Good afternoon, and welcome to Design's conference call. At this time, all participants are on a listen-only mode. There will be a question and answer session after the prepared remarks. Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Dr. Sean Jeffries, Chief Operating Officer of Design Therapeutics. Sir, you may begin.
Thank you. Welcome, and, and thank you to everyone for joining us today. We are pleased to share with you these initial results from our phase I multiple ascending dose study of DT-216 for the treatment of Friedreich's ataxia. Earlier today, we issued a press release outlining initial data from this study. The slides that we'll be using during today's call will be available, along with a recording of this call, in the investor section of our website at designtx.com. With me on the call today, are President and CEO, João Siffert, and Chief Medical Officer, Dr. Jae Kim. During this call, we will be using forward-looking statements related to our current expectations and plans, including our program development plans, which are subject to risks and uncertainties.
Actual results may differ materially due to various important factors, including those described in the risk factor section of our most recently filed 10-Q. These statements represent our views as of this call and should not be relied upon as representing our views as of any date in the future. We undertake no obligation to publicly update any forward-looking statements. On slide 3, serious inherited degenerative diseases affect millions of people across the globe. Research has identified nucleotide repeats in the genome as the underlying cause of a number of these diseases. However, there are currently no therapeutic options that address their root cause. At Design, we're approaching the problem of genetic disease differently.
Our founding scientific breakthrough showed the potential of a small molecule genomic medicine that works with a patient's natural genome, allowing the patient's own cells to make the gene product that it needs. We call these GeneTAC small molecules. These are designed to harness an individual's natural genome to either dial up or dial down the expression of an individual mutant gene to address the root cause of inherited nucleotide repeat diseases, while retaining the favorable pharmaceutical properties of a small molecule. We're evaluating our lead GeneTAC small molecule, DT-216, for the treatment of one such degenerative disease, Friedreich's ataxia, or FA. By way of background on slide 4, FA is a monogenic disease caused by a homozygous GAA repeat expansion in the first intron of the frataxin gene.
These repeats act like a roadblock and prevent the normal transcription of frataxin, a gene important for mitochondrial function. Lower frataxin levels cause earlier onset and faster progression of FA symptoms. The main clinical manifestations of FA are shown on the right side of this slide and involve multiple organs, including central and peripheral nervous systems, heart, pancreas, and importantly, skeletal muscle. Before we get into the data, I'd like to review the therapeutic hypothesis of DT-216 as a treatment for people living with FA. As outlined on slide five, DT-216 is a novel GeneTAC small molecule designed using our platform technology. The illustration on the left-hand side depicts the impairment of frataxin transcription due to the GAA repeat expansion mutation that causes FA. These long stretches of GAA repeats reduce frataxin transcription, leading to all the disease manifestations of FA.
On the right-hand side, we designed DT-216 as a heterobifunctional small GeneTAC molecule, where one end of the molecule binds into the minor groove of intact double-stranded DNA in a sequence-specific fashion, targeting the GAA repeats. The other end of the molecule binds and recruits the transcriptional elongation complex by interacting with BRD4, enabling transcription through the intronic GAA repeat expansion and restoring the expression of a patient's own natural frataxin. The intronic GAA repeats are subsequently removed through the normal splicing process, and the endogenous frataxin mRNA is translated into normal functional protein. Therefore, transcription of mature endogenous frataxin mRNA serves as a key biomarker of pharmacology in our clinical studies. With that, I'd like to turn the call over to Jae Kim, our Chief Medical Officer. Jae is a cardiologist and has decades of successful development of therapeutics, including multiple genomic medicines.
He joined Design in early 2022 and leads our clinical programs. Jae?
Thank you, Sean. Before we dive into the DT-216 multiple ascending dose study, let's first discuss an observational study that Design conducted, shown on slide 6. We developed procedures and methods to measure endogenous frataxin mRNA and protein and skeletal muscle to enable evaluation of clinical activity directly in tissues relevant for disease symptoms. We biopsied three populations, normal healthy volunteer controls, heterozygous FA carriers, and FA patients. It is important to emphasize that carriers who have only one mutant allele with a GAA repeat expansion are phenotypically normal and clinically healthy. The plot on the left illustrates interquartile ranges and 10th and 90th percentiles. The biopsy data show that endogenous frataxin mRNA across the three populations are significantly different from each other.
The interquartile range of FA patients, shown in blue, do not overlap with that of clinically normal carriers, shown in purple, demonstrating that frataxin mRNA levels from these two populations are largely distinct. We believe that the data supports use of our muscle frataxin mRNA assay as a sensitive indicator of clinical activity in FA, with the ability to discriminate clinically meaningful changes in endogenous frataxin mRNA expression. We would like to also propose that any significant increase in endogenous frataxin may be clinically meaningful, especially increases in frataxin mRNA beyond the upper quartile of FA patients or into the carrier range. I would like to now discuss frataxin protein on slide 7. On the left plot, we show frataxin protein measurements in carrier and FA patients using our measurements from muscle biopsy, from muscle biopsy samples.
In contrast with mRNA, frataxin protein measurements were much more variable and had substantial overlap between the FA patient and carrier population. On the right plot, we show the intra-individual variability from the 11 FA patients who underwent 2 biopsies approximately 3 days apart, with percent change in frataxin protein shown between the two visits. The red lines show more than half of FA patients at 25% or more visit-to-visit variation, with intra-individual coefficient of variation of 69%, which is beyond the range typically acceptable for reasonable assay. This variability substantially limited the utility of these frataxin protein measurements in skeletal muscle. In summary, this observational data provide context for frataxin measurements using the procedures and methods developed in our DT-216 multiple ascending dose study.
On slide 8, I will now review the design and rationale of our DT-216 phase I program in FA patients. The completed single ascending dose study evaluated IV doses ranging from 25 to 600 milligrams of DT-216. As we previously shared, there were injection site thrombophlebitis events in the SAD study, and these were only observed at the highest dose levels, at 400 and 600 milligrams. As a result, our phase I MAD study, shown on the right, explored initial multiple doses of 100, 200, and 300 milligrams, shown in blue, green, and orange respectively. These doses were selected based upon anticipated tissue exposures projected to be in the therapeutic range, and injection site tolerability, guided by our single ascending dose experience.
Participants were randomized, double-blinded, to either DT-216 or matching placebo, administered as 3 weekly IV injections. The MAD study was designed to assess safety and tolerability and pharmacokinetics of multiple doses of intravenously administered DT-216. Exploratory clinical activity was measured by levels of endogenous frataxin mRNA in muscle biopsies taken at pre-dose baseline, and then 2 days and 7 days after the third weekly dose. Muscle biopsies were performed in the 200 and 300 milligram cohorts only. All initial data we will walk through today is based upon a data cut-off of August 7. The study is fully enrolled, currently ongoing, with blinded PK and PD data available in full 100 and 200 milligram dose cohorts, and 11 of 14 participants in the 300 milligram dose cohort. Safety data remain blinded.
Baseline characteristics of the enrolled population are detailed on slide 9. A total of 29 adults with clinically diagnosed FA, with genetically confirmed homozygous GAA repeat expansion mutation, were enrolled in this study. You can see, the study enrolled a representative sample of symptomatic FA patients distributed across the dose cohorts. MAD study safety data blinded to treatment assignment are summarized on slide 10. Multiple doses of DT-216 were generally well-tolerated, but injection site reactions were observed. There were no serious AEs and no discontinuations due to treatment-related adverse events. All AEs were mild or moderate, none were severe. There were 5 events of injection-site thrombophlebitis. 4 of these events were mild, and 1 was considered moderate. These events in the MAD study were observed across the 3 dose cohorts, and we will provide further perspective on these injection site reactions in the summary.
There were otherwise no new clinically significant safety observations. As we review the biopsy data in the next few slides, note that 2 participants did not return for post-dose biopsies due to acute COVID. Slide 11 summarizes the plasma pharmacokinetics of 3 weekly doses of DT-216. As shown in the left panel, plasma DT-216 levels were approximately dose proportional. The first and third dose PK profiles were also similar, showing a lack of significant drug accumulation at the 3 doses. On the right, average DT-216 concentrations measured in skeletal muscle were approximately 8-10 nanomolar, 2 days after the third weekly dose on both the 200 and 300 mg cohorts. Muscle PK declined to approximately 1 nanomolar by 7 days after the third weekly dose.
These DT-216 concentrations in muscle were lower than projected based on non-clinical studies in animals, but were sufficient to drive substantial pharmacology, as we will show in the next slide. Slide 12 summarizes the clinical activity of DT-216 in skeletal muscle by measurement of endogenous frataxin mRNA. The left panel shows mean percent change from baseline in frataxin mRNA in 200 and 300 milligram cohorts. Frataxin mRNA expression in muscles was significantly increased from baseline at 2 days after the 3rd weekly dose of 300 milligrams, shown in the left orange bar, compared to placebo, shown in the left gray bar, with a p-value less than 0.05. Frataxin mRNA increased 30% with DT-216 treatment, which corresponded to levels in the 75th percentile, or the top upper quartile of reference FA patients from our observational study.
We also observed durable increases in frataxin expression, with a positive trend in increased frataxin mRNA seven days post-dose, as shown in the right-hand orange bar. The right panel shows a waterfall plot of individual FA patient frataxin mRNA and muscle. Increases in individual frataxin mRNA show a depth of response across individuals that favors DT-216 treatment. Using ranges from the observational study, reference frataxin mRNA by percentiles is overlaid in the lower blue shaded area for FA patients and the upper purple shaded area for clinically healthy carriers. Treatment with DT-216 restored frataxin mRNA in muscle to what we believe is a clinically normal range for one patient in the 300 milligram dose group, with approximately half of DT-216-treated patients' response above or approximately at the upper quartile of reference FA patients.
For context, higher frataxin expression among FA patients previously has been shown to be associated with milder disease. Additionally, exploratory statistical analyses demonstrated a significant DT-216 dose response trend and tissue exposure-response relationship for muscle frataxin mRNA, both at p-values less than 0.05, adding to the multiple lines of evidence that frataxin mRNA increase in muscle with DT-216 treatment is a robust finding. On slide 13, we summarize additional exploratory evaluations. On the left, we assess muscle frataxin protein in the MAD study, and these measurements were highly variable, consistent with findings from the observational study. We did not detect an observable frataxin protein signal above the measurement noise. These results were therefore inconclusive due to assay variability. On the right, we evaluated frataxin mRNA in PBMCs.
In the MAD study, we observed a transient increase of frataxin mRNA in PBMCs 24 hours after the dose, which was consistent with and confirms the results from the single-dose study. As of this data snapshot, the PBMC protein results are not yet available. Turning to slide 14, in summary, we are enthusiastic that this phase I multiple ascending dose study has demonstrated proof of concept, showing clinical activity of DT-216 in skeletal muscle of FA patients of relevant disease-affected tissue. We observed significant endogenous frataxin mRNA increase 2 days after the 3rd dose at p < 0.05, with trends and durable increases to 7 days. Increases in frataxin mRNA corresponded with levels in the observational study that might portend less severe disease.
A significant dose response trend and exposure-response correlation in skeletal muscle, both at less than p less than 0.05, adds to the internal consistency of the evidence in support of DT-216's ability to reverse the transcriptional block of endogenous frataxin mRNA expression that is a root cause of FA. DT-216 levels in muscle biopsies were lower than projected from animal studies, but substantial and dose proportional pharmacology was observed in human disease exposures. Multiple doses of DT-216 were generally well tolerated, with a favorable systemic profile. Local injection site thrombophlebitis occurred across the three dose cohorts, João will provide additional perspective on how we plan to advance DT-216 for the treatment of FA patients. With that, I'd like to turn the call over to João Siffert, our CEO.
Thanks, Jae. Let's turn to slide 15. We're very encouraged by the initial results from our phase I multiple ascending dose study, which confirmed clinical activity of DT-216 and support its continued development as a potential disease-modifying treatment for Friedreich's ataxia. However, we elected to complete the dose escalation in this phase 1 study of the 300 milligram cohort due to concern for potential worsening of injection site thrombophlebitis at higher doses with multiple administrations. We have since turned our focus to developing DT-216 with an improved formulation, which we expect will enable exploring the full pharmacodynamic potential in long-term treatment of FA.
We have conducted non-clinical studies that show that the injection site reactions were attributable to the excipients in the current formulation, and we have since shown that an improved DT-216 formulation had favorable injection site tolerability following multiple intravenous administrations in animals and enabled dosing to increase tissue exposure. We're now conducting bridging non-clinical studies so we can resume clinical development and expect to begin a multiple dose phase I clinical trial to assess safety, pharmacokinetics and pharmacodynamics of the improved DT-216 formulation in the second half of 2024, with initial clinical data in the first half of 2025. I understand that this hiatus before we can resume clinical development of DT-216 is disappointing to the FA community, especially after showing clinical activity in phase I.
We're confident in our path forward and remain highly committed to bringing disease-modifying treatments to those suffering with FA. We look forward to keeping you updated on our progress along the way. Before I review our pipeline progress and upcoming milestones, I wish to thank all the FA patients, their caregivers, and other volunteers who participated in our studies, the Friedreich's Ataxia Research Alliance, or FARA, and of course, our great team here at Design Therapeutics. Turning on to slide 16. As we look ahead, we're very excited about the future of Design, because we believe the confirmation of clinical activity of our FA GeneTAC molecule supports the therapeutic potential of a broader GeneTAC pipeline and platform, with multiple novel small molecules being advanced for the treatment of other nucleotide repeat expansion disorders.
One such example is our program in Fuchs endothelial corneal dystrophy, or FECD, a disease which affects millions of people and is the leading cause of corneal transplants in the United States. We're on track to submit an IND later this year for our DT-168 eye drop for Fuchs, We look forward to sharing more on this program soon. As our other pipeline programs continue to advance, we anticipate having three programs in the clinic over the next three years. With that, thanks for joining us today, we'd be happy to take your questions. Thank you. Operator?
Thank you. To ask a question, please press star one one on your phone and wait for your name to be announced. To withdraw your question, please press star one one again. Stand by as we compile the Q&A roster. One moment, please, for our first question. Our first question will come from Yasmeen Rahimi of Piper Sandler. Your line is open.
Hi, team. Thank you so much for the update. A few questions to you. Maybe the first question to ask is, do you, do you plan on... I mean, we understand that you're gonna work through coming up with a new formulation and work is in progress, and you're gonna expedite the development in terms of being in the clinic. But how do you overcome sort of the variability with protein levels and what the next steps are? I think we learned now, which we didn't know, that there's quite a bit of variability in frataxin levels in the protein. How do you overcome that, even with a new formulation? Do you think that we will get a definitive answer of GeneTAC's ability to restore protein levels?
Two, would the new formulation allow you to go to dose higher beyond 300, and then how would your design with the new formulation differ from the current study that you conducted? Sorry for the multipronged question, but I appreciate color on those topics, please.
Okay, thanks. Yes, this is João. I'll start with the one of your questions. We have, in fact, identified a formulation that is better tolerated, and we've tested this in animal in multiple studies, so we're really moving forward with developing so we can resume clinical development of DT-216. As for the biomarker, obviously, there has been, you know, currently and so far, the method and procedures we use to measure frataxin protein and muscle have issued variability, and of course, we'll continue to work on this and potentially other approaches as we continue to develop DT-216. I think it's important to underscore that the mRNA is in fact the, the, the actual direct evidence of pharmacology of DT-216, which is restoring the transcription of frataxin at the DNA level, making RNA.
In this case, this was very clearly demonstrating that this, this current exposure of DT-216 was sufficient to elicit a significant response in frataxin mRNA in muscle, skeletal muscle, which is an affected tissue in the disease, FA, and this was dose response, dose-related. As we look ahead with a formulation that is not limited by injection site tolerability, we can both plan to dose patients both at higher doses if needed and also for longer-term treatment, which is the ultimate goal for, for treating FA.
As we progress in the development of DT-216, we'll continue to provide updates, and then, as we get come closer to the beginning new clinical studies in the second half of 2024, we'll provide more specifics on both of the study design as well as potential assessment of biomarkers.
Thank you so much, João. I'll jump back into the queue.
Thank you.
Thank you. One moment, please, for our next question. Our next question will come from the line of Laura Chico of Wedbush. Your line is open.
Hey, good afternoon. Thanks for taking the question. I guess I, I have two. Just kind of following up on the last question with respect to excipient. Could you just clarify a little bit more about, kind of your understanding of what's actually causing these thrombophlebitic events? I guess why was this, initial excipient chosen, and what gives you confidence in the alternatives that you're pursuing there? Then I have one quick follow-up.
Yeah, obviously, the excipients used in the current formulation are suitable for clinical use. As we proceeded with dose escalation, larger volumes, these started to show signals of intravascular tolerability at the superficial vein right at the site where they're injected. It's hard to know exactly what's taking place, but we, generally speaking, think that this is a combination of the physical, chemical characteristics of the whole formulation, the mixture of excipients. When tested in animals, in the vehicle group, you see the same effect. Without the drug in the formulation, you see the same effects and tolerability in the veins of animals.
With the new formulation, we modified the excipient composition, and then when tested now in animals again, we see that these are well tolerated, both with and without the drug in the formulation. That's basically what gives us the sort of has helped us decide to move the program now focusing on the improved formulation, that will essentially open up the possibility to explore the full pharmacodynamic potential, both through, you know, dose ranging and duration of treatment. You have a second question, I guess, on the biomarker, right? I'll turn it over to Sean.
Yeah, actually, before we get into that, Laura, you know, I think it's important to recognize that, you know, non-clinical species are particularly sensitive to these types of reactions because, you know, they're smaller and they have smaller veins. You know, we saw the, the reactions were much more mild in, in humans, but unfortunately, as we started to push the excipient volume, you know, we started to see some injection site reactions. You said you had a follow-up?
Yeah, I guess I just wanted to clarify. If I'm understanding the timeline of events, the study would be restarted in 2024. Data, I guess, can you just remind us what is the current cash runway expectation based on the operating plan? Does this really change meaningfully in terms of the R&D spend between now and data in 2025? Thanks.
Yeah. Okay, we, we ended the quarter with $303 million in cash, and we've updated the guidance to cash through 2026, which enables us to execute on the current operating plan and the, and the upcoming milestones. Does that answer your question?
Okay, thanks very much. Yeah, it does. Thank you.
Thanks, Laura.
Thank you. One moment, please, for our next question. Our next question will come from Leonid Timashev of RBC Capital Markets. Your line is open.
Great, thanks. I, I just want to continue to build on the questions about the new formulation. I, I guess, can you help us understand maybe the decision to not advance into some phase II work with maybe longer follow-up, 3 months, maybe in whole blood for frataxin, and then do the PK bridging work in parallel, just given the severity of the disease and the unmet need, why not move the programs in parallel? Then with the new formulation, do you have any initial thoughts on how much further you can push the exposure and how that may translate into mRNA increases? Thanks.
Okay, it's a multipronged question. Thanks, Leo. Let me see if I answer your question. If there's something missing, please remind me to answer this. As we came to the end of the MAD, it is exactly this decision. Should we start a phase II trial and try to push the dose and work with this formulation, or should we make a switch over to the improved formulation? The decision, it became clear in that in the MAD, we saw injection site thrombophlebitis even at the doses of 100, 200, and 300.
Although the events in and of themselves were mild or moderate and, and generally self-limited, we felt that there was a concern if you were to then push doses higher or treat longer, which is ultimately what's required for treating a chronic disease like FA, that this eventually could push the, the envelope in terms of injection site tolerability and could put a halt on the program prematurely, which is not related to the, to the drug itself, right? Ultimately, what we want to develop is DT-216, but it has to be within the context of a formulation. When you reformulate a drug, you have to test the drug under the current formulation. That's standard drug development.
The sooner we start with that, the better off in terms of minimizing the hiatus between where we concluded now with phase I until we resume multiple dose testing in second half of 2024.
Leo, to answer your second question, you know, you, you asked about, you know, how much more exposure can we get, you know, with an updated formulation. I just want to remind you that, you know, to this point, DT-216 has been systemically very well tolerated, both in clinical trials but also in our non-clinical studies, where, you know, systemic tolerability, the NOEL was, was really the, the top dose tested. I think the, the answer to that question is, is still to be determined. You know, we have an opportunity, with the resolution of, of injection site reactions to, to continue to advance the dose. And so far, you know, the molecule has shown to be very well tolerated.
Got it. Thanks so much.
Thank you.
Thank you. One moment, please, for our next question. Our next question will come from Joseph Schwartz of Leerink Partners. Your line is open.
Thanks very much. So my first question is, now that you've accumulated some experience in patients and you're able to compare it to what you've seen in animals, how useful would you say that the animal models are for predicting what you might see in patients in terms of the ISRs? How much better behaved is the new excipient? Can you quantify this in any way? Does your animal data to date suggest that you'll be able to dose higher or longer without seeing the same degree? Can you, can you quantify, you know, that goal in any way? Thank you.
Thanks, Joe. Yeah, the current formulation had shown signs of thrombophlebitis in animal studies. We know the animals themselves, rodents and non-human primates, are a sensitive species, if you will. Both sensitive species to detect any kind of vascular abnormalities or reactions. In terms of the actual peripheral, the vein itself, that's, that's the design we're, we're trying to overcome. As for systemic tolerability, which is the doses we push to in tox studies, these were well in excess than we even deployed in the phase 1 trial. We, you know, from the systemic tolerability of, say, liver, kidney, et cetera, et cetera, we could have escalated the dose further beyond the 300 milligram dose level.
The only rate-limiting was the injection-site Thrombophlebitis, which in the MAD study and the SAD study, in of themselves, were not that severe, but we're really looking forward to a, to a, drug development and ultimately approval of a drug, hopefully, that is for chronic use. As to how do we gain confidence that the improved formulation will not run into these issues, which is, of course, an important question, is one that we have explored already. We dosed this in multiple doses in animals, in rodents, which... where we had seen injection-site Thrombophlebitis. So far, we have not encountered the, the same, injection-site Thrombophlebitis that we had observed with the current formulation.
being that these are more sensitive than humans to, to these reactions, we feel pretty confident that we have a formulation with improved characteristics, and that's why we decided to bring this forward in the bridging studies and ultimately developing it back into the clinic.
Okay. Thank you. In terms of the Fuchs program, I was wondering, how are you thinking about the potential to have PD markers there? What are the main technical challenges you think that you might have to overcome in order to demonstrate disease modification, target engagement, potential in Fuchs?
Okay, I'll, I'll turn it over to Sean to, to answer that. Sean?
Yeah. Thank you, Joe. Yeah, I mean, you know, Fuchs is, you know, also a genetic disease, you know, caused by a, a CTG repeat expansion in the, in an intron of the TCF4 gene. There's certainly multiple opportunities to look at, you know, genetic biomarkers in this disease. You know, the, the, the disease affects the corneal endothelium, and so being able to look at the corneal endothelium, you know, from, from patients, potentially post-surgical patients, is certainly an opportunity. We haven't provided definitive guidance on the endpoints in, you know, in the, in subsequent studies in our, you know, clinical program, but there certainly are multiple opportunities to, to examine pharmacology, you know, in disease-affected tissue.
Thank you.
Thank you. One moment, please, for our next question. We have a follow-up from Yasmeen Rahimi of Piper Sandler. Your line is open.
Team, just a clarification question. Do you have to file an IND for the new product, for the new formulation, or there's no regulatory refiling of the IND needed? If you could just provide some color.
Yeah, of course, we'll, we'll, we'll work with the FDA prospectively to, to ensure that we're aligned on the development program. The expectations is a brand new formulation requires a separate IND. We have, of course, a fair amount of experience with DT216 itself, right? Where we tested both in animals and in people, and this gives us a lot of know-how and, and, and knowledge that we can reference in our development plans for DT216 going forward.
Then, João-
Wait.
Yeah.
Jae Kim wanted to just add something. Yeah.
Yes. One additional point, Yasmin, is that, a new IND is a rather administrative step, you know, and that is, in line with precedent for a new formulation, for revised formulations in, in the current day. There's a lot of diligence that has been done in the non-clinical arena that could be referenced in the new IND.
Thank you, team. When you look at the non-clinical data with the new formulation, are you able to quantify how much higher it is relative to 116? Is it, like, two times higher, three times higher, four times higher? Is there, is there an opportunity to figure that out?
In terms of doses we can achieve?
Yeah.
Yeah. just as a reminder, in the single ascending dose study, we had dosed patients with single doses up to 600. Just right there, you can see that theoretically, we could have gone up to 600 milligram dosing in the MAD. At least doubling just based on clinical data alone. Of course, as we progress with testing the new formulation forward, we can then adjust how much we can go. As Sean mentioned earlier, when we tested this in toxicity studies, the top dose was actually the no observed adverse effect level dose, meaning that we could escalate the dose in the top studies all the way to the top dose tested, and systemically, was well tolerated. We think we have room to go. The question is, how much do we need to go up?
Maybe not much, actually, as it turns out. If you look at the data we presented today, and look at the step up between the 200 and the 300 milligram dose cohorts, you see an increase in the mRNA response about 2, 2.3-fold, going from 200 to 300 in a very clear dose-response relationship. That, I think, bodes well that to... perhaps even modest increases in doses could elicit a greater protection response. Obviously, all this will be tested as we move forward.
Thank you so much, team.
Sure. Thank you.
Thank you. I see no more further questions in the queue. I would now like to turn the conference back to João Siffert for closing remarks.
Well, thank you everyone again for joining today in short notice. We look forward to keeping you apprised of our progress across the pipeline. Thank you. Have a good evening.
This concludes today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day.