Q3 2022 Viridian Therapeutics Inc Earnings Call
Greetings and welcome to Viridian Therapeutics third quarter 2022 earnings call.
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A question and answer session will follow the formal presentation.
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I would now like to turn the conference over to your host John Jordan, Vice President of Investor Relations. Please go ahead.
Thank you Brian Good morning, everyone and welcome to the Verde <unk> conference call to discuss the positive clinical data reported earlier today for BRD and or one in patients with thyroid eye disease.
Before we begin I'd like to remind everyone that this conference call and webcast will contain forward looking statements about the company.
These statements are subject to risks and uncertainties that could cause actual results to differ. Please note that these forward looking statements reflect our opinions only as of today.
Except as required by law, we specifically disclaim any obligation to update or revise these forward looking statements in light of new information or future events.
<unk> that could cause actual results or outcomes to differ materially from those expressed in or implied by such forward looking statements are discussed in greater detail in our most recent filings on Form 10-K, and 10-Q and other reports on file with the SEC.
I'm joined today by Dr. Jonathan violin, President and CEO , Dr. Barry <unk>, our Chief Medical Officer, and Christian humor, our Chief Financial Officer, and Chief Business Officer.
I'd now like to turn the call over to Jonathan.
John and good morning, everyone. Thanks for joining us over the last quarter Caribbean continued to execute on all pillars of our strategy designed to deliver the most complete portfolio of products for the treatment of thyroid eye disease across the world.
Ted as you know is currently a $2 billion market in just the United States and is expected to grow to over $4 billion globally with just one product currently approved we're advancing a portfolio of intravenous and subcutaneous programs towards this opportunity.
For our IV <unk> program, we're excited to share positive results from our second proof of concept cohort.
Data will review today for 'twenty makes per keg confirm the profile. We initially presented for 10 Meg per kg a few months ago.
The data compares favorably on each key endpoints, including Proptosis response rate overall response change in clinical activity score or Cas proportion of patients achieving a castle zero or one and resolution of the pump yet.
The <unk> safety profile continues to look very promising with all adverse events mild to moderate no SAE is no hearing impairment no drug related hyperglycemia and no infusion reactions reported in the 20th May particular.
I am pleased to share that the three Meg per kg cohorts for <unk>. One is now fully enrolled in fact over enrolled to the patient demand and we plan to present top line data in early January 2023.
I'm also excited to share this month, we initiated our first phase III trial. The prior trials in active Ted sites are now active and are screening patients.
And the thrive program, we're evaluating two regimens of <unk> one the standard eight infusion of course in a shorter patient friendly five dose regimen, which would be 43% shorter than the eight infusions peasant regiments.
Our confidence in the efficacy of the shorter five dose regimen is enhanced by new 12 week data from attended a particular word showing the between six and 12 with no further dosing <unk> one activities maintained.
This supports our assessment that's five infusions of the idea of one with a 12 week course will deliver the meaningful benefit patients need.
In parallel to the <unk>. One program. We also continued to make progress with our subcutaneous programs, where we aim to deliver a convenient low volume auto injector. The patients can self administer at home and we aim to be the first to market with this offering globally.
Today, we reported the final data for BRD and O. Two from our healthy volunteer study confirming <unk> exceeded our expectations, but the half life of up to 43 days about fourfold better than just further the ardian below one and all other IGF oner antibodies in development. This is actually longer than you.
Initially estimated 30 to 40 day half life, we reported a few months ago.
And positions <unk> well for its upcoming subcutaneous proof of concept trial and Ted patients.
Both Vod on O two and a half life extended version of <unk> called <unk> three are on track and advancing quickly.
We're poised to bring the first self administered therapy to patients in need of better options.
And we're very well funded to execute on these plans with cash to advance rapidly through multiple key milestones. We've ended the quarter with over $430 million in cash providing a runway into the second half of 2025.
Let's now discuss the data and the 'twenty make particular in more detail I'll hand, the call over to Barrett Cats brilliance Chief Medical Officer.
Thank you John .
This cohort like the 10 milligram per kilogram cohort for which we announced data in August enrolled eight patients six randomized to receive two infusions a V or a D. N O O. One weeks apart two patients randomized to receive placebo.
We measure safety Tolerability and efficacy at baseline and at six weeks.
Let's start with the baseline patient characteristics and epidemiology, which had been very similar across drug and placebo groups across our trials ended the Japan phase two and phase III trials with similar levels of baseline Proptosis Cas scores and rates.
As opposed to yes.
As you saw in our press release. This morning, we are pleased to announce data from our 20 milligram per kilogram cohort. After the last patients six week visit but last week and the data further validates the efficacy of D. R. D N O one and its rapid and.
Clinically meaningful effects.
I'd like to start with an overview of the data.
Well review the data from today's 20 milligram per kilogram cohort as well as the data for all patients treated with V. R. D. N O O. One in the 10 milligram and 20 milligram per kilogram cohort.
I'm encouraged to see the reproducibility of our findings V. R. D N O O one performs at least as well as to pass at the six week time point with robust and consistent results on every single measure.
Nearly doubling the overall response rate of deposit hours, 75%, 44% for capacity, we saw 75% prep ptosis responder rate defined as at least a two millimeter change from baseline, perhaps doses versus by 56%.
For comparison we.
We saw a larger mean change of prep ptosis from baseline we saw almost three times the proportion of patients achieving a cash at zero or one are complete or near complete therapeutic effect.
And doubles, the mean change from baseline cash 4.0 versus 2.1.
Similar in both cohorts.
We saw more than double the rate of patients with complete resolution of their diplopia.
Hours, 75% compared to 36%.
These results speak for themselves VR D. N O. One is a highly active drug and compares favorably with <unk> the only approved drug.
Let me review the data in detail.
What are the key things we were seeking to learn from the 20 milligram per kilogram cohort is if the 10 milligram per kilogram maximized activity as we expected from the PK and PD data and as we expected the results are highly consistent between.
Both cohorts.
When we look at the individual patient prep ptosis responses on the left panel the.
The magnitude of improvement is distributed similarly for the two doses.
Majority of patients in each dose cohort had a proptosis response of at least two millimeter reduction from baseline.
Further we observed a similar trend for individual cast responses shown in the middle panel.
Every V R. A D N O O one treated patient had a cash reduction of at least two points from baseline with the depth of the improvements again distributed similarly between the two doses likewise, the IGF one increases as in healthy.
Tears, which you presented at the American Thyroid Association annual meeting last month.
I G F. One increases in 10 patients treated with 10, and 20 milligram a V or a D N O one and there are no different from each other.
Taken together the clinical activity data and the IGF, one data confirm that VR D&O or one dose of 10 milligrams per kilogram achieved maximum clinical activity.
This data confirms our choice of 10 milligrams per kilogram as our go forward dose for our phase III thrive program, which is underway.
Let's review the prep ptosis results, we've evaluated prep ptosis by both P. I administered hertel, except for monetary. We've also evaluated proptosis by a more objective orbital MRI, which is read centrally in a blinded fashion by two independent masked reader.
There's.
This is important because while the hurricane is robust and reliable for studies with large sample sizes.
It is a manually applied in red device prone to variability I've seen in the literature.
And a smaller studies such as our proof of concept cohort, it's useful to have a second independent and confirmatory measurement practices, such as MRI scans, which have been of course used to we said assess Ted patients.
Thus, we set out to implement a robust MRI analysis with a centrally read blinded review.
For our study.
And what I read is were trained and screened for test retest reliability.
Images were ready independently by two masked readers, who use imaging software to measure the distance between the lateral orbital rim and the anterior definition of the eyeball.
As you can see on this slide as of today, we have centrally read MRI data available for all four placebo patients and nine of 12 drug treated patients.
The results are highly instructive and exciting here on the left we show individual patient changes and perhaps ptosis as measured by MRI and you can see all four placebo patients had little change actually three of the four placebo patients had slight increases in proptosis.
From baseline.
Now if you look at the T O V. R. D. N O. One bars, you can see the majority of V. R. A D N O O one treated patients had proptosis reduction of two to six millimeters.
Each of these we're also responders by except for my imagery.
We found that two placebo patients and one V. R. A D N O one patient where proptosis responders by X out for monetary.
But the response was not confirmed by MRI.
Show me the middle panel in the four placebo patients proptosis by centrally read MRI slightly worsened at week, six and average increase of 0.3 millimeters in.
In the nine drug treated patients for whom we have MRI data prep ptosis improved on average by a reduction of $2 75 millimeters from baseline.
This is a remarkable reduction in proptosis. After just two doses a V. R. D N O one.
As shown on the right path that Proptosis changes observed by XL from monetary when adjusted by excluding the responders who were not confirmed by MRI showed a 0.5 millimeter reduction in the placebo arm and a 2.05.
Eliminated reduction for VR D N O y ringing.
Reinforcing the treatment benefit of V. R. D N O one by two independent measures of perhaps ptosis, except for monitoring and MRI.
To put the V. R D N Ho on Proptosis response in context, we can compare it to the mean change from baseline practices, which are pez at week six in their phase two and three trials, which was one eight and $1 nine versus 2.04 millimeters for.
<unk> V. Our D N O O one treated patients.
Proptosis responder rate defined as the percentage of patients who have at least a two millimeter change from baseline practices is shown on the right at week six.
75% of patients who received V. R. A D N O one where proptosis responders.
Compared to 55% and 56% for capacity in their phase two and three study.
Let's turn now to clinical activity score or Cas.
Which is a seven point composite scale of assessments of patient experience pain redness and swelling.
We observed a 4.0 point improvement from baseline cash after V. R. D N O one treatment.
Far exceeding the placebo response.
Given this rapid and sizable change in mean Cass, it's not surprising to observe so many subjects with near total reduction.
And inflammatory signs and symptoms defined as achieving a cast of zero or one.
58%, a V or a D N O one patient met this criteria.
One placebo patient too.
Indeed, two thirds of drug treated patients had a four point or greater reduction in Cas no placebo patients did.
Comparing the effects of D. R. D N O one on cash with the data seen for <unk> we.
We see that the four point mean change we observed for V. R. D. N O. One compares favorably to the effects reported for capacity.
And for our subjects treated with VR D N O O one their percent achieving complete or near complete therapeutic response is two and a half to three fold higher than that seen with <unk>.
So we've seen dramatic improvements in both Proptosis and cats.
What about the combination of the overall response analysis.
This is a more stringent assessment of efficacy as it includes Proptosis improvement, but also includes both signs and symptoms of Ted.
Bothersome to patients.
And overall responder is defined as one who has at least a two millimeter reduction from baseline proptosis and at least a two point change in clinical activity score.
As you can see 75% of our subjects, where overall responders nine of 12 patients that is showed a clinically meaningful improvement in perhaps houses along with at least a two point reduction of cash well.
Only one of the placebo subjects exhibited this combined to change.
Our overall responder rate compares favorably to data for phase II and phase III trials are to pass that.
Which demonstrated overall responder rates of about 46% and 44% respectively.
Finally, let's turn to diplopia or double vision that is perhaps the most disruptive and distressing symptom for Ted patients.
Similar to the to peasant trials about two thirds of patients had diplopia at baseline and for those that do the most important results in the most stringent endpoint is complete resolution the complete alleviation of that double vision.
Following V. R. D N O one treatment, 75% of patients with baseline diplopia experienced complete resolution six of eight patients with baseline diplopia demonstrated complete resolution of their double vision after but two infusions.
A V R D N O one.
This is more than double the rate observed in either to pass a phase two or phase III trial.
We've just shown compelling improvement in Proptosis Cas and diplopia.
Often with complete or near complete resolution of the signs and symptoms as Ted.
Now, let's review safety and Tolerability.
There were no reports hearing loss drug related hyperglycemia or infusion reactions and the 20 milligram per kilogram cohort and all aes were mild or severe.
Some of the known on target IGF, one our effects were observed as expected. We saw two cases in muscle spasm. Both miles did not require intervention. In fact, one was considered unrelated to drug by the mast investigator.
When we look across the safety and Tolerability profile of both cohorts, we're very pleased at the encouraging profile.
And we look forward to collecting more safety data in our phase III program.
I'll now turn the presentation.
Over to John Thank you Barrett as.
As you've heard for every relevant measure and in particular for the more stringent measures. We consistently observed signals at least as strong as we reported for deposit and in many cases substantially higher.
We now have a clear opportunity to differentiate <unk> from the desert.
We believe we can offer patients a shorter course of treatment to offer them faster symptom relief and possibly greater efficacy as well as an attractive safety profile.
Our phase III program is designed to harness these opportunities.
The program consists of two pivotal efficacy studies thrive and active Ted and thrive too and chronic Ted Theyre expected to read out in the middle and end of 2024, respectively.
In support of our global efforts, we recently completed a type C meeting with the FDA and to scientific advice meetings in the EU and which we discussed our phase III plans.
Based on these interactions our phase III program is designed to deliver all the data necessary to support successful BLA and MAA filings in the U S and EU respectively.
As Barry mentioned, we're pleased to share that we've initiated the thrive study and active Ted patients with sites active and screening patients.
The thrive and thrive two trials will evaluate identical dosing regiments all of the 24 week primary endpoint with three study arms first and eight infusion regimen matching with the peso regimens.
A shorter five infusion regimen, which would allow patients to complete their treatment course in just three months, 43% faster than deposits and finally, a placebo arm.
To further improve the treatment regimen, we're using a shorter 30 minute infusion time instead of the 60 to 90 minutes required for Capella.
Yes.
One of the reasons. We think this shorter course of treatment will work is that published data show little to no benefit from the last two infusions that together the.
The other reason is that the efficacy of IGF, one antagonist is surprisingly durable post treatment.
We now have our own data for <unk> to support this durability from the 10 Meg per kg cohort.
We found that at 12 weeks nine weeks after the second of last infusion of the Rd one efficacy.
And largely unchanged.
Patients who responded to the idea of Oh, well one at week six nearly all maintain that response.
Fortify proptosis responders four or five overall responders.
Four of five patients with cask reduced to zero or one.
And for Diplopia resolution all three patients with complete resolution that week six maintains that absence of double vision and the fourth patient with diplopia, who had partially improved at week six continued to improve between week six or 12, achieving a complete diplopia response at that point, so 100% of patients were free of double vision that we 12.
And when we looked at mean change in Proptosis shown on the slide we observed the same thing maintenance of efficacy between week six and week 12.
This durable response further suggest that a short three month course of treatment will provide durable efficacy to the 24 week end point and beyond.
We're excited to have launched the <unk>, one phase III program and look forward to updating you on our progress.
I'd like to close by summarizing what we've learned and what's next.
The <unk> continues to deliver significant improvements in the signs and symptoms of Ted in both cohorts of 10 patients with observed rapid profound improvements on all the key signs of symptoms of disease.
Based on this data we're extremely excited about our phase III program, which we initiated earlier this month.
Separately, we've also initiated a proof of concept cohorts in chronic Ted with initial data expected in the first half of next year and we're on track to launch the thrive two phase III trials in chronic Ted shortly thereafter around midyear next year.
This puts us on track to read out both pivotal studies in 2024.
We're also excited to share data in early January for a final acute Ted proof of concept cohort evaluating three that extra kick which has completed enrollment.
Data from this cohort one in the form of feasibility on every four week subcutaneous dosing paradigm for a sub Q programs, the <unk> two and <unk> three.
And these next generation subcutaneous auto injector programs are also advancing rapidly.
We now have final PK data for Vod on O two establishing a half life of up to 43 days better than the 30 to 40 day half life, we estimated at the interim analysis in August .
This means that the Ardian O. Two is about four times the half life. The first generation antibodies like separate turning them up.
We're on track to have the RDM Oh, two subcutaneous proof of concept data in Ted patients using every two weeks and every four week dosing in the second half of next year.
Dr. Tien <unk>, three which is via our gen. One, but incorporating the same half life extension technology is Dr. Dan O. Two is also advancing quickly to R&D in the second quarter next year.
And nonhuman primate data supports a half life at least as good as the Audi on O two.
By the end of next year, we expect to have all the data we need to choose either <unk> or two or three to advance the pivotal studies and plan to initiate phase III in early 2024.
Together, our intravenous and subcutaneous programs would represent the most complete commercial offering for Ted patients.
Well initially enter the IV market projected to exceed $4 billion globally with the Rd. One followed shortly thereafter by our sub Q auto injector product.
We believe our new entrant with a differentiated drug in a simpler dosing regimen will be highly competitive and a new start market every year 20 to 25000, new active Ted patients in the U S and 35 to 40000 in EU will choose a therapy and we believe our products can be of choice for many of them.
In summary, we're thrilled with the new data, we presented today confirming the profound treatment benefits of <unk> and a growing number of Ted patients each.
These results increase our confidence in our phase III program and we're pleased to have just started our phase III thrive trial earlier this month.
We're well funded and moving rapidly to advance the most complete portfolio of Ted assets toward a market projected to exceed $4 billion and in need of better therapies.
Before we open the call for questions Christian will review our financials.
Thank you John and good morning, everyone I'd like to give a brief summary of our Q3 earnings.
Cash cash equivalents and short term investments were $431 million as of September 30 of 2022.
That was $197 million as of December 31st 2021.
We believe that our current cash cash equivalents and short term investments, excluding a $75 million credit facility will be sufficient to fund our operations into the second half of 2025.
As of September 30th 2022, Meridian had approximately $56 2 million shares of common stock outstanding as converted basis, which included $40 2 million shares of common stock outstanding.
And in the aggregate of approximately 16 million shares of common stock issuable. Upon the conversion of 188050 1000 shares series, a and series B preferred stock respectively.
Please refer to our earnings press release for a more detailed Q3 financial update.
With that we can open the call up for Q&A.
Thank you.
At this time, we'll be conducting a question and answer session.
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One moment, please while we poll for questions.
Our first question today comes from Rami Caputo of lifestyle capital. Please proceed with your question.
Hey, guys congrats on the update and thanks for taking my questions. A couple quick ones for me.
First can you provide more color on the discrepancy in the percent of patients who achieve a casted your one between 10 and 20 make cricket cohorts.
Sure. Thanks, Rami Hi.
So.
First of all as you saw both cohorts, how the percentage of patients achieving that casts a zero or one higher than either of those studies. So in both cohorts so great, but you're right we had five or six patients in the first cohort in two of six in the second cohort. So is there a difference there now if you look at the baseline.
You'll note that the baseline Cas and the 20 Meg per kg cohort is little higher than the 10 million particular heart or indeed, the deposit cohort.
Phase two and phase III trials.
So we think that explains why we're seeing very similar magnitude of cost improvements $3 seven and four three points in the two cohorts showing up as what appears to be a bigger difference in that percentage of patients get into castles. There. One in fact, if you look at the individual patient's out of there was there too.
That interest one.
The 20th maker kit cohort had seven point score.
Baseline of seven out of seven.
Had a five point improvement a huge change in cost but of course that that took the patients who are too so.
So large improvement didn't get to the castle zero or one like why the second patient started at six had a four point change got to a score of two so we're consistently seeing a tremendous improvement in clinical activity score. It's just a slight difference in the.
Baseline characteristics across two floors.
Yeah.
Got it makes sense and then can you touch upon if we've seen variability in Proptosis change would be hertzel softball monitor in our other studies.
Sure Yeah. So.
The.
It's a peasant studies if you look at the New England Journal Phase three supplements from 2020, you can look at the individual patient responses overtime and if you look at the 12 week data you can see that the average change with placebo was very close to zero, but the range is from plus three to minus four five.
No that's fine when you've got a large sample size.
Study size was about 40 patients per arm same as our phase III.
But when you have a smaller sample size youre going to be more sensitive to that noise and it's not surprising.
So this is this is a manual device supply to the patients faced by by the investigator. The question is how do we how do we deal with that.
And in a smaller study and so you want to use an independent orthogonal and ideally more robust confirmatory measure that's why we turned to MRI and as you've heard this is a centrally read process were too blinded reviewers in parallel a measure of the data. So it's extremely rigorous and most of the tiny MRI confirmed except the monitoring results.
What do you do when it doesn't which do you believe for the manual that's up a monetary which we know can be variable with a more rigorous MRI and so we I think sensibly review the view of the MRI is more accurate.
And that confirmation step is what enabled us to clearly assess the performance of our drug in the small sample size now and going forward in phase III and we're gonna have a similar sample size to the Tesla studies, so that variability to X Ophthalmometer will average out that's a it's a great endpoint for larger sample size.
The MRI is useful in a smaller study and of course, we'll will include MRI measurements going forward. It's a great measure may actually deliver some differentiate into out of for us.
It makes a lot of sense Congrats again guys.
Thank you.
The next question is from Kevin Clark Gardner of Evercore ISI. Please proceed with your question.
Great. Thanks for taking the question so I had two.
First is there any scenario, where you would consider adding weekly dosing cohort for the subcutaneous Ted proof of concept trial, which I guess you'd like to end up.
So based on what we know of the performance of VR Genoa, one the house like we've seen for Vod N O. Two we're really confident in the every other week dosing paradigm really the question is can can we get to even less frequent than every other week.
And we'll learn about that with the upcoming three Meg per kg cohorts, if if that shows.
Positive data, then well know that lower doses lower exposures are required and hence we can spread out the dosing paradigm. So really we're looking at already in hand, having every other week and the question is can we get to every four weeks.
Yeah, I've got it and then one on the commercial side do you know roughly what percent of covered lives have site of care restrictions for capella and require infusions to be given outside of the hospital outpatient setting.
We actually don't have that information now as you can imagine we're ramping up a large amount of commercial work given the very strong data we reported in August and now again today.
So you'll be hearing a lot more from us on the commercial front going forward.
Sounds great. Thanks.
The next question is from Thomas Smith of S. V. B Securities. Please proceed with your question.
Yeah.
Hey, guys. Good morning, Congrats on the data and thanks for taking our questions I guess just first on the the 20 make for acute data for clarification I know, it's a small number of patients.
Can you clarify what the mean Proptosis reduction was in the placebo patients with this updated dataset.
So the mean proptosis when we when we exclude the patients that they couldnt confirm by MRI. The mean change was an improvement of about half a millimeter very consistent with what was seen in the peso studies.
Okay.
And then.
Thinking forward here to the the three Meg per kg data side can you talk about I guess your expectations for efficacy. There are you expecting roughly equivalent efficacy based on what you've seen on the PD effect in healthy volunteers or should we be expecting a moderation in efficacy with a lower dosing.
Yeah. So the pharmacodynamic measurements the increases in plasma IGF, one that we reported for healthy volunteers in August does suggest that there is a full receptor engagement systemically.
So while we can't draw a direct line between systemic target engagement and efficacy I'd say, it's a strong hypothesis that we will see robust ethic is it three mix per gig. The question is what does it mean for us right.
The where we think the 10 Meg per kg dose for BRD and old ones the right dose to carry forward in phase III.
Desk balances.
Perspective, the potential benefit and a risk. So that's why we're moving that forward in phase III.
What's the three minute per kicked out and will do again is really inform what we think we'll be able to achieve with a subcutaneous product is it going to be every two weeks, which would be commercially compelling or even better once a month or maybe even longer.
Okay.
Okay got it and then just maybe.
Lastly, I know when you have the 10 make her keg topline data you were able to get a little bit of color on the safety and Tolerability you were seeing in the <unk> cohort I guess, what can you say about the ongoing three Meg per kg cohort at this point any color on safety or Tolerability.
I haven't seen any data from that cohort safety otherwise the only thing I can say is that there'd been no as it is reported that that's all we know so far.
Okay got it thanks, guys I appreciate you taking the questions and congrats on the data.
Thanks, Tom.
The next question is from Laura Chico of Wedbush Securities. Please proceed with your question.
Hey, good morning, guys. Thanks for taking our questions I guess I had one on safety and then one related to the phase III studies. So first.
Could you offer any additional color on the hyperglycemia that 20 Meg per kg cohort and just you know was this exacerbated in response to treatment, maybe how high did glucose levels increase our apologies if I missed that earlier.
Sure I'll ask Barrett to comment on that is thanks Laura.
Because we wanted to study the same population.
Horizon studies.
We allowed for the enrollment of patients with known diabetes and known glucose intolerance.
In this cohort, we actually enrolled patients with known diabetes, and let's just say lesson elegant diabetes management. The patient came in was known hyperglycemia on an oral agent for their control.
Hum.
Track from it.
What's the hallmark of diabetes, the hallmark of diabetes is glycemic variability.
This patient during their time with us showed some variability of their glucose measures.
The investigator who is mass was falling and taken care of this patient and felt that that variability was entirely consistent with the underlying disease.
The diabetes and the expected variability in glucose levels, which as you know are influenced by what the patient age when they eat at times between meals and so the P. I made the decision that any change in this variability and bouncing around of glucose in this known diabetic wasn't fact.
Due to the disease itself and not drug related.
That's super helpful. Thank you Barrett maybe one follow up question then I think Jonathan you mentioned you completed the type C meeting with FDA around the phase III design I just wanted to confirm then no comparison to active drug would be required and then related to the current drive design, where you've got the five cycle.
Each cycle of course arms would you anticipate the potential for hearing impairment might diminish over a shorter infusion cycle. Thanks guys.
Sure. Thanks, Laura.
So correct the dosing.
The arms of the study that I described are what we're moving forward with forward with and of course were discussed with the agency. So two active arms one placebo arm.
With respect to the potential of this shorter course of treatment.
The answer is yes, one of the reasons. We're excited about this is not just that it's more convenient for patients and prescribers, there's potential that by limiting the duration of exposure to drug you might limit the.
The incidence of adverse events.
I don't know that the.
The adverse event profile that we've seen so far is extremely encouraging and we're excited to collect more safety data as we've been so phase III.
Thanks, very much guys.
The next question is from cockpit Patel of B Riley Securities. Please proceed with your question.
Yes, Hey, good morning, Thanks for taking the questions I'm on slide seven I guess.
John do you have any thoughts on why the IGF one increases were lower for the 20 milligram per kilogram versus the 10 and also I think there theres five patients worth of data.
Was there anything about that one patient that that wasn't reported.
Oh yeah.
Yeah. So we have we have data from five patients because the IGF one I thought I'd, just take a little while to come in and as you heard.
The last patient six week visit was just last week. So we just don't have the IGF one data for the last that last patient yes.
And in terms of the levels of IGF one across the two cohorts honestly, we think they're quite similar you're right numerically there little lower we've seen that before but mechanistically, there's no basis for thinking.
Between these two cohorts once you get to full receptor occupancy should be maximizing the effects of the drug.
And so that's why we think the conservative approach the right way to look at this is to consider these two doses equivalent and that's why I would we're discussing the data for all 12 patients.
Okay.
And then I think you guided to choose either 002 or all three for phase III development by early 2024.
You know based on your timelines I don't think you'll have any patient data for all three by then so I guess what gives you the confidence for selecting you know either of these candidates by early yeah yeah.
Yeah. Thank you.
So keep in mind that the origin or threes at the exact same antibody as a one except for the half life extension technology and the way. These antibodies work the variable domain drives target engagement and then the half life extended modifications are in the FC domain and the other end of the antibody and they do not affect.
The.
E antigen binding function down about it which we've proven that with Oh wanted to have a three day. They bind the same affinity drive the same receptor antagonism.
So what that means Oh three works just like the one just with much better PK in non human primates and again, we're expecting a similar PK to VR DNO two in humans.
So the cool thing about that is that we can take the exposure response data from Dr. Tien <unk> and use that for Vod and over three when we have PK from healthy volunteers will have everything we need to know based on the old one exposure response to pick doses for phase III. So that's why this is.
This bake off between O. Two went out with three worked so well we'll have a O. Two proof of concepts will have its own PK PD and then in parallel the healthy volunteer data for our three which can leverage the old one patient data set us up to make it very robust choice of which molecule moves forward in the phase III will be phase III ready and ready to kick off pivotal.
Studies early 2024.
Okay very helpful. Thanks for taking the questions.
The next question is from Jason Butler of JMP Securities. Please proceed with your question.
Hi, Thanks for taking the questions and let me add my congratulations on the data as well I guess first if I'm if you get to a greater than every two weeks out of every four weeks with with one can you just talk about the the overall you know our product portfolio thinking about I would say one out of three and how how commercial.
They would all fit together.
Sure. So we're moving <unk> forward as the IV product offering when we talk about every two week dosing. That's what we know we have in hand already for poor over two and three.
Oh, one might also work as a sub Q, we'll learn about that with a three minute per K cohort.
But honestly, we want to bring the best product forward in the half life extension is working so well that are sub two offering will be either one two or three again as we just talked about will pick at the end of next year, which molecule moves forward.
So that the portfolio, we bring forward is O O. One IV and then either one two or three sub Q and because she went out with three of the only half life extended antibodies in development.
<unk> really seem to deliver an optimal profile for an IGF one of our antibody. We think those either one of those will be a best in class, it's very hard to beat.
Great and then.
I think the answer is largely mechanistic, but can you talk about now you have a larger sample size that the non responders and if theres anything and you know about the baseline characteristics of those patients or are you, saying that.
Could help you.
Patients in the future.
Hum honestly the results are so consistent.
When we have a patient who doesn't reach.
Responder status for Proptosis that usually showing substantial changes in task or or diplopia. So we don't we haven't identified a true non responder population. This drug works very well across the population one of the things like about it.
Great. Thanks for taking my questions.
Thanks, Jason.
There are no additional questions at this time I would like to turn the call back to Jonathan violin for closing remarks.
Thank you I'd like to thank the investigators patients and meridian employees, who have contributed to our programs. Our data provides an incredibly strong foundation to advance our programs rapidly and with purpose to create valuable new therapeutics for thyroid eye disease.
And with that we'll close the call thanks for joining us.
This concludes today's conference you may disconnect your lines at this time. Thank you for your participation.
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