Welcome to the Entrata Therapeutics conference call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today. Carla McDonald, Chief Corporate Affairs Officer. Please go ahead.

Good morning, everyone, and thank you for joining us today. I'm Carla McDonald, Chief Corporate Affairs Officer at Entrata Therapeutics. Today, we will be reviewing the positive top-line results from Cohort 1 of participants living with Duchenne muscular dystrophy, or DMD, treated with ENTR 60144 in our Phase 1-2 Elevate 44-201 study. Our news release, along with the accompanying slides, can be found in the Investor section of our website. Before we begin, I would like to note that we will be making some forward-looking statements during our presentation within the meaning of the U.S. Securities Act of 1934. These statements are based on Entrada's current beliefs and assumptions, are subject to risks and uncertainties, and are not guarantees of future performance. Further, we undertake no obligations to revise or update any forward-looking statements. We encourage you to review our SEC filings for more information. Speaking on today's call are Deepal Doshi, our Chief Executive Officer, Dr. Natarajan Sethuraman, our President of Research and Development, and Dr. Laurent Servais, Professor of Pediatric Neuromuscular Diseases at the University of Oxford. Dr. Survey is an expert in the treatment of DMV and other neuromuscular diseases and serves as an investigator in our Elevate 44-201 study. We are thrilled to have him on the call with us today. Also, Nate Dowden, our President and Chief Operating Officer, and Corey Wentworth, our Chief Financial Officer, are on the line to answer any questions. Turning to today's agenda, DEPA will begin with an introduction and overview of our development strategy for our DMD franchise. Dr. Survey will then discuss the urgent need for new therapies for people living with Duchenne. Following his remarks, Natarajan will review the Cohort 1 top-line results and outline the next steps for our Elevate 44-201 study. People will conclude by reviewing the upcoming clinical milestones across our pipeline before opening the call for questions. I will now turn the call over to our Chief Executive Officer, Deepal Doshi.

Thank you, Carla. Good morning, everyone, and thank you for joining us. Today marks an exciting and important moment for Entrada. We are incredibly pleased to share positive top-line results from Cohort 1 of our Phase 1-2 Elevate 44201 study evaluating ENTR 60144 in ambulatory individuals with a confirmed mutation in the DMD gene amenable to exon 44 skipping. This is the first data readout from this important clinical trial, and we are encouraged by the results we have seen to date. We are also honored to be joined by Dr. Survey, who will provide clinical context for the data we are sharing today. Taking a step back, Intrada is a clinical stage biopharma company developing proprietary genetic medicines to deliver best-in-class outcomes in high-unmet need diseases. As we look at the year ahead, Entrata is positioned to have a milestone-rich 2026. We have a deep and expanding pipeline with multiple value inflection points in 2026, including four clinical catalysts in DMD and DM1, with additional pipeline expansion efforts ongoing. Our programs are differentiated in untapped markets. Notably, in our DMD program, we are pursuing an accelerated approval strategy in a market with profound unmet patient need. Additionally, our ENTR 60144 program has progressed to the second cohort at the increased dose of 12 mg per kg at the recommendation of an independent data monitoring committee. Today's Cohort 1 data, our Elevate 44-201 open label period data, as well as the Cohort 2 data by year-end 2026, have the potential to de-risk and establish PRUPA concepts across our neuromuscular programs. With the cash runway into the third quarter of 2027, we are well capitalized to realize our value catalysts. On slide six, our efforts to establish a new class of genetic medicines have enabled us to build a growing and diverse pipeline of therapeutics focused on disease areas with a substantial patient population and a significant unmet medical need. Specifically, we're pleased to share positive top-line results from Cohort 1 of the Elevate 44-201 study. Natarajan will dive deeper into the data, but at a high level, results demonstrated a favorable safety and tolerability profile and meaningful, potentially differentiated functional benefits in participants treated with ENTR 60144. We're on track to report data from the open label period and from Cohort 2 at 12 mg per kg by the end of the year. In December, the FDA also granted rare pediatric disease designation to ENTR 60144. Moving along, we are also currently dosing patients in our Elevate 45 201 study and expect this to be both a best-in-class and first-in-class program to meet the needs of a large segment of the DMD community. We expect to deliver data from Cohort 1 in mid-2026. Our ENTR 60150 candidate received regulatory authorization from the UK's MHRA and Research Ethics Committee, and for both ENTR 60150 and ENTR 60151, we expect to submit additional regulatory applications and obtain authorization following a review of data from the ongoing studies of our LEAD programs. Our partners at Vertex continue to enroll and dose the MAD portion of the GALILEO Global Phase I-II Clinical Study of VX670 in people with DM1. The study assesses both safety and efficacy and is on track to complete enrollment and dosing in the trial and share results in the second half of 2026. Beyond the strong progress in our clinical programs, we've generated positive preclinical data from programs focused on ocular and metabolic diseases, which include pneumoides. This includes the advancement of two novel oligonucleotide-based programs for the potential treatment of inherited retinal diseases, where there is a high unmet need. The first ocular candidate, ENTR801, an exon-13 skipping therapy targeting a subgroup of patients with Usher syndrome or Usher 2A was announced in December 2025. We expect to name a second clinical candidate in inocular disease in the second half of 2026. On slide 7, I will now turn the call over to Dr. Servais, who is a professor of pediatric neuromuscular diseases at the University of Oxford, current president of the World Muscle Society, and serves as an investigator in our Elevate 44-201 trial. Dr. Cervais will discuss the urgent need for new therapies for people living with DMD and what the initial cohort one results mean for the DMD community.

So thank you very much, Deepal.

And before going into what is actually Duchenne muscular dystrophy, I would like to show you one of my patients with this condition. He's four and a half years old. And as you will see, he has a lot of difficulties to climb stairs. He would like to do it as fast as possible, but he needs the banister, he needs to push on his leg to be able to climb the stairs. And we know that, unfortunately, things are not going to be better with time, and this proximal weakness will be more and more obvious with time, and this young boy, unfortunately, will lose the ability to climb stairs and to rise from floor, and eventually will lose ambulation between the age of 10 and 20. So Duchenne muscular dystrophy is related to a mutation into the dystrophin gene, and the dystrophin gene codes for a protein that is called dystrophin, and dystrophin is a giant. It's a very big protein, and it's actually the shock absorber of the muscle cells, but not only. Yes, the main function is shock absorbing, but also it binds with several very important protein and that's why it is that important if we try to restore dystrophin to try to keep the main domains and eventually to get the longest dystrophin and as we can when we try to restore dystrophin and you know what happened in a car if you don't have a shock absorber it breaks right the very same apply applies to a muscle cell if a shock absorber is missing, the muscle cell can be destroyed, and then you have a process of necrosis and regeneration that characterise dystrophy in general. So fortunately, we have stem cells that can multiplicate and give new muscle cells, but Unfortunately, the genetic defect is also present in the stem cells, and you have a kind of very accelerated turnover of the muscle cells. And the problem of Duchenne muscular dystrophy is that it affects all muscle, including heart, right? And the burden for the family, for the kids, of course, but for the family and also for the society is huge. It starts with contractures and that needs physiotherapy and sometimes even orthopedic management. Those kids will need mobility support like a wheelchair because of the steroids. They will have endocrine issues and because of steroids and because of the immobility, they could have bone health issues. because of the weakness they can develop with scoliosis, insufficiency to ventilate, and then respiratory issues. Some of these kids may also present with cognitive issues and eventually heart problems. So it is a very complex condition that will represent for the family and for society a very significant burden. It's very interesting to figure out that some patients may have a slightly milder phenotype and lose embolation four to five years older than the others. And those are the patients who are capable for the 44. And why do these patients present this difference in loss of embolation? It's because they naturally express 5% of dystrophin. So we know that if we could express something like 5% of dystrophin, and if we could do it since birth, then we could be potentially instrumental on the age at loss of ambulation. And if we can express more than 5%, it will make a lot of sense for the patient and for the family. And that's why I think it's very exciting to see products that even at the low dose may induce a significant exonscapping and some dystrophin expression, which is in line with the exonscapping that is observed. Of course, we need a longer exposition to the drug because we also know that with time, the amount of dystrophin that is expressed by drugs that promotes exonscaping will increase. And I'm very excited with the fact that escalating the dose could allow to improve more exonscaping and more dystrophin in this voice. Thank you for your attention.

Thank you, Dr. Sobey. We very much appreciate your continued support as we advance our clinical programs in DMD. Today, I'm very excited to share the top-line results from Cohort 1 of our ongoing Elevate 44-201 trial. First, let me go through key takeaways from our data. We met the primary objective of the study with favorable safety and tolerability of EMDR 60144 at six milligrams per gig dose. All eight patients have transitioned to open-label portion of the study. Markers of kidney function were within normal range and comparable to placebo. We were surprised and highly encouraged to observe earlier than expected functional responses. A statistically significant improvement in treated participants time to rise velocity versus placebo. Time to rise velocity is an approvable clinical endpoint in phase three studies. We have seen positive changes in TTR velocity across the majority of participants irrespective of the severity of the disease or age. We have also observed lower than expected plasma exposure and consequently lower dystrophin levels in pediatric DMD patients when compared to the exposures we have seen in healthy adult volunteers and adult NHP. This, however, is consistent with the exposure data we recently received from our Junile NHP studies. As such, we have updated our PK modeling and believe the plasma exposures will be significantly increased in cohort two, resulting in higher muscle concentration, exonskipping, and dystrophin production. We believe we have a highly differentiated delivery mechanism, including ability to access quiescent satellite cells, which are critical drivers of muscle regeneration and repair. This unique mechanism of action may explain why there's different levels in Cohort 1 that's sufficient to improve time-to-rise velocity. Ultimately, the goal of any therapy is functional benefit, and that is why these early results with ENTR-60144 are uniquely important. Now, I would like to provide some background on our drug candidate, ENTR60144, which is an investigational genetic medicine and review the trial design. ENTR60144 is designed to address the underlying cause of Dushan, facilitating the production of functional disturbance from mRNAs with character reading frame. ENTR44 is a proprietary endosomal escape vehicle conjugated oligonucleotide. The oligo sequence is optimized for skipping exon 44 for patients with a mutation in the DMD gene that is amenable for exon 44 skipping. This comprises approximately 8% of the Duchenne patient population globally. Elevate 44201 is a global two-part randomized double-blind placebo-controlled phase 1-2 study evaluating the safety, tolerability, and effectiveness of ENTR 60144 in ambulatory participants ages 4 to 20 who are exam 44 skip amenable. Multiple ascending dose part A portion of this study evaluates the safety, pharmacokinetics, pharmacodynamics, and functional parameters following intravenous administration of ENTR 60144 to study participants in UK and EU. There are three cohorts in this study. Today we will be talking about Cohort 1 results, and the Cohort 1 portion of the study enrolled eight participants ages 6 to 17. They were randomized 3 to 1 to receive ENTR 60144 at a dose of 6 milligrams per kg or placebo administered through intravenous infusion. During this double-blind period, doses were administered on days 1, 43, and 85. Muscle biopsies were performed at the time of screening and 6 weeks post the last dose. Following the initial three-dose administration in Part A, all participants continued to the Phase II portion or open label portion of the trial for evaluating safety and efficacy over longer period of time. This study is designed to enable registrational conversation with the FDA, leveraging the accelerated approval pathway. Future phase three confirmatory studies are expected to enable full approval in the US and beyond. Let's look at the demographics on baseline characteristics of cohort one participants. The average age of treated participants in the study was 9.3 years. Per protocol, all participants were ambulatory. all were on stable doses of steroids. Baseline dystrophin in both placebo untreated population was lower than what has been reported for other exam-skipping clinical studies. This is important to note as dystrophin increases after treatment, generally correlate with higher baseline dystrophin levels. Now let us look at the safety data. We saw very favorable safety and tolerability, the primary endpoint of our study with ENTR 60144 at 6 milligrams per gain. All patient, all treatment emergent adverse events or TEAEs were mild to moderate with most common AE being headache. There were no reported serious adverse events or SAEs and no adverse events, leading to discontinuation from the study. Importantly, no renal safety concerns were observed in the study participants who received ENCR 60144. All eight cohort 1 participants have now transitioned to open-label portion of the study. We are pleased to see markers of kidney function, including EGFR, Cystatin-C, and magnesium, were in normal ranges and comparable to placebo, reinforcing the strong safety profile of ENTR-60144 in patients with Dushan at 6 milligrams per K dose. Let's change gears and review the PKN biomarker data. We observed a lower-than-expected plasma CMAX and AUC, or area under the curve, in pediatric DMD patients, about 50% less than levels seen in healthy adult volunteers and healthy NHPs. This, however, is consistent with the recently received PK data in juvenile NHPs. However, in juvenile NHPs, there was more than dose proportional increase in plasma AUC at high doses. We believe that the low plasma exposure at the starting dose of 6 milligrams per keg in cohort 1 resulted in lower exam skipping, about 2.3 percent above baseline, and dystrophin levels, about 2.3 percent above baseline in pediatric patient population. As I mentioned before, the baseline dystrophin was lower in one patient than what we had reported, what has been reported in other studies. At date 127, six weeks post the last dose, the dystrophin level in treated patients was approximately 6%. While we were surprised to see significant differences in exposures between juveniles and adults. The consistency seen between NHPs and humans fully explains the difference and gives us confidence that we will see meaningful plasma exposure in cohort two, which we expect will deliver higher exam skipping, higher levels of dystrophin, and sustained gains in muscle function. We originally projected PK and exam skipping based on adult human normal volunteer study because that was the only human data available at the time of Cohort 1 dose selection. Data from juvenile NHP study did not become available until the end of the first quarter of 2026. Thus, at the time of Cohort 1 design, the adult normal human volunteer study and adult NHP data were the best available anchors for human PK projection, and this is not unique to Entra. Now that we have both Cohort 1 patient PK data and juvenile NHP data, we have right-shifted projections. The juvenile NHP data reinforces the lower-prover initial AUC set point in younger subjects and suggests that we will see dose-dependent increase in AUC. More importantly, journal NHP data also shows a steep non-linear exon skipping response at higher IAUC levels, suggesting Cohort 2 will see a disproportionate increase in exon skipping to the dose increase. This gives us much more relevant basis for Cohort 2 and Cohort 3 projections than the adult data provided for Cohort 1. Our updated PK analysis projects higher levels of plasma concentration, exon skipping, and dystrophin in Cohort 2 and Cohort 3, supporting our path to accelerated approval and eventually full approval. The DMT community at large continues to learn about the biology of Duchenne and the relationship between dystrophin and functional benefit. Despite lower plasma exposure and dystrophin level, we obtained earlier than expected functional response that was statistically significant, which we will go through in the following slides. As I mentioned, the ultimate goal of any therapy is functional benefit, and that is why we are so encouraged to see earlier than expected and functional response that were both statistically significant and clinically meaningful. Let me give some background on time-to-rise functional assessment. TTR is a measure which carries the largest absolute and proportional annual signal and is used as an early prognostic factor for disease progression and loss of ambulation. It is generally the first functional metric to respond to therapy and has good statistical properties for evaluating motor function in individuals with DMT. Rising from the floor engages most of the proximal muscle groups that fail earliest and most dramatically. TTR velocity is expressed as traces per second and is designed to reduce the impact of outlines. With that background, in Cohort 1, we have shown statistically significant improvement in treated patients' time-to-rise velocity versus placebo. The mean change of TTR velocity was 0.08, 3.5 times higher than minimal clinically important difference, or MCID, threshold of 0.023, suggesting that ENTR TTR 60144 is potentially changing the trajectory of the disease. Positive change in TTR velocity was seen across majority of the participants irrespective of the severity of their disease or age, which likely suggests that cohort 1's functional benefit is drug-related effect. Further, the end of cohort 1 disruption level correlated with the end of cohort 1 TTR velocity suggesting that dystrophin production may have crossed a critical threshold for functional improvement. Additionally, we have also seen a positive trend in 10-meter walk-run assessment, another metric used to evaluate motor function in DMT. It is important to note that TTR velocity is recognized as an approval phase three endpoint in DMT clinical studies that has been and is currently being used by companies. We are already generating clinically meaningful functional benefits at the lowest dose tested in the study, and the TTR velocity we saw in cohort one data is unprecedented. TTR velocity treatment difference of 0.115 rises per second is nearly two times, or to be a great 1.7 times compared to what was seen with femelorone signal that FDA accepted as a registrational primary endpoint at 0.06 prices per second in their Vision DMD study. The fact that we achieved statistical significance with just eight participants at the lowest planned dose leads us to feel confident that we will see further functional benefits as we dose up in Cohort 2 and 3. Let's now drive into why we believe a highly differentiated delivery mechanism with ENTR 60144 could lead to these differences. DMD progression is driven by both aggressive muscle breakdown and impact muscle regeneration. A therapy can therefore be protective, regenerative, or both. An ideal therapy shifts the balance back towards regeneration to parent protection. One potential path to establishing a functional cure is by assessing quiescent satellite cells, which are the stem cells the body lays upon to repair and regenerate damaged muscles. These critical drivers of musculoskeletal muscle repair are emerging as potential significant competitive differentiator by addressing the disruption doublehead problem. We believe we have highly differentiated delivery mechanism, including ability to access quiescent satellite cells, suggesting the potential not only to protect existing muscles from further damage but to provide basis for regeneration of new, healthy muscles. One potential driver of functional benefit that we saw in cohort one could be due to our ability to access quiescent satellite cells, the target cell population that transfer into receptor-targeted antibody conjugates and other platforms do not reach. Driving muscle repair and regeneration that manifests as improvements in muscle function before it fully manifests as disturbance level in a western blood from a muscle biopsy. Now, I'll turn it back to people.

Thank you, Dr. Rajan. We'll now shift gears and take a look at our 2026 inflection points. We have significant clinical momentum and are well positioned to continue to advance our pipeline through multiple near-term clinical milestones. All eight study participants in Cohort 1 of Elevate 44-201 have now progressed to the open label period, where they are receiving six doses of ENTR 601-44 at the 6 mg per kg dose. We expect to see a continued benefit of functional response over time, and we look forward to sharing data from the open label period by the end of this year. Additional study participants are now being dosed in Cohort 2, in which they will receive placebo or three doses of 12 mg per kg of ENTR 601-44. We anticipate we'll see an increase in exon skipping and discipline expression in Cohort 2 with continued functional benefit. We plan to share data from Cohort 2 by the end of this year as well. Our Elevate 45-201 study is now fully enrolled with a data readout expected in the middle of 2026. Because the design of Cohort 1 is based on previous modeling, we expect plasma exposures to be similar to those seen in Elevate 44201 Cohort 1. This implies the potential for lower than expected exon skipping and dystrophin, but the potential for functional improvement at the 5 mix per k dose. I'd like to take a moment to emphasize how incredibly grateful we are to those living with Duchenne, their care partners and the study investigators and personnel who are taking part in our clinical study. Advancing potential therapies is not possible without the participation of the community, and we're inspired every day by their commitment to make progress for those living with Duchenne. To wrap up today, we have established significant clinical momentum with our top-line results from Elevate 44 Cohort 1. One, importantly, we believe that we have achieved a drug treatment response that has pushed the disturbance levels above a certain threshold required for functional benefit. We continue to remain on track towards multiple near-term value drivers, including our Elevate 44 data readouts for the Cohort 1 open label period and Cohort 2 by the end of the year, and the Elevate 45 Cohort 1 data readout plan for the middle of 2026. We are executing well against the goal to have four clinical stage programs in our DMD franchise in 2026, and our partners at Vertex are on track to complete enrollment and dosing in that study and share results in the second half of 2026. Beyond neuromuscular, we expanded our pipeline late last year to include ENTR801, our first IRD clinical candidate targeting Usher syndrome type 2A, and we plan to nominate our second IRD candidate this year. We are confident that our efforts to establish a new class of genetic medicines will unlock new disease targets, all within our proven, efficient development framework. With cash runway into the third quarter of 2027, we have the team, the pipeline, and the financing to deliver on our bold mission for both patients and investors alike. With that, we're happy to take your questions.

As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while I compile the Q&A roster. Our first question comes from Costas Biliaris from Oppenheimer. Please go ahead.

Thank you for taking our question and congrats on the update here. Maybe a two-fold question from us. Could you share what dystrophin levels does your updated model predict for 12 mg per kg and 18 mg per kg as investors are trying to compare your dystrophin levels against the competitor avidity? And the second question is, is there a way you can demonstrate that your clinical benefit or functional benefit is superior to competitors, even with lower dystrophin levels? And maybe how physicians will be thinking about that in the commercial setting if you have lower dystrophin levels than competitors, but your functional benefit is superior to others. Any thoughts around that would be helpful.

Great. Thanks, Kostas. Appreciate the question. First and foremost, I really do believe that today is an important day as it's a win-win for patients. Not only have we established safety at the six mg per kg dose, but as you just called out, we also have, you know, very strong functional benefit at a low dose. That's a big deal because that's what it's really about, safety plus functional benefit. To your direct question, you know, on the dystrophin levels for cohort two and cohort three, what we're essentially doing is we're right shifting everything by one cohort. So we expect to see double-digit dystrophin levels in cohort two and then, you know, a linear or nonlinear increase above that for cohort three. So we fundamentally and fully believe that based upon this updated modeling on the juvenile LNHP model, that we will be very competitive when it comes to dystrophin levels alone as we look towards Cohort 2 and certainly Cohort 3. To your second question, in terms of benefit and how we kind of match up, you know, I think we've already shared a lot of functional benefit today. The time-to-rise velocity metric is a very rigorous, non-biased, non-noise-generated functional measurement. And what we've shown today is not only statistically significant, but also clinically meaningful benefits within that one TTRV measurement. We do also have good trends within the 10-meter walk as well. But, you know, these data are early, right? This is at the day 127, hence our surprise that we already received functional benefits. And those are probably because of some mechanistic differentials between our approach versus other companies as well, too. But as it stands today, our functional benefit is better than others as well. And it's also very clean. We represented the data as the data showed. It was all based upon six patients, and then, of course, 2-1 placebo. Other companies that you had mentioned, you know, look at this from a pooled response. So it's kind of very difficult to do an apples-to-apples comparison between ENTR 601-44 and other companies. But what we can say for TTRV, as it stands today, we are in very, very good shape when it comes to functional benefit.

Thank you. Our next question comes from Jonathan Miller from Evercore ISI. Please go ahead.

Hi, guys. Thanks so much for taking my questions. I'd like to start with the AUC, which seems to be driving the delta and dystrophin from what we expected. And I'd love to get more color on why you think it didn't translate so neatly from healthy volunteers. It seems like there's a really substantial drop in the realized exposure here that I'm not sure we can say other programs in this space have seen, at least when we think about the doses they've gone forward with in patients versus healthy volunteers. So why would why would your program here have a have a bigger difference between healthy volunteers and patients and others have observed? And then maybe secondly, when we think about the functional benefits, can you give us a little bit more granularity on the baseline TTR for both the placebo or treatment arms and maybe the range of changes, the variability in TTRV for the treatment arm? How variable is that on a patient-to-patient basis?

Great. Thanks, John. I'm going to ask Natarajan to address the AUC question, and then we'll go to the second question after that.

Yeah, thanks, John. One, it is a new modality, so it's difficult to kind of predict what the adult and the pediatric population will do. Secondly, there's not much data on, you know, the plasma exposures for other platforms. So, I think it is very difficult to conclude that they had similar exposures between pediatric population and adult population. I think we do see similar trends in the NHPs. So, you know, from a mechanistic point of view, that kind of makes sense that, you know, we saw lower exposures in pediatric patients, and we saw lower exposures in pediatric juvenile NHP as well.

Okay. And the second question, John, was more around TTR. I think it was a two-part question. One was, and correct me if I'm wrong, one was the baseline TTR and what we observed, and then second was the variability around the TTRV as a measurement. I think I'll ask Nanarajan to jump in, but why don't you take it first?

I think the TTR velocities, initial velocities, are going to vary between patients, and we have only six patients. But what is great about our results is that regardless of where they start or regardless of the severity of the disease or the age of the disease, we saw trends towards improvement in TTR velocity after treatment. I think that's probably the most important thing to remember is that regardless of where they started, they ended up improving the TTR velocity.

And I think the variability question, I think the variability question between TTR and TTRV is answered by the calculation around TTRV. I think TTR has some bias associated with it, and the calculation to get to TTRV, which is essentially one over TTR, takes out a lot of that bias, takes out the outliers, takes out some of the noise that's associated with it. And I think that's why most companies, not only us, but other companies as well, too, are looking at this as an endpoint today.

Sure, Deepa, but the range of values in TTRV among the six patients in the experimental arm, like how variable is it in your cohort?

Yeah, it is variable because, you know, TTRs, you know, across the spectrum.

As would be expected, right? Because the severity of the disease is different amongst the six patients that were on treatment. So there is variability around what the TTRs look like. Everyone is going to be a little bit different from that measurement. But what we did see, John, I think the point that we did see was that the results were very consistent. They were clinically meaningful, and they were statistically significant.

Thank you. Our next question comes from Joseph Thome from TD Calwin. Please go ahead.

Hi there. Good morning. Thank you for taking my questions. Maybe just one, I guess still trying to understand a little bit in the recently completed juvenile NHP study that you've completed. I guess mechanistically why exposures would be lower in juvenile NHPs versus adults, if you can kind of help us with that. And are you anticipating presenting that data going forward? And then second, when we look to the second cohort as well, should we also be expecting more than a dose proportional increase in exposure in the satellite cells? I guess that's kind of a way of getting it. What do you expect for the functional outpoints, endpoints in the second cohort? Great. Thanks, Joe.

Thanks for those questions. Anarajan, do you want to talk about the juvenile? I think we still are understanding the mechanism why the exposures would be low in the juvenile patients. But the consistency that we see with the NHP data between the adults and juvenile, you know, explains some of the differences. It could be because of the differences in lean mass muscle differences between the two populations. When it comes to what we expect in terms of cohort two, we are expecting a linear increase in exposure in cohort two. So, and based on the modeling from the juvenile NHP data, I think that should give robust exon skipping and distribution. And as people mentioned, you know, we have right-shifted it, you know, what we expected from Cohort 1 is now probably what we would get from Cohort 2 in double-digit.

And to build on that, Joe, just from a functional benefit perspective, our expectation is the functional benefit will continue when we go to the second cohort. And that alone would be a big win, the sustainability of that functional benefit over a significant period of time. Great.

And maybe one more, if I can. for the placebo patients is just a little bit higher than the age of the active arm. I guess, do you think that played in at all to the results here? I guess we can't see the individual ages, so I guess, what should we read into that?

Yeah, it's a good question. I think though the average age in the placebo looks to be higher than the treatment, but we have all age groups represented in the treatment group as well.

And just a note on top of that, just recall that all the patients were ambulatory and all were on steroids as well. So, there was a consistency around those parameters, too. Great. Thank you very much. Thank you, Jeff.

Our next question comes from Paul Choi from Goldman Sachs. Please go ahead.

Oh, hi. Thank you. Good morning, and thanks for taking our questions. My first question is with regard to CK, and if you could elaborate a little bit more on that. Specifically, do you think this is the evidence that you've seen to date is more sign of protection or potential evidence of improvement in the patients given the distribution data? If you could help us triangulate that, that would be great. And my second question is, with the 45 readout coming up here in the near term as well, Now, can you clarify if, you know, your learnings from your PKA and AUC modeling here for the 44 program have implications for it for 45 and just any changes in assumptions we should make for that program?

Thank you.

Thanks, Paul. Well, Nataraj, why don't you answer the first question? I'll take the second one, please. Paul, that's a good question. You know, with this change in discipline, modest change in discipline, we didn't see statistically significant changes in CK and that is understandable because we are not probably addressing the muscle fibers issue but we are addressing the regeneration issue by satellite cells and that's why there is that you know this kind of between the functional improvement PC and the distribution levels that we see. In terms of your second question on 45, we do expect the exposures to be lower in 45 as well. But again, the bar for 45 is not very high. You know, the competitor is 1% or so, this different. And so I think, you know, from that point of view, 45 is a different beast.

I think that's an important point, especially around the second question, Paul. The numbers are very different. The district and baseline numbers are very different since, as Natarajan said, that they're lower. We've also been guiding to single digits when it comes to a district and production perspective, and we also, you know, believe that that will still stay intact. We will see how it goes with cohort one, but I think that that's still intact in terms of our expectations. But like what we said with cohort one for 44, you know, we have this dose escalation, and that becomes very, very important. It's always been an important part of the Entrada strategy, the ability to go in at a low dose but then escalate beyond that. So we have many shots on goal here, and this is a long game, of course. To your first question, just to go back a little bit, you know, I think it's a very good question in terms of what is the role of dystrophin. And, you know, I'd definitely like to ask Dr. Surveys to get his viewpoint on this because we feel as though there's a dual role in dystrophin. And, you know, I'll pause there, and maybe, Dr. Cervais, if you can hear us, maybe you can answer part of Paul Choi's question.

Thank you. Our next question, Bill.

No, I had one second, operator.

Dr. Cervais, can you hear us? Yeah, I think they – sorry, guys. I think we're having a tough time. Dr. Cervais is traveling through Europe right now, and he was very generous with his time. But let me ask Dr. Cervais one more time. And Dr. Savace, if you can hear us, you know, perhaps you can address the question around the dual role of dystrophin and the importance of regeneration, if you can hear us. Well, we'll pass on that. But, Paul, to that answer...

Can you unmute? Oh, go ahead, Dr. Savace. Yes, you can. Yes, sorry. I was on mute. So, actually, dystrophin is the shock absorber of the muscle cell, the social, but also it fixes several protein. And I wanted to emphasize that muscle biopsy is just a snapshot at a very specific moment in time and at a very specific place. If you look at all programs of Duchenne muscular dystrophy, obviously in very early biopsy that has been performed, the level of dystrophy is actually much lower. If you look at the first data from DINE or from WAVE, the very early dystrophin level of PEPGIN was also much lower than anticipated. So there is really a time-sensitive issue here in the questions of the amount of dystrophin that was expressed.

Great. Thank you, Dr. Sadez.

Thank you. Our next question comes from Miles Mentor from William Blair. Please go ahead.

Thanks, sir, for the comprehensive presentation here. I was just wondering whether you could comment on the actual tissue concentration of the 44 skipper that you're treating with here. You know, we did have some questions going into the data whether you were going to achieve adequate amounts here with this dose. And then maybe just from your preclinical data, just the idea of the split percentage of where the 44 skipper's going to the actual muscle tissue versus the satellite cells. That would be helpful. Thanks very much.

Great. Yeah, thank you, Mark. So when we looked at the muscle, so the muscle biopsy was taken six weeks post the dose and the Cmax for muscle exposure is less than 24 hours. So we did expect low, you know, muscle concentration. We saw single-digit nanomolar at the time of biopsy on an average. There were outliers on both sides, but on an average I would say single-digit nanomolar that is a nanomever, but the good news is that we do have good exposure, you know, as we would have expected based on plasma exposures, corresponding exposures in the muscles. In terms of your second question, what proportion goes to the myofiber versus satellite cells? I don't think we have done that experiment yet in pre-tellingal studies.

Thank you.

Our next question comes from Yanny Siroutsidis. from canter please go ahead hi folks uh appreciate the time today um just just a couple questions i mean one i think it's pretty remarkable that the safety was so clean and so with that in mind um as you kind of shift things to the right in terms of the the dosing uh cohorts is there any opportunity to um kind of assess and open uh the 18 mg per kid cohort uh in advance to start running some of these in parallel and then secondarily um a lot of the um this friend skipping and kind of tissue uptake seem to be dependent on kind of clearing or saturating clearance. Just kind of curious if there's any signals of that early on, if that's, you know, some of the excretion data that you had previously reported, if you could use some of those metrics here to kind of gauge how close you are to that threshold to really start seeing the exome skipping component begin to accelerate?

Great. Natarajan? Yeah, so we have not looked at urinary excretion in the cohort one. We would add those things as we go to the other cohort. So we don't have excretion data. But the general principle is true. I think, you know, as a first-part organ, kidney does receive the first bowl of the oligos. And then when it gets saturated, then you get a lot more to the muscle. So based on the exposures that we have gotten in the plasma, I would say I think that is why we have a good confidence that, you know, the exposure in the muscle should at least linearly increase to get to probably about 50 to 100 range in the 12 milligrams per take. That should give very robust .

Got it. And from... Yanni, you're back on stage.

Yeah, just a follow-up to that, with regards to kind of opening up the cohorts in parallel, is there any flexibility to do that to assess kind of safety as a 12-inch progression to then, you know, kind of accelerate things?

Yeah, it's a good question, Yanni. I think it'll be pretty difficult based upon the protocol that we have to be able to run both in parallel. I think one builds off of the other, right? So even our six mix per cake, you know, going to 12 mix per cake was predicated on what the six mix per cake looked like from mostly from a safety perspective. I think that's for these first in human trials in Europe. That's what they're looking for. And they're going to look for the same thing when we go to 12 mix per cake and then if and when we go to 18 mix per cake as well. So I think it's pretty difficult to find those efficiencies. But the good thing here is that the 12 mix per cake data is expected before year end. And then on top of that, we also expect to have the six-mix-per-cake cohort one open label data before year-end as well, too. And so, in the next six, seven months, we should have clarity on both of those, too.

Got it. Anderson, thank you so much.

Thank you, Ian. Thank you. Our next question comes from Anzi Gattisales from Guggenheim. Please go ahead.

Thank you for taking our questions. we just have two quick questions around what prompted you to do the juvenile non-human primate study in the first place and the second going to satellite cells what your hypothesis is about whether the drug targets the satellite cells preferentially or it is just that this slow So this little dystrophy increase is sufficient to kind of achieve a threshold where you start getting productive asymmetric cell divisions.

Perfect. Thank you for that question. Narasim? Yeah, the journal study is part of the preclinical package that we do in terms of long-term studies in journal monkeys to enable, you know, of treatment of genital population. To the second question, I do believe that there is a threshold level, and, you know, what is the threshold level for, you know, producing a discipline level that shows up in a western lot may be very different from the threshold level that is required to activate satellite cells. So, some of the preclinical experiments that we have done where we treat animals for three doses and give 12 weeks of washout, we still see majority of the satellite cells to stain for PMO. So it may be, you know, because of the proximity to the blood vessels, etc., it may be a physiological thing that satellite cells do get more. We still have to figure that out. We are doing experiments to do that, but the results do indicate that we probably have more regeneration than the path of this book.

And I think it's a good question, and I think also just to provide context, right? So, you know, we're still learning. We, meaning Intrada, but also, I would say, other pharmaceutical sponsors, patient groups, KOL, the center, we're still learning about what the role is of dystrophin and how it correlates to functional benefit. And so to your point about the threshold, that becomes a very, very important belief. And we feel as though we have the preclinical data that shows the ability to get into these stem cells. And I think that's a very unique characteristic. And the ability to regenerate quickly may be the driver that's allowing us to get to that threshold that then allows us to show functional benefit, albeit at a lower dystrophin level. But at the end of the day, what's really important here is the establishment of safety and, of course, the functional benefit for these patients. Distropin is important, but the role of distropin is something that I think is still being informed. And Intrada's unique ability to get to the satellite cells is a great effect. But more analysis will be done by the company to answer some critical questions that's the point of a clinical study.

Great. Thank you.

Thank you. Thank you. Our next question comes from Regaram Saveraju from H.C. Wainwright. Please go ahead.

Hi, this is Yon-Z, sitting in for ROM. Thank you for taking my question for the data. So, my first question relates to ENTR801. What remaining IND-enabling work and regulatory interactions need to be completed before clinical entry? And should first human dosing be viewed as a possible 26 then, or something that's more likely as a 27 once? Great.

It's a great question. Thank you. So ENTR801 is our first development candidate that's going into inherited retinal diseases that we're very, very excited about. You know, these programs are still, as you said, they're pre-IND. So, I think they just need to continue to go through the normal course of tox studies and whatnot as we prepare, you know, to submit a formal IND. In terms of timing as to when we will begin that study, we haven't guided to that. We have to get through some of these preclinical analyses, but, you know, it's likely a 2027, you know, start for that program. I would also like to point out that we also will be nominating a second development candidate in the second half of this year, too. So, by the end of this year, we'll have two development candidates with IND soon thereafter within inherited retinal diseases.

Got it. Thank you. And beyond the ENTR 60145 Cohort 1 readout, that's expected in mid-26, what are the gating items for 60150? It's 5.0 and 6.01 and 5.1. And when do you think we can, when could initial clinical data from those programs realistically follow?

Yeah, another good question, right? And so we purposely staggered our D&D programs to, one, to learn from each other. So we learn from 44, we apply that to 45, so forth and so on. For 50 and 51, you know, 50 has approval to move forward in the UK. But what we're going to do is we're going to – what we want to be able to do is we want to be able to learn more about these data that we just generated today from Cohort 1 for 44, see what the applications are to the 50 and 51 programs and the 45 program for that matter as well, and then decide how best to proceed from a regulatory perspective. that we have a lot of different opportunities here. The satellite cell information and perhaps changing the course of the disease via the entry into the satellite cells puts us into a very unique situation to have, you know, discussions with regulatory agencies about the role of dystrophin and the role of satellite cells. So, we'll come back, you know, to the community, you know, later on this year with more specificity around how these data positively, and I want to make sure that that word is understood, how these data positively affect the 50 and 51 programs.

Fantastic. And if I may just a quick follow-up. Given that cohort one functional signal and the updated PK modeling, what would determine whether 12 MIGs per queue is sufficient to carry forward versus needing cohort three before selecting a registrational dose? And how do you think we should not think about the relevant regulators?

Yeah, I think it's a good question. I'll start, and Natarajan should certainly jump in. I think first and foremost, you know, safety needs to be established again, right? So we have that at six mix per keg. There was no renal signals. I mean, safety in this oligonucleotide class of therapeutics alone as a standalone is a big accomplishment, in our opinion, looking at a lot of the other approaches that have come and gone over the years. We want to reestablish that, of course, as we dose escalate by 100% and go to 12 mix per keg. So I think that's the first. The second really becomes the maintenance or continuation of functional benefit. We want to be able to see the functional benefit continue at the 12 mix per keg. I think that becomes really important as well. I will say the third factor, and it's always been the third factor, but an important one. But once again, it depends upon the relationship between dystrophin and functional benefit. The third becomes, how much does discipline increase in the second cohort, and what is our belief system as to how that affects functional benefit, right? So, I think those are the three things that we'd be looking for in the second cohort. And I think those answers will then determine how we evaluate the third cohort. If we – I'll be a little bit more clear here. If we maintain a strong safety signal, plus we maintain and continue the functional benefit, we may be done. And that may be enough because functional benefit at the end of the day plus safety is what drives the regulatory process when it comes to these types of drugs.

Fantastic. Thank you for taking my questions.

Thank you. Well, thank you, everyone.

Thank you. That concludes the Q&A session. I will now turn it over to management for closing remarks.

Thank you, everyone. We appreciate you joining us this morning. As you can see, we're very excited about the positive top-line results from Cohort 1, and importantly, the clinical path ahead for our DMD franchise, which really has the potential to transform the lives of people living with DMD. We look forward to keeping you updated on our progress and wish you all a great day.

This concludes today's conference call. Thank you for participating. You may now disconnect.