ublituximab treatment resulting in historically low levels of ARR. We believe these results are highly encouraging and showcase the potential of ublituximab to provide an efficacious treatment option in a one-hour infusion every six months following the first dose.
The expert feedback we have received thus far has been very positive, and our one-hour infusion is viewed as an important benefit for both physicians and especially their patients. These trials were conducted under Special Protocol Assessment with the FDA, and we are on track to complete a BLA submission for ublituximab to treat RMS this quarter. Briefly, before I turn the call over to Adam, I want to provide a quick update to our combination and pipeline programs that we hope will be drivers of future growth. Starting with U2 plus venetoclax, which has moved forward now into phase III for patients with CLL within the ULTRA-V trial. The phase II portion of the ULTRA-V study completed enrollment earlier this year.
You may recall that at last ASH in December, Dr. Paul Barr of the Wilmot Cancer Institute in Rochester, N.Y., presented preliminary results from his phase I study of the U2 plus venetoclax combination, which included results from the first 27 patients in the study to complete the 12 cycles of fixed duration therapy. In those patients, there was 100% overall response rate and greater than 75% of the patients achieved undetectable MRD in the bone marrow. We view these results as highly encouraging, and we look forward to presenting updated data from this phase I trial later this year with approximately double the number of patients through 12 cycles of treatment. Next, let's discuss TG-1701, our investigational BTK inhibitor.
We were pleased to present updated results from the phase I trial of TG-1701 as a monotherapy and in combination with U2 last month during the summer oncology meetings, including ASCO, EHA, and ICML. We were pleased to see that with additional patients treated with TG-1701, it continued to show encouraging clinical activity paired with what appears to be a tolerable safety profile. As I mentioned earlier, we view these triple therapy trials as a way to enhance the utility of U2 in the treatment of CLL. Further in the clinical pipeline are our CD19/CD47 bispecific antibody, referred to as TG-1801, and our PD-L1 antibody, referred to as TG-1501, or cosibelimab. Both are moving through early stages of testing with the possibility of data later this year or next.
2021 has been a very busy year for us as we've made significant progress on both the clinical and regulatory fronts. We look forward to an impactful end of year and into 2022 as we strive to expand our commercialization efforts into CLL and MS. With that, I'm excited to turn the call over to our Chief Commercialization Officer, Adam Waldman, to share some highlights from our early commercialization efforts. Adam?
Yeah. Thanks, Mike, and I'm very excited to provide a commercial update for the first full quarter of the UKONIQ launch. Let me start with some numbers and then provide some qualitative assessment. As you've already seen in the financial press release, we achieved $1.5 million in net sales of UKONIQ for the second quarter, which was our first full quarter of sale. While we were quite pleased with the extent of our launch penetration, which by our estimate reflects UKONIQ capturing 3%-4% of new patient starts in our labeled indication. In our view, that is a great starting point that is ahead of our internal projections. Importantly, our net sales figure doesn't fully capture the total demand for UKONIQ seen this past quarter, as the amount of free UKONIQ provided to patients through our patient assistance program has been significant.
Many of our patients are covered by Medicare Part D, and their out-of-pocket costs are very high due to the Part D benefit design. In addition, unfortunately, unlike CLL, there's a general lack of financial assistance available to support marginal zone and follicular patients with their out-of-pocket costs at the current time. This dynamic is leading to a high percentage of patients qualifying to receive free products. To give you a sense of the extent of the free product offered, we provided over 35% of UKONIQ bottles to patients free of charge through our patient assistance program in the second quarter. As we have said over and over, we are committed to helping patients access our products, and we are proud to be able to help those in need by providing UKONIQ free of charge.
When we look at the volume of our overall demand, which includes free product, we are extremely pleased by the early uptake for UKONIQ. As we've stated before, our goal with this initial launch is to get as many accounts, prescribers, and patients to have a positive experience with UKONIQ as we build towards the potential CLL launch early next year, and we believe ensuring patient access is a strong step towards achieving that goal. Based on these early trends and current assumptions, we are targeting $7.5 million to $12.5 million in net sales for the full year 2021, assuming a similar rate of free goods for the remainder of the year to support UKONIQ for those who cannot afford it.
Further, we would expect to see nice growth in our net sales for 2022, and currently, we are targeting net revenues for 2022 to be between $50 million and $75 million, assuming an approval of U2 by the March 25th PDUFA date, allowing for partial sales of U2 in both frontline and relapsed/refractory CLL, and a small contribution from ublituximab in MS, for which we hope to have a third quarter 2022 PDUFA date. All of which puts us on pace for our 2025 goal of achieving $1 billion in corporate-wide sales. Now, let me provide some additional color beyond the numbers. While it is still early into our launch, we are pleased with our execution and believe we have made significant progress to date.
Our strategy has been to focus on the approximately 1,000 higher volume community and academic accounts, representing approximately 3,000 hematologist oncologists that see the vast majority of the eligible patients in our indications. What we have seen is that most of the initial adoption has occurred within these targeted accounts, and in fact, a large percentage of the initial utilization is coming from centers that were involved in our clinical trials. In many cases, we are seeing repeat prescribing at these accounts as well, which we also view as a positive sign. Although still early, we are pleased with the initial refill rates we are seeing, which we view as a reflection of both the clinical profile of UKONIQ and that providers are effectively navigating potential toxicities and keeping patients on therapy where appropriate.
This growing experience builds comfort and confidence for our expanding prescriber base, and our team is doing a fantastic job with educating and supporting clinicians in safely managing patients. We continue to receive very favorable feedback on the UKONIQ clinical profile. Insights from our recent launch tracking studies show strong product performance, message recall, product perceptions, and importantly, intent to prescribe when physicians have appropriate patients. When our teams have engaged our target healthcare providers, they see UKONIQ as having a differentiated profile and view it as a valuable treatment option for both relapsed/refractory marginal zone and follicular patients. However, gaining access to our customers remains a challenge. COVID-related restrictions have persisted, affecting our ability to access all of our targeted accounts.
Although the situation did improve modestly throughout the quarter with an increasing percentage of in-person engagements, the most recent trends in the Delta variant have caused some institutions to reinstitute certain visitor restrictions, potentially reducing the opportunities for in-person engagements in the coming weeks and months. One other important COVID-related trend relates to patient visits. marginal zone and follicular, as you know, are relatively small patient populations to begin with, and most physicians only see a few of these patients that fall within our labeled indications in a given year. It appears that since the onset of COVID, patient visit and treatment starts have decreased in lymphoma across the board. Most of these patients are elderly and may have been reticent to visit oncology offices during the pandemic.
We believe this continues to be an issue, and we have not recovered back to pre-pandemic numbers quite yet. These trends make our initial uptake even more impressive and essentially bode well for increasing patient flow once the pandemic is behind us. Another positive note is that payer coverage has not been a challenge to date. The team has done an exceptional job here. We have been able to achieve broad coverage of UKONIQ very quickly. More than 90% of commercial and Medicare lives have confirmed coverage to our label or NCCN compendia. We are committed to making sure that each and every eligible patient and healthcare provider has a positive experience with TG and UKONIQ.
When a healthcare provider and their patient have a positive experience with UKONIQ, with strong educational and access support from the TG team, we believe that the healthcare provider is way more likely to prescribe UKONIQ for additional appropriate patients in the future. We also believe that this will carry through to their CLL patients, assuming approval of U2. As Mike mentioned, we estimate there's roughly an 85% overlap of healthcare providers within our target base across lymphoma and CLL. We're reinforcing the importance of what we're doing in establishing our footprint with this launch. With that, I'd like to thank you very much for being here and I'd like to hand it over to Sean Power.
Thank you, Adam, and thanks everyone again for joining us. Earlier this morning, we reported our detailed second quarter 2021 financial results, which can be viewed on the investors and media section of our corporate website. For today's call, I'll keep my remarks brief and touch on a few highlights from the quarter, beginning with our cash position. We ended the second quarter with approximately $456 million in cash equivalents, and investment securities, which we believe will be sufficient to take us into 2023. As Adam noted earlier, we were pleased to report $1.5 million of UKONIQ net product revenue in the second quarter, our first full quarter of product sales.
Our net loss for the second quarter of 2021, excluding non-cash items, was approximately $62 million, which was a decrease of $12 million quarter-over-quarter from Q1 of 2021, where we saw a net loss, excluding non-cash items, of approximately $74 million. Given that Q1 of this year was our first quarter as a fully commercial entity, it's probably a more apples to apples comparison to what we saw this quarter. As compared to the first quarter of 2021, the decrease of approximately $12 million was primarily driven by one-time licensing milestone payments of approximately $14 million occurring in Q1 of this year.
If we shift and compare this quarter to Q2 of 2020, where we saw a net loss excluding non-cash items of approximately $46 million, that increase is primarily related to increased selling, general and administrative expenses associated with the launch of UKONIQ and planning for the potential future launches of U2 in CLL and ublituximab in RMS. Our GAAP net loss for the second quarter of 2021, inclusive of non-cash items, was $78.5 million, or $0.59 per share, compared to a net loss of $52.9 million or $0.47 per share during the comparable quarter in 2020. With that, I'll now turn the call back over to the conference operator to begin the Q&A.
Thank you. At this time, we'll now be conducting the question-and-answer session. If you'd like to ask a question, please press star one on your telephone keypad and a confirmation tone to indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants that are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment please while we poll for questions. Thank you. Our first question is from the line of Alethia Young with Cantor Fitzgerald. Please proceed with your questions.
Hey, guys. Thanks for taking my questions and congrats on the early progress with the launch. Maybe just a couple from me. One, I wanted to get a little bit more color about how you were talking about during kind of the COVID trends, just how much penetration has occurred into the roughly around, I guess, 3,000 heme-onc? Kind of how's that kind of ebbed and flowed? It sounded like it might start to slow a little bit in light of the Delta variant.
My second question is just as far as a differentiated clinical profile, like in MZL and follicular, especially on the safety, I just wanted to get some color around how's that going and some of the early experience. I know it's still super early, but just any kind of color you can provide there. I was intrigued by when you said the 2025 $1 billion in sales. Can you give us a little bit of framework about how to think about what that breakout might be between multiple sclerosis and the hematology indications? Thanks.
Yeah, sure. Mike, you want me to take those? Hello?
Shoot. I'm sorry. Yes, please, Adam. I was on mute.
Yeah. Okay. Okay. Yeah. Alethia Young, thank you. Over the line is a little tough. Sorry. The first question around penetration. I think given the pandemic, and as I've mentioned before, we've hired a really experienced team that came in here with relationships and existing connections. Our penetration has been very good, especially in the top centers. The issue is just with frequency and just how often you can get into these centers. With a new product, it does take multiple visits sometimes to discuss the full profile, the mechanism, the patient populations, and it does take some time. To answer your question, penetration's been good, especially into the top accounts. We're working on frequency.
We're starting to see that, and as I mentioned, things did get modestly better in the second quarter. We were seeing increases in live engagements, which we think is a more effective way of communicating. However, with the Delta variant in the last few weeks, we are seeing a reversal of those trends. We're starting to see cancer centers start to restrict live engagements again. We'll have to watch that and see how it goes. In general, we feel like live engagements are better. Our penetration has been good, but obviously it's a fluid situation. Alethia, can you remind me of the second question?
Oh, feedback on kind of the use, as far as the safety differentiation that could be seen with UKONIQ.
Yeah. The feedback has been really positive on the profile. They see it as very differentiated. As I mentioned before, the lack of a black box warning is seen as differentiating versus the other PI3Ks out there. I think it just takes time for when they see a patient and when a patient presents themselves and these patients don't show up on an individual physician basis that often throughout the year. When we're able to get a good frequency of interaction and a patient shows up, that's when we're getting use. The feedback on the product has been very positive.
As far as the breakdown in the $1 billion, as I mentioned, we expect a small contribution from MS, given that we're expecting a late in the year approval there. We expect to get some contribution from U2, given that we would have three quarters of approval and our ability to promote U2 in CLL, starting in the second quarter is our expectation. The continued launch of marginal zone and follicular will continue to form the base of the revenue projection.
Alethia, just to clarify, Adam was referring to 2022 in his answer.
Oh 2022. Oh, got it.
Yeah.
Sorry. Oh, cool.
He's talking about 2020. That was your 2022. For the $1 billion in 2025, I don't think we've gone as far as say that, but I think at that point, we should be at a 50/50 or trending toward a larger contribution from MS at that point.
Okay.
The models that we have in forecast there is some flux between bull and bear cases. I think we're giving ourselves a little bit of flexibility there as well.
Okay, cool. I guess just follow up, you talked about these 8,000 follicular and MZL, which could be a sizable opportunity itself. I guess I was just trying to get a feel between 2022 and 2025, how confident you are in being able to kind of penetrate this core group over time.
Yeah, I think in terms of marginal and follicular, we feel pretty good about the potential for penetration. I don't know what peak penetration expectations are overall, but I think if we were 20%-30% penetration, that would be pretty fantastic, in any group where there's multiple drugs available.
Awesome. Great. Thank you.
The next question comes from the line of Josh Schimmer with Evercore ISI. Please proceed with your questions.
Great. Thanks so much for taking the questions. First on reimbursement and access, how do you expect it to evolve from here for UKONIQ or for U2? Are there reasons to expect it will improve, and if so, what would those reasons be? Second, if you could discuss the pathway for full approval of UKONIQ and what you expect it'll take to achieve that. Last, maybe you could talk or even consider rank ordering the obstacles to UKONIQ adoption. How much of it is COVID? How much is reimbursement? How much of it is awareness? How much is competitive therapies, and you think those obstacles may alleviate in the coming months and years? Thank you.
Yeah. Adam, why don't you go ahead with some reimbursement access and where you see things heading.
Sure. Yeah. Thanks for the question, Josh. On the access and reimbursement front, we really haven't seen many challenges. I think, as I mentioned, we have achieved broad coverage, the broad payer coverage, and are not experiencing any issues with regards to that. I think what you may be getting to, well, we can clarify, but I think we're good on the access and reimbursement side. I'll take the obstacles and competitive question, and I'll let you, Mike, talk about the full approval.
Yep.
I think the obstacles, yeah, as Michael Weiss mentioned in his remarks, launching in a pandemic is difficult. When we get in front of physicians, as I mentioned, they have a very positive feedback on the product. That's when we get in front of them, and we're continuing to make progress there. When we have those interactions, they are largely very positive interactions and from our market research, it shows that they see it as a differentiated product and one in which is very compelling for marginal zone and follicular patients in our indications.
I think the obstacles are the COVID and just getting access. I think there is some decrease in patient visits or patient treatment starts, just given the reticence of some patients, as I mentioned, coming in to start a new treatment. I think those are the biggest challenges, and I think they will hopefully alleviate when we get further down the line and get away from the pandemic going forward.
Josh, on the pathway for full approval of UKONIQ. I guess two points. One, the UNITY-CLL trial will ideally support a full approval of UKONIQ in CLL. Then converting the marginal zone follicular accelerated approval into a full approval will require a randomized trial that we're in the process of finalizing the design with the FDA. Hopefully that study will commence before year-end. The concept there will be some trial that will be in slightly earlier lines of follicular, and then randomized trials with UKONIQ.
Adam, maybe you can kind of clarify on the reimbursement, the 35% free drug, whether that's something you expect to continue or whether that may improve going forward, and if so, why?
Yeah, gotcha. Okay. Yeah. Good to clarify. In marginal zone and follicular specifically, we're seeing a general lack of co-pay support funds available for Medicare Part D patients. A large percentage of our patients in this specific indication are Medicare Part D over the age of 65, and specifically in marginal and follicular, where we are not seeing availability of co-pay funds. We do expect that that would change with CLL. We see much more funding available in CLL, and this is much less of an issue in CLL. MS is a different ballgame altogether. We're talking about largely commercial patients, so not as relevant. We would expect this to persist for this year, and then as we get into CLL, we would expect it to come down as an overall issue, given the funding that's available in that patient population.
Thanks very much.
Thanks, Josh.
Thank you. Our next question is from the line of Eric Joseph with JP Morgan. Please proceed with your question.
Good morning. Thanks for taking the questions. The first is around your 2022 sales guidance. I'm just wondering what that anticipates in terms of CLL penetration and whether there is any anticipated impact to UKONIQ net price as combo therapy as opposed to use as single agent in follicular and marginal zone. I'd also be curious to get a sense of what your latest thinking is around the European or EU commercial and regulatory strategies across the different franchises, both in heme-onc as well as in RMS. Thanks.
Thanks, Eric. Adam, do you want to take a crack or want me to take a crack at the first one?
Yeah, go once you start, and then I'll weigh in.
Yeah. In terms of CLL, in terms of penetration, I think we're assuming, given the point in time of the year that we'll get launch, which will be probably into the second quarter, that there'll be obviously some contribution from CLL in the year. In terms of the amount of penetration, I think we're even using even more modest penetration numbers than we were seeing right now with UKONIQ in MZ and follicular.
We've been pretty conservative in those assessments. In terms of the UKONIQ pricing as part of the package, yeah, we have not finalized pricing yet, so it's hard for us to give too much detail because, again, I don't think anyone knows. We haven't given any guidance on obinutuzumab pricing. There most likely will be some discounting to UKONIQ in that setting. It will become a function of where we price obinutuzumab, and we'll come together to basically come up with a total price that we think is fair for the patient population.
Sorry, go ahead.
Second.
For latest thinking on approaching the European commercial opportunity, perhaps with the various product franchises.
Yeah. We're in the process of scoping that out still. We're moving forward. I think we're working toward the first application. Yeah, I think. I'd have to go back and check with the regulatory team, the first application in Europe may be in MS. We may actually end up staging it MS first and then CLL second there. I think I need to probably get back to you on that. We are definitely moving forward. We think that the MS opportunity in Europe is a very interesting one for us and one that's managed probably more cleanly with a smaller team, certainly than we require in the U.S.
That pricing in Europe will be a big driver of uptake. We're still exploring that to make sure that those assumptions are valid. Assuming that's the case, we think there's a pretty interesting opportunity for a European launch at MS, while we're still continuing to scope out how that pricing interplay with CLL will occur. I think for the moment, I'm pretty sure we're going to head forward with MS first and then CLL second, ex-US.
Okay. Great. Thanks for taking the questions. Appreciate it.
Sure.
The next question is from the line of Chris Howerton with Jefferies. Please proceed with your questions.
Great. Thanks so much for taking the questions, and congratulations on all the progress.
Thanks, Chris.
Sure. Of course. First, with respect to the U2 + venetoclax trials, I guess I couldn't quite remember what the regulatory path is. Would the phase II study be sufficient for an accelerated approval opportunity? I guess it's just a pretty simple question. With respect to the phase II study itself, what would be the expected data disclosure? I know there was, at least in my head, some anticipation that we would get some of the data at ASH, but might not be the full results. I guess some thinking around that would be helpful. The last question was just ensuring that everything is good to go with respect to CMC, particularly as it relates to obinutuzumab. Thank you.
Sure. In terms of the U2Ven program, we've been focused on almost three full phases, right? We had a phase I that Dr. Paul Barr conducted as a lead investigator, and that phase I is what we've presented previously at last year's ASH, and it's what we've been committing to present later this year, an update to. I think we have 27 patients through 12 months the first go around, and we're looking for somewhere between 40 and 50 patients through 12 months for the completion of the patients in that trial. That is the U2Ven data that we've been talking about as being presented later this year. In terms of ULTRA-V, as we've said, the enrollment completed earlier this year into the phase II portion. That data, to have all the patients through 12 months, would not occur until well after ASH.
In fact, to be prepared for ASH, you'd need probably two months prior data. The ULTRA-V data set, as I've noted multiple times, would be incomplete for this ASH. If we could present a partial data set or not was really a function of what the principal investigator wanted to do. We're still trying to figure that out today, whether we'll do a partial data set. My general feeling is that it probably will not occur this year. I've said this in multiple occasions, if it were me and I was the PI, and we were that close to having all patients through 12 months, I wouldn't want to release a partial set when I could do a full set within a reasonable timeframe of that. We'll wait to hear back from the PI and what his decision is.
I think from where I sit, I wouldn't be surprised at all, and in fact, I'd be surprised if he said he wanted to present the partial data set. We'll see. We'll see where it goes. For the moment, the phase I is where we'll see the U2Ven data later this year, and ULTRA-V is more likely than not going to be a more complete data set next year. Then in terms of the regulatory side of that question, once we have the full phase II data, at least all the patients through the 12-month time frame, we'll look at that data, and we'll have a conversation with the FDA. Ideally, U2 will be approved at that time.
Hopefully it'll have an easier pathway from the FDA to approval of U2 already being approved and venetoclax already being approved. As we've, again, said multiple times, there's no assurance that phase II data will be usable for approval. If it is not usable for approval, of course, the phase II portion will be published. We'll certainly send it over to NCCN and see if they're interested in adding it to their guidelines. The phase III is enrolling as we speak. That's the current status of that program.
Great. Okay. That's awesome. I guess just anything to note on CMC?
Nothing to note. We filed the CMC. I think it was the first section we filed as part of the rolling submission for obinutuzumab. For the CLL application for ublituximab. To my knowledge, there's been a dialogue back and forth. The FDA has been reviewing that file. As typical of any filing, there's questions that come in and go back out to the FDA, and that is the process that is ongoing. Nothing to the team's great concern as far as I know.
Okay. Fantastic. Well, thank you, Mike. Appreciate it, and hope to talk to you soon.
Thanks, Chris.
The next question is from the line of Ed White with H.C. Wainwright. Please proceed with your question.
Good morning. Thanks for taking my questions. Maybe the first question to Sean. You gave some guidance on SG&A expenses trending higher. I was wondering if you could make any comments on R&D. I know there was the $4 million charge in the quarter. How should we be thinking about the second half of this year?
Thanks, Ed. SG&A trended higher over last year, over last second quarter, of course, as you'd expect, given the commercial launch. I think it'll continue to tick up a little bit over the course of the rest of this year, as I said, as we prepare for the CLL and MS launches. I wouldn't expect all that much on the R&D front. I would say not a whole lot of volatility there over the remainder of the year.
Okay, great. Thank you. Mike, just some pipeline questions. You had just commented on ULTRA-V phase II. Can you give us any update on how the phase III enrollment is going? Are there any trends you can look at now to let us know when you think the trial will be fully enrolled? You had mentioned data later in the year for the phase I trial. I'm just wondering for the other combinations and drugs in development, what we could potentially see at ASH this year.
Sure. In terms of full enrollment into ULTRA-V, it's way too early, unfortunately, to give any kind of good projection. Enrollment only started about one month or two ago, we're in very early days. For early stage of a trial, it's going quite well. Obviously we've got to see a big ramp at some point and then we'll have a better sense of what the target enrollment timeframe would be for that. In terms of data from the rest of the pipeline for later this year, certainly we continue to enroll more patients in the TG-1701 study in the BTK. That one we'll continue to eke out data at all the conferences, keep people updated on the progress of that program. With CD47, CD19, and TG-1801, those are continuing to be in the early stages. Again, I cannot promise data this year.
As I noted, potentially later this year. For sure next year. We will have certainly something to present by next year, but potential for later this year. I think in terms of what to expect during the remainder of this year, I'll put in quotes, the final data from the phase I of U2 plus ven we'll see sometime later this year, more updated data on 1701 to come out. I know the team is working on sub-analysis of all the different trials. There's other things that people are working on. In terms of datasets that you have visibility of for the moment, I think those are probably the two primary datasets that are remaining and like I said, some sub-analysis that we'll be coming out with.
Okay, thanks, Mike. My final question is, you mentioned when you were talking about MS, other autoinflammatory disease indications and other forms of MS. I was just wondering, how should we be thinking about that potential? Should we be seeing potential study start in next year, or is this further down the road than that?
I think it's possible to see some studies starting next year. We're working on a few concepts. If they come to fruition, yeah, I would expect some studies to start next year. We'll keep you posted for sure.
Okay. Thanks, Michael.
Thanks, Ed.
Our next question is from the line of Graig Suvannavejh with Goldman Sachs. Please proceed with your questions.
Yeah, thanks. Good morning. I've got a couple of questions, if I could. One, just on UKONIQ, and it might be too early for you to comment, but can you provide an update on number of accounts that you've penetrated? This might certainly be too early, but if you're seeing any reordering. I'm just trying to get a sense of what the ordering pattern dynamic might be for UKONIQ. Then a follow-up on UKONIQ is, it seems as if the way you're positioning the product relative to the portfolio is that it's a very good product for patients and prescribers to get an overall good experience with TG Therapeutics. With that in mind, I was wondering if you might be comfortable providing what you currently believe the peak revenue opportunity of UKONIQ might be.
Moving beyond UKONIQ, just looking at the MS landscape, any color that you might be able to provide would be appreciated just on what you're seeing in the anti-CD20 marketplace. Obviously, you've got Ocrevus there, and Kesimpta is relatively new, but just wondering if you can comment on just how you're seeing Kesimpta in that launch and how that's having an impact either on Ocrevus alone or just the overall anti-CD20 market, in general. Thanks.
Sure. Actually, Adam, you want to start at the last question? I'll work our way backwards through. There's some questions about accounts and reordering on the UKONIQ side, but maybe while that question is fresh, maybe some MS commentary.
We just saw, I think Roche and Novartis just had a conference call last week. There was some dialogue around their launch there. We're looking at that. It looks like there was some recovery from earlier in the pandemic. Looks like they're continuing to get some traction in the anti-CD20 space. The class itself is on a growth trend. Kesimpta is getting some traction in the market, but both seem to be holding steady and it's not growing now again as the pandemic continues on here. We're encouraged by it. I think the physicians that we talk to continue to be very excited about the class, excited about the use of the product earlier and earlier in arresting the disease.
We think it's good trends overall and that the class itself is growing, which we think is very positive. Let me talk about the UKONIQ. I think the first question was around accounts and reordering. As I mentioned, where we're seeing usage is in our top accounts, in the highest volume accounts. The split that we're seeing is about 60/40 academic to community. We are seeing reordering from accounts. We don't have the specificity as a lot of it's going through specialty distributors.
We don't have the preciseness that we'd like to, and perhaps we'll look into for future calls. As I mentioned, we're getting good penetration in our top accounts and most of our usage is coming from there. We are seeing reordering. I think there was a question around peak revenue in, I think it was specifically for UKONIQ. I don't know if that question was around marginal zone follicular specifically. Our view on that has not changed. We still see this as being a significant revenue opportunity. I think Mike, remind me what we've said in the past?
Yeah. I'll take that one. In terms of the positioning of UKONIQ in MZ follicular basically as a way for us to introduce TG to the world, that's been something that we've said one year before the launch, six months before the launch, at the launch, and now four months after the launch. We continue to believe that the UKONIQ introduction in marginal zone follicular is most important is not about revenues, it's about introducing interest in TG and UKONIQ for future impact, primarily in CLL. We've said that consistently. We've said we think it's still marginal zone follicular could be a few hundred million dollar revenue opportunity over time. I think that, remember, we're taking away almost 40% of all sales right now, and if that's a trend that continues, that's a pretty big discount.
Again, we think certainly at the point in which there's a few hundred million dollars of revenue potential, TG could be in a position to help fund, hopefully with others, charitable organizations that can provide support for those patients. I think at these levels, it's interesting to see that we're giving away so much free UKONIQ. Like I said, we made this very clear, that we wanted to have a great experience for UKONIQ in marginal zone follicular. We did not anticipate giving away almost 40% free goods. Having said that's fine. We're happy to do it if it builds goodwill in the industry, and we want to make sure patients all have access. I think in terms of the consistency of that message, we've been extremely consistent about where we're positioning this launch.
Having said that, I think in terms of penetration that we've seen, we've exceeded our expectations to date, and I think if we continue to grow in this marketplace and achieve somewhere in the order of 20% to maybe even as high as 30%, depending on in a bull scenario, marginal zone follicular, a few hundred million dollar opportunity. We've never, and we continue to say that the company is not being built on the back of the revenues from certainly from the launch phase of marginal zone follicular, but we are going to be built on the impression and the positive feedback we get from the UKONIQ launch in marginal zone and follicular.
Yeah. Graig, just to clarify my comments on the reordering. We're seeing reordering both in terms of multiple patients from the same accounts, and we're seeing a reordering in terms of refills as well. Just wanted to clarify that.
Okay, thanks for that.
Thanks, Graig.
The next question is coming from the line of Matt Kaplan with Ladenburg Thalmann. Please proceed with your question.
Hey, good morning, guys, and thanks for taking the questions. Just a little follow-up on the ULTRA-V program. Can you give us some more color, I guess, on the ULTRA-V phase III study design? Specifically, are there any differences from the phase II portion of the study?
The phase III study design is U2 plus VEN versus U2. In terms of the actual treatment with U2 plus VEN, I got to double-check for you, Matt, but I think we may be using potentially up to three months more of VEN than we used in the phase II portion. That was only, again, just to match up with the current schedule for VEN. Let me just double-check for you. Otherwise, not much in terms of differences.
Right. Helpful. Then, with respect to your BTK inhibitor program 1701, you presented some positive data recently at the medical meetings. What are your current thoughts on the regulatory path forward? Have you identified, I guess, paths or pathways for the product? Can you continue to develop it?
Yeah. I mean, we feel really good about that molecule. The performance has been quite impressive. We've spent a lot of time trying to understand the differences between the doses and in terms of tolerability profile. Our goal has and continues to be to try to identify the most tolerable regimen to make sure we have the most tolerable BTK inhibitor. We're working hard on that. In terms of the phase III program, the registration, we've got a few good opportunities. We haven't picked the one yet, but I would expect by early next year, we'll be in a phase III for 1701.
Okay, very good. I guess lastly, just a little follow-up on, I think it was Ed's question with respect to autoimmune indications, additional autoimmune indications for ublituximab. Beyond MS, what's your current thinking in terms of where you're going to bring the product next?
Yeah. We haven't given any guidance on that yet, Matt, but we're scoping out a number of different opportunities, and as soon as we have some in place, we'll certainly disclose those.
Well, congrats on the recent progress, and thanks for taking the questions.
Thanks, Matt.
Thank you. Our final question is from the line of Mayank Mamtani with B. Riley Securities. Please proceed with your questions.
Good morning, team. Thanks for taking our questions and appreciate the helpful detail here. Just a quick one, Adam, on the UKONIQ launch. Any early color on what the real-world discontinuation and maybe progression rate might be? I know it's early days, but just to get a handle on what the duration of therapy might be, and then I have a couple of quick follow-ups.
Yeah, thanks for the question, Mayank. No, I think it's too early, honestly, to comment on that. It's just too early to comment on that.
Okay, great. Mike, on the near and long-term guidance, that was very helpful. Any color on the path to profitability, number one, also on the 2025 number for sales, does that include a partner for MS sales?
It does not include a partner for MS sales. In terms of a path to profitability, again, I think, if we achieve our goal of 2025, $1 billion in sales, my guess is we should be profitable by then.
Okay, great. Just on the pipeline side, anything next we should expect to hear for the CD19, CD47, and maybe a program you don't talk about much, but IRAK4 is of increasing interest to investors. Just when and what we may expect to hear on those two programs, if you may.
Yeah. In terms of IRAK4, we've been pretty clear that that program is probably not moving forward for some time now. In terms of the CD47, CD19, that one is moving forward nicely. We've just opened up the U.S. and hoping, like I said, to have data later this year. If not later this year, into next year.
Okay. Thanks, Michael Weiss, and congrats again on the progress. Take care.
Thank you. We have reached the end of the question-and-answer session. I'll now turn the call over to Michael Weiss for closing remarks.
Great. Thank you very much, and thanks, everyone, again. Just want to wrap up today's call by once again reviewing our upcoming key goals and objectives. Clearly we're going to continue to focus on the commercialization efforts of UKONIQ in relapsed/refractory marginal zone lymphoma, and expand those commercial capabilities in preparation for a potential launching of U2 in CLL, and also, of course, for ublituximab in relapsing forms of MS. We are working hard towards submitting our BLA for ublituximab in the treatment of relapsing forms of MS this quarter. That, of course, as everyone knows, is based on the positive results from the ULTIMATE I & II phase III trials.
In terms of continuing enrollment into studies, obviously, we're going to push hard on the enrollment into the ULTRA-V phase III trial, and enrollment into our 1701 phase II, and hopefully soon to start a TG-1701 phase III trial early next year. Continue to push forward with the pipeline of 1501, which is the PD-L1, and 1801, the CD47/CD19. We've talked at length today about the potential data presentations for later this year. We are working hard, I can tell you, working very hard, to obtain the approval for U2 in CLL by the PDUFA goal date of March 25th, 2022. On behalf of all of us at TG, I'd like to thank everyone for joining us today, and have a great day.
Thank you everyone joining us today. This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation.