Q4 2021 Celldex Therapeutics Inc Earnings Call
Ladies and gentlemen, this is the operator today's conference call will begin in two minutes until that time your lines will again be placed on hold thank you for your patience, ladies and gentlemen. This is the operator today's conference call will begin in two minutes until that time your lines will again be placed on hold.
Thank you for your patience.
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Ladies and gentlemen, thank you for standing by and welcome to the South Texas Therapeutics year end 2021 conference call. At this time, all participants are in a listen only mode.
After the speaker's presentation, there will be a question and answer session.
Coffee question during the session you will need to press star one on your telephone please be advised that today's conference call is being recorded.
Any further assistance. Please press star Zero I would now like to hand, the conference where to your speaker today, Sarah Catherine. Thank you. Please go ahead.
Good afternoon, and welcome to the <unk> Therapeutics fourth quarter and full year 2021 financial results and corporate update conference call just to remind everyone certain matters discussed in today's conference call and our answers that maybe given to questions asked are forward looking statements that are subject to risks and uncertainties relating to future events and are in the <unk>.
Future performance of the company.
Actual results could differ materially from those anticipated in these forward looking statements.
The risk factors that may affect results are detailed in <unk>. Most recent filings with the U S Securities and Exchange Commission, including our annual report on Form 10-K for the year ended December 31, 2021, which can be found on our website <unk> dot com or on SEC Dot Gov. A question and answer session will follow the formal presentation. As a reminder, the call is.
Is being recorded our press release and the slides that accompanies today's call are posted on our website I will now turn the call over to Anthony Marucci CEO of <unk> Therapeutics. Please go ahead Anthony.
Thank you Sir good afternoon, everyone and thank you for joining us on today's conference call. We are excited to provide a recap of our recent progress and discuss our ongoing development plans in more detail.
Joining me on the call today are Dr. Tibor Keller co founder and Chief Scientific Officer Dr.
Dr. Diane Young senior Vice President and Chief Medical Officer.
Dr. Margo Heath <unk> senior Vice President of regulatory Affairs and Dr. Diego Alvarado, our executive director of research are also joining us remotely from our New Haven office for Q&A.
We had a very strong year in 2021 with promising clinical data across our programs and follow on offering that further secured our balance sheet.
Finding us sort of an expected cash runway through the end of 2025.
In July 2021, we reported positive data from our lead candidates Cvs 159, a unique mass cell depleting antibody.
The phase one in chronic inducible urticaria results were presented during the late breaking poster discussion session at <unk>.
Annual Congress and demonstrated that patients experienced a 95% complete response rate and an overall response rate of a 100% after only a single dose of our 159.
These responses were rapid and durable with a favorable safety profile.
Importantly, we validated our serum biomarker tryptase by demonstrating correlation with depletion of skin mast cells and with the clinical end points.
In September of 2021 at the Adv Congress. We further bolstered these results when we reported additional data demonstrating notable improvements in symptom control and quality of life for the patients on study.
In total these data are unprecedented in this patient population and clearly demonstrate that our 159 has the potential to become an important new treatment option for patients suffering from chronic inducible urticaria.
In the latter part of 2021, we initiated two additional studies for <unk> $5 nine.
But first a phase one healthy volunteer study with our subcutaneous formulation.
And the second was the initiation of <unk> nine and <unk> in a phase <unk> placebo controlled study.
Today, we are pleased to report positive results from our phase one subcutaneous formulation of <unk> five nine in healthy volunteers.
Subcutaneous administration of <unk> five nine eliminated the mild infusion reactions observed in some individuals dosed with the IV formulation and we were very pleased that none of the volunteers had injection site reactions as sometime as observed with some subcutaneous formulations.
The study also demonstrated favorable pharmacokinetic and Pharmacodynamic properties supporting the use of the subcutaneous formulation and our upcoming phase III studies in CSU in <unk> as well as other indications moving forward.
The successful development of <unk> $105 nine subcutaneous formulation is a key step forward in the development of this programs as it offers a convenient administration routes patients and physicians.
People will discuss these data in more detail later during this call.
Our strong in house development capabilities allowed us to rapidly advance this formulation and complete in house manufacturing activities.
In Q1 2022, we initiated the transfer of our current <unk> manufacturing process to a contract manufacturing organization to optimize and scale up current process to support late stage trials and to prepare for future commercialization.
And further support of our phase II readiness activities for the <unk> studies. We are pleased to report positive interim data after completing the analyzed dosing portion of our six month product toxicology study in nonhuman primates.
Results from this study were fully in line with our expectations and we believe these data strongly support our upcoming phase II trial, initiations, and CSU and Cindy next quarter.
And continued expansion into future indications.
She will also discuss these findings in more detail.
In addition to our preparation for our phase II studies in CSU and Cindy we are expecting more data this year from the Cvs 0159 with data from the phase one multiple ascending dose IV study in chronic spontaneous or a car.
Planned to be submitted for presentation at <unk> 2022 and July .
On today's call Gaiam will provide updates on our pipeline programs and discuss in more detail our expansion into our fourth indication for <unk> $5, nine eosinophilic esophagitis or <unk> and.
In assessing future indications for expansion, we consider multiple factors, including the patient need scientific rationale and what other insights. These indications may give us instead of potential future opportunities for Cvs 0159.
BOE is the most important type of eosinophilic gastrointestinal disease and recent studies have suggested that mast cells may be an important driver in the disease.
Given the lack of effective therapies for iOS.
And <unk> potential as a mass cell depleting agent. We believe there is an important indication and look forward to initiating this new study in the fourth quarter.
At <unk>, our core focus is to mine our deep experience in antibody drug discovery to develop therapeutics for patients with devastating diseases.
We seek to design and execute robust rigorous clinical trials as efficiently as possible and in order to support regulatory approvals and provide the broadest possible access to patients who might benefit from our investigational medicines.
We believe the updates to our programs outlined today and the emerging data strongly position us to execute on these execute on these future goals.
With that I will turn the call over to Tibor to go through the <unk> $5 nine subcutaneous formulation data results and discuss the completion of the phase II readiness activities Tibor.
Thanks Anthony.
On slide six you can see the trial design for a randomized double blind placebo controlled phase one subcutaneous formulation of <unk> 509 in healthy volunteers.
This study evaluated single ascending doses of <unk> five nine.
At 50, 150, 306 hundred milligrams administered subcutaneously to healthy volunteers, who were then followed for 12 weeks.
We enrolled four cohort with eight volunteers per cohort six active to placebo.
On slide seven you can see an overview of the positive results from this study.
The key takeaway here is that <unk> five nine subcutaneous administration demonstrated a favorable safety profile.
And profound Tryptase depression, a single dose resulted in rapid and sustained decreases in serum tryptase relative to placebo.
<unk> was well tolerated at all dose levels and no injection site reactions were observed.
On slide eight you can see the tryptase data in detail as I, just highlighted a single dose of <unk> $5 nine decreased tryptase in a dose dependent manner, demonstrating profound and sustained Tryptase depression, which importantly, we have shown correlates with mast cell depletion and relief of clinical symptoms.
It's a very to carrier.
Slide nine shows the serum tryptase kinetics of the sub Q3 hundred milligram dose compared to previous studies with the IV three milligram per kilogram formulation in healthy volunteers and chronic inducible urticaria patients.
I'd like to draw your attention to the fact that Tryptase reduction kinetics with the sub Q administration are rapid and comparable to the kinetics of Tryptase decrease observed with the IV dosing.
On slide 10, we showed the circulating stem cell factor levels near the Tryptase data with a rapid dose dependent increase which plateaued between three and four fold over baseline values.
<unk>, a systemic stem cell factor blockade.
Again with sub Q dosing as compared with IV administration, we observed similar kinetics for this biomarker between the two routes of administration.
Pharmacokinetic data has been completed through day 42 for the 50, $150 and 300 milligram dose cohorts and are shown on slide 11.
The PK demonstrate dose dependent exposure is consistent.
A subcutaneous administration.
For comparison, we also show the pharmacokinetics of <unk> nine dosed in healthy volunteers by IV administration.
<unk> with the similar pharmacodynamic effects on Tryptase and stem cell factor, we see that exposures to IV three milligrams per kilogram is similar to the sub Q3 hundred milligrams flat dose.
Together, the PK and PD data give us great confidence in selecting appropriate doses for our phase III studies.
A key highlight of the study as outlined on slide 12 is that sub Q dosing was well tolerated across all dose levels.
Consistent with our IV healthy volunteer study no pre medications were allowed on study.
We were pleased to see that there were no injection site reactions observed with sub Q administration.
As a reminder, this compares favorably to the IV administration, where we previously reported 45% to 50% of patients experiencing mild infusion reactions.
The vast majority of volunteers treated with $105 nine did not report any treatment related adverse events.
The events, we did see over the 12 week follow up period, where mild almost all grade one and resolved quickly most on the same day they were observed.
There were three grade two events reported.
One and a volunteer treated with 50 milligrams or 159 that developed allergic contact dermatitis on her lips, one week after receiving blinded study treatment.
The event resolved following treatment with topical creams.
The other two events occurred in a second volunteers treated with 600 milligrams or 159, who reported urticaria four days post dosing and a sore in your mouth eight days after treatment.
<unk> to carrier resolved upon treatment with topical cream and antihistamine and the sore resolved without treatment.
Slide 13 outlines the miles and asymptomatic decreases in hematology parameters that were observed in this study.
Presented here are the mean values over time for each of the active groups overlaid on the placebo, 95% confidence interval of the mean shown as the blue shaded region.
Deadline at the bottom displays the lower limit of normal.
As you can see the mean white blood cells and absolute neutrophil count Gen.
Generally fall within the 95% confidence interval for the placebo and are within the normal range for the analytes.
Overall, we are very satisfied with the results from this study and are excited to provide patients with a more convenient form of drug administration that will also benefit the execution of the upcoming phase II clinical trials.
And further support of our phase III <unk> to carry a program. We recently completed the in life dosing portion of our six month chronic toxicology study.
This study was a standard chronic toxicology studies designed to support longer term dosing in our phase III studies.
We conducted the study in sexually mature nonhuman primates to allow us to also capture data and potential impact on reproductive organs.
In this study dosing with every two weeks at $10 or 75 milligrams per kilogram for six months, resulting in much higher exposure than we will.
Use in humans.
Tox studies by their nature are designed to inform about potential toxicities bikes exceeding the exposure expected in that.
Today, we are summarizing the high level findings from the interim data report that is based on analysis at the completion of the dosing portion of this study at 26 weeks.
This study will also continue to follow a subset of animals beyond clearance of the <unk> antibody.
On slide 15, we provide an overview of these findings.
The only clinically adverse finding reported with <unk> Genesis and expected and well understood effect of <unk> inhibition.
Importantly, previous studies have demonstrated full reverse the ability of impaired <unk>.
Genesis upon removal of <unk> inhibition.
I want to emphasize there were no other clinically adverse findings or unexpected results reported in this study.
Extended dosing and exposure did not further impact hematology and these data were consistent with prior results from our 13 week study and within normal ranges for this species.
We believe these data support our previously stated expectation that chronic dosing with <unk> $5 nine will prolong, but not enhanced suppression.
<unk> continues to demonstrate a well tolerated safety profile and we believe these data strongly support the company's phase III programs and future indications.
I'll now turn the call over to Diane to expand on the clinical update.
Thanks Tibor.
As you can see outlined on slide 17 in the two years since we first introduced this molecule. We have made considerable progress even with the backdrop of a global pandemic, we have advanced to phase one development completed the critical sub Q and chronic tox studies necessary to support the initiation of phase II clinical.
Trials in CSU and seem do next quarter and have expanded development into two additional indications for <unk> last year and eosinophilic esophagitis this year.
As Anthony mentioned and supported by the data presented.
Our phase two CSU Ensign do trials are on track and expected to initiate later in the second quarter of this year an important next step for this program. The chronic Tox study results were exactly as we expected and planned and with the biologic activity seen in both our single study and the <unk>.
<unk> healthy volunteer study, we are confident we have identified the appropriate therapeutic doses to advance into our phase II clinical studies.
We believe that with the compelling data we've seen to date across our clinical trials and with the success of the sub Q formulation or future <unk> $5 nine studies will be very appealing to patients and their physician.
We are initiating two phase two studies in order to carry it to begin next quarter, one in chronic spontaneous urticaria and one in chronic inducible urticaria.
The inducible study, we plan to enroll patients with the two most common forms of inducible urticaria symptomatic dermagraph system, and cold urticaria, which make up over 75% of all inducible urticaria.
The CSU in syndrome studies will both be placebo controlled double blinded multi dose studies in 150 to 200 patients. Each we are planning to evaluate dose of 75 milligrams and 150 milligrams administered every four weeks and 300.
Grams administered every eight weeks.
These doses will be administered as five two millimeter injection volumes, allowing for a single injection as we advance towards potential commercialization.
Our phase one IV studies in both spontaneous and inducible urticaria and <unk> continue to enroll patients.
We remain on track to submit data from the CSU multi dose study for a late breaking presentation at the July meeting, including the 0.515 and three milligram per kilogram cohort.
Our focus and priority moving forward will be on advancing later stage programs with the sub Q formulation and exploring <unk> potential across a growing broad development plan as we also complete the ongoing IV study.
With this in mind, we have amended our phase <unk> trial to make this trial simpler for patients and physicians and support our enrollment goals. We have decreased the steady population from 40% to 30 patients and we will assess single doses at one five and three milligrams per kilogram.
Paired to placebo following patients for 24 weeks after dosing.
These changes to the Pn study enable us to achieve our critical calls and a more efficient patient friendly manner. So we can move into subcutaneous studies.
As we've discussed in the past after reading out the <unk> data at Yoki last summer we added two additional exploratory cohorts to increase our learnings of one five milligram per kilogram cohort and cold early carrier and a three milligram per kilogram cohort and culinary ticker to carrier.
Enrollment of both of these cohorts is ongoing we are working to expand outreach for the cholinergic cohort we were hopeful that by including this cohort we can learn more about cholinergic artic area as it is less well understood than other forms of inducible urticaria.
That said it has been challenging to identify appropriate patients in multiple cases patients who presented to the clinic, we symptoms consistent with cholinergic urticaria have not tested positive on provocation testing and exercise test.
We will continue the study because we would like to add to the knowledge base in the field on this indication, but we will not have data in July as we'd originally hoped and moving forward, we will allow it to enroll in its own pace in the background.
As I said earlier this has no impact on our future plans for inducible urticaria, where we plan to advance in the more common forms of the disease called urticaria and symptomatic Dermagraph anthem.
We are also excited to expand clinical development of <unk> five nine into the eosinophilic esophagitis. The most common type of eosinophilic gastrointestinal disease.
You see on slide 19.
<unk> is a chronic inflammatory disease of the esophagus characterized by the infiltration of eosinophils.
Chronic inflammation can result in trouble swallowing chest pain, vomiting, and impaction of food in the esophagus, which is a medical emergency.
One of the more interesting things we have learned as we explore this indication if the thought leaders in the field have suggested eosinophilic esophagitis is maybe a misnomer and it may actually be called allergic esophagitis. This.
<unk> is where we believe CTX 159 comes into play.
Oral studies have suggested that mast cells may be an important driver in the disease and slide 20 outlines some of this evidence.
Mast cells are significantly increased in the biopsies of the esophagus in patients with <unk>, including the esophageal epithelium.
There is also strong evidence of mast cell activation and degree emulation, which is correlated with inflammation immune infiltration fibrosis and pain associated with the disease.
Furthermore, Mac filter associated with specific.
Specific molecular signatures.
Increased <unk> sales have also been found in biopsies of patients with histologic eosinophilic remission, they still have persistent symptoms and endoscopic findings.
Currently there are limited treatment options for <unk>.
Individuals often participate in an elimination diet to identify potential food allergens that may contribute to eo.
Avoid difficult to swallow foods and undergo esophageal dilation.
Well not approved for proton.
Proton pump inhibitors and the swallowing of topical corticosteroids are also used to address the disease.
Industry sources estimate there are approximately 160000 patients in the United States with <unk>.
Who have undergone treatment within the last 12 months and of these approximately 48000 would be biologic eligible.
Given the high unmet need in that.
Compelling science that mat sales may be key drivers of esophageal inflammation and <unk> potential as a mass cell depleting agent. We believe is an important indication for future study.
We look forward to initiating a phase II study using our subcutaneous formulation in early in the fourth quarter.
We are very pleased with the progress we have made overall and in particular with our successful efforts towards the advancement of CTX or five 9% to the next stage of development. We believe <unk> is a potential pipeline in a product and 2022 should be an exciting year.
Alongside <unk> nine our oncology program CTX 11, 40 in CDN $5 27 continue to enroll patients and we look forward to providing updates on these programs later in 2022.
With that I will ask Anthony to close the call.
Thank you Diane to.
To summarize on slide 22, we believe the data presented today further supports the unique profile of <unk> five nine.
And suggest that suggests a potential treatment option, which could represent a significant advancement over current standard of care in the treatment of diseases with mass cell involvement.
On Slide 23, you can see an overview of our expected initial 2022 milestones. We ended the year of 2021 with $408 million cash supporting a cash runway through 2025.
With multiple ongoing clinical trials and expected data readout. This summer, we are very well positioned to execute and further advance our pipeline.
Lastly, I'd like to thank all the patients and the physicians, who are collaborating with us to advance treatment options in these diseases.
I'd like to now open up the call for questions. Operator, if you can begin the Q&A session. Please.
As a reminder to ask a question you will need to press star one on your telephone keypad again Thats Star then the number one on your telephone keypad. Please standby will compile the Q&A roster.
Okay.
Your first question comes from the line of <unk> Huang from Guggenheim Partners. Your line is now open.
Hey, guys. Thank you for taking my question just a couple for me maybe first on the phase one b.
Data that's coming at Yankee.
<unk> do you anticipate including any factory any patient that are attractive to biologics.
And with regard to your disclosure it seems like the $4 five milligram cohort data that might not be there do you need data from that.
Cohort before you're holding of doors for us with just a deal or you think the three milligram is enough to get you. The full information as you think about the dosing.
Yeah, Thanks, Jonathan I'll, let Diane take that question.
Hi, yes.
We have included in the study we have allowed patients to enroll there.
Refractory to <unk>.
Two biologic therapies, so we expect.
Some of those patients in the study.
In terms of the $4 five milligram cohort, we don't believe that we need that data to move forward.
We believe that based.
Based on the compelling clinical activity, we've seen at the three milligram per kilogram IV and then the recent data with the sub Q with profound reductions in <unk> and 300 milligram that we.
You do not need that dose to go forward.
Got it.
Maybe just one more on the sub Q and then I'll go back in the queue can you just talk about the Haynesville filed that you are seeing with sub Q, how it might be relative to the IV dosing.
Got to the two <unk>.
Pam you said that you disclose neutrophils and white blood cell counts.
See any patient that went below the normal range.
Yeah.
Yes, so basically we see them.
Similar.
Very similar and consistent profile to what we've seen before.
In terms of just.
Miles decreases in heme parameters.
Marco May want to comment further.
This is Mike yes.
As shown on slide 13.
Very similar to what we saw with IV in normal volunteers.
And we did.
Including the shaded area, which is the 95% confidence interval on the placebos.
<unk>.
Any excursions out of the normal range as we've said from.
Previous studies again in this study.
Subjects, who start closer to the bottom of the normal range or the ones that are most likely to see a transient excursions below and then come back. So the consistent pattern of a drop than stabilizes and comes back with continued observation is what we've seen across normal volunteers and the pay.
<unk> seen made per keg inducible urticaria study. So it really is a very consistent pattern. It doesn't look different than what we've previously seen.
Got it got it. Thank you very much if I can squeeze one more question.
We got to the new indication to indication I think you touched on the shopping phenotype.
More associated with mast cell activity.
Biomarkers that can help you find these patients.
Our enrolled these patients as you plan a phase two thank.
Thank you so much.
So Diego made no Thats Diego do you know the Biomarkers.
At.
No I don't think theres any biomarker that I know of necessarily that would predict that I think maybe a bank can comment further on this.
We will plan to just enroll.
All comers from the point of view of muscle involvement.
Yes, it's tougher for our study we're going to for this initial study we're going to look at really what we consider a biologic eligible population that's clearly diagnosed with with the OE because we really want to really understand what happens to the mast cells, and then understand better what biomarkers might be used in the <unk>.
Sure.
Okay.
Does that help you.
Yeah very good. Thank you so much thank.
Thank you.
Your next question comes from the line of Chris Howerton from Jefferies. Your line is now open.
Great.
Thanks, so much for hosting the call and taking the questions.
I guess the one for me was just maybe.
Z clarification with respect to the.
The CSU data.
For the phase one b I assume that's a foreign informing your phase two work in that indication is that going to be gating before you actually start the phase two.
Do you already have those data and Youre, just not sharing it or I guess I was just a little confused as to.
How does the kind of current phase one b is going to inform and gate going into the phase two if at all and then the second question I had.
Was it I guess was there any kind of other findings with respect to.
Gamete prediction, let's say with female nonhuman primates was there any observations there and is that.
So quite late to that I guess for Diego, what would be the kind of kinetics in terms of the expectations for normalization for spermatogenesis to kind of resume thank you.
Okay. So let's go with Diego <unk> since that was your last question and then we'll work backwards.
Diego.
Yes. Thanks, So obviously from the point of view of a 159, we don't know necessarily that kinetics. What we do know is that at least in mice. It takes about a month for sperm count to resume once it has been.
So we might we might expect a bit of a lag once a drug clears.
So Chris it's Florida, just to point out that we need 0159 to clear out of the system before you would expect primates.
Recovery as some added Genesis.
On slide nine we've given at such high doses, we expect it to take a good long time before the antibody gets cleared and then we will cease firmly coverage.
It's not going to be something that occurs quickly people that might have a better understanding of.
What we think the time profile with you, but it will take quite a.
Long time to clear the finite first.
Yes, that's a good point Margo and we expect to be able to inform further about the recovery from this permitted Genesis probably late this year.
Okay.
And was there any observations in female game a prediction.
So we're very pleased to see that from this study we did not observe any.
Effects in terms of from the histology analysis female reproductive organs. So that certainly is very very comforting.
We do have additional work to do on potential reproductive effects, but.
Our data so far really support.
Lack of any significant concern from a female reproduction point of view.
Okay.
Yeah. This is diane so in terms of the.
The CSU data.
It's not gaining we don't need that information too.
To plan the study.
The study.
Got it okay.
Well I really appreciate you taking the questions and I'll hop back in the queue in case, there's any follow ups and thanks again for taking the questions.
Thanks, Chris appreciate it.
Okay.
Your next question comes from the line of Thomas Wei from SBB Leerink. Your line is now open.
Yeah.
Hey, guys. Thanks for taking the questions and congrats on the progress just wanted to follow up on the stage when the CSU study and the four five makes for cake dose understand that the data are going to be at Yaqui and theyre not really gating for the phase II study, but are you still planning to enroll this cohort and if so when do you think Bob <unk>.
<unk> into that data and then separately when can we expect to see the initial data from the phase one we wanted to happening per keg.
Year to carry a cohort.
Okay. This is Diane again so.
Terms of the phase IV, we are planning to enroll that cohort that's really a matter of just.
Just wanting to have additional data that exposure is higher than you are planning to go forward early in the drug development program.
In terms of the one five milligram per kilogram dose data work, we're going to enroll that.
We will presented at a subsequent meeting when we have sufficient data we haven't really guided.
Okay.
Yeah.
Okay great.
Just a follow up I guess people are on maybe your comments can you just walk us through I guess the.
Remaining reproductive tox work.
That's ongoing as well as planned.
Sure so.
These are standard toxicology.
<unk> that are required by <unk>.
Outlined by FDA guidelines.
That we would look at.
Fact of antibody treatment.
Pregnant through pregnancy and birth.
And Thats these are called <unk> studies.
And those are.
Our studies that will.
We will evaluate the effect of a 159 on field development.
And birth again, our expectation there is.
Based on what's known in the literature is really not not concerning but of course, we need to go through those studies.
We also believe we will need to do some juvenile toxicology studies before we go into pediatric populations.
And of course, there's some evaluation in terms of development of reproductive organs, there as well.
The timings of that.
Fully developed.
Developed yet, but we're working with the CRO is to get those done soon.
Okay got it alright, guys. Thanks for taking the questions I appreciate it.
Thanks, Tom.
Your next question comes from the line of Tom <unk>.
<unk> from <unk> capital Your line is now open.
Hey, good afternoon, everyone and thanks for taking the questions. Just two quick ones for me first for cooling nurses or to carry out I guess is there potential to include that Cindy subtype into Registrational study or should we would mainly be focused on SDN Colbert to carrier as we think about potential approvals.
Hi, Sam.
Diane I mean, I think I think potentially.
Three we might include it.
I think right now we're focusing on the two most common forms the ones that are best understood, which are our cold and symptomatic dermagraph as and then were.
We're continuing to enroll in a.
Cohort to see if we can learn more.
Finding the right patient population to treat.
Okay got it and then lastly, just outside of the ongoing productive preclinical studies.
Any other key ones there need at this point are we through the bulk of them.
Yeah.
I'm sorry.
Alright here that can you say that again.
Yeah, I was just saying outside of the ongoing reproductive preclinical studies I guess are you through the bulk of preclinical Tox studies or are there any others that we should expect updates on.
These are the major studies that need to be executed.
For support of 0159, so the current six month chronic study is one that performs.
To support chronic dosing that we plan to do with our phase III programs going forward. So we're in good shape.
Tibor brought out at the other piece that we would need to do the juvenile indications and we're working on those as well.
Okay great.
Thanks Sam.
Your next question is from the line of Christian Cusco from Cantor Fitzgerald. Your line is now open.
Hi, good afternoon, everybody. Thanks for taking my question. The first one I had is whether you had any thoughts on how the placebo arm might perform in the CSU study across the key end points at different time times based on what we've seen from other datasets, including some findings that were ripped.
Ported over this weekend and then on efficacy getting a lot of questions specifically about what you would view asics.
Last year excuse me and how much of this might be determined based on understanding the patient profiles on an individual basis, such as their previous exposure to biologics.
This is for the CSU study Kristen.
Yes.
Yeah, so yeah.
And in terms of the placebo response.
I think it depends on what endpoint you are looking at them and what study there.
It's anywhere from 20% to 40% in some of the endpoints we're looking at.
I think does that does that answer your question.
Did you have something more specific.
Yeah, No that's fine thanks.
Okay, and then in terms of.
The success criteria for the CSU study.
We've always said that we're expecting to see results similar to or better than.
Whats been seen refill there, which.
In one or more dose groups given that we're looking at several doses and reasonably small numbers of patients, but yeah, so without a doubt.
That is 50%.
Just thoughts in terms of having well controls or to carrier by the U.
You have seven and then hopefully having a good percentage of those be complete response right.
And we're also anxious to see how we would do with the recurrent patient study as well.
And we expect that we expect at least the people who have recurrent after xolair should respond.
And student naive with the same way that we saw that in our system.
Okay.
Okay. Thank you for that and then I know part of your strategy in choosing indications for <unk> $105 nine has been to understand specific disease aspect. So just each for pn. So when you chose as the fourth indication maybe could you speak to what you're hoping to learn more broadly across the platform with the.
This indication as well as future opportunities that could go beyond.
Understanding the role 159 in Marcellus here.
Yeah. So we're very excited about <unk> because of the the recent data that suggests that mast cells can be a driver.
In the disease as well as the unmet medical need.
Other really nice thing is that as well.
Routine.
Care in these patients they require biopsies.
It's a really will be able to see really really well with what actually happens to tissue mast cells.
The Gi track and really understand what's going on and.
That could lead us to two.
Two other.
Gastrointestinal diseases, where.
Hospitals are involved.
Got it thanks for taking the question.
Thanks Kristen.
Your next question comes from the line of Joe on Chinese from HFC Wainwright. Your line is now open.
Hey, guys. Good afternoon, thanks for taking the question.
So just wanted to go back in.
Regarding the spermatogenesis observation in the nonhuman primates.
Can you all do three things clarify expand and even repeat.
A little bit of what you just said that these nonhuman primates, obviously are.
A couple of you said are receiving very high doses. So that's part of the observation. These doses are much higher than what would be seen in the clinic. So.
What level of confidence do you have that this may or may not be seen once it reaches.
With regard to human doses.
This is tibor Joe I'll take that question. So let me, let me start by clarifying or expanding.
<unk>, what we said which was that.
The one single clinically adverse finding reported from our six month chronic Tox study was an impact on it's prevented Genesis.
We fully expected because this has been well described and studied as an effect of <unk>.
<unk> inhibition.
We also discussed that.
Prior studies that have published on antibodies that impact that block kits signaling.
Reported this effect in spermatogenesis, both in mice as well as in nonhuman primates and in both cases have reported full reverse stability.
That.
The dose response with regards to what our expectations are.
Unclear as you've mentioned, we used extremely high doses, when we do toxicology studies and repeated dosing, which accumulates in these animals.
So that's perhaps something that we can learn in terms of as has.
As the antibody clears and we see reverse ability, we might be able to make some.
Predictions about.
Dose levels that are relevant to.
[noise] impacts <unk> Genesis, but at this point that would be speculation.
No. That's helpful color, Thanks, Tibor and I guess I'd like to maybe just go to a higher level now with the with regard to earn a carrier.
From a macro standpoint, obviously.
Even over the last month or so the field seen a lot of additional news from other <unk>.
Competitive products or other assets in there to carry us for treating carrier to carrier and I guess I'm not asking for a compare and contrast, but look you've certainly made the case already regarding the role of mast cells as the underlying core part of the disease. So I guess I would ask my question. This way do you feel that any of the other approaches out.
There may be complementary to our $1 five nine's approach.
Yeah.
Yes.
Complementary.
Thank God.
I don't like to use the word competitive because I think our just our mechanism of action is different where theyre targeting receptors on the mast cell we are targeting the mass cell itself.
So I just think that our mechanism of action is different than the others that are out there.
Sure No very fair and just to switch gears real quick thanks for the patients.
Regarding $11 40, and 527, Diane you mentioned about how things are going and hopefully get a little view on how enrollment is going overall.
How should we view your communication strategy around those two programs are you really gaining obviously, it's data driven but are you gaining around certain patient numbers or overall, what should we expect.
Okay.
Tibor again, Joe I think we're as you know in the expansion cohorts for both of those programs.
And our view is we'd like to complete enrollment into those expansion cohorts and then we'd have something more meaningful to say about that.
The next steps for each of those.
Understood. Thanks, a lot guys.
Thank you Joe.
We have a follow up from Chris Howerton from Jefferies. Your line is now open.
Okay.
Hey, thanks, so much for taking the follow up I guess, one would be I just wanted to clarify Anthony I think you were saying that.
You had started the tech transfer to for <unk> for a 159.
Has is it started or has it been completed or I guess, how would you characterize the status of that process was just a clarification.
Yes, it's been started and we will complete it sometime this year, but it has been started.
Work is already being done.
Got it and then the other one is.
Probably early and I'm sure you guys know, what you'll say already but I'll ask anyway, which is if you look at the volumes of your subcutaneous formulations, probably can't be self administered so I guess is that correct in my estimation that that will probably be administered by some sort of medical staff.
And if that's true do you think that that matters from a commercialization perspective.
I think that long term, we are going to try to formulate it. So it is self administering Chris I mean, obviously, we'll try to work through that through clinical development, but we're going to started out as <unk>.
<unk> administered by a professional in the clinical trials that work our way.
Upon commercialization that they would be self administered.
Yeah, just to add to what Anthony said the.
Current doses that were planning range from five to two millimeters, which are within the range of what patients eventually could self administer.
Okay.
Alright.
Again, I really appreciate you taking the follow ups and congratulations on the progress.
Chris I appreciate it.
We also have a follow up from me at the Internet how from Guggenheim. Your line is now open.
Hey, guys. Thank you for taking the follow up this is on.
And it's more related to the mechanism of actions can you just talk about what is the relationship of what do we know about the relationship between mast cell numbers.
And you've seen a film numbers because it is our understanding that in.
Yes.
The clinical endpoint is actually you have to show that.
In the U S numbers I'm, just trying to get a sense of where does that relationship.
Sure I can ask Diego to take that Diego.
Yes, things, yet and I appreciate the question so.
As a lot of evidence in the literature of Boston I think in the OEM and other disorders.
And just in biological studies that.
Eosinophils and mast cells regulate one another from couplets.
And muscles are known to.
To create one other mediators for example, and are looking phy, which is known to recruits use in the fields and.
And we know based on preclinical studies, albeit in different use and if so like disorders.
Precursor molecule to a 159 actually significantly reduces your cynical.
Infiltration.
And to the relevant tissues. So I think this is.
Strong rationale for for believing that muscles will influence <unk> infiltration.
The secretion of tier two cytokines, including IL five.
Got it very good thank you so much.
Thank you John .
I am showing no further questions at this time I would now like to turn the conference back to Anthony Marucci.
Thank you operator, and thanks, everyone today for joining with US we're very excited and look forward to providing future updates as soon throughout the year. So have a great night and look forward to catching up soon thank you.
This concludes today's conference call. Thank you all for your participation you may now disconnect.
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