Cymabay Therapeutics, Inc. (NASDAQ:CBAY) Second Quarter 2022 Earnings Conference Call August 11, 2022 4:30 p. m. Eastern Time
Participating companies
Paul Quinlan – General Counsel, Chief Compliance Officer and Corporate Secretary
Sujal Shah – President, CEO and Director
Charles McWherter, Senior Vice President and Chief Scientific Officer
Daniel Menold – Vice President, Finance
Lewis Stuart – Commercial Director
Dennis Kim – Managing Director
Conference Call Participants
Yasmeen Rahimi – Piper Sandler
Steven Seedhouse – Raymond James
Thomas Yip – H. C. Wainwright
Mayank Mamtani – B. Riley Values
Cory Jubinville – LifeSci Capital
Michael Kratky – SVB Values
Kristen Kluska – Cantor Fitzgerald
Operator
Good morning, girls and gentlemen, and welcome to the call of CymaBay’s 2020 quarter business update and monetary effects convention. [Operator Instructions]. Please note that the call will be recorded at the request of the company. It is also streamed live on CymaBay’s investor segment in www. cymabay. com.
I would now like to turn to Mr. Paul Quinlan, General Counsel of CymaBay. Mr. Quinlan, continue.
Paul Quinlan
Thank you, operator, and good afternoon, everyone. I hope you have had the opportunity to read the press release we issued announcing our monetary effects and business updates for the quarter of 2022. You can find this press release on our online page under the Investors tab.
I am joined today by Sujal Shah, Executive Director; Chuck McWherter, Chief Scientific Officer; Dennis Kim, chief medical officer; Lewis Stuart, Chief Commercial Officer; and Dan Menold, Vice President of Finance. After our comments ready, we will open the call for questions and answers.
Before we begin, I would like to remind everyone that the statements made during this convention call, adding the query of questions and answers related to CymaBay’s expected long-term performance, business prospects, occasions or plans, adding clinical plans, regulatory approvals, financing and reimbursement schedules, forecasts, schedules and the date of publication of the knowledge, cash flow and marketing plans are forward-looking statements, as explained in the Private Securities Litigation Reform Act of 1995. Although the Company believes that the expectations reflected in those forward-looking statements are based on assumptions, actual effects are subject to hazards and uncertainties and may differ materially from those expected due to the influence of factors. The Company assumes no legal responsibility to update or supplement any forward-looking statements, whether as a result of new information, long-term occasions or otherwise, unless required by applicable law.
Participants are directed to the warning statements set forth in today’s press release and the threat points set forth in CymaBay’s quarterly and annual reports filed with the SEC for points that may cause actual effects to differ materially from those expected in the forward-looking statements. . .
This convening of the convention is the property of CymaBay, and any recording or reproduction is expressly prohibited with the written consent of CymaBay.
At this point, I would like to do Sujal’s.
Sumal Shah
Thank you Paul. Hello and thank you for being with us today. I am very pleased to begin our call today, highlighting the achievement of a milestone in the progression of seladelpar for patients with a rare autoimmune liver disease, biliary cholangitis number one or CBP.
Last week, we announced the end of the reaction logs. Our global Phase III registry examines the comparison of seladelpar in PATIENTS with CBP who have had an insufficient reaction or are intolerant to the first-line remedy compared to deoxycholic acid. Thanks to the tireless efforts of our team here at CymaBay, the commitment of our patients and their families, the expertise of our researchers and staff, and the help of our investors, we have been able to get closer to our purpose of improving the lives of CBP patients. The progression program for seladelpar is one of the most physically potent ever performed in patients with PBC with more than six hundred participants, more than 325 of whom are already receiving remedy in our ongoing studies. We explored a wide diversity of doses between 2 and two hundred milligrams and studied a wide diversity of patients, adding non-cirrhotic and cirrhotic compensated with and without portal hypertension. Our current experience includes patients who have undergone remedy between 3 months and up to 3 years.
Today, I will ask our medical director, Dr. Dennis Kim, to provide a review of our progress on RESPONSE, as well as CBP’s overall progression program. Over the years, a key component of our progression program has been to publish and provide our findings at major medical meetings. Since the progression of PBC began in 2015, we have consistently shared knowledge with medical networks and today our Chief Scientific Officer, Dr. Chuck McWherter, will review some of our most recent knowledge provided at the EASL Liver Congress-sponsored International last June. Finally, as we look ahead to complete RESPONSE and report the key effects of the trial in the third quarter of 2023. We will continue our pre-commercial research to identify methods that maximize the effect that seladelpar can have on PDC. Our Chief Commercial Officer, Lewis Stuart, will speak briefly about the ongoing and in-depth investigations at a virtual investor event we plan to host in September.
Before answering questions, we will conclude our ready-made remarks with our Vice President of Finance, Dan Menold, reviewing our last quarter’s finances. Let me first call Dennis.
daniel kim
Thank you Sujal. I have the privilege of speaking about the progress we have made in our Phase III progression program to stay in PBC. Completing patient enrollment in RESPONSE is a vital step that allows us to establish timelines and plan in more detail for the final touch of the completion of the full examination, the analysis of knowledge, the availability of high-level efficacy and protection results, and the transition to the implementation of an NDA for prospective marketing approval of seladelpar as a new remedy option for patients. living with PBC.
At the end of our registration for the relative exam, we conducted an extensive screening effort at more than 150 active sites in more than 20 countries. In the end, we concluded enrollment with a total of 193 randomized patients. Patient enrollment and enrollment are still pending. One of the most challenging operational facets of any clinical trial, however, the RESPONSE study found more demanding situations similar to the global pandemic, which began several months before the reaction was launched. Demanding situations similar to COVID, such as the closure of offices, the editing of clinics and hospitals. resources to combat COVID infections, labor shortages, and the participation of some patients in clinical trials, among other factors similar to those of COVID, have forced us to go further, deepen and be artistic with a patient recruitment strategy. Studies have also been conducted targeting a comparable CBP patient profile in parallel and ten geopolitical reactions. Tensions in Russia and Ukraine have posed more obstacles to overcome.
To address those challenges, we have expanded our footprint in terms of the number of screening sites, countries, and patient recruitment partners. We sought to build new relationships with high-potential researchers in parts of the world where we had already conducted trials, focusing on more information on the involvement of those pre-existing relationships and on the study sites, which we knew had a chance of working well.
Our thriving past delights in participating in CBC clinical trials with many of the same CBC experts, principal investigators, allied fitness professionals, and patient advocacy teams has served us well in leveraging those relationships to address challenges.
In fact, as Sujal mentioned, our seladelpar clinical program represents the most powerful and rigorous body of knowledge to date for a drug candidate in progression at CBP. III studies with more than one hundred patients and more than 50 patients who have had at least 1 year and 2 years of enjoyment with seladelpar treatment, respectively.
In our ongoing open-label extension study, make sure more than 150 patients are recently receiving a daily dose of seladelpar. With the 193 patients randomized in the RESPONSE study, our core body of knowledge will be supported by the consistent efficacy and protective effects we observed. in our previous essays. This gives us more confidence in our ability to offer life-changing remedy features for other people with PBC. encouraging data and emotions from our partners. The ongoing ASSURE exam is a vital differentiator of our program. All patients gain open-label seladelpar daily, which will carry significant amounts of knowledge of long-term efficacy for biochemical reaction and pruritus, as well as create a giant protective knowledge pool.
The Data Security Oversight Committee for RESPONSE allowed us to continue without any changes. Our researchers’ feedback on their clinical experience in those studies has been overwhelmingly positive. Many of those researchers have also been involved in our previous studies, adding our first Phase III study. , ENHANCE, which showed encouraging efficacy and protective effects at 3 and 6 months. As a reminder, 10 milligrams daily of the seladelpar remedy in our latest open-label phase II and long-term extension study demonstrated consistent, sustained, and progressive innovations in alkaline phosphatase. of the order of approximately 50% relief after 2 years of treatment with 79% of patients achieving the composite endpoint of alpha less than 1. 67 x the overall recorded, more than 15% relief in immediate and overall bilirubin is less than the upper limit of the general range. We have also reported in the past progressive innovations in liver transaminases and LDL cholesterol over a 2-year overdose period.
Similarly, in ENHANCE, 10 milligrams of consistent seladelpar per day for 3 months allowed 78% of patients to achieve compound endpoint number one and more than 25% of patients to achieve alkaline phosphatase normalization from an average starting price of approximately 290 consistent sets per liter. These biochemical effects were accompanied by improved measures of pruritus, a vital and significant symptom of PBC, which many patients enjoy and are ashamed of a foundation.
Importantly, it is worth being confronted and well tolerated in those earlier contexts. With the focus now on our existing study, we planned percentage of key RESPONSE knowledge in the third quarter of 2023.
I will now pass on to Chuck the highlights of some of the most recent presentations we made at EASL in June. Chuck?
charles mcwherter
We know that our science is not complete until it has been communicated to the clinical and medical network and despite everything published in peer-reviewed journals. It was at the liver assembly in 2016 and we presented the effects. of our first study of seladelpar in patients with PBC. And this was followed some time later through its publication in Lancet Gastroenterology and Hepatology, one of the leading journals specializing in liver diseases. Since 2016, we have presented seladelpar studies at each and every AASLD and EASL assembly with 33 presentations made to date, 6 of which have been decided for last minute presentations, and only about a third have been oral presentations.
This year, we published the effects of the 52-week Phase II study of seladelpar in PBC in the Journal of Hepatology, one of the leading journals in the area of healing. A secondary research reporting on innovations in pruritus, sleep, and fatigue published in Liver International, another journal known for publishing effects at the forefront of hepatology. Last June, we continued our percentage of effects commitment with 3 presentations at the EASL-sponsored International Liver Congress in London.
The first presentation was a poster describing studies conducted by Bettina Hansen, leader of the PBC Global Study Group, the organization best known for creating blood tests for alkaline phosphatase and bilirubin levels that are used as surrogates through the FDA and the EMA. as approval criteria. at CBP. Seladelpar Remedy Poster of Number One Biliary Cholangitis Patients Over 2 Years Improves GLOBE PBC Score and Predicts Greater Graft-Free Survival, used the validated threat assessment tool called the GLOBE score. He observed the reaction to the remedy with seladelpar over a period of 2 years in 50 patients with PBC. Patients were decided on the basis of incomplete reaction or intolerance to the first-line remedy with UDCA. Finding number one was that the addition of seladelpar resulted in a reduction in the predicted risk of liver transplantation or death with a relative risk of 0. 66 compared to no prior seladelpar treatment. The improvement in GLOBE score and predicted survival did not account for patient age. However, a study of subpopulations of high-risk patients using the GLOBE score found that patients of all ages improved. Younger high-risk patients tended to have greater improvements. This suggests the possibility of a greater effect on the treatment of the previous disease with seladelpar.
In an oral presentation through our collaborator, Professor Bernd Schnabl, Professor of Medicine at the University of California, San Diego, described a sublime framework of studies constructing that seladelpar acts via PPAR delta to suppress bile acid synthesis through upregulation of FGF21 in hepatocytes. This explains Seladelpar’s ability to suppress poisonous bile acids that accumulate in the liver due to cholestasis. It is vital to note that their studies have established that suppression of bile acid synthesis is done through a completely different direction than FXR agonists, such as Ocaliva, which is the only second-line remedy for CBP approved today. FGF19 released through intestinal cells will have to travel to the liver to exert effects on the suppression of bile acids. The involvement of FGF21 is possibly one of the many reasons why the seladelpar mechanism appears to have the ability to produce favorable biochemical responses related to stepped cholestasis.
The final presentation was a poster from the CymaBay study team examining the effect of seladelpar on fibrosis and liver in mice after damage caused by repeated low-dose carbon tetrachloride treatment. Our technique was to let the fibrosis settle for five weeks before starting a 3-week remedy with seladelpar or vehicle. However, unlike other fibrosis styles, we continued to deliver the carbon tetrachloride insult throughout the following 3-week treatment period. Seladelpar, unlike the comparator FXR or the beta-agonist THR, was able to decrease fibrosis in the face of continuous injury. Molecular studies using RNA sequencing strategies were able to identify that the seladelpar remedy alters the signature of genes related to injury and fibrosis. This is the third animal style in which we have noticed that seladelpar can reduce the degrees of fibrosis identified. And we believe this is consistent with the effects of seladelpar on fibrosis that have been observed in patients with NASH. We continue to use strategies to read about the translational effects of seladelpar on gene transcription to perceive its pharmacology in patients.
As you can see, we are committed to sharing the effects of our clinical and mechanical research, and we plan to participate in the AASLD assembly this fall and other primary medical assemblies in the future. As we move forward, through the later stages of development, we are also committed to methods to maximize the number of patients who can gain advantages from treatment.
I will now turn the call on to our sales manager, Lewis Stuart, to talk about our first pre-commercial plans. Lewis?
Luis Estuardo
With our clinical team focused on ANSWER, our adjusted sales team worked diligently over the past year to conduct an assessment of the global PBC market with a special focus on the United States, Canada, Europe, Japan, and China.
Throughout our number one studies, we were pleased with the reception of healthcare providers who reviewed the profile of the target product seladelpar. Our market research and qualified advisors indicate that significant unmet desires remain for an improved biochemical reaction and improvement in CBP symptoms.
Starting in 2022, we have focused on several US-based pre-commercial projects designed to tell our go-to-market strategy. We started by mapping the 25,000 to 30,000 or so patients in the United States that make up the online US market right now. Our research demonstrates an immediate opportunity in non-cirrhotic patients who have a complete response to UDCA and/or who have discontinued obeticholic acid treatment, who constitute only about 60% of the timeline target population. In addition, we estimate that there are up to 15,000 cirrhotic patients on first-line therapy, more than a portion of whom have had a partial or complete reaction to UDCA and would possibly constitute a separate population for the timeline remedy through seladelpar, especially given black box warnings for obeticholic. acid in this population. Other vital care across the spectrum of complete and comprehensive responders to UDCA is the more than 15,000 patients who have experienced moderate to severe pruritus and can turn to seladelpar to improve symptoms. Overall, our segmentation research shows that seladelpar’s product profile may also be a popular choice for the vast majority of those different patient segments.
In the current quarter, we conducted patient-centered research, on their adventure with PBC. And we are encouraged by the active participation of patients and their families in all of their care. In addition, we are excited about the general wisdom of patients with PBC and their willingness to be more informed about potential new treatments. Unsurprisingly, they have been very descriptive of the symptoms they endure, offering separate main points related to severe pruritus, fatigue and/or brain loss that are an integral component of their daily lives. Together with your physical care provider, they constantly monitor major biochemical markers and are constantly concerned about the overall condition of your liver.
At CymaBay, we can provide education to patients and caregivers, upload verbal exchange on quality of life issues, and become a trusted source of data throughout the wonderful paintings of defense teams like PBCiers, the PBC Foundation, the Canadian PBC Group, and others we have engaged with globally.
During the last quarter, we also conducted an assessment of the market access landscape, as well as number one market studies with payers to identify opportunities and barriers in fitness plans, seeking advertising and government coverage. We will use those early findings to indicate Seladelpar’s pricing proposal and overall payment and patient facilities strategy.
Finally, as Sujal noted, we plan to hold a virtual investor day on September 22, where we will provide a more detailed look at the global market opportunity to seladelpar.
This program will come with a clinical examination through Dr. Chris Cowley, one of the world’s leading experts in the treatment of PBC. the main points of the occasion in the coming weeks.
I would now like to speak with Dan Menold, Vice President of Finance, for a review of our finances in the current quarter. Dan?
daniel menold
As noted by other team members, during the current quarter we continued to make progress on more enrollments in our ASSURE study. And last week, we announced the final touch with the enrollment of 193 patients in the RESPONSE study, achieving a key milestone in our CBP progression plan. We also continue to advance other required clinical activities related to our long-term RESPONSE and other clinical studies that enable NDA, which are mandatory to complete our seladelpar progression in the late stage of PBC. And finally, we have made progress in production progression, as well as in medical and advertising matters, where we are advancing our efforts to plan an imaginable long-term release of seladelpar on PBC.
Let us now turn to a brief review of our monetary position and the effects of operations for the current quarter. Our money, money equivalents and investments totaled $170. 8 million as of June 30, 2022. This available money is enough to fund our current operating plan through 2023.
Our net loss for the quarters ended June 30, 2022 and 2021 was $27. 1 million and $23. 2 million or $0. 31 and $0. 34 consistent with participation, respectively. Net loss for the 6 months ended June 30, 2022 and 2021 was $54. 9 million and $40. 8 million or $0. 62 and $0. 59 consistent with participation, respectively. Net loss was consistent in the three and six months ended June 30, 2022, compared to the corresponding consistent periods in 2021, largely due to an accrual in the clinical trial or consistent with relevant expenses with continued progression of the last stage of seladelpar in PBC, as well as an accumulation in interest expenses not consistent with the payment of interest similar to the Abingworth progressive financing agreement. In particular, our steady accumulation of charges was primarily due to an expansion of our clinical site activation, patient recruitment and other relevant clinical trial activities with RESPONSE and ASSURE, our 2 global PBC assets in late-stage clinical trials. and consistent with the reimbursement of the relevant worker with the hiring of more staff for PBC’s global progression program. We expect our ongoing expenses to increase over the long term as we continue to execute our plans for clinical progression readiness, production and publicity for CBP.
Leave me now the call to Sujal.
Sumal Shah
In addition to our number one seladelpar in PBC, the phase IIa pharmacological evidence study of MBX-2982 continued to enroll patients in the current trimester.
Challenges similar to the COVID-19 pandemic have continued to have an effect on the speed of enrollment in this exam, but we believe that our partners who are fully engaged and completing this test can lead to the final touch of enrollment at the end of this year. As a reminder, MBX-2982 is a GPR119 agonist discovered and evolved through CymaBay. And although this test is fully funded through Leona M. and Harry B. Helmsley Charitable Trust, retain all rights to MBX-2982. The product concept studied for MBX-2982 in this study is that of an agent that could save it or minimize hypoglycemia in patients with type 1 diabetes. In addition to protection and tolerability, the number one objective of the study is to assess the release of counterregulatory glucagon levels in hypoglycemia situations. We look forward to providing further updates on the progress of this study in the coming months. It’s been another hectic quarter at CymaBay, where we’re proud to have reached key milestones and, more importantly, excited about the news ahead.
We believe that the possibility of seladelpar comprehensively improving the lives of PATIENTS with CBP represents one of the most attractive and least risky opportunities in the last stage of our industry. Our purpose has been to put seladelpar in the hands of the largest number of patients they can get in the world. If we are successful in completing the progression program and registering seladelpar. As part of this, we continue to compare opportunities for components with components located in geographies outside the U. S. .
Seladelpar remains one of the only late-stage opportunities in this domain that remains completely free. With a solid balance sheet, quality investors, experienced internal groups and associations with the most productive PBC experts in the world. We couldn’t be better positioned to continue creating value for all of our stakeholders, aggregating the patients we focus on every day.
We are now satisfied with the questions. Operator?
Q&A session
Operator
[Operator Instructions]. Our first comes from Yasmeen Rahimi’s line with Piper Sandler.
Yasmine Rahimi
Congratulations again on the final touch of the record. Several questions for you. Perhaps the first question is whether you’ve had a chance to take a look at RESPONSE’s basic demographics. And help us understand what is aligned with the ENHANCE study?That’s the first question.
The consultation of the moment is perhaps a reminder of the fundamental speculation of the RESPONSE study. And then the third query is, have you interacted with the FDA regarding what a post-marketing requirement might look like?I know we’ve noticed in competitive trials that placebo-controlled postmarketing studies might not be feasible.
Sumal Shah
Thanks, Yas, I appreciate the questions. I’ll start and maybe ask the team to elaborate on some of those points. I think, first of all, regarding the ANSWER. We’ve talked a lot in the beyond about how much of this is, I’d like to say a rinse and repeat of what we fully enrolled, moved forward and ran in the ENHANCE phase III study beyond. We are looking at the same patient population, the same optimal dose of 10 milligrams of seladelpar, and the same number one and secondary endpoints.
Of course, blindly, we have the opportunity to see some of the fundamental high-level demographics. patients enrolled in our previous open-label Phase II exam, as well as the 265 patients we enrolled in IMPROVE. Therefore, you will most likely see very comparable alkaline phosphatase levels, especially at first. And again, I think the overall demographics would be very consistent with what we’ve noticed before.
I know your query at the moment has to do with that, in terms of remembering about the reaction diet. I think that when you take a look at the knowledge of ENHANCE in particular, we shared knowledge for 3 months, about the main composite criterion used to sign in Ocaliva, this would be the registration criterion to labell, in particular, this is the criterion in which to be an answering machine. A patient lowers his alkaline phosphatase point below 1. 67 times the upper limit of overall, with a minimum of at least 15% in alkaline phosphatase and general bilirubin.
And as you will recall, in the insights we presented at previous medical meetings, even in just 3 months of treatment, we saw that 10 milligrams of seladelpar resulted in a reaction rate of around 78% at this number one endpoint compared to around 12. 5% for patients in the placebo group, and that included about 55 patients consistent with the arm. Therefore, in the main criterion, this p-value was less than 0. 0001. So it’s a long way to tell you that at endpoint number one with 193 patients randomized in ANSWER 2:1, it is labelled 10 milligrams to placebo.
We are very hard to demonstrate this type of effect on the key secondary endpoint with respect to alkaline phosphatase normalization, well above 90% in each of those cases. Our initial purpose of 180 patients in RESPONSE was largely based on some of the assumptions about the number of patients who would have moderate to severe itching. We believe we could enroll in the Phase III RESPONSE study. Thus, the purpose of 180 largely fulfills an assumption of around 80%, at least 80% to show a merit of 20% or a merit of 2 points in the effect of seladelpar on the numerical scoring scale of the worst imaginary itch in the last 24 hours period. Again, this key secondary endpoint is largely what made us decide the overall purpose in terms of patients in the RESPONSE.
Finally, Yasmeen, I think you asked us a little bit about our conversation with the company as part of the examination of the effects of phase IV, of course, the approval of this main parameter in RESPONSE because replacement is based as a substitute parameter. in the approval of subcomponent H, so we must have interaction in a phase IV effects study. In fact, we’ve had years of discussion with the company about various types of studio designs. He talked a little bit about others in the field, having difficulty enrolling patients in what would possibly in the end be long-term placebo-controlled trials to compare and having enough opportunities to demonstrate that clinical benefit. Our conversation with the company focused on newer approaches than we’ve noticed with other sponsors. . This discussion continues today.
And as we conclude this conversation with the agency, we will share it publicly, as we put the finishing touch on the Phase III progression program and likely launch a study of Phase IV results.
I will say, Yasmeen, that we, as sponsors, also recognize the importance of proceeding to generate real-world knowledge, registry knowledge about the effects of our potential remedy opportunities for PATIENTS with PBC compared to those who are not in our remedy, and we have noticed that others generate at least this set of knowledge, it is very difficult to see if this body of knowledge alone is sufficient for full approval. I think it’s vital and it’s up to sponsors like CymaBay to devote time and resources to generating knowledge sets that can prospectively target those outcomes, various other methods on behalf of patients, because that’s a key commitment for regulators.
Yasmine Rahimi
And again, I can’t be so satisfied for you at the end of your registration as we approach the information every month.
Operator
The next one comes from Steve Seedhouse’s lineage with Raymond James.
steven seed house
I wanted to ask: I appreciate the summary of the market research you have carried out. That’s very useful. I just wanted to ask in ANSWER, are you satisfied with the type of sample you have of the other Marketplace segments you have described and can you generate an update on each of them at the end to serve a label or detail the ones that Marketplaceplace?Segments.
Sumal Shah
Yes, of course. I’m going to start and I’m going to ask Lewis to provide an additional color. I think, Steve, obviously, the first purpose is in the patient population with the greatest unmet need. The second-line setting, of course, are patients who are largely incomplete or insufficient responders to UDCA, as well as alkaline phosphatase levels, biomarkers of cholestasis that are linked to an increased threat of population progression, of course, included in our RESPONSE study are those with alkaline phosphatase levels. above 1. 67 times the upper limit of normal, as you well know. Obviously, this is a strategy to potentially bring Seladelpar back to market for those patients and the ultimate unmet vital need.
What we see more broadly is an effect on relief, as a point estimate, of the percentage of relief in alkaline phosphatase in patients, almost independent of baseline alkaline phosphatase levels. So the kinds of effects we see in patients who have an alkaline phosphatase level above 1. 67 times the upper limit of normal, we would expect to see similar percentage discounts for patients who still have an elevation above the upper limits of normal, which may explain how we think about long-term opportunities to expand the patient population that can be loaded. And maybe, Lewis, I can ask you to load any cargo color.
Luis Estuardo
Oui. Je I think that, as I mentioned before, one of the critical spaces we are concentrating on is indeed the Chemical RESPONSE, but we would also concentrate on 2 other critical segments that I discussed. I think this perception of being able to cope with either cirrhotic and non-cirrhotic patients and being able to do so, I think, will be a very vital differentiator.
And then, probably, the maximum living spaces that we know patients have constantly discussed are this factor related to pruritus or quality of life. And I think this opportunity to adjust symptom improvement will also be a very important consideration.
steven seed house
And what about patients who have stopped OCA on the market?He seems to have done some studies on that, and it’s a very large number of patients. So, are you going to have significant knowledge of RESPONSE to communicate to those who have already been exposed or not to the OCA?And are they even predefined subgroup analyses, for example, from the study?
Sumal Shah
Based on our experience, even in our previous phase III study, ENHANCE, we had patients who stopped treatment with OCA, obeticholic acid. We are waiting and we know we have patients, including at RESPONSE, who also discontinued OCA treatment. So, we’ll continue to gather that information and really have a chance to get more percentages. conclusion related to this impact. But again, we saw significant responses in patients taking selelapar, even those who not only did not respond adequately to UDCA, but also those who also discontinued previous remedies such as OCA.
Luis Estuardo
And just to load in terms of numbers, in fact, the OCA manufacturer already has that its overall penetration in the line market at the moment is around 30% to 35%. We saw with this 35% a giant number of patients who stopped treatment with OCA. And we look at the numbers of units, we think there are probably between 5000 and 7000 other patients who can get benefits from seladelpar right away and who actually stopped taking the drug. Therefore, we believe that this is a very important segment for early approval.
steven seed house
It is ok. Last question, I just wanted to check the number of biopsies volunteers in the study. Are you satisfied with having enough to check the box with the FDA?I know it’s a feature of this study.
Sumal Shah
Yes. Thank you, Steve. We know that a smart proportion of patients volunteered for a biopsy in this trial based on our previous conversations with the agency.
Operator
Our next comes from Ed Arce’s lineage with H. C. Wow.
Yip Shots
It is Thomas Yip who asks Ed. Congratulations on the ANSWER studies to complete the registration. So, first ask about the ANSWER exam compared to what you saw in ENHANCE, what are your expectations for the ANSWER exam and the recordings for the number one compound?endpoint and also for key secondary endpoints like ALT verbal exchange and also pruritus?
Sumal Shah
I think one thing to highlight is our past experience, not only in the first Phase III ENHANCE exam conducted, once again, but also in our open Phase II exam that included just north of a hundred enrolled patients. We saw a very consistent reaction in the minimum percentage of alkaline phosphatase over the actual magnitude of alkaline phosphatase relief and how those discounts translate into compound criterion number one.
So if you don’t forget about our open-label Phase II study, in fact, over 12 months of treatment, we saw that just under 80% of patients met this number one endpoint, which is very consistent with what we saw at 3 months in GET BETTER. We are very happy that although we have shared datasets for patients who have passed 1 year of treatment, we continue to see, in fact, innovations in alkaline phosphatase reductions and, in particular, even the normalization of alkaline phosphatase from about 40% to 50% – 30% – Sorry, 40% between year 1 and year 2. We discovered a very consistent ongoing reaction in our previous studies. And we’re going to look at what we see, of course, in RESPONSE, as I pointed out, it’s the same patient population that we’ve studied in those previous trials. That’s why we believe this program no longer has risks at this point, the expectation would be to see something similar to what I’ve noticed in the past.
Yip Shots
You may ask us about the long-term ASSURE study, can you talk about the approximate percentage of patients for RESPONSE?And also so far, what is the average duration and longest behavior of the patients in the study?
Sumal Shah
Let me ask Chuck to enlighten you, especially at the time of this question.
charles mcwherter
Yes. Thank you, Thomas. ASSURE started its registration basically in February last year. So, the first patients coming from our legacy studies, the low-dose study we published in the Journal of Hepatology and ENHANCE. So, those patients have accumulated this era until today. And most of it, almost all patients to date come from those inherited studies. As you know, we announced that we started registering for RESPONSE necessarily in April of last year. And now we have few patients who have finished the first year of treatment and are in the process of passing the ASSURE exam.
Based on our previous experience, we would expect to have very intelligent patient retention and a keen interest in participating in extension studies. And therefore, we would expect most patients in RESPONSE to enter SECURE. So in general, this means that we’re looking for a very large dataset with a lot of processing experience when it comes to taking the data cut to request an NDA. And we think it will be useful for regulators who have to make a resolution based on protection but also on efficacy, biochemical response, durability and also on the release of symptoms.
Yip Shots
Fantastic. We look forward to read the next newspaper.
Operator
Our next one comes from the kristen Kluska line with Cantor Fitzgerald.
kristen kluska
Let me also upload my congratulations on getting the full registration for ANSWER. So I saw a genuine publication of the study that reported that pruritus was seen in more patients than in the past with PBC above 80%. So I know you’re talking about some market measures for patients who don’t respond or have tolerability issues with other therapies. But in light of some of those statistics, how do you see yourself as a second-line drug?
charles mcwherter
Well, I’ll probably start myself, and then Lewis can approach it from the perspective of the market. I think I agree that we continually receive feedback on the importance of pruritus in the population. For percentage of your query alone, our team visited over 70 clinical sites to consult to help with recruitment for RESPONSE. And I can tell you that time and time again, anecdotally, we’ve received significant feedback from researchers, exam coordinators in particular, physician assistants, nurse practitioners involved in the study. About his patients and the need for anything to treat pruritus. And I think you see that more and more in the literature that you’ve alluded to, and you’ve possibly heard some of the recent roundtable symposia at EASL, as well as at the AASLD, where eminent experts have begun the discussion about the importance of doctors, who are the target audience for those presentations, pay more attention to the symptoms.
One of the disorders considers patients who are reluctant to communicate something that can only be shared through the way they feel. Lately there is nothing that can be measured directly. This is just a symptom and not a sign. And it can be very much for patients.
So I think, and I’m going to pass the floor to Lewis, I think this represents a genuine opportunity for us to highlight this and a kind of assistance with the whole picture to replace this discussion because, first of all, it turns out that seladelpar has a very clever effect on pruritus. And that is all that will be vital to perceive and take advantage of.
Luis Estuardo
And Chuck may not delve deeper into that description, as we tap into and interview several patients in our paintings about the patient journey. We spend a lot of time listening to them describe how difficult their everyday life is to deal with those symptoms, whether it’s pruritus, trouble sleeping, not seeing, i. e. at night, when the pruritus actually exacerbates. And then of course, fatigue that’s an integral component of their disease, that they just don’t get much sleep because of the itching and they’re very, very tired of saying, when you look at the numbers, if you come back if it’s a total responder, if it’s a component responder, if it’s a total responder, all of those patients, whether they’re getting UDCA or mixed therapy, many of them have this moderate to severe pruritus. I would also like to point out, of course, that cirrhotic patients also have those symptoms. Therefore, it is a plentiful problem. And very, very encouraged by what seladelpar can do to really help this particular population.
Sumal Shah
And Chris, the only thing I would add is that we are incredibly encouraged by the fact that seladelpar as a possible cure option has this effect on biochemical markers of the disease that, in fact, can also improve long-term outcomes for patients. as this has an effect on improving clinical symptoms. Of course, other diverse approaches are being studied to treat in particular itching or pruritus in patients with PBC. The real opportunity here with seladelpar is to have a unique agent in a very undeniable way. for treating doctors, of course, as well as for patients taking a single remedy, the choice of either can be quite convincing, in our opinion.
kristen kluska
It is ok. I am aware that. And at his recent meetings this year, he took his knowledge and trimmed it in other ways, appearing that the effects are consistent across other parameters. So I’m curious, from the point of view of the doctors and the audience that has been, if there is anything specific that has marked them. That you think will play a decisive role if approved in your business conversations.
charles mcwherter
Thank you, Kristen. I would highlight the ability to safely elicit a biochemical reaction at other stages of the disease. And it was, as I discussed on the exam tours, [indistinguishable], it’s something that was discussed over and over again, and it’s anecdotal, of course. But in reality, the ability to see it not only in patients without cirrhosis, but also in patients who have compensated cirrhosis or compensated cirrhosis is portal hypertension. And this last category has now, of course, been excluded from approved second-line therapy. It is no longer available. It’s anything that I think has the prospect of being a feature. Because if you think about it, patients progress and progress at other rates with other threat factors, in fact it would be comforting to know that you can use it on a patient without cirrhosis, if your disease progressed, it would not enter harmful territory. So we think it’s something that’s going to be very vital to document. We have a smart set of knowledge so far. And of course we will seek to verify this with the answer, which also helped patients with compensated cirrhosis.
Sumal Shah
And maybe, Kristen, and we’ll ask Dennis to upload one of his thoughts about being with us at EASL, more recently, with us on our billboards in terms of impact and responses from a lot of them from the medical community. .
daniel kim
Of course. Yes, I think, obviously, that the efficacy of the biochemical reaction, as well as the improvement of pruritus, are very important characteristics of the drug and are well perceived by prescribers and doctors. The other aspect of currency, of course, is protection and tolerability. And I think it’s probably not something that’s talked about a lot, but it’s probably something that we want to point out because it’s something that concerns patients and that is positioned not only in terms of tolerability. and have no known aspect effects or debilitating aspect effects. But also in front of patients who would possibly have decompensating occasions such as cirrhosis or other cirrhosis headaches.
And it turns out there’s a little halo effect there, we’ve studied cirrhotic patients in the past, and we continue to examine those patients. And it turns out that so far the drug is well tolerated in those teams of patients. Prescribers recognize that these are patients in poor health, possibly having occasions of compensatory decompensation at any time. So, they don’t need to use a drug that can also increase that risk, I think we have a drug in seladelpar that can mitigate some of the risks. We’ll see if knowledge confirms it. But I think that’s another thing that prescribers appreciate and that they’re concerned about and that I think hopefully we’ll be able to find with our knowledge base.
Operator
Our next comes from the Mayank Mamtani lineage of B. Riley Securities.
mayank mamtani
Congratulations on the over-registration of RESPONSE. So, maybe just a quick follow-up for Dennis. Could you comment on the failure rate of the RESPONSE assessment?I’m just curious to know how many of those unbearable or insufficient answering machines don’t meet the criteria of this clinical trial of alphas, composed of bilirubin. Could you comment on that? And then I have a follow-up for Chuck.
daniel kim
Of course. Therefore, our screen failure rate was very consistent with our experience beyond. As you can imagine, there is a huge list of inclusion and exclusion criteria for each of the studies. The design of the RESPONSE exam was almost the same as that of ENHANCE. predicted what our failure rate would be in screening tests. And it turned out to be pretty much in line with what we actually saw. This is not incompatible with other general clinical trials you might see. up to 75%, 80% depending on the inclusion criteria and demand for this type of comorbidities and biochemical responses or biochemical status. So, laboratory results, of course, are regularly the non-unusual maximum charge of exclusion – exclusion from the meeting. And that’s what we’ve also noticed in this RESPONSE detection effort. So it’s very consistent with what we’ve noticed in the afterlife and consistent with other trials that we’ve had, that we’ve done.
mayank mamtani
And Chuck, coming from the EASL datasets, how much of this antifibrotic component do you intend to examine further?, but also in terms of this detail of the final results and conversion from accelerated approval to full approval, is there any additional evaluation you can do to perceive how effective an antifibrotic drug is based on your NASH results?
charles mcwherter
Yes. Thank you for this question. I think it’s important. We try to take what the science has informed in the NASH study, take it and apply it. A little different, of course. We have a biopsy in this study, and they may tell us a little bit about the effects on fibrosis, but it’s relatively short-term. it’s a year. And of course, not every single patient will have a biopsy. However, there is an emerging approach, recently published in the Journal of Hepatology and gaining more and more attention, which examines liver stiffness using the fibroscan methodology, which is necessarily a brief elastography that was correlated with the histological level of liver stiffness. the illness. It is therefore an article presented through the leader Christoph Corporate Show. And we come with fibroscan measurements in RESPONSE and ASSURE. And we’re very interested in understanding how these can also be used in clinical studies as prospective endpoint markers, that may not be the case at the moment, however, in the future, it may also be that regulators are considering. However, also in medical practice, the fibroscan generation is becoming more and more available, it is part of general practices, giant gastrointestinal practices, clearly university or university medical centers, but even sober hospitals and the like.
And it is also widely used in NASH. Therefore, we can sail with the tailwinds for their wonderful availability. We believe that examining liver stiffness deserves to infer effects on fibrosis, whether it’s a lack of progression through searching serial measurements, or even, hopefully, a regression may simply be a wave of the future and this may be vital for a drug like seladelpar that has antifibrotic effects.
mayank mamtani
And my last question is about the open-label liver test you do. Can you provide us with an update on that? And just confirm, are you exploring the 10 mg dose level?Or do you reduce doses with it?
Sumal Shah
Let me ask Dennis to give you another color here. This is an obvious study, as you mentioned, a study on liver failure in patients with PBC that we can better understand, especially the protection but also the efficacy in more complex patients. patients. And they are those patients who have cirrhosis compensated through the child’s BP and a small subset of patients with decompensated cirrhosis through child B and C. So, I’ll let Dennis do a review of that, Mike, it’s an ongoing exam. So until the moment we finish the trial, we will share updates in terms of test data. But Dennis, you can give a little more information about the test itself.
daniel kim
Of course. Thank you for the question, and thank you also, Sujal, for the preamble. Your. . . Sujal is surely right. These are the patients we are looking for in the exam. It is an ongoing examination, of which we do not make too many comments. Suffice it to say that those patients are rare patients, because patients with CPB, then patients with CPA with portal hypertension, are also quite uncommon. We are making progress in enrolling patients for study and activating more study sites. We have plenty of time to complete the study. Therefore, we plan to include this database in the NDA.
We check a dose of 10 milligrams, but we stick to it: we have the flexibility to move to a minimum dose. If we see radiometabolism and pharmacokinetic exposure in patients with complex cirrhosis, this would require a minimal dose. So we have that flexibility, and we’ll let you know how it will be carried out once we’ve finished the study.
Operator
The next one comes from Patrick Dolezal’s line with LifeSci.
cory jubinville
Cory speaks to Patrick. Congratulations on signing up. So first of us. He recently had the right knowledge about the effect of seladelpar on the GLOBE score. Obviously, seladelpar has a strong perspective for a differentiated point when it comes to pruritus. But is there in all likelihood an opportunity for a label?To what extent do regulators and doctors give credit to GLOBE given that it is a predictive measure?
charles mcwherter
Yes. Thank you, Cory. Therefore, the GLOBE score is an ongoing measure of threat that has been validated for expected results. This is based on the paintings of the PBC Global Working Group. It includes the elements that pass to él. la age, then the laboratory parameters, which would be the levels of alkaline phosphatase, bilirubin, platelets and albumin. And those are all liver parameters that inform about the overall health of the liver. And therefore, the price in clinical research, is regularly used in medical practice. There’s a website, it can happen and a doctor can just enter the parameters based on the lab effects and get an idea of what’s going on with the patient, maybe look at those measurements in series. Therefore, it is regularly a type of PBC-specific Threat Assessment so that the attending physician can make medical judgments about everything you want to do, any adjustments to the treatment.
How we use it is a variable to take a look at the reaction to the remedy. And that has several advantages, I think, over categorical variables, the ones that, for example, regulators are employing right now, we’re responding or you’re not responding. and it doesn’t actually provide much granularity. It is actually a tool of combined interest, especially in clinical research. Therefore, having a continuous variable allows for finer gradations and judging the threat and also reading about the differences. in remedy between 2 groups. So that’s another difficult measure.
I think right now, as far as our program is concerned, we’re employing a past endpoint, the FDA and the EMA are settling for that, we’re not going to replace that, the GLOBE score is an exploratory parameter. We can use it to get to the bottom of the differences, for example, between post-hoc research between subsets.
cory jubinville
Are there regions or sites that are enriched or patients with deficits?
Sumal Shah
That’s a smart query, Cory. Je would possibly answer that query and if there’s something I missed, Dennis can upload anything. Like ENHANCE, first of all, most patients, of course, come from the United States given the distribution of sites and the number of sites we have in the United States. But I really think we had a very intelligent representation on a global scale. In Europe, in Asia and in particular, in this case, in South America. that we saw more than one contribution in the countries that took a step forward. In fact, in RESPONSE, this possibly, in fact, would have been more affected by COVID restrictions the 15 months we signed in RESPONSE. These restrictions would possibly have been lighter in some other areas.
And we continue to build in terms of dating. There are many sites that overlap with our previous ENHANCE study, but there are many new dating and spouse sites that we are building, even when it comes to RESPONSE. I think we had a very smart distribution in all those regions, especially in Europe, Asia and especially South America in addition, again, to the majority of patients from the United States.
Operator
The next one comes from Thomas Smith’s line with SVB Securities.
michel kratky
As you start thinking about transitioning to business operations, what kind of data do you expect to provide in September on your next virtual investor day, especially about some of the initial learnings uncovered and metrics you expect to follow as you go?forward with the launch?
charles mcwherter
Yes. Thanks for the question. Yes, we are ahead of September. I think one of the things we need to do is have a little more holistic view of all the plans we’ve made and percentage of some of the knowledge we have about either American and ex-American geographies. We’re also in the paying landscape here in the U. S. We have already done some paintings in Europe.
We’re going to share a little bit of that with you, I just need to communicate with you a little bit about the advertising landscape and government policy here and what we can expect around those issues. And I think the other thing I’m going to do is say is that we expect our education on go-to-market strategies to be maintained here in the current part of the year. We will also tell not only about our pre-ad advertising work, but also our focus on medical matters. I think the way we’re going to check to measure and compare things here will have a lot to do with our interaction with THE KOL and how we have interaction payers here in the pre-announcement framework to start articulating a price proposition. So, more to come in a lot of that, however, we’ll go into a little more detail here in the coming weeks.
Operator
There are no more questions in the queue. I would like to pass the call to control for final comments.
Sumal Shah
Thank you, operator. As we look ahead to the rest of the year, we will continue to focus on the execution of RESPONSE and any ongoing active studies to prepare for long-term regulatory filings. Therefore, the efficacy and protection knowledge of our ongoing studies reflects what we have observed in our previous Phase II and Phase III studies. Seladelpar, as mentioned, has the prospect of drastically improving the lives of PATIENTS WITHP. I think it’s worth repeating. We continue that our progression program remains one of the most powerful and least threatened in this indication today. We see many opportunities ahead to unlock the short- and long-term price of laundering in PBC and look to the future to share long-term updates as we go. We look forward to sharing more about our story and this opportunity during our virtual Investor Day on September 22 that Lewis talked about. I would like to thank everyone once again for joining our call today, and we look forward to speaking with you very soon.
Operator
Ladies and gentlemen, this concludes today’s teleconference. Thank you for your participation. You can disconnect your lines right now and have a glorious day.