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Constellation Pharmaceuticals (NASDAQ:CNST)
Q2 2020 Earnings Call
Aug 7, 2020, 10:00 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Thank you for standing by and welcome to the Constellation Pharmaceuticals Second Quarter 2020 earnings conference call. At this time all participants are in a listen-only mode. After the speakers' presentation there will be a question-and-answer session. Please be advised that today's conference is being recorded. [Operator Instructions] I would now like to hand the conference over to your speaker today, Ms. Kia Khaleghpour. Thank you. Please go ahead.

Kia Khaleghpour -- Vice President, Investor Relations and Communications

Thank you, Polly. Good morning everyone, and welcome to this conference call to discuss Constellation's second quarter 2020 financial results and operational performance. Participating on our call this morning are Jigar Raythatha, Constellation's Chief Executive Officer, Dr. Jeff Humphrey, our new Chief Medical Officer, Dr. Patrick Trojer, our Chief Scientific Officer and Emma Reeve, our Chief Financial Officer.

Please turn to slide 2. Before we begin, I want to point out that our presentation today will include forward-looking statements, which are subject to certain risks and uncertainties. Actual results may differ materially due to various important factors, including those described in the Risk Factors section, as well as discussions of potential risks, uncertainties and other important factors in the company's most recent filings with the Securities and Exchange Commission, including the company's quarterly report on Form 10-Q for the quarter ended June 30, 2020.

And now, I'll turn the call over to Jigar.

Jigar Raythatha -- President and Chief Executive Officer

Thank you, Kia and good morning everyone. I'm very pleased to have three members of our management team joining me on the call; Jeff Humphrey, our new CMO is a medical oncologist with over 20 years of experience in drug development. Prior to joining Constellation, he was Chief Development Officer at Kyowa Kirin Company where he oversaw the development of the company's global portfolio of experimental therapeutics for Western markets. He began his industry clinical research at Bristol-Myers Squibb and subsequently served the management positions for early and late drug development and medical affairs at Pfizer, Bayer and Bristol-Myers Squibb. Our Chief Scientific Officer, Patrick Trojer, who many of you know, is joining our call today. Patrick is one of our founding scientists and he is internationally recognized for his expertise in chromatin regulation, transcription and oncology drug discovery. He leads are discovery, translational science and CMC organizations. And of course, you all know Emma Reeve, our CFO, who has been instrumental in building Constellation's financial strength to enable us to develop and eventually commercialize our lead programs.

Please turn to slide 3. At Constellation, we are building a fully integrated pharmaceutical company in order to bring important medicines to patients with significant unmet needs. The underpinning of that vision is our investment in a productive discovery platform, which in turn drives a sustainable pipeline of innovative product candidates to develop and commercialize. Specifically, we believe that we can transform the standard of care of myelofibrosis with our BET inhibitor CPI-0610, which has the potential to be disease-modifying. We are working to deliver what we believe is a best-in-class EZH2 inhibitor, CPI-0209, which has a profile that can expand the addressable patient population for this promising class therapy. And we also aim to discover and develop novel and impactful hematology and oncology treatments from our discovery platform. To accomplish our vision of Constellation as a fully integrated commercial stage company, we are assembling experienced leadership team across the company to guide our next leg of the journey, including the three members that we have here with us today.

Please turn to slide 4. I'd like to remind you of the next steps for our lead programs. With CPI-0610, we plan to start a Phase 3 clinical trial. We intend to also provide an update on the program later this year that will include additional clinical data and new translational data to further support the disease modifying potential of CPI-0610. With CPI-0209, we are in the dose escalation portion of a Phase 1-2 study and we anticipate determining the recommended Phase 2 dose in the second half of the year and then moving into the expansion cohorts. We'll talk more about the Phase 2 development plan, when we announce the recommended Phase 2 dose. Both of these product candidates emerged from our own discovery platform and we intend to discuss additional programs that emerge from our efforts at a later date.

Before describing our program-specific developments. I'd like to give you an update on how COVID-19 is impacting our operations and how we're managing through the pandemic. Prior to COVID, the pace of enrollment in MANIFEST was ahead of schedule. The trajectory slowed in near to the end of the first quarter but started to pick up in the second quarter and we continued to target initiating MANIFEST-2, our Phase 3 clinical trial for CPI-0610 in the second half of 2020. The Phase 1 trial for CPI-0209 is proceeding as planned. And our clinical supply of material for all of our clinical studies is on track. Lastly, in May, we began reopening our offices in accordance with the directives of the state of Massachusetts and our facilities are now open with the focus on our laboratory personnel.

Please turn to slide 5. I'd like to discuss the progress that we're making with CPI-0610. To recap, during the second quarter, we presented results from the April 17 data cut of MANIFEST at the European Hematology Association meeting. Those results demonstrated that CPI-0610, in combination with ruxolitinib or as monotherapy showed preliminary evidence of clinical activity and potential disease modifying effects. In Arm 3, in JAK-inhibitor-naive patients, 63% of patients treated with CPI-0610 in combination with ruxolitinib achieved SVR35 at 24 weeks. In historical Phase 3 studies of ruxolitinib alone, SVR35 rates were in the range of 29% to 42%. In addition, we've been enrolling in various cohorts of JAK-inhibitor experienced patients. In this difficult to treat second line setting, we saw 21% of transfusion dependent patients on CPI-0610 monotherapy and 34% of transfusion dependent patients as an add-on to ruxolitinib convert to transfusion independence, 24% of non-transfusion dependent second-line patients in monotherapy, and 22% as an add-on to rux achieved an SVR35.

In a similar setting, in SIMPLIFY-2, JAK inhibitors were shown to have SVR response rate of 6% to 7%. CPI-0610 was generally well tolerated as a monotherapy and in combination with ruxolitinib in both first and second line. We also generated preliminary data showing hemoglobin increases and bone marrow fibrosis improvement with CPI-0610. Please refer to our EHA posters posted on our website and recent filings with the SEC for additional information regarding the activity and safety of CPI-0610. We believe that CPI-0610 has the potential to be a disease-modifying therapy and redefine the standard of care in MF. We are pleased with the MF data we've seen to date and we are excited to move forward.

Please turn to slide 6. We would now like to talk about the path forward for CPI-0610 based on the discussions that we've had with the FDA. There are two key messages, I'd like to convey regarding these discussions. First, I'm pleased to share that we've aligned with the FDA on the design of our global randomized, double-blind pivotal Phase 3 trial in JAK-inhibitor-naive patients called MANIFEST-2. We are on track to initiate this study in the second half of 2020. In a moment, Jeff will share with you the details of the design of this trial. Second, we will continue to build on the collaborative dialog that we've had with the FDA and we'll explore other opportunities to bring CPI-0610 to patients.

And now, Jeff will take us through the design of MANIFEST-2.

Jeffrey Humphrey -- Chief Medical Officer

Good morning. I'm Jeff Humphrey, the Chief Medical Officer at Constellation, and I'm excited to join the company. I believe in Constellation's pipeline I'm excited about 0610 and I look forward to helping to bring CPI-0610 to MF patients in need as soon as possible. As Jigar mentioned, we've had a collaborative dialog with the FDA and we look forward to continuing that collaboration. We are in the final stages of preparation to initiate MANIFEST-2 and are eager to enroll the first patient in the second half of 2020. The trial is designed as a blinded randomized pivotal study with CPI-0610 in combination with ruxolitinib versus placebo plus ruxolitinib in JAK-inhibitor-naive patients with primary myelofibrosis or post-ET or post-PV myelofibrosis who have advanced disease with splenomegaly and symptoms requiring therapy. MANIFEST-2 is designed to enroll approximately 310 patients. We plan to randomize patients, 1-to-1 to the CTI- 0610 plus ruxolitinib arm or the placebo plus ruxolitinib arm and to stratify patients based on the DIPSS risk category, the platelet count and the spleen volume. The dosing schedule is based on a 21-day cycle. CPI-0610 and ruxolitinib would be doses similar to our current dosing regimen in MANIFEST. Patients would start at 125 milligrams of CPI-0610 once daily. Ruxolitinib would be dosed at 5 milligrams below the labeled dose in the first cycle and would be at the labeled dose starting at cycle two.

The primary endpoint of the study is SVR35 response at 24-weeks. A key secondary endpoint of the study is 50% improvement in total symptom score or TSS50 at 24 weeks. Other endpoints that we will measure include bone marrow fibrosis grade improvements, duration of transfusion independence, rate of RBC transfusion for the first 24 weeks and hemoglobin response. The trial is powered at approximately 90% and we expect that will take a couple of years to complete.

Please turn to slide 7. We believe there are opportunities to expand the use of CPI-0610 more broadly into indications and other hematologic malignancies. As one example, today we are announcing that we plan to initiate a new cohort Arm 4 in MANIFEST to study CPI-0610 monotherapy and essential thrombocythemia or ET in the second half of 2020. ET is a myeloproliferative disorder that can progress to MF and AML and is characterized by excessive production of platelets as well as symptoms such as fatigue, lightheadedness, headaches, vision changes and an increased risk of blood clots.

Please turn to slide 8. We are exploring CPI-0610 in ET because we know there is a strong mechanistic rationale for such treatment. We know that CPI-0610 can reduce platelet counts and in MANIFEST we've seen normalization of platelet numbers in some patients with very high platelet levels at baseline. We also know that ET patients can be symptomatic and we've seen a profound impact on symptoms from CPI-0610 in MANIFEST. As you can see in this example, a post-ET MF patient with high baseline platelet count in the MANIFEST study achieved normalized platelets and meaningful improvement in total symptom score. Data like these are the basis for our rationale for exploring ET further in Arm 4. In Arm 4, which we plan to begin in the second half of 2020, we will explore proof of concept of CPI-0610 monotherapy in treatment of approximately 20 hydroxyurea resistant or intolerant patients with BT. The primary endpoint of this study will be complete hematologic response within 24 weeks as measured by normalization of platelet count and white blood cell count with a key secondary endpoint of TSS50 at 24 weeks. This cohort will help us not only to understand CPI-0610 in this population, but also to identify endpoints that can be useful in a larger pivotal trial.

And now I'll hand the call over to my colleague, Patrick to discuss CPI-0209 and our discovery platform. Patrick?

Patrick Trojer -- Chief Scientific Officer

Thank you, Jeff. I'm Patrick Trojer, I'm the CSO of Constellation and I'm excited to share with you details of our second program in the clinic, the EZH2 inhibitor CPI-0209. Please turn to Slide 9. You will recall that EZH2 is a histone methyltransferase. Its role if it's trimethylate histone H3 at lysine 27 and thereby to suppress the expression of specific sets of genes. We believe that CPI-0209 has the potential to be a best-in-class EZH2 inhibitor. We designed CPI-0209 to improve on first generation EZH2 inhibitors in a number of ways, including increased potency longer residence time and maintaining exposure levels by not inducing its own metabolism. With that type of profile, we can now pursue the very broad application of EZH2 inhibition, doubling down on context where EZH2 inhibitors already have shown clinical activity and where EZH2 is an oncogenic driver which synergizes with other oncogenic driver pathway, but also exploring additional context where CPI-0209 may interfere with progress system from both tumor immunity and exploit synthetic lethal relationship. And we are planning to explore CPI-0209 in all of these contexts.

Please turn to slide 10. This slide presents data that corroborates the three key properties of CPI-0209 that support its best in class potential; increased potency, longer residence time and lack of induced metabolism. The table on the left illustrates the superior biochemical potency of CPI-0209 compared to other clinical stage EZH2 inhibitors. Data in the middle show the remarkably slow operator CPI-0209 compared to another EZH2 inhibitor, indicating a residence time on EZH2 that it potentially differentiating. On the right, you can see the exposure profile of CPI-0209 when orally administered to mice after a single dose D-1 and maintenance of CPI-0209 exposure at steady state after 12 days of once daily dosing D-12. This is consistent with the observation that the compound does not induced its own metabolism. With this profile we believe CPI-0209 may extract the full therapeutic potential of EZH2 biology.

Please turn to slide 11. The properties I just highlighted are translating into superior efficacy in pre-clinical mouse model on a once daily dosing schedule with respect to dose used and magnitude of observed tumor growth inhibition. Here we see data from two in vivo studies showing CPI-0209 performance achieving tumor regression in models of both hematologic cancers and solid tumors. Its comprehensive EZH2 target engagement achieved by potency, long residence time and a favorable exposure profile may allow us to harness deeper responses and to expanse into patient populations, such as patients with certain solid tumors that are not at risk adequately with first generation EZH2 inhibitors. We are currently assessing CPI-0209 in a Phase 1 dose escalation study in an all-comer solid tumor patient population. We intend to establish safety parameters and a recommended Phase 2 dose in the second half of the year and to begin our Phase 2 expansion cohorts shortly thereafter. We plan to explore multiple disease context with CPI-0209 based on biomarker driven strategies, including the assessment of mutations in genes like EZH2 and ARID1A. We'll further elucidate on the development plan around CPI-0209 as we determine the recommended Phase 2 dose.

Please turn to slide 12. All the assets we have discussed today have emerged from our internal discovery efforts and thus I would like to take a minute to discuss Constellation's oncology research platform, which continues to be an engine of our current and future drug discovery pipeline. As we continue to mature as an organization with an increasing number of clinical development activities, we have established at translational focus to identify proprietary biomarkers and features of product candidate that differentiate us from competitors. The identification of myelofibrosis as the lead indication for CPI-0610 clinical development, is an example of our translationally focused research efforts. Second, with our increasing investment in development, we are now leveraging our increased disease area expertise and directing discovery efforts around certain types of cancers such as myeloproliferative neoplasms or genitourinary cancers. To strengthen our anchor product candidate CPI-0610 and CPI-0209, we build around those product candidates and are opportunistic in identifying mechanisms that combine with those product candidates or can extend our footprint in these diseases with additional innovative products. And third, we continue to take advantage of our strong and proven expertise and track record in chromatin regulation and gene control to identify novel mechanisms that may create compelling future product opportunities. And now I will turn over the floor to Emma. Emma?

Emma Reeve -- Chief Financial Officer

Thanks, Patrick, and good morning, everybody. Please turn to slide 13. First, I'd like to discuss our progress toward meeting our milestones for 2020. As planned, we presented encouraging MANIFEST data at EHA in June and we continue to expect to initiate our MANIFEST-2 clinical trial in the second half of 2020, as discussed earlier. Importantly, we also plan to provide a further update from the Phase 2 MANIFEST study later this year, including both updated clinical and new translational data. The translational data could help to elucidate the potential disease-modifying properties of CPI-0610. We're in the process of submitting abstracts to ASH this week related to this program. Please note that those abstracts are based on the same April 17 data cut included in our EHA presentation and don't contain updated clinical data. So again, we expect to present updated clinical data at the ASH meeting itself, assuming we're accepted, rather than in the abstracts. For CPI-0209, we continue to anticipate providing an update in the second half of the year, primarily focused around establishing a recommended Phase II dose.

Now let's turn to Slide 14 to review the financial results for the quarter. We had a net loss attributable to common stockholders of $29.8 million in the second quarter, which was in line with our expectations. The net loss per share was $0.70 in the second quarter compared with $0.80 per share in the second quarter of 2019. R&D expenses increased by $6.7 million year-over-year, mainly due to work related to CPI-0610. Personnel costs also increased compared with the prior year quarter as we continued to build out our organization. With our recent financing, our cash, cash equivalents and marketable securities were $520.5 million as of June 30, which we expect will fund our operations into mid 2023. We plan to use these resources to complete the MANIFEST trial, to complete MANIFEST-2, our Phase III clinical trial for CPI-0610 and to start to build the commercial organization needed to launch the compound. In addition, our cash will help us to complete the Phase 1, 2 clinical trial for CPI-0209 as well as to support our discovery platform.

That concludes our prepared remarks for this morning, so I'll turn things back over to the operator. Polly, would you please open the line for questions?

Questions and Answers:

Operator

Thank you. [Operator Instructions] And your first question comes from the line of Anupam Rama with JPMorgan.

Anupam Rama -- JPMorgan -- Analyst

Hey, guys. Thanks so much for taking the question. Two quick ones from me. How are you thinking about the second line opportunity go-forward strategy in MF and did regulators give you any feedback on this treatment setting? And any differences to highlight between the transfusion-dependent or non-dependent population from regulators? And then on CPI-0209, what are the potential biomarkers you'll be looking at for a potential enrichment strategy? Thanks so much.

Jigar Raythatha -- President and Chief Executive Officer

So thanks, Anupam, for the question. And I'll start with that and then maybe ask Jeff or Patrick to add additional remarks if needed. So I think the first question you asked was on kind of the path forward in second line. And as we said in the past, our focus really has been in naive patients to be able to drive to a broad label based on an approval pathway in that first-line setting, in that naive setting. But we did obviously have generated substantial information from our various cohorts of patients in the second line context, including exploring novel end points like transfusion dependence conversion. And we have reviewed some of those data and pathways with the agency and we're incorporating the constructive feedback that we received and we'll continue to assess additional potential paths forward.

Specifically on transfusion dependence conversion, I think what we determined is that, that is certainly an end point that, based on our discussion with the agency, that there's belief that that's an end point that speaks to unmet need. At this point, we don't have additional information on how to drive specifically forward in that patient population, but we'll incorporate the feedback that we got and potentially have additional discussions. And if we have something new to say there, we'll certainly report back on that. And then on 0209 -- sorry, Jeff, why don't you go ahead if there's additional you want to add there.

Jeffrey Humphrey -- Chief Medical Officer

Yes. Sorry about that. Yes. No, I just wanted to also point out that we have aligned with the FDA now on the key elements of the MANIFEST-2 protocol, and we are very excited to start the first patient in this year. And then, Jigar, I'm sorry I probably stole your thunder, you were about to say, on CPI-0209, the biomarkers of interest as Patrick said, are EZH2 and ARID1A. Those will be the biomarker strategy for extension of 0209. Thanks.

Jigar Raythatha -- President and Chief Executive Officer

Yes. As well as other potential avenues, Patrick, do you want to chime in on that.

Patrick Trojer -- Chief Scientific Officer

Yes. So what we publicly disclosed is clearly an interest around ARID1A. I think it's clear that EZH2 is part of it. But there are other molecular biomarkers that come from our pre-clinical, as well as our clinical data that may inform future development of CPI-0209.

Anupam Rama -- JPMorgan -- Analyst

Got it. Thanks so much for taking our questions.

Operator

And your next question comes from the line of Brian Abrahams with RBC Capital Markets.

Brian Abrahams -- RBC Capital Markets -- Analyst

Hey, guys. Thanks so much for taking my questions and congrats on all the progress. Congrats on all the progress. A couple from me on the new MANIFEST-2 study and then one on MANIFEST-1. I guess on MANIFEST-2, did the FDA confirm that a single study would be sufficient for approval? And is there a certain p-value threshold that you would need to meet in MANIFEST-2?

Jeffrey Humphrey -- Chief Medical Officer

Yes. Thanks for the question. I mean, certainly, a trial needs to meet statistical significance, and we're very pleased that we've powered the trial at 90% for the key end point of SVR35. And the FDA has aligned on the design of MANIFEST-2. There -- and I think, yes, those are the things that we're excited about. The FDA will never make a decision about the adequacy of your development program until you have data, right? It depends on the data. It's always a review.

Jigar Raythatha -- President and Chief Executive Officer

Brian, I think it's fair to say that based on the discussion that we have, we feel pretty comfortable that one study is sufficient.

Brian Abrahams -- RBC Capital Markets -- Analyst

Got it. Okay. That's helpful. And then with respect to the powering assumptions, can you maybe talk a little bit more about the specific delta on SVR and TSS that you are powered at 90% for? And then I know it was mentioned in your filing this morning that there's the opportunity to resize the study to adjust, I guess, adjust the sample size as you go along. Are there kind of specific cut points where there will be interim analyses to support potential resizing? Are there interim futility or efficacy analyses built in at those points? And would you be planning to announce those?

Jeffrey Humphrey -- Chief Medical Officer

Yes. Thanks for the question. I mean, as Jigar said, the SVR35 we have as an estimate for MANIFEST is 63% compared to a historical rate of 29% to 42% from the pivotal studies of ruxolitinib. We have a mechanism for resizing the trial. And at this point, we're not ready to discuss details of that mechanism. But we feel very comfortable that we will be 90% powered on the end points that are important for approval, SVR35 and TSS50, by completion of the study.

Brian Abrahams -- RBC Capital Markets -- Analyst

Got it. That's really helpful. And then one last one, maybe just building on your answer to the prior question. Just wondering, if you could talk a little bit more about -- it sounds like the current MANIFEST data is not necessarily sufficient to support early approval of the combination of 0610 but -- plus ruxolitinib. Can you talk a little bit more about any additional clarity you may have gotten from the FDA on what they might look for to potentially support a more rapid path? Would you be looking -- steering more toward monotherapy, updated data containing more patients, a certain threshold on a particular end point that you could potentially aim to hit? I know the frontline is sort of the primary goal but just wondering if there's any -- if you could expand on some of these other things you might be exploring. Thanks.

Jigar Raythatha -- President and Chief Executive Officer

Yes. I will start with that, Brian. And then Jeff, you should certainly chime in with additional information. I think, as we said in the past, we believe that, in particular for the naive patient population that a randomized study is probably necessary to tease out the contributions of the components. Having said that, we think that there's sufficient excitement based on the data we have on MANIFEST-2 that really support that the -- sorry, for MANIFEST, both in the naive patients but also from some of the experienced patients, including monotherapy that really support the notion that we have, genuine activity being contributed here from CPI-0610. It's very, very meaningful.

And so we can't get into specifics on additional possibilities around potential paths, alternative paths beyond that today, except to say that we had very constructive dialogue. We've gotten feedback that will help us to determine additional paths and we'll incorporate that feedback and likely have additional discussions over time.

Brian Abrahams -- RBC Capital Markets -- Analyst

Make sense. Thanks so much.

Operator

And your next question comes...

Jigar Raythatha -- President and Chief Executive Officer

Sorry, if -- I wanted to make sure that Jeff didn't have anything more to add to that.

Jeffrey Humphrey -- Chief Medical Officer

No. Well, I would just add that we have fast track designation. The FDA has been very open to having repeated discussions with us as they and we are collaborating to look for the earliest path. And -- but it is clear that we need to understand contribution of components, as Jigar said and that -- both SVR and TSS50 need to be met in the MANIFEST-2 study. Thanks.

Operator

Thank you. And your next question comes from the line of Marc Frahm with Cowen and Company.

Marc Frahm -- Cowen and Company -- Analyst

Hi. Thanks for taking my questions. Maybe just following up on the last couple of questions about the FDA discussions. Putting together some of your comments. It seems like, given the necessity to kind of determine the contribution of each component of a combination, is the only potential way forward in the second line as of monotherapy than using kind of the MANIFEST-1 data given your reluctance to start a Phase 2 trial -- or a Phase 3 trial that's randomized given that the time lines would, I believe, overlap with the first line?

Jigar Raythatha -- President and Chief Executive Officer

Sorry, Marc. Can you repeat that question? I want to make sure I just got it correctly.

Marc Frahm -- Cowen and Company -- Analyst

Just it seems like you're really stressing the -- having to figure out the relative contribution of each component of a combination which obviously -- which kind of requires a combinate -- a randomized trial. So in terms of your discussions with the FDA on the second-line opportunity, does that mean that the only path forward that you guys see kind to continue pursuing with the FDA is as a monotherapy? Or are you still discussing the combination data as well?

Jigar Raythatha -- President and Chief Executive Officer

Yes. I think that we see potential opportunities across the board. And I think it's a little bit premature for us to comment specifically on what those could be in the second-line setting as we have a little bit more work to do to incorporate some of the feedback that we've gotten. But we'll definitely be able to respond to that over time. But we're very excited about the data that we have in the second line both as a monotherapy but as well as an add-on to ruxolitinib. And as you know, that there's plenty of strategies out there that folks are pursuing in that setting with some creativity as well.

Marc Frahm -- Cowen and Company -- Analyst

Okay. And then also commentary about the FDA clearly believing the conversion from transfusion dependence to transfusion independence is an unmet need, but you're still exploring ways forward. Is the debate with the FDA on how to define transfusion dependence and transfusion independence? Or is it more about kind of the effect size that you're showing and how many patients and those types of aspects of the data?

Jigar Raythatha -- President and Chief Executive Officer

Yes. So I think -- I don't think there's a debate necessarily on the unmet need. As I mentioned, I think it's very much recognized that as this is -- when patients become transfusion-dependent that they are significantly hampered both from a quality-of-life perspective but also from a -- the prospective of being anemic is -- creates a propensity -- or sort of prognostic factor is one of the most important ones. So from a -- I think the -- to your point, I think from a trial kind of design perspective, as well as end point measurement perspective, just getting clarity on kind of declined transfusion dependence and developing the evidence that's necessary to support the -- how that translates into clinical benefit are things that we'll focus more on as we examine that potential end point.

Marc Frahm -- Cowen and Company -- Analyst

Okay. Thanks. That's helpful. And then quickly on 0209. I recognize it's kind of a broad Phase 1 that has very open enrollment criteria. But given the patients that you've actually seen enrolling into the trial, is there -- do you think there's a chance that, with this initial data set, we could start to see the differentiation clinically versus the existing EZH2 inhibitors that you guys have put in clinic and others have also pursued? Or is it just going to be too broad of a population to early days to kind of establish that?

Jigar Raythatha -- President and Chief Executive Officer

We'll certainly try our best, but this has -- this was designed as a all-comers solid tumor dose-escalation cohort, which can be quite diverse in its patient population.

Marc Frahm -- Cowen and Company -- Analyst

Okay. Thanks.

Operator

And your next question comes from the line of Mike Ulz with Baird.

Michael Ulz -- Robert W. Baird -- Analyst

Hey guys. Thanks for taking the question. I just had one on the Phase 3 MANIFEST-2 study. So you guys are on track to start the study in the second half but just wondering if you can talk about what are the remaining steps to getting that study under way. And then are there any things you're doing to sort of manage some of the potential challenges created by the ongoing pandemic? Thanks.

Jigar Raythatha -- President and Chief Executive Officer

Hey, Mike. Yes, so by the way, nothing has changed on our guidance on MANIFEST-2. We continue to remain on track. And as we've indicated before, it's the pieces that are in our control, kind of the operational elements around site recruiting and contracting, that's well in hand and under way. And the piece that we've been keeping a careful eye on is -- and studying very closely as we identify sites is their ability to really manage these patients who will need to be cared for through this uncertain time with COVID. And so that's really kind of the piece that we are just making sure that we've examined and have in hand very closely with those -- particularly those early sites.

And in case -- in terms of specific plans, in terms of how to manage, it's very much in line with how we're managing today which is to ensure that there is flexibility on how patients can receive their drug in terms of ship directly to them, as well as flexibility around, if needed, timing and place of where data can be collected, whether it's labs or imaging data. And so we've sort of built in those measures to be able to ensure data integrity in that study but very similar to what we're doing today.

Michael Ulz -- Robert W. Baird -- Analyst

Okay. Great. Thank you.

Operator

And your next question comes from the line of Biren Amin from Jefferies.

Biren Amin -- Jefferies LLC -- Analyst

Hey guys. Thanks for taking my question. Maybe just to start on MANIFEST-2, I think the trial is going to be enrolling about 35% more patients than what AbbVie announced in ClinicalTrials.gov with Navitoclax's TRANSFORM-1 trial. So just trying to understand, I think, your comments on resizing and whether you would look at analysis at a lower number of patients in MANIFEST-2. And I guess second question is what's the treatment effect that you're assuming on the primary end point over the control arm?

Jigar Raythatha -- President and Chief Executive Officer

I'll start with the competitive piece, and then maybe I'll ask Jeff to comment specifically on the specifics. I think, first, I think it's hard for us to really comment on what AbbVie's design and we certainly took notice of their trial design. I do want to just highlight that from what we've seen publicly from them, the data is in a limited number of patients in second line. And so we haven't really seen much data to make any judgments if there's any to report on in the first-line setting. In contrast, we've had -- as of our last data update, we had 50 patients of data in the first-line setting, which has given us a lot of comfort around how we are thinking about the statistics of CPI-0610 and MANIFEST-2.

And with regard to the interim analysis, I think we've got a lot of comfort around the separation that we're seeing around SVR. As Jeff mentioned before, response rate is north of 60% versus in line with 30% to 40% is what you'd expect at rux. And so there's ample room to be sufficiently powered even with the most conservative assumptions that you can make around what rux can do based on historical studies. And really kind of what we are thinking through with the reestimation piece of it is TSS is in a single-arm study. You can only interpret so much from those end points, those data. And so as we get some more experience, we'll be able to make sure that we adequately power the study for TSS as well.

Jeffrey Humphrey -- Chief Medical Officer

Yes. I don't have much to add. But Biren, we can't really comment on AbbVie's design. As Jigar was saying, we've generated a very large data set in the relevant population. We've sized the study. We've got an alignment with the FDA on the key elements, and we've heard a lot of enthusiasm from our Phase 2 investigators. So we're focused on the base case of Phase 3 MANIFEST-2 as our approach to market.

Biren Amin -- Jefferies LLC -- Analyst

And then maybe just a question on the ET trial within MANIFEST, the Arm 4 component. What doses are you planning to evaluate? And also, are you looking at improvements in ET-related symptoms like fatigue, itching, bone pain and night sweats?

Jeffrey Humphrey -- Chief Medical Officer

Yes. Thank you. As previously mentioned by Emma, we will guide on the recommended dose, Phase 2 dose later this year and we will be measuring other symptoms including fatigue. And as mentioned, the MPN Symptom Assessment Form, so those correlative symptom changes will be measured as well. And as I mentioned, maybe primary end point...

Jigar Raythatha -- President and Chief Executive Officer

Maybe if I can just jump...

Jeffrey Humphrey -- Chief Medical Officer

Sure.

Jigar Raythatha -- President and Chief Executive Officer

If I can just jump in on that, Jeff. I think the dose that we would look at for ET would be -- would likely be around the MTD what we have at 0610, which is 225 once a day. And so that's probably the dose that we would use in the ET study.

Biren Amin -- Jefferies LLC -- Analyst

Great. Thank you.

Jigar Raythatha -- President and Chief Executive Officer

Yeah.

Operator

And your next question comes from the line of Kripa Devarakonda with Truist Securities.

Srikripa Devarakonda -- Truist Securities -- Analyst

Hey guys. Thank you so much for taking my question. And congrats on the progress. So for the Phase 3 alignment with the FDA that you mentioned, were there any changes to the Phase III design that the agency recommended? And also, I know this came up earlier as well but just wanted to clarify where you were with drug availability. Will you have everything ready by the time the trial starts? I know you mentioned earlier that you have multiple vendors now. So will you -- are you thinking more in terms of having a steady-state supply as you go through the Phase 3 study? Thank you.

Jigar Raythatha -- President and Chief Executive Officer

Yes. Sure. So on the design and the specific kind of components of it, there's nothing I think that I would say is surprising or any feedback that was out of what we expected to receive there. And it was a very constructive dialogue. And as Jeff mentioned, the design will be very similar to what we have been doing already with MANIFEST-2 -- sorry, with MANIFEST-1 as part of MANIFEST-2.

In terms of drug supply, we've had ample experience now in terms of manufacturing CPI-0610 and continue to make drug supply on a continuous basis. That is with sufficient inventory to continue to drive forward comfortably.

Srikripa Devarakonda -- Truist Securities -- Analyst

Okay. Thank you.

Operator

And your next question comes from the line of Jay Olson with Oppenheimer.

Jay Olson -- Oppenheimer -- Analyst

Hey, congrats on the progress. And thank you for taking the questions. Can you comment on any communications you've had with ex-U.S. regulators regarding 0610? And as you plan to build out your commercial capabilities to prepare for launch, is that a U.S. focus? Or are you making plans for ex-U.S. commercialization as well?

Jigar Raythatha -- President and Chief Executive Officer

Yes. So on the first question with regard to the European regulators, we focused a lot of our efforts, so far, on the FDA. We're assessing -- it's a strategic discussion sometimes in terms of when is the right time to approach the EMA, but we'll be obtaining country feedback as part of our CTA process, as we initiate the studies in the various countries in Europe. And sorry, can you repeat your second question?

Jay Olson -- Oppenheimer -- Analyst

Well, you mentioned in your prepared remarks that you were planning to build commercial capabilities to prepare for launch, so I was wondering if that was focused on the U.S. or if you had any plans for ex U.S. or if you're maybe talking to partners or what your plans were outside the U.S. for commercialization.

Jigar Raythatha -- President and Chief Executive Officer

Yes. I think it's a fair assumption that -- an emphasis of what we're doing is on the U.S. I think we haven't yet committed about how to think about commercializing outside of the U.S. It wouldn't be atypical to think about having ex-U.S. partnerships regionally, whether that's Asia, potentially Europe, but it's a little early for us to comment on that right now.

Jay Olson -- Oppenheimer -- Analyst

Okay. And then for the MANIFEST update that you expect by the end of the year, what are the key learnings we should expect to capture from that update?

Jigar Raythatha -- President and Chief Executive Officer

So there is several things. So one will be additional patients that will have either mature and enroll in the MANIFEST study across all of the cohorts. So in particular in Arm 3, the naive patients, we had 50 patients that were -- or 51 patients that were at 12 weeks. And a substantial number of those, when we take the data cut, should be at 24 weeks. And so again, really kind of growing the data set, the mature data set that we have with a significant number of more patients to further support the activity of CPI-0610. But in addition to that, we've been generating additional data translationally, maybe I'll ask Patrick to chime in on that to help support the mechanism of action that's at play here. Patrick, do you want to just describe a bit more about what we plan to present potentially toward the end of the year?

Patrick Trojer -- Chief Scientific Officer

Yes, happy to. So as Jigar said, we are really focused in understanding better the underlying potential disease modifying aspects of CPI-0610 and that will come from further analysis and molecular analysis of bone marrow biopsies that were taken from patients prior the initiation of treatment and compare those with ongoing treatment during the course of treatment and in addition taking the blood samples from the patients and analyzing them for changes in composition and changes in gene expression pattern that could explain potentially the mechanism of action. Both of these data sets from clinical samples as well as some ex vivo-treated samples, we'll update on at the ASH conference later this year.

Jay Olson -- Oppenheimer -- Analyst

Great. That's very helpful. Thank you for taking the questions.

Operator

And your next question comes from Reni Benjamin with JMP Securities.

Justin Walsh -- JMP Securities -- Analyst

Hi. This is Justin Walsh on for Reni. I know you guys discontinued CPI-1205, but are there any key takeaways or data points that we should be looking for to inform us about the EZH2 program overall when you present the full ProSTAR data set? And do you have a sense of when that data will be presented?

Jigar Raythatha -- President and Chief Executive Officer

Patrick, do you want to take that?

Patrick Trojer -- Chief Scientific Officer

Sure. Yes. So we obviously have taken all the samples we can get our hands on to analyze from the ProSTAR trial, and there are interesting observations that make us want to explore EZH2 inhibitors in prostate cancer further. And we would obviously leverage these molecular data that we have obtained from ProSTAR to guide our future development efforts in prostate cancer. From a disclosure perspective, we haven't made internally the decision when or where exactly we would disclose the ProSTAR data in its entirety. The study as such has not yet been closed, so it's potentially at a later point when the study closes.

Justin Walsh -- JMP Securities -- Analyst

Perfect. And I guess just one other question, what are your -- some of your thoughts regarding the evolving competitive landscape in MF? And in particular, what about any other BET inhibitors that are being developed, either alone or in combination with rux?

Jigar Raythatha -- President and Chief Executive Officer

Yes. I'll take that one. So in terms of -- I'll take the -- your second part of your question first, in terms of other BET inhibitors. And this is a class of molecules that has been extensively studied by a variety of companies. And what we think is unique about CPI-0610 is based on some of the properties in the molecule, we have a very flexible therapeutic window that's allowed us to progress this molecule to the state that we have. We haven't yet seen evidence from other BET inhibitors that seem to be equivalent to CPI-0610. Having said that, I think, subsequent to some of the disclosures that we've made publicly around the activity that we've seen in myelofibrosis, we do know that a couple of other folks have tried to kind of follow on our path. And there are now at least 2 BET inhibitors that are being studied in MF. But they're early and they're just getting going perhaps not even yet dosing in patients. And so as you think about kind of from a timing perspective, we're on the doorstep of starting our Phase III study where some of these other molecules, they just will be studied in Phase 1 to establish their safety. There's quite a bit of distance to cover there in terms of understanding the therapeutic window as well -- as a single agent as well as a combination therapy with some of the other BET inhibitor approaches that are being studied.

And so we feel pretty comfortable that we've got a substantial enough lead that, that continues to give us an advantage, even if those are able to identify therapeutic windows that we have, which is still an open question. And then in terms of other modalities, there's -- they're certainly, I think, evolving. But we haven't seen, at least from the latest kind of public data presentation at EHA, we haven't seen anything that's really jumped out to us that is significantly competitive with CPI-0610 at this point. Particularly additional data in the frontline setting, we haven't seen any other company present data in that context. In the JAK-experienced patient population, there's certainly several other mechanisms that are being studied either single-agent therapies like other JAK inhibitors or therapies in combination with ruxolitinib. And there is a variety of data out there that are intriguing but still unproven, and so we'll continue to monitor those as well.

Justin Walsh -- JMP Securities -- Analyst

Great. Thank you very much. That was very helpful.

Operator

[Operator Instructions] And at this time, there are no further audio questions. We'll now turn the conference back over to Jigar for closing remarks.

Jigar Raythatha -- President and Chief Executive Officer

Well, thanks everybody for your time today. Really appreciate the great questions and look forward to additional conversations. Thank you very much and we can disconnect the line.

Operator

[Operator Closing Remarks]

Duration: 55 minutes

Call participants:

Kia Khaleghpour -- Vice President, Investor Relations and Communications

Jigar Raythatha -- President and Chief Executive Officer

Jeffrey Humphrey -- Chief Medical Officer

Patrick Trojer -- Chief Scientific Officer

Emma Reeve -- Chief Financial Officer

Anupam Rama -- JPMorgan -- Analyst

Brian Abrahams -- RBC Capital Markets -- Analyst

Marc Frahm -- Cowen and Company -- Analyst

Michael Ulz -- Robert W. Baird -- Analyst

Biren Amin -- Jefferies LLC -- Analyst

Srikripa Devarakonda -- Truist Securities -- Analyst

Jay Olson -- Oppenheimer -- Analyst

Justin Walsh -- JMP Securities -- Analyst

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