Q2 2023 Acelyrin Inc Earnings Call
Good afternoon, and welcome to the seller and Inc Conference call to discuss its financial results for the second quarter 2023, and other corporate updates. This conference call is being recorded today August 14th 2000.
Twenty-three I would now like to turn the conference call over to Tyler Moore Senior Vice President of Investor Relations Communications and corporate operations for a seller in Tyler.
Thank you good luck.
Everyone. Thank you for joining us.
Before we begin I'd like to remind the audience at this conference call will contain forward looking statements such as those related to our development milestones, including progress of our clinical trials and anticipated data readout our.
Our future financial and operating results and investment pipeline going to program potential a visit.
And our ability to commercialize our product candidates.
Forward looking statements involve risks and uncertainties that could cause our actual results and events to differ materially from those contained in such statements.
We urge you to review the risk factors section of our quarterly report on Form 10-Q for the quarter ended June 30 filed with the SEC and also available through the Investor Relations section of our website at <unk> Dot com.
Along with statements contained in today's press release, and our slide presentation, which identify certain factors that could cause our actual results performance and events to differ materially from those contained in such forward looking statements.
Additionally, these statements are based on information available to US today August 14, 2023, and we undertake no obligation to update them as circumstances may change.
Joining us on today's call are Dr. Shao Lee Lin, our founder and Chief Executive Officer, Dr to pulp Bill Wilson, our Chief Medical Officer, and Yoga briefly our interim Chief Financial Officer.
I will now turn the call over to Dr. Lynn.
Thank you Tyler.
And this afternoon, everyone and thank you for joining us for <unk> first quarterly earnings call as a public company.
So it is a late stage clinical Biopharma company focused on identifying acquiring and accelerating the development and commercialization of transformative medicines.
We are driven by our sense of urgency to bring life changing therapies to patients globally core value that we referred to as greatest Kerry.
And our initial focus is on the treatment of hematologic diseases, an area, where our team brings industry leading expertise.
We acquired a portfolio of product candidates with the intend to develop and commercialize novel therapies that we believe may provide the opportunity to offer a clinically meaningful differentiated benefit for patients. Our strategy is to identify candidates we believe assignments in the world.
We're based on molecular characteristics, our collective experience and expertise in the evolving scientific and medical understanding we can establish development plan the test whether or not our hypotheses are correct and if so what's the potential benefits could be for patients.
Since our founding in 2020, we have created a robust portfolio.
This includes our lead program is a cover which is a small therapeutic proteins. Its high potency and small molecular size. We believe can drive clinically meaningful differentiated benefit for patients across multiple indications truly a potential pipeline and appropriate.
Beyond in Chicago, We're also advancing our earlier clinical stage programs along with it.
Silver and 517 initially being developed.
Disease, and chronic urticaria, respectively.
We have previously shared some of the compelling data, we did Chicago across two indications hidradenitis suppurativa.
Yeah like arthritis.
Each of these and even more so the both together have supported our original hypothesis, but the small size and high potency and this could offer the potential for clinically meaningful differentiated therapeutic.
Later in the call I look forward to sharing with you more context for our clinical progress, including new data related to improvements in training tunnels from the open label part a of our phase <unk> trial of is Chicago in Hs.
In addition to continuing to advance our leading immunology portfolio. We continued to build an exceptional team of experienced biopharma leaders with proven track records of building strong innovative and diverse teams across the health care industry. Most recently, we had the pleasure of welcoming veteran even though sales and marketing here, Ken Wong to our team as chief.
Officer.
This is a key leadership position for us as we adapt as the product towards commercialization, Ken brings decades of commercial leadership expertise in dermatology and rheumatology and we're looking forward to his contributions to our ongoing success.
Also we previously announced that Mardi Dier, Chief Financial Officer, and Chief Business Officer has resigned.
Marty served with us during important times for the company and we thank her for her contributions and wish her well in her future endeavors.
I am pleased that field of virtually has agreed to join us as interim CFO .
Gil previously served as CFO of the company from July until November of 2022, when he left biotech to address personal phone users.
His availability at this time enables seamless continuity of ongoing activities and he will address our financials in greater detail later on this call.
However, I do want to make one more comment related to the financials and that is to reiterate our strong financial position from which we plan to deliver on key milestones across several indications.
Following our successful Upsized IPO in Mi we are fortunate to be operating from a position of strength with more than $820 million at June 30.
We continue to build a leading sustainable biopharmaceutical company with the goal of serving multiple large global markets with clinically differentiated new medicines in immunology and beyond.
We are incredibly grateful to all of our investors new and interesting for their continued support and confidence in our ability to deliver on our ambitious vision.
Given this is our first earnings call I'd like to spend a little time diving deeper into the exciting and rapid progress we continue to make with our clinical programs.
Today I will review our lead program is a car that across multiple indications and then I will turn the call over to Chief Medical Officer popular so for a review of our promising earlier stage programs with one of his mum and of silver and 5%.
Recall that in Chicago is a small protein therapeutic designed to inhibit the other 17. It was high potency through tight binding affinity the potential for robust tissue penetration due to a small molecular size about 110th the size of a monoclonal antibody and an albumin binding domain that extends out.
And we have hypothesized that this high potency and small size can lead to clinically meaningful differences in efficacy relative to the marketed monoclonal antibodies against these targets and without the introduction of the safety liabilities.
We are pursuing late stage development of these kind of up across a number of indications where IL 17 inhibition has been validated. These include H S Psa you'd be others and axial spondylarthritis.
Let me begin with the progress we've made with our Hs program.
Hs is a chronic inflammatory disease characterized by skin absent. These inflammatory nodules training total scar tissue, no odor and pain, often resulting in permanent disfigurement and social stigma and all of this contributing to poor quality.
It just affects more than 300000 patients in the U S with more than half of these patients considered with moderate to severe.
There is currently only one FDA approved treatment for agents and a significant need remains for new medicines that provide more rapid and complete resolution of disease.
We've long known that drug exposures in Hs are lower compared to other inflammatory conditions and had hypothesized that the high closely to Chicago or two out a 17 day as well as the small molecular size again about a 10th of the size of a monoclonal antibody to generate these models are critical response to the robust tissue penetration and potent target engagement.
We designed our phase <unk> trial with a part a and part b.
Part of it was an open label study of 30 patients that we conducted to test our hypothesis or benchmark for success in part able to determine if we could demonstrate clinical response as good as or better than the leading data available and without introducing new safety wise relative to the safety profile of the marketed IL 17 inhibitors we.
Presented results from part a during the late breaker podium session at AAD earlier, this year and reported high orders with efficacy responses at 12 weeks, including achievement of High School 100 response, and a third of patients.
High School 100 is a stringent measure of disease resolution in Hs as it requires the same individuals to achieve both abscess and nodules resolution without formation of nutrient tons.
Today, We also announced additional analysis from part a of the phase II B trials in Hs when patients with at least one rating tunnel at baseline.
Important to note that this analysis is based off of a small dataset with numbers of patients in the high single to low double digits.
In this data.
Frequently it has resulted in improvement of at least one draining tunnel as early as week for two thirds of continuing patients.
Week four was the first time point assessed and this percentage remained consistent continue to continuing to patients through week 12.
Furthermore, <unk> is continuing patients improved by at least two draining tunnels by week, eight which remain consistent 2012.
This is an exciting development for patients because of the speed of response, its ultimate magnitude and consistency over time.
The combination of the high school 100 results as presented at AAD and today's data on numbers of draining tunnels are encouraging.
We believe that the full control of active inflammation is important to enable the early improvements observed in a number of training tunnels.
As a reminder, part b of the phase three trial is a double blind placebo controlled randomized trial of more than 170 patients intended to serve as part of the Registrational package or is it kind of NHS enrolled.
Enrollment of part B completed ahead of schedule accelerating anticipated top line results into the third quarter of 2023 from the end of 'twenty.
In part B participants were randomized to receive either 160 milligrams of is Chicago weekly or every other week or placebo.
An independent data monitoring committee conducted a pre planned review of unblinded efficacy and safety data from part B and confirm the dose of 160 milligrams weekly for the second phase III trial in Hs consistence with the understanding that higher exposures enabled by the high potency and small size the visit content.
Our required for greater efficacy NHS.
With the dose confirmed in May we initiated and dose the first patient in the second phase III trial in June .
And that trial continues to actively enroll.
And then other chronic inflammatory conditions, maintaining therapeutic exposures has been demonstrated as critical to maintaining or improving disease control over time.
Chicago This has been validated in PSA with our phase III positive results at week 16 that continue to deepen out through week 46.
We have two Registrational studies ongoing in Hs and we look forward to reporting topline data from the first Registrational study soon.
Turning now to our late stage program NPSA. We are evaluating is a car that's been a phase <unk> clinical trial.
Psoriatic arthritis is a chronic inflammatory disease with multiple clinical manifestations, including arthritis psoriasis.
Spondylitis that colitis, and importantly, emphasize which is which is an inflammation of the strong dense poorly basketball tissues that anchor our ligaments and tendons to vote.
Emphasize impacts the majority of moderate to severe PSA patients. It has been historically very difficult to treat it as a marker of disease severity and a source of residual pain and physical.
Function the impacts the quality of life for patients there are approximately $1 6 million PSA patients in the U S and about 60% of those are considered moderate to severe.
Here again as with Hs more complete and more rapid resolution of the totality of all key manifestations of disease is critical to improving patient quality of life and remains an unmet need.
But you are in June of 2022, we presented 16 week placebo controlled data from our phase II trial in PSA showing that is demonstrated clinically meaningful benefits across disease manifestations, including 52% achieving ACR 50 response, a marker of arthritis improvement 85% achieve.
Pardon me 75 response, and 88% achieving resolution of emphasizing to switch while not head to head to our knowledge is a level of resolution that has not previously been reported for any other agents.
As it Hs. This also validates our hypothesis that the high potency of small size. It gives the cloud that could make a difference in difficult to treat tissues.
In April of this year, we were excited to report 46 week results from the Phase II trial with TSA that showed continued deepening improvements beyond 16 weeks across key manifestations of the disease.
All participants receiving is a cause of 80 milligrams every other week, 79% achieved ACR 50 response versus 52% and week 16, and even higher orders of political response, including resolution of disease were observed with 50% achieving ACR 70 response, 71%.
Cheating policy 100 response, and 89% achieving emphasize resolution.
As a hematologist. These are exciting results across all manifestations of disease as they are beyond well not head to head what we have seen historically with other approved agents all contributing to even greater improvements in quality of life for Psa patients.
Internal modeling has suggested that the magnitude of clinical response, we've continued to increase with longer duration of treatment that's been demonstrated tomorrow.
The model also predicted further differentiation may be achieved with increasing dose levels.
Supported by that modeling and as a result of the phase II data at 16 weeks last year, we accelerated the initiation of a phase <unk> trial in Psoriatic arthritis, evaluating a range of doses, including hundred doses.
And then the completed phase II trial.
Enrollment in this trial has been completed accelerating anticipated top line results into first quarter of 2024.
The totality of evidence across these two independent datasets of HSN PSA continues to support the hypothesis that the high potency and small molecular size of disciplines that can lead to clinically meaningful differentiated benefits for patients in Hs I scored 100 responses and 33% of pace.
At week 12, and improvements in training tunnels within the first month of therapy.
And in PSA resolution of important manifestations of disease, including joints skin and emphasize all associated with residual pain and severity of disease impacting quality of life.
We are also planning to initiate a phase III program evaluating <unk> for the treatment of axial spondylarthritis in 2024.
Emphasize this is a central feature of asphalt and we believe the rates are into slightest resolution demonstrated in the phase III Psoriatic arthritis trials suggest the potential for clinically meaningful differentiated benefits for patients with this disease as well.
Finally, a phase <unk> clinical trial of this product as a treatment for uveitis is enrolling.
Previously reported data for second Timna delivered intravenously have validated the inhibition of IL 17, eight as a potential therapeutic approach for uveitis.
Clinical dose response was demonstrated with IV levels are set to kidnap exposure. However that response was lost with lower levels of exposure. Thank you delivered subcutaneously, leading to discontinuation of development of a second kitimat easy ice based on its high potency and small size is a car that can achieve that could keep them out of IV levels of exposure with the <unk>.
So cutaneous injection. We believe this provides the potential to unlock this mechanism as an approach to treating uveitis, where there is only one approved therapy and significant unmet need remains.
And now let me turn the call over to Paul will review our opportunities with our earlier stage clinical programs, one route map and $5 seven Paul.
Thank you Charlie and good afternoon, everyone as.
As Charlie noted earlier, we've added two promising programs to our portfolio earlier. This year and are quickly advance this product candidate into important clinical studies to accelerate their development in areas of critical unmet need for patients.
Lot of good or bad it's a humanized IGT one monoclonal antibody against IGF, one are with up to 75 fold higher potency than temperature map.
And it's currently under investigation for the treatment of thyroid eye disease or Ted Ted.
That is a potentially vision threatening progressive chronic autoimmune disease in which the eye muscles islets tiered Glenn and fatty tissue behind the IV come in flame and in large.
It's estimated there are more than 100000, chronic ted patients in the United States.
Recent studies have demonstrated that the inhibition of <unk> is effective in patients with both acute as well as chronic by revised disease. There is currently a single FDA approved therapy for Ted that is administered intravenously and has a fixed six months course.
As such opportunities remain for improved efficacy safety and more convenient administration.
As a chronic inflammatory illness.
Course dosing regimen is insufficient for some patients, resulting in a lack of complete resolution of disease and potential for disease relapse.
Safety considerations, including hearing impairment and hearing loss also remain a concern for the current standard of care with rates of 10% to 45% of hearing impairment in the clinical trials and in real world experience.
Recent updates from the FDA to the warnings and precautions of the temperature map label.
I like hearing impairment as a serious.
Essentially permanent side effects.
Hearing impairment may be directly related to targeting IGF, one R or IGF, one functions to regenerate cells of the inner ear subsequent to auditory insults.
Finally, the need for intravenous infusion complicates care between patients and facilities, which we avoid with patient administered subcutaneous delivery.
We hypothesized that the characteristics of <unk> can optimize efficacy.
By maintaining minimum drug levels needed to achieve improved depth and durability of response.
Limit safety and liability, including hearing impairment and hearing loss potentially associated with high maximum drug concentrations.
Maximize patient convenience through single injection subcutaneous delivery.
While temperature map dosing requires three to five doses to achieve optimal minimum drug levels. Lana good amount may achieve these minimal drug levels with the first dose with the potential to better control disease earlier.
There is potential for a more complete control throughout the disease course, with chronic dosing beyond six months facilitated through the potential for at home subcutaneous injection. Our goal is to treat patients to complete and lasting resolution of Sciences Center.
<unk>.
Furthermore, we believe that the characteristics of <unk> that enables subcutaneous delivery.
Also allow a further reduction of the maximum ceiling serum concentrations incurred with current intravenous therapy.
Decreasing the maximum concentration limits the potential for an anti IGF, one therapy to cross the blood labyrinth barrier and inhibits the normal function of IGF, one to regenerate the cells of the inner ear.
Finally based on published exposure response modeling of Tempur tumor map and the relative potency of lawn Agouta math as well as our completed single ascending dose trial lawn Agouta map achieved targeted exposures when given as a single subcutaneous injection.
<unk>.
The phase one two proof of concept trial up long ago to Mac delivered subcutaneously in thyroid eye disease patients is ongoing and we expect to announce topline results by late 2023 early 2024.
<unk> hundred seven is a monoclonal antibody targeting C kit.
Inhibition of which can reduce mass cell proliferation and activity in various allergy and inflammatory diseases with SLR around $5. Seven we are aiming to address the root cause of mast cell driven diseases by locking about cell proliferation.
And reducing the degranulation of mast cells limiting their toxic cellular products from being released into the circulation.
<unk> seven is a fully human IGT, one monoclonal antibody with no agonistic activity that is no mass cell degranulation.
Demonstrated high potency against the target across binding and functional assays and therefore has the potential for low subcutaneous volume injections.
But fully human nature of SLR and $5 seven insured also limited potential for Immunogenicity and therefore, the potential for acute reaction.
Additionally, its high potency and relatively short half life of approximately 16 days allows for rapid depletion of mast cells, while limiting opportunities for the adverse effects of <unk> inhibition on spermatogenesis haircolor he matter.
Court itself, including neutrophils.
In addition to our initial focus in chronic urticaria SLR and 501 seven also has the potential to address several other mass cell German disorders, including <unk>.
<unk> Pemphigoid and <unk>.
The phase <unk> proof of concept trial of <unk> $501 of it is ongoing and will include healthy volunteers and chronic or to carrier patients. We expect top line results in the second half of 2024.
With that clinical overview, let me turn the call over to Gil for a review of our financial scale.
Thank you Paul for that overview of our earlier stage clinical programs and good afternoon, everyone.
First of all I.
I could not be more pleased to realize that the team has accelerated a very talented and experienced team.
Thoroughly enjoyed working days of the business I know well.
As you've just heard from Charlie and Paul It has truly been a transformative year for accelerated.
Related by meaningful progress across all areas of the organization critical.
Corporate and financial.
On the financial front in early May.
Were delighted to close Upsized initial public offering.
Which included the full exercise of the underwriter's option at $18 per share, which was at the high end of the pricing range.
The IPO generated $641 million in gross proceeds to accelerate.
At June 30th.
Cash and cash equivalents and short term marketable securities totaled $823 million.
Which we expect to fund operations through key value driving milestones across all three clinical programs.
Research and development expenses were $30 million for the second quarter as.
As compared to $12 7 million for the same period in 2022.
Comparing 2023 to 2022.
The company has undergone significant growth, including the expansion.
That program.
Cross multiple indications and the addition of two programs in 2023.
Both of which are now in clinical stage development.
General and administrative expenses were $12 7 million for the second quarter.
As compared to $2 2 million for the same period in 2022.
This increase in expenses was primarily a result of expanding our organizational capability to support the development and commercialization of our broad portfolio of immunology product candidates.
Finally.
Our net loss totaled $46 million for the second quarter of 2023.
<unk> to $14 5 million for the second quarter of 2022.
As you can see we continue to invest responsibly and meaningfully and furthering our robust clinical pipeline and building our capabilities.
And we're delighted to have a strong financial foundation.
From which to continue our important work with patients.
And now I would like to turn it back to Shelby shall we.
Thank you Bill.
As you have heard it's been a tremendous year for silver Wheaton.
We had much to look forward to as we continue to execute on our vision to accelerate the development and commercialization of transformative medicines for patients.
Our lead program there is a kind of a it's a true pipeline in a program with potential across multiple indications representing multibillion dollar opportunities in yet.
We now have meaningful evidence in two independent datasets in Hff's NPSA supporting our hypothesis the high potency and small size visa card that can lead to clinically meaningful differentiated benefits for patients, including resolution of important manifestations of each disease associated with residual pain severity.
<unk> disease, as well as physical function, all impacting patient quality of life.
This evidence also leads us to believe that the potential for them to conduct to demonstrate important efficacy <unk> is quite high.
Both on the grid Mod and of silver and $5 seven continued to progress through early clinical stage trials and we believe have potential similar to as a kind of to address significant unmet efficacy safety and convenience.
In thyroid eye disease, chronic urticaria and beyond.
These programs are expected to collectively deliver multiple important data readouts through the end of 2024 that include for the HFC Phase <unk> trial, which was previously shared is expected in Q3 that was accelerated from the end of the year.
PSA phase <unk> trial, which is now expected in Q1 accelerated from mid 2024.
Both of which were designed to enable the potential to be part of Registrational packages for each of these indications.
In addition, we anticipate proof of concept and you hit on a good night and thyroid eye disease and May tweak nearly 24 and $475 seven in chronic urticaria and the second half of 2024.
These are ambitious goals, we feel confident we will achieve them. Thanks to our experienced team the right pipeline and strong financial foundation to enable our execution.
We have created a culture designed to foster a robust innovation at all stages of drug development and one that encourages collaborative teams and harnesses the power of inclusion and diversity to fuel creative solutions.
You have seen the results of this incredible culture, and we look forward to continuing to deliver on our promise for patients and for our shareholders.
Finally, before I open the call to your questions I want to thank all of our patients investigators investors and employees, who are partnering with us on this mission to accelerate the development and delivery of transformative new medicines to the patients who need them.
We are now ready to open the call to questions. Thank you.
Thank you as a reminder to ask a question. Please press star one one on your telephone and wait for your name to be announced.
Withdraw your question. Please press star one one again.
Please standby, while we compile the Q&A roster.
Our first question comes from the line of Tyler Van Buren from T D Cowen.
Hey, guys. Good afternoon, congrats on all the progress great to see the new HSBC.
PSA pivotal accelerated Q1 I have a couple for you guys on Hff's given all the near term focus.
The first one is for the new training tunnel Hs data from part a that you disclosed that focuses on improvement and at least one or two draining tunnels can you help us put that into context with the mood like tunnel will come out data recently reported which focuses on change in PD counts, our DTE 100, and or any data that can come out.
As presented.
And then the second question is for the upcoming Phase <unk> three Hs data readout.
The ultimate goal in terms of efficacy is at the show a placebo adjusted high score 75 rate that is equivalent or better than what demand that's okay put up.
Phase II or on top of this as it also to demonstrate high score 100 responses in a meaningful percentage of patients.
Thanks.
Thanks for those questions Tyler really appreciate it and great to be here today with everybody.
So in terms of the draining tunnel counts, we're super excited to be able to share that with you today I think the most important new development. There is to our knowledge. This is the first report of improvement in training tools as early as one month into into treatment sort of across the therapeutics two are under.
Standard.
You asked for some comparison relative to what's on our local Mab phase II showed recently as well indicating that data.
To our knowledge I don't think vintages never shared any change into any tunnel data to date.
From a solar welcome that perspective I'd say.
It's been a little bit more difficult to tease out.
High placebo response within the context of that dataset in the middle in the mid two thousands I think so a little bit tougher to make a clear comparison I think what we would like to highlight within the context of what we've seen and why we're still excited is again as early as the month.
Limitations so thats.
I think we've reported now 'twenty sorry.
Alright.
Third is the patient.
By week, four with one draining tunnel I'll add.
On the order of a third of patients.
With two draining tunnel as early as two months, and then going up to 50% of those patients.
We gave that number continuing out to week 12. So we're very excited about these in terms of the consistency from week to week in terms of the.
Speed magnitude improving over time.
As well and we think that the reason that we're seeing this happen.
As early as we are is because of <unk>.
Frankly, the achievement in terms of high score or that's a natural 100 accounts, which is why I towards defined us without any new training tunnels and I think it really requires this level.
Active control over the absent these nodules and resolution of that inflammation that is allowing us to see this kind of early response.
In that difficult to treat tissue.
I think your second question Tyler was around what our expectations are how we would guide folks to think about the upcoming part be randomized control phase III data I appreciate that question.
Our goals are actually no different at this juncture than when we started out asking ourselves whether or not the high potency and small size the visit.
Who I didn't make a difference of meaningful meaningfully differentiated difference in this disease state that really requires.
Inherently the disease itself, a great deal more exposure and has such difficult to penetrate tissues.
We saw in our open label part a experienced that we were reaching and.
I'll confess one even surprised us at the time lines for 100 levels of response.
As many of the third of the patients.
Early at week 12.
Granted that was a small data set and exactly what that point estimate ends up being within the context of the larger part b.
To be determined but from our perspective.
And especially given now that we have two datasets that are suggesting the ability to approach the potential for resolution of disease.
We are laser like focused on that concept and that this molecule has the potential to.
Really bring us to something that may be more paradigm shifting.
More patients across these indications.
So we've always talked about being at least as good as if not better than whatever we consider the best agent out there to be without any new safety liability.
We think that we've been consistent with that debate.
We are going to hold ourselves to that same standard moving forward and we think that.
Or is really on the potential to continue to talk about resolution of disease for patients.
Thanks very much.
Thank you Tom.
Thank you.
One moment for our next question.
Our next question comes from the line of Yasmin Rahimi from Piper Sandler.
Hi, This is jungle on three other paper. Thank you for taking our questions.
Given that enrollment completion part B was announced on my first investors I'm wondering if you could provide any color on timing of top line and whether it can be in the first half or second half of September .
Congrats on the PSA data coming out in Q4 could you help us understand how this dataset will provide me through into your guidance and axial Spondylarthritis studies.
And last what do you hope to see in phase one first of all 1517 to move forward into phase two b and make differentiation clear. Thank you so much.
Okay that was what.
Let me take them piece by piece.
I might ask Paul to help ease of $5 seven on my end and I'll.
I'll take certainly the guidance with regards to the HFC phase <unk> III study that we accelerated from.
From Q4 or end of year into Q3.
That still sits firmly within Q3.
That's probably the extent of the guidance that I would like to provide at this time.
With regards to the PSA data now having completed enrolment in the <unk> study.
Being accelerated and.
That primary endpoint top line readout will now be in first quarter 'twenty four instead of mid 24, obviously very very excited about that as well we've talked about both phase III primary endpoint.
Data that read out last year as well as the 46 week data that we shared earlier this year with outsized benefits and even the concept of resolution within the context of that disease state as well and so we think your specific question was around the weed through two additional indications at Paul you'd be edits potentially even others, let's say.
And that we're excited about the read through.
We talked about the totality of evidence across HSN, PSA really enabling us to talk about the concept of the potential for resolution of disease.
And so we think that there's read through there with regards to what this means from a from a technology and platform perspective for <unk> in particular emphasize is tremendously central to that disease, perhaps even more central in lot of ways.
Then it is in PSA.
Spondylarthritis as the name suggests is all about inflammation.
It's fine.
There are ligaments up and down the front and back of our mines that are connected at every single for people level or spinal level.
Why emphasize by tiny little bits of tissue that.
Our whole job is to connect our ligaments and tendons.
They are incredibly strong and.
Fully vascular and when they get inflamed, it's really really tough to dissolve that inflammation and what we're seeing within the context of our phase two Psa dataset.
We think it's the first time that we've been able to have this kind of magnitude of resolution of that that's a manifestation of disease that is associated with residual pain severity of disease.
Portions of the function and therefore of course impact on quality of life, given that and again, we're talking about resolution of emphasize on the order of 80%, 90% at this juncture, where historically it's been it has not even approach that.
We think that the implications for asphalt.
Given that neutrality, and then decided to basketball is going to be very very important.
Going to be excited to advance that program as well and then as we said for uveitis another difficult to penetrate tissue the back of the eye.
Already derisked with regards to kitimat, having shown dose responsive efficacy there with very high exposures from an IV perspective, losing that response when it went down to sub <unk> levels of exposure.
Therefore, discontinuing that program, we think that this high potency and small size of the Sky bet delivered in a single injection is going to enable us to unlock this mechanism for uveitis patients.
And so obviously a lot more to come there.
Alright. Thank you so much very helpful. Paul is going to cover the $5 seven yes.
I believe the question was related to what we expect to see in the proof of concept studies, we have launched.
Single ascending dose studies.
Already and.
We do know that.
For this mechanism we have a great biomarker in terms of Tryptase and also that the trip taste levels in healthy go down in a way that's very similar to the tryptase levels in patients with chronic spontaneous or the carrier. So we will start and healthy and we will move.
Onto chronic spontaneous or the carrier and our belief is given the greater potency that we will be able to achieve meaningful suppression.
Tryptase and therefore meaningful suppression of disease activity measured by itch and heard a carrier in a low volume subcutaneous injection and thats ongoing.
Factory, where we expect to be and.
We'll look forward to seeing those tryptase responses across a variety of doses.
Alright, Thank you again.
Thank you one moment far next question.
Our next question comes from the line of our cash to worry from Jefferies.
Hey, thanks, so much so I just want to.
Going to the high court 75 expectation for weeks.
So I think.
Yes, sorry, we were having trouble hearing you will college.
Can you hear me now.
Now I can yes.
75% and nothing after that.
Okay, sorry about that so just in terms of the bar for high Schoolers 75 at week 16, I think previously when we've spoken about some of the moon like data.
Bar the data that they showed NHS seems to be kind of doable, but not.
Bar that.
That is a key that couldn't actually hit.
If they showed about 28% at week 16, and we know that from week 12 to 16, there is about a 2% to 4% benefit.
Just with longer duration would it be fair to say that your expectation for your drug at week 16 on high <unk> 75 is between 30% to 35% and kind of circling back on a question that came up earlier do you feel like high scores 75 would be somewhere where you could differentiate <unk>.
First is the compound or the UCB compounds or will that really be high school 100.
We should be thinking about.
And then just maybe finally on you mentioned that Youre DSM be allowed you to move forward with your weekly sub Q.
And it looked at both safety and efficacy consistent with the idea that higher exposure is that better.
It's something that you want to pursue.
Can you give a little more color on what your kind of protocol looked at to recommend that weekly dose specifically on ISR dropouts and then efficacy for both your biweekly weekly dose. Thanks, so much.
That was a mouthful cash thank you.
So let me let me take this.
Bit by bit.
With regards to high school 75 as the bar.
Our data from our open label study had a high school High School, a point estimate 75 point estimate of 57%.
That was obviously, a small and open label experience.
Our understanding of kind of historical placebo response rates for <unk> hundred 70 fives are in the in the range of.
10% to 15% or thereabouts.
So.
It's pretty straightforward math I think that could we be within the range that you've described.
Short answer is yes is that our goal I would say I would describe the ball the same way I described it earlier, which is that our our mission as a company is about making transformative meaningfully transformed as we meaningfully different medicines.
And so.
Could one continued to differentiate in high school 75, I think that was part of your question I think the answer is yes, if we're.
We're still in the 50%, 60% range could we demand to have higher orders of response, there I think the answer is yes.
To your question about what we're looking for though again a.
At least as good as if not better than the best agents out there for a given disease state I'll, even broaden that beyond Hs.
Then also in the specific case of Hs and given the specific molecules that are out there without any additional safety liability relative to that so that's our goal.
With regards to the data that we have seen and have been pleasantly.
Surprised but pleased with in terms of the high score 90, and even 100 response rates and now training tunnels happening improving as early as before I would say.
That again, where we.
We hope that where movie.
The expectations for what we can offer patients within the context of Hs treatments and fundamentally that's what we're going to be focused on.
Uhm.
And then I think your last the last part of your question was about our DMC.
We had a preplanned independent our independent data monitoring committee to look at our.
Part B.
Data at an interim look and confirm for us whether or not our expectation of the highest exposure 160 milligrams.
Every week.
What's a reasonable dose to continue to move forward with our planned second confirmatory Hs study there.
There, we met was really to tell us whether or not they felt that that wasn't a safety reason, we shouldnt do that or whether or not that.
Was any efficacy reasons, we should not do that and they confirmed for us that neither of those materials in fact that week.
And from that perspective shows going forward with that dose level and Thats why the second study kicked off the way they did.
Hopefully thats.
Covers your questions. Thank you.
Really helpful. Thanks, So much propane with me at the first earnings call. So you've got all of them are excited.
Yes.
Thank you Kash take care.
Thank you one moment far next question.
Our next question comes from the line of Vikram to Rohit <unk> from Morgan Stanley .
Hi, good afternoon, thanks for taking our questions. So two from our side one follow up on the part D. We had unexpected <unk> and then one broader commercial question. So first question is what sort of mechanistic read through do you think is fair for people to draw from the part B data in Hs to other indication.
The development for <unk>.
Like PSA and then secondly.
On commercial what do you see as the overall addressable patient population NHS for all biologic therapies and I'm looking forward a few years, how do you see potentially multiple IL 17 targeting agents.
Adding into the treatment paradigm and what do you think is going to drive preferential use one IL 17 versus another.
Alright, so so thanks, thanks very much for that.
Vikram so let's see the first question was about.
If part B is positive what's the read through to PSA and potentially other indications if I heard that right.
I think in that.
I'll reiterate that from our perspective.
Positive looks like currently meaningfully differentiated efficacy without any additional safety liability.
We think that that would be an extremely exciting place. We think that we have positive PSA phase II data already.
So.
That's just additional confirmation if you will about the totality of evidence of the high potency in small cell as was described as being able to.
A differentiated.
Offering within the context of these disease states and I think that the potential.
Potential read through to other indications, we talked about at spar already I think there is some.
Frankly that it brings about the potential paradigm shift to think about the fact that small therapeutics can penetrate these difficult to treat tissue is better and at the high potency may allow them once they get into sort of.
In their business in a more effective way as well and so from our perspective, that's very exciting not just for <unk> and its indications with potentially for housing.
Think about applying that concept more broadly within the context of drug development.
With regards to the addressable patient population in Hs.
And kind of the evolution I guess I'll summarize to say the evolution of the treatment paradigm and how.
Help physicians and patients might choose together moving forward.
Overall population I think as we mentioned in our prepared remarks is on the order of 370000 patients in the U S about.
About half of those are moderate to severe what we know from our commercial real more total addressable market size perspective is that currently that's on the order of one plus maybe $2 billion.
Estimated to grow to between four and five within the context of now and 2030, so so really a growing market size as we know.
Many areas or disease areas, where we gained better and better treatments.
We gain an initial even after treatment to begin with that there are more patients that.
Our out there than we previously predicted because we haven't had the agent medicine as before.
To appropriately have the reason to identify them and therefore have the opportunity to treat them.
What we're seeing is in the context of the Hs as a field is incredibly exciting.
In that we're moving.
Both the higher orders of response, whether we're talking about higher high School 75, all high 497, hundreds I think across the agents that we see in development. Currently we're all moving to higher Oregon have response, which is fantastic for patients.
And is there kind of shifts that we've seen in psoriasis in the past for instance, where we can now talk about sort of all clear skin.
Stirred up 50% improvement from 75 improvements in terms of clearance of your skin lesions, we hope to get there.
And we believe that's what we're seeing for hidradenitis Suppurativa as well and in addition to not only talking about that but we're talking about the ability to improve even on those responses those 12 to 16 week responses.
Up through a year of treatment and we've seen that with a couple of other data sets out there now if I could get a map of images and that both have demonstrated that continued improvement over time, given the continued improvement over time that we've seen with <unk> in our PSA phase III datasets and even in an outsized way relative to.
Other molecules like segregate them out that had been approved for PSA, we think that the likelihood of seeing that floor.
Turning to <unk> and Hs is also very real.
And so we're terribly excited for patients overall.
We're altogether movies the practice of medicine.
In this disease state.
Got it thank you.
Thank you.
One moment for our next question.
Yeah.
Our next question comes from the line of Yasmin Rahimi from Piper Sandler.
Okay.
Hi, Thank you for taking my question I had another one on.
So given that the DMC decision on the 150 milligram weekly in the Hs study with more effective.
Supposed to infer that this weekly dose is going to be moving forward over the two weeks or could you provide a little bit more color on that as well.
Yeah, no thanks for that and sorry, if I wasn't clear earlier, yes. So the choice was made.
To pick a single.
Dose moving forward into the second confirmatory HSA <unk> study and that dose is 160 milligrams weekly which is the dose we anticipated based on our understanding of the disease state.
And why we set up the DMC to help us with that evaluation at the time, we set up the first study.
Two dose levels versus placebo, because one does need to demonstrate that you are utilizing a minimally effective dose.
And and not.
Overdosing for instance patients for no reason when you have.
Within the context of a registrational package in Brazil that was purpose also of ensuring that that's what we were doing for patients.
Alright, thank you so much again.
Thank you at this time I would now like to turn the conference back over to Dr. Kim for closing remarks.
Thanks, Gigi is document. Thank you everybody for your engagement and questions today really appreciate our very first earnings call take care.
This concludes today's conference call. Thank you for participating you may now disconnect.
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