Q4 2022 Immunovant Inc Earnings Call
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Okay.
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Good morning, My name is Melissa and I will serve as your conference call operator.
At this time all participants are in a listen only mode. A brief question and answer session will follow the formal presentation.
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As a reminder, this call is being recorded.
Joining me on the call today will be Dr. Piet Saltzman, Chief Executive officer of it means that.
Before we begin I would like to remind everyone that today's conference call will include certain forward looking statements within the meaning of the private Securities Litigation Reform Act of 1995.
These forward looking statements include among other things statements regarding I mean, if that is planned to initiate two phase III clinical trials for Pedro climate and Ted in the second half of calendar year 2022, with an expected topline data readout in the first half of calendar year 2002.
25, and it's planned to initiate a phase III clinical trial in Mg by the end of June 2022.
With an expected readout in the second half of calendar year 2024.
I mean events plans to develop better claim at across a broad range of autoimmune indications the potential efficacy and safety of immune events product candidate and we and if that's expectations regarding the timing design and results of clinical trials, including the timing of future data Readouts.
And then announcement of additional indications and whether if approved beta cleanup will be successful.
It's actually distributed marketed and commercialized all forward looking statements are based on estimates and assumptions by Amin event management that although I mean event believes to be reasonable are inherently uncertain are forward looking statements are subject to risks and uncertainties that may cause actual results to differ materially.
From those that I mean is that expected.
For more information investors are encouraged to review I mean, if it's annual report on Form 10-K for the year ended March 31st 2022 filed with the SEC on June eight 2022 and in the event subsequent filings with the SEC any forward looking statement speaks only as of the date on which it was.
Meat and immune event undertakes no obligation to publicly update or revise any forward looking statements, whether as a result of new information future events or otherwise.
Now I'd like to turn the call over to Dr. Piet Saltzman. Thank you Dr Yourself spin. Please go ahead.
Thank you Melissa and thanks to everyone for joining the call today.
I'm very excited to share that immune event recently achieved alignment with the FDA division of ophthalmology to move forward with a pivotal program in thyroid eye disease or Ted.
This is a big milestone from unit and we now plan to initiate two placebo controlled phase III trials for Ted in the second half of 2022.
We expect to have topline data for these trials in the first half of 2025.
How does the second pivotal program, we have announced for the token map and represents a first in class program with an exciting market opportunity.
As we heard from physicians and as we discussed at our R&D day. This past March there has been a paradigm shift in the treatment of pet.
As many of you know the FDA approved temperature of the Mab in January of 2020, which is now the only FDA approved treatment.
Treatment option for thyroid eye disease.
When new medications are approved for a disease with high unmet need and a historical lack of innovation and some patients who are already under the care of a physician can rapidly gain access to the new medications. In addition, these types of approvals raise awareness of the disease. Among other patients who may not yet be under the care of a physician or a specialist.
The growing patient awareness also impacts physician decision, making in the market expands we.
We've seen this unfolding thyroid eye disease, the market opportunity continues to grow as the awareness of the disease continues to expand and we believe this will be the case for quite a while similar to the steady market growth experienced in other immunology markets. After the first big innovation.
At the same time, the Ted market has some very unique features.
Disease itself is heterogeneous and therefore lends itself to complementary mechanisms of action.
Duration of dosing specified in the FDA labels for Ted also supports the development of new and complementary mechanisms of action.
The net result is what we believe to be an exciting opportunity for patients and for epitope.
Today I'll introduce our third phase III clinical design and focus on the important points of differentiation for them and help them out and thyroid eye disease.
Okay.
I'll start by reviewing some of the fundamental biology for how they took them out and they work and Tad and why do we believe that T. S. H receptor auto antibodies are key drivers of grapes hypothyroidism and upset.
And the top of them to figure anti TSH receptor autoantibodies circulate in the body and bind to the TSH receptor and the rate. While this figure the auto antibody is binding to a T. S. H receptor in the thyroid gland.
This activates the thyroid volatile increasing cellular metabolism and the release of thyroid related hormones.
Of course this is not the end of the story since TSH receptor antibodies can circulate in the blood and buying to other target cells that also expressed the TSH receptor.
In the middle figure the auto antibodies are shown binding to the Ta's H receptor in the peri orbital space, where they activate orbital fibroblast.
This leads to a proliferation of the Perry orbital tissue and differentiation of these fibroblasts.
Absence of a joke about anti T. S. HR antibodies are recycled back into the blood by the FC receptor and endothelial cells.
We remain present to re circulate and reengage receptors throughout the body.
Note that beside the TSH receptor the insulin growth factor one receptor shown on this slide in blue and adjacent to the T. S. H receptor also plays a role in the pathophysiology of the disease.
Once an auto antibody binds the T. S. Atreus. After there was cross talk between the T S H and the IGF one receptors.
And the engagement of both receptors leads to activation of intracellular pathways linked to the clinical signs and symptoms of chat.
So this cross talk between the TSH receptor and the IGF one receptor appears to be crucial to the path.
So cause the algae.
Yes.
As most of you likely know, but took them out reduces circulating ITG by binding to the FC receptor and inhibiting S. CRM mediated recycling of ITG that normally takes place and endothelial cells.
I'll review some data later in the presentation regarding the Tokyo maps observed impact on anti T. S. H R antibody and Ted patients from our prior study.
Although proptosis as a prominent and important feature of thyroid eye disease cat is actually a heterogeneous condition.
Indeed patients experience a variety of symptoms.
This slide includes pictures of two different people with thyroid eye disease and together provided an example of how Ted can vary patient to patient.
Both people in these photos have proptosis, but the degree of inflammatory changes differs between them.
Patient in the top panel is much more islet edema and conjunctiva of Redness, then the patient in the bottom panel.
The symptom heterogeneity is common and Ted.
We also found that even with treatment patients with active Ted report, making substantial lifestyle modifications.
Based on our market research, 80% of participants reported making moderate or major lifestyle modifications, despite ongoing systemic therapy to which they were responding.
The patients we surveyed were between 30 and 60 years old, reflecting a prime working age range consistent with the 10 population.
In fact, the impact on work life was highlighted is particularly challenging as participants reported difficulty working on electronic devices difficulty driving and challenges engaging in social situations.
When we ask participants to rank the most important treatment goal there was not a single top treatment goal share across the patient population.
Rather the most important coal very patient to patient.
While improving proptosis by two millimeters or more is clinically significant and very important there are symptoms other than emperor doses that can be an even higher priority for certain patients.
We believe it's possible that mechanisms with different mechanism that medications with different mechanisms of action will address different symptoms in different ways and can therefore be complementary in the treatment paradigm.
Yeah.
As I mentioned in my opening comments temperature my mom has made a meaningful impact on the treatment of Ted since its launch in early 2020.
The launch has probably improved diagnosis rates and Ted and has certainly reframed the urgency to treat compared to the historic watch and wait approach that was frequently applied.
This sort of post launch market development is common for a disease that hasn't had any innovation in a long time.
In addition to this favorable market growth, which we expect to continue the Ted market also has some unique features centered around a fixed duration of dosing specified in the FDA label.
Fixed duration of dosing is uncommon.
Allergy, but common in ophthalmology.
In fact, we believe that FDA labels for Ted will continue to specify dosing duration defined by the length of the controlled period of the clinical trial.
This is important because the dosing duration specified in the label maybe insufficient for many patients.
As noted here in the optic 48 week off treatment follow up period, 44% up to present patients who were proptosis responders at week 24, and optics, we're not proptosis responders at week 72, highlighting an opportunity for additional treatment.
We believe this opportunity is ideally suited for a new mechanism of action.
Not only because reimbursement is often strictly limited to the frequency and duration specified in the FDA label.
But also because Ted is a heterogeneous disease that is likely amount of bulk to complementary mechanisms of action.
Such a complementary treatment in series.
Of course, the longer and so a simple subcutaneous route of information.
The administration becomes even more important at least for one of the medications.
Okay.
So what is the bottom line, how many Ted patients do we believe could benefit from a therapy with a new mechanism of action.
We estimate the total addressable population in the U S to be between eight and 18000 patients annually.
Assuming success in our pivotal program and product approval, we anticipate some patients would be treated first with the talk about.
When comparing potential product profiles, many patients and physicians in our market research selected up a profile like the one they took them out and they have for patients on the moderate side of the moderate to severe active Ted spectrum.
A chronic given by simple subcutaneous injection without hearing loss issues and with solid proptosis efficacy, even if a bit less than depends on this dimension is attractive as initial therapy for patients on the moderate and the moderate to severe spectrum.
This group makes up about half of the potential addressable market for a new mechanism of action.
The second logical group is made up of patients who respond well to the peso, but have some residual symptoms at the end of their 24 week course of treatment.
Or relapse at some point off treatment.
This group also makes up about half of the potential addressable market for a new mechanism of action.
Collectively we believe 8000 to 18000 patients in the United States could be candidates for treatment with a token mab.
And this may even be complimentary to to pay those to pass those growth.
So we see this as a very exciting market that is really just beginning to show its full potential.
Now I'd like to briefly review, our clinical development with Ted to date.
Yeah.
The data on this slide is from a cell based assay that looks specifically at those auto antibodies, which stimulate the T. S H receptor <unk>.
Not just those antibodies that bind to it this is important because some auto antibodies bind the receptor, but they don't stimulate it.
And it's really only the stimulatory antibodies that are important to the pathophysiology of pets.
The primary graph shows the dose dependent decreases in stimulatory auto antibodies that were observed with 12 weeks of dosing and the gradual recovery audit of auto antibodies after the dosing period.
Data in the table on the right side of the slide shows the percentage of subjects in each group, whose stimulatory auto antibodies came down into the normal range based on the cell based functional assay.
The upper limit of normal in this assay is 140 and getting below 140 indicates a seroconversion where the level of stimulatory auto antibodies is no longer considered different than what is observed in controls here.
So over a 12 week period, the observed level zero conversion was highest in the 680 milligram arm.
This was one of several data points, leading to a final study design that includes an initial 12 weeks of dosing with 600 milligrams delivered subcutaneously.
This slide shows exploratory proptosis data from the same study.
As a reminder, the data on this slide is from week six of our 10 phase two b trial.
Although the primary endpoint for this prematurely terminated trial was not significant at week 12, we selected week six for this post hoc analysis because it represents the latest time point with the largest amount of patient data available prior to dosing being stopped due to the voluntary pause.
At this early time point at week six the observed Proptosis response rate was numerically higher at the higher dosages.
Again, all treatment was weekly by subcutaneous injection.
This slide shows C. T scan data that I find very intriguing.
C. T scans were done in a few centers and were interpreted by a specialized central reader.
This graph shows data for all subjects, who had a baseline C T and who also had an end of treatment C. T scan after completing 12 weeks of dosing.
As you can see on the Y axis, the bars show percent change from baseline in total extra ocular muscle volume.
Looking at week 12 C. T scan data on this slide we observed a suggestion of a dose dependent effect on muscle volume with a 30% reduction of total muscle volume observed at the 680 milligram, but telco map group.
We observed numerically smaller decreases in other telco map groups, while placebo placebo subjects increased slightly on average.
Of course, these are exploratory endpoints in a small number of patients.
At the same time at the same time the readings were done by a blinded central reader and this is the complete C. T dataset from the trial.
Overall, we believe that data from our prior 10 trials are very encouraging for our pivotal development program and Betokened map in viral disease. We also believe that these data suggest that higher levels of Igt's depression, maybe required initially.
That leads to our trial side.
Yeah.
Whereas our 340 milligram weekly dose provides agg lowering typical of other anti F <unk> development.
680 milligram weekly dose has consistently shown IGT reduction around 80% with subcutaneous dosing dosing something unique to the Tokyo map within the anti F series class.
This initial 12 week dosing period with 680 milligram.
Adds differentiation beyond even first in class.
As the Ophthalmology division of the FDA has provided guidance that two pivotal trials are required for new medications and Ted we've designed two identical studies to run parallel.
We expect to enroll approximately 100 subjects for each trial with two to one randomization to either <unk> or to placebo for 'twenty, one with 24 week treatment period.
Subjects randomized to two the Potomac map arm will receive 680 milligrams Betoken Mab delivered weekly for the first 12 weeks followed by 340 milligrams of Betoken Mab delivered weekly for the next 12 weeks.
The key inclusion criteria are similar to other pivotal programs and Ted and the primary efficacy endpoint will be measured as proptosis responders at week 24 versus placebo were responders are defined as greater than or equal to two millimeter reduction from baseline in proptosis in the study eye without deterioration in the fellow eye.
As I mentioned previously this design takes advantage of the telco maps specific attributes, namely the deep IGT reduction and simple subcutaneous route of administration.
We plan to initiate these phase III trials and Ted in the second half of calendar year 2022, and expect to have the topline data from both trials in the first half of 2025.
Finally, here's a review of our overall development program for Betoken map.
We plan to initiate our phase III myasthenia gravis trial later this month and as a reminder, this phase III Mg trial represents our first pivotal program with Betoken map with topline data expected in the second half of calendar year 2024.
Building on our progress and MTN, Ted we plan to engage with the Hematology division of the FDA to discuss development for warm autoimmune hemolytic anemia, we.
We also expect to announce two new indications as previously committed by August of 2022.
Beyond MTN, Ted we're planning to initiate a pivotal trial in one more indication in 2022, bringing the total to three pivotal trials expected to be initiated in calendar year 2022.
This development plan reflects the enthusiasm our team has for the anti F. C N N space in general and for <unk> in particular.
Thank you so much for your time and with that I'd like to open it up for questions.
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Our first question comes from the line of Robin Karnofsky. That's true Securities. Please proceed with your question.
Oh hi, Thank you for taking my question. Its first can you just talk a little bit about in your market research about I think you've mentioned that you're getting that for them.
He says that patient if it has a similar profile has that which I think you're seeing around 88 are used to mean, 83% for the primary endpoint.
But you could see I use as a first line therapy, so what sort of market research with background thoughts about why you choose one product over the other and what would make a piece of it or a doctor to do that and the second question.
For follow up for you expect that the FDA will give you a similar label excuse me.
Say it'll be around six months do you think there's any flexibility there.
Uh huh.
Thanks.
Yeah.
Thanks Robin for those questions I appreciate it so for the first question with regard to the market research just go into a little bit more detail. There. The market research. We conducted it was it was relatively recently conducted so it was it was in the U S. It was after the launch it as a and patients in the market research had active thyroid eye disease.
Across the spectrum for moderate to severe and they were on systemic therapy with either steroids or to peso with about an even split.
In terms of the.
Medication between both of those groups.
They they are all actually reported 100% of them reported improvement in their symptoms, but 80% of them as I mentioned reported that they were still making moderate.
Or or even more than moderate lifestyle modifications in spite of improvements with them with therapy.
There was then there was a section of the market research, where we asked them to consider product profiles. So four to pezza. They the product profile was was just equivalent to the FDA approved label.
For but told them AB the profile.
Included the what I mentioned so.
Cutaneous route of administration, a proptosis efficacy that was a little bit less than chip has and and the lack of of any hearing loss is not as an assumption in that product profile and when comparing those two product profiles you know different people chose different things and across the spectrum actually some people chose such a.
It has a profile some people chose the betoken that profile, but there was more there were more people in the on the moderate side of the spectrum, who tended towards the that the telco map profile and I think that's consistent with.
Just treatment of a lot of conditions, where when someone has a very they're very very severely impacted than the outstanding efficacy that deposit has demonstrated.
It's probably going to lead to the that being the first choice in spite of any adverse events on the other hand for someone who is whose impacted for sure, but a little bit more moderate.
They're they're more drawn to a profile that provides efficacy, but with them potentially less safety issues or no.
Irreversible safety issues. So that was that was how that split came out in the subcutaneous route of administration also played a pretty.
A pretty big role I have to say in spite of the fact that you know these were people who were being treated with a systemic course of therapy and we're aware of that's a total duration of therapy was only was only six months.
To that point with regards to the label.
Our interactions with the division of ophthalmology.
Strongly suggests that they have are really standard approach to development programs and Ted.
And are likely to have a very standard approach to labeling. So I think the the key tenants of the peso label will be reflected in any other product. That's approved for thyroid eye disease that has a similar program, meaning a 24 week placebo control program.
Got it and just as a follow up do you think you'll be allowed to have patients that have previously been on supposedly I would let me a washout period end.
Yeah.
Also kind of asking just around the guidance for 2025 data.
In the shorter timeframe for.
The trial like what is your assumption for enrollment.
Slower given that there's more awareness of <unk>.
It doesn't mean.
Yeah.
Yeah.
So.
In terms of the timing for the trial. The they are enrollment assumptions or these two trials, which should be running in parallel.
Is sort of halfway between the actual experience of the two deposit trials for their first trial in the second trial. The second trial was obviously faster they had sites up and running and the first trial was positive. So those two things I think we're an accelerator for the for the second trial compared to the first one so we took a position sort of down.
Down the metal Theres no question that the approval of a chip.
The peso has generated additional awareness and we do expect to enroll patients in the U S.
In spite of being on the market.
But there will be a little bit you know, there's there's always more competition. When you have an approved proof product, which is which is true for now at least in not only in the U S.
And that leaves a little bit to the so the first question, which was will we include patients who were previously treated with <unk> and we will not for the pivotal program. The our goal with the pivotal program is to have as close to an apples to apples comparison with regard to the patient population as as deposit had them.
There so.
So that's our that's the rationale for having naive patients in our pivotal trial.
That could be an opportunity for a future phase four trial or something like that but for the phase III trial. It will be Ah patients who are naive to any biologic therapy.
Okay, great. Thank you.
Yeah, you're welcome.
Thank you. Our next question comes from the line of Derek Kerr came out with Wells Fargo. Please proceed with your question.
Hey, good morning, and thanks for taking the questions and thanks for the update just a couple from us.
Track, though I mean, I just wanted to kind of get your thoughts on.
The recent kind of failure and way offer of Boston and how that might kind of enter your thinking about moving forward in a way ha with medical math and thinking about the opportunity. There and then second question just on the cash guidance out to 2025 does that assume that you have cash through the topline Ted data. Thanks.
Yeah.
Yeah, Great question, Derik I'll ask the first one the second one first yes.
That's easy easy answer using direct cancer.
The first question is very interesting and calls happening I guess in parallel.
I did have a chance to review the press release, which had a fair amount of information this morning, and as I'm sure you saw there is a.
Big variation in the placebo response rate by geography, whereas the response rate or fast Imatinib by geography was was relatively similar.
Why might that be I, I think you know in any trial in immunology, where there's a potential to use.
Non steroid immunosuppressive therapy.
Which which was allowed and I think at least one of them more what's out in the phase two trial.
The protocol for which it's been published I'm not totally sure about the phase III trial, but I would guess there might be a similarity there non steroid immuno suppressants.
As you know one of their big limitations as they take a long time to work that's a big limitation clinically it's.
It's also a something that can cause issues in clinical trials, if you have them.
One of the placebo arm, whose non steroid immuno suppressive therapy is just kicking it midway through the trial.
This is an area, where you've gotten a lot of nuanced feedback from.
Investigators across our clinical trials, particularly the ones that have a longer duration, but it's actually applies everywhere where were these medications are used.
So it's possible that that that might explain it.
The placebo response rates that they saw.
Uh huh.
In eastern Europe or in some of those geographies seem much higher than again, what hematologists are telling us.
One would expect in a true placebo arm. So then you wonder if you know the concomitant medications are kicking in and and crossing are causing a confounding there.
I guess, how does that kind of like factor into your thoughts about going into <unk>.
Now that may be that competitor is not there versus.
Undisclosed indications.
Yeah, Yeah, yeah, well I mean I think the.
You know the first thing is to make sure. The trial design is really carefully to the points I was just making in terms of what you know.
With or without Foster mountain that we're really excited about this opportunity.
Because there's.
There's just so there's just there's been a lack of innovation in Oaxaca. The this the therapies that are most of us are steroids actually even more so in the non steroids at least within the major markets.
Moderate doses of prednisone with occasional blood transfusions, which is really just not a.
Very satisfactory long term solution.
Targeted therapy.
And.
Even if even if a hospital has had reported positive results. This morning, I mean, it is an oral therapy, but the the Gi side effects I think you know maybe maybe limiting for chronic use.
So you know this.
Is.
I'm not sure it changes a lot of our thinking is centered around what the total amount that you can do which we believe could be pretty exciting in a while.
Got it thanks for the questions.
Yeah.
Thank you. Our next question comes from the line of Thomas Smith SVP Securities. Please proceed with your question.
Hey, guys. Good morning, Thanks for taking the questions.
Just a couple on the plans and Ted can you give us a little bit more visibility into some of the regulatory dialogue and achieving alignment here with FDA, but were there any discussions around.
The need for a lipid management program in Ted and I guess, where did you guys settled on that.
Great question, Tom Thanks for asking we will apply the same identical safety monitoring program to that Ted clinical trial as we have previously discussed for Mg the same.
Narrow exclusion criteria.
For people, who have a baseline LDL greater than 190, or who have existing cardio vascular disease and have any all LDL greater than 160.
As with the myasthenia trial should a patient come into the trial on a statin that's fine.
And we would expect that there'll be some patients who have controlled hyperlipidemia out of statin just based on the broad prevalence of that of the population and that's that's not a problem.
However, there won't be any statin use initiated during the clinical trial and there won't be any UN blinding due to due.
Due to LDL excursions.
The the discussion was was straightforward and similar to the one with the Neuro Division for Mg program.
Yes.
Okay got it that makes sense and then.
Maybe following up on Robin's question on the targeted patient enrollment.
Highlighted the potential role in patients with maybe less severe disease more in the moderate and the moderate to severe spectrum is there anything specific in the inclusion exclusion criteria for these phase III studies that could drive maybe greater enrollment are they more moderate patient population.
The disease severity spectrum.
No in fact, it's a it's probably a little bit the opposite in the sense that there's a four well the clinical activity score of four which is which is common.
Versus you know dropping it to a three or something like that and so the population is really the same as the moderate to severe population and often people who are enrolled in clinical trials. Just generally are a little bit more severe I mean, that's totally fine I mean, we expect to have good efficacy in the more severe group of Oh that moderate to severe spectrum.
The what I was discussing really related more just kind of to clinical decision, making if you have two different products. They have a different profile and you have a spectrum of patients.
You know.
She position it will generally pick a sort of a sub profile that they prefer for one product some profile of patients that they prefer for one product has a profile, that's just kind of kind of natural and the.
The the moderate to severe Ted patients. That's a that's a large and heterogeneous pool. So I think it's actually going to be relatively straightforward for physicians to make a decision that works for each of them clinically to decide where they would use but hoping that first where they would use deposit first assuming took them apps approved I think in the.
End of the day, many patients will end up getting both which is what I meant by a complementary therapy, giving in series.
And the question that is which one do you get first and you know that.
I outlined our thinking in terms of how those decisions will be made but individual clinicians will probably vary in their decisions there.
Yeah.
Okay got it that makes sense and then just maybe lastly on.
On enrolment there are a few other programs out there that could also be enrolling later stage studies and Ted just as you think about kind of the geographical and regional enrollment I know you mentioned that youre going to you expect to get some patients.
From the U S. But do you have a sense for kind of regional breakdown between the U S and Canada versus western Europe versus versus eastern Europe at this point.
Okay.
I don't have detailed projections by country, yet, but we do expect all regions to be important and that was true in our.
Previous to be trial, and where we're looking to be as expansive as possible in all of our pivotal trials to ensure that you know anywhere there's a there's a good clinical trial site that we have an opportunity to tap into that that pool of potential patients given the compete.
Competing trials across a lot of rare diseases. So that's definitely something we're looking at just generally.
Okay got it makes sense alright. Thanks, Pete appreciate you taking the questions.
Thank you Tom.
Thank you. Our next question comes from the line of Douglas Tsao with H C. Wainwright. Please proceed with your question.
Hi, good morning, Thanks for taking the questions just a.
Pete in terms of that work that you did that sort of suggest that there should that moderate patients might be get some more traction as first line therapy. Just curious from that I think you mentioned tolerability as a key attribute it for.
Attack.
It's tracking so I'm just curious what the relative Tolerability what is there anything in particular that it came out in terms of the market research any particular tolerability issues that we're appealing the decision.
Right. So both listen it's a great question, Doug I appreciate you asking it so both with <unk> and patients we didn't highlight potential product profiles that we were testing that in the betokened profile.
There could be changes in LDL and that some physicians may choose to monitor.
Even though there's not.
Monitoring and the trial that leads to unwinding in the clinical setting that that could that could be the case and that didn't seem to be something which led to him.
Negative perception with.
With regard to decision, making on the part of physicians or preference on the part of patients.
Outside of outside of the blood monitoring, which for these types of patients with thyroid eye disease is done regularly anyway, because many of them have.
You know, even if they're there they're youth item I read in the trial, but many of them are being.
Treated to maintain their youth irate state so they're used to getting blood.
Blood draws for thyroid function levels.
Outside of outside of the blood draws that maybe required you know the MTF certain classes of hole in Betoken maps, specifically has been generally well tolerated so some of the.
Adverse events that had been reported consistently poor it depends Oh, you know for some people are a tradeoff, particularly when they have another another option.
So that was kind of how the decision making went in that market research.
Okay, Great and then just do you anticipate you'll have the Mg phase III completed do you.
State needing additional sort of safety extension data to potentially file in Ted.
Yeah. So all of these you know every every division has a.
Cause slightly unique, but but generally similar requirements for for safety exposures and.
So you know, where we work with each division to understand them and and Ah. The good news is that consistently across the F. D. A safety exposures can be cooled so having.
Patients in different being studied in different indications that those those safety exposures that we'll have for example in Ted outside of.
Ted BLA patients in the MG program can be submitted and vice versa. So that's that's helpful.
In terms of meeting that safety database requirements.
Okay, and then just one final one I think you indicated that you know.
Of you know one you expect to initiate an additional pivotal trial by year end.
Essentially one fun.
Did you indications that havent been disclosed I mean, how are you thinking about sort of that risk reward in terms of.
Going into indications and pivotal study, where you haven't necessarily done as much clinical work previously.
Right. That's a great question does the.
On whether to go for a directly into a pivotal trial.
Or a creep.
Pre pivotal trial, that's in some ways. The second order. The second question is important questions. That's the second question. The first most important question. We ask ourselves is what are the indications we want to develop maybe.
Yes, and there we're looking at the three of them that need the size of the.
Patient population.
Our addressable for a new therapy.
And then the probability of technical success that you you highlighted in your question and when we're thinking about the probability of technical success, we consider not only our own data, but also other anti STR and since there's such a good biomarker.
For for MTS here on development programs.
So then having selected a pool of indications and we have a we have a leading list. That's you know that's that's long end and reasonably prioritize beyond the three that we've disclosed.
Then the.
The next question is whether to go straight to pivotal which is great for long term value creation, because you get faster to BLA.
Or whether to do a pre pivotal trial and that edge of generating some additional catalysts data, but also for certain indications has a chance of advancing our scientific understanding and making our pivotal program stronger I think ultimately you know, having a really really strong.
Result in your pivotal trial.
You know that's that's the most important thing if you can avoid an issue.
Like what Rachel's are announcing this morning.
By having you know your inclusion exclusion criteria, a little bit more optimized and that's gonna be gonna be desirable and for some of them, but there is a scientific information.
To do that yourself approach and that would be the most value, creating so you know at the Mart that'll.
That'll that'll be the most important thing is which indicate and the second most important thing.
Well the.
Pivotal is our pivotal.
Okay, great. Thank you so much.
Youre welcome.
Yeah.
Thank you. Our next question comes from the line of Yadkin to knee jerk with Guggenheim Securities. Please proceed with your question.
Hey, this is Evan on for you and thanks for taking our questions. Two quick ones for me first can you remind us what the bar is for Ted.
In seconds.
It gives you confidence to move forward and Ted given some of the prior mixed results that you've seen.
Yeah, Great question, Devin So I think that the bar is for efficacy is equal to or greater than what you see with steroids and.
Steroid data is not as robustly characterized as to present data, obviously, which had too.
Very well controlled.
Pivotal trials.
But generally the steroids have an efficacy.
Perhaps hostess responsive around 50%, so I think the.
Anything between between the steroid and that's as a result is that's where the efficacy bar lives for a for a new medication with a with a strong tolerability profile like we believe it took them up we will have.
Our confidence really comes from Triangulating a lot of information. So you know our two b trial.
We had deposit midstream, which which made the data difficult to interpret you had a lot of patients who had a varying degree of exposure.
Throughout the trial.
So rather than looking at it as you would evaluate a pivotal trial where you.
First look at the primary endpoint is statistically significant and then which gated secondaries that we looked at it more as you would look at a proof of concept trial, where you triangulate a lot of the information to see if there's consistency.
Across various clinical and clinical scores and Biomarkers and whether there's a dose response. So that's one of the I think one of the most important things when making a decision.
For a proof of concept.
And because if you did you see inverse dose response or something like that then you wonder if the the results that you're seeing in a smaller trial or experience across a lot of biomarkers and a radiological markers and clinical parameters. We saw we saw that that we observed a dose response as I highlighted a little bit and in the slides.
Today, and even in more detail at our R&D day, so that that gives us a.
Our strong conviction that that we have a we have an effect here on that where we're likely to hit the bar that I outlined in terms of efficacy.
Got it thanks, and maybe if I could just one quick follow up.
For that post hoc proptosis data.
What proportion of the total patient numbers in each arm is included in that analysis.
Yeah. That's so then that's it.
A tricky question to answer because what are you putting the denominator you put everybody who has ever randomized everybody who finished the week 12. There were some people that got to 11 weeks not 12 weeks. So you know I think.
Just generally there's about half as many people that got two weeks says as to you know the later say week 11 or week 12. So it's it's a smaller number of people sort of a half to two thirds, depending on how are you.
How you are what you put in the denominator.
Got it thanks, Pete very helpful.
Yeah no problem.
Yes.
Thank you, ladies and gentlemen that concludes our question and answer session I'll turn the floor back to Dr. Hoffman for any final comments.
Thanks Melissa.
Thanks again, everyone for joining us. This morning, we're really excited by this unique first in class opportunity and Ted and I appreciate very much the opportunity to discuss it with you all this morning.
Goodbye.
Thank you. This concludes today's conference you may disconnect. Your lines at this time. Thank you for your participation.