Q3 2023 Acelyrin Inc Earnings Call

Speaker 1: You

Okay.

Good day.

Thank you for standing by.

Speaker 2: Welcome to the acceleration Q3 2023 earnings conference call. At this time, all participants are in listen only mode. After the speaker's presentation, there will be a question and answer session.

Welcome to the salary in Q3 2023 earnings conference call.

At this time, all participants are in listen only mode.

After the speaker's presentation, there will be a question and answer session.

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Speaker 2: I would now like to hand the conference over to Tyler Marciniak, Vice President of Investor Relations Communications and Corporate Operations. Please go ahead.

I would now like to hand, the conference over to Tyler <unk>, Vice President of Investor Relations Communications and corporate operations. Please go ahead.

Thank you operator.

Speaker 3: Thank you operator good afternoon everyone and thank you for joining us before we begin I'd like to remind the audience that this conference call will contain forward looking statements, such as those related to progress of our clinical trials and anticipated data. Readout our future financial and operating results and investments. And our ability to commercialize our product candidates.

Good afternoon, everyone and thank you for joining us before we begin I'd like to remind the audience that this conference call will contain forward looking statements such as those related to progress of our clinical trials and anticipate data readouts for future financial and operating results and investments and our ability to commercialize our product candidates.

These forward looking statements involve risks and uncertainties that could cause our actual results and events to differ materially.

Speaker 3: These forward-looking statements involve risks and uncertainties that could cause our actual results and events to differ materially. We urge you to review the risk factors section of our Form 10Q for the quarter ended June 30, 2023, filed at the SEC, and also available on our website at acellerin.com, along with statements 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.

Heard you to review the risk factors section of our Form 10-Q for the quarter ended June 32023 filed with the SEC and also available on our web site at a stellar in dot com along with statements 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.

Okay.

Speaker 3: Additionally, these statements are based on information available to us today, November 7, 2023, and we undertake no obligation to update them as circumstances may change.

Additionally, these statements are based on information available to US today November seven 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 CEO and Gillman grocery our chief Financial Officer.

Speaker 3: Joining us on today's call are Dr. Xiaoli Lin, our founder and CEO , and Gilda Bruchteri, our chief financial officer. I will now turn the call over to Dr. Lin. Xiaoli? Thank you, Tyler.

I will now turn the call over to Dr. <unk>.

Shelly.

Thank you Todd.

Good afternoon, everyone.

Thank you for joining us for <unk> third quarter update call.

Speaker 4: As we approach the end of 2023, we feel fortunate for the progress we have made throughout the course of the year.

As we approach the end of 2023 forks.

Fortunately the progress we have made throughout the course of the year.

Speaker 4: We began in January with the transformative expansion of our portfolio through the acquisition of another private ionic.

Again in January when the transformative expansion of our portfolio with the acquisition of another private company.

And in May we were pleased to close a successful IPO in a challenging market environment.

Speaker 4: And in May, we were pleased to close a successful IPO in a challenging market environment.

We are grateful to our investors walking alongside with us.

Speaker 4: We are grateful to our investors for walking alongside with us in our journey as we remain focused on building a leading I&I company.

As we remain focused on building a leading electronics.

And continuing to advance programs across multiple autoimmune and inflammatory diseases with a goal to deliver transformative medicines for patients.

Speaker 4: and continuing to advance programs across multiple autoimmune and inflammatory diseases with the goal to deliver transformative medicines for patients.

Our strategy remains steadfast to IDEXX.

Speaker 4: To identify candidates, we believe our diamonds in the rough where based on molecule characteristics, our collective experience and expertise and the evolving scientific.

Candidates, we believe our guidance were based on molecule characteristics, our collective experience and expertise in the evolving scientific and medical understanding we can establish.

Speaker 4: We can establish a development plan to test our hypotheses around clinical differentiation and the potential benefit for patients.

I wish development test, our hypotheses around clinical differentiation and a potential benefit.

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Speaker 4: We are advancing our portfolio of programs across multiple indications, including Isocaiva, the next generation inhibitor of IL-17A, being studied in multiple trials with registrational potential within the rheumatology, dermatology, and ophthalmology settings.

We are advancing our portfolio of programs across multiple indications, including the.

The next generation inhibitor <unk> being studied in multiple trials with registrational potential within the rheumatology dermatology and ophthalmology Salix.

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Speaker 4: a subcutaneously delivered inhibitor of IGF-1 receptor being developed for thyroid...

Subcutaneously delivered inhibitor of IGF one receptor.

Developed with <unk>.

Yes, So 1517 and earlier stage program, we are evaluating for allergy related muscle group of diseases, such as kind of trying to catch up.

Speaker 4: And SOM 5.7, an earlier stage program we are evaluating for allergy-related mast cell-driven disease.

In addition to our clinical progress we continue to build our organizational capability and capacity to support our portfolio.

Speaker 4: In addition to our clinical progress, we continue to build our organizational capability and capacity to support our portfolio.

Speaker 4: Most recently, we announced the appointment of Patricia Turney as our Chief Technical Operations Officer, responsible for overseeing technical operations, CMC regulatory, corporate quality, and...

Most recently, we announced the appointment of Dr. Patricia <unk>, Chief Technical operations Officer responsible for overseeing technical operations CMC regulatory corporate quality.

Patricia brings to account for 25 years of biopharmaceutical experience across R&D clinical and commercial supply management and expands our capacity for multi asset late stage manufacturing at a pivotal time as we advance a robust portfolio.

Speaker 4: Patricia brings to a cell in more than 25 years of biopharmaceutical experience across R&D, clinical and commercial supply management, and expands our capacity for multi-asset late-stage manufacturing at a pivotal time as we advance a robust portfolio.

Speaker 4: with multiple large-scale clinical trials underway and prepare for potential regulatory filings and commercial launches.

With multiple large scale clinical trials underway and prepare for potential regulatory filings and commercial launches.

We also welcomed in September Dr. Sheppard.

Speaker 4: Our Senior Vice President of Development, responsible for clinical development and translational science.

Our senior Vice President of development responsible for clinical development and translational Sciences.

Speaker 4: Chef brings more than 20 years of industry experience, including a long tenure at Novartis, where he most recently served as Senior Vice President and Chief Medical Officer for Novartis G Therapy.

Jeff brings more than 20 years of industry experience, including a long tenure as far as where he most recently served as senior Vice President and Chief Medical Officer for large gene therapies.

Speaker 4: Prior to that, Shep was the global lead for Cetakinumab, where he advanced the product from early development through to multiple approvals across the indications, including psoriatic arthritis, or PSA, hyperadenitis subcutaneous, or HS.

Prior to that chip with the global lead first that the kitimat, where he advanced products from early development through multiple approvals across indications, including Psoriatic arthritis Psa.

Neither <unk> or Hs uveitis and axial spondylarthritis for Xbox.

Speaker 4: uveitis, and axial spondyloarthritis, or AST.

Speaker 4: His extensive experience will be key as we advance our pipeline across many of the...

His extensive experience will be key as we advance our pipelines across many of the same release dates.

Speaker 4: While Gil will review our financials in greater detail later on the call, I do want to underscore our strong financial position.

Paul Gilbert who will review our financials in greater detail later on the call.

Just wanted to underscore our strong financial position.

Speaker 4: With nearly $800 million on our balance sheet, we can execute on our strategy over the coming months and years and achieve numerous key milestones across the entire portfolio of programs.

With nearly $800 million on our balance sheet, we can execute on our strategy over the coming months and years and achieved numerous key milestones across the entire portfolio of programs and indications.

Speaker 4: Let's turn now to a review of our progress across the portfolio.

Let's turn now to a review of our progress across the portfolio.

Speaker 4: As a recap, Isocibat is a small protein therapeutic designed to inhibit IL-17A with a high potency through type-binding...

As a recap is it kind of is a small protein therapeutic designed to inhibit IL 17, a with a high potency <unk>.

Binding affinity it has the potential for robust tissue penetration due to its small molecular sides, which is about 110th the size of a monoclonal antibody and has an albumin binding domain that extends hustling.

Speaker 4: that has the potential for robust tissue penetration due to its small molecular size, which is about one-tenth the size of a monoclonal antibody, and has an albumin binding domain that extends halfway.

We have hypothesized that the high potency and small size it isn't quite that can lead to clinically meaningfully differentiated responses for patients across multiple indications where this mechanism of action has been validated and that this can be achieved with a safety profile consistent with that of the IL 17, a class that has been demonstrated by the current market.

Speaker 4: We have hypothesized that the high potency and small size of Izanika can lead to clinically meaningfully differentiated responses for patients across multiple indications where this mechanism of action has been validated, and that this can be achieved with a safety profile consistent with that of the IL-17A class, as has been demonstrated by the currently marketed monoclonal antibodies that begin available.

Monoclonal antibodies.

Any pictures of that.

Speaker 4: IL-17A as a target has not demonstrated dose-limiting toxicity over 10 years of post-marketing and millions of patient years of safety.

I also have a target has not demonstrated dose limiting toxicity over 10 years of post marketing a million patient years of safety experience. This will be important as we discuss what appears to be an evolving understanding around targeting the IL 17 assets more broadly that selectively targeting IL 17.

Speaker 4: This will be important as we discuss what appears to be an evolving understanding around targeting the I-017 axis more broadly than selectively targeting I-017A.

Let me begin with Psoriatic arthritis.

Speaker 4: It's our most advanced program and represents the largest potential indication for IZAKOTA. Psoriatic arthritis is a chronic condition.

Our most advanced program it represents the largest potential indication for use with us.

Psoriatic arthritis is a chronic inflammatory disease with multiple clinical manifestations, including arthritis psoriasis spun device that device and importantly, emphasize which is an inflammation of the strong gets poorly vascular tissues that anchor our ligaments and tendons.

Speaker 4: multiple clinical manifestations, including arthritis, psoriasis, spondylitis, dactylitis, and importantly, emphysitis, which is an inflammation of the...

Speaker 4: poorly vascular tissues that anchor our ligaments and tendons to fall.

Well.

Speaker 4: the majority of moderate to severe psoriatic arthritis patients, and has been historically very difficult to treat.

At the sight of impacts the majority of moderate to severe psoriatic arthritis patients. It has been historically very difficult to treat.

Speaker 4: is a marker of disease severity and a source of residual pain and physical dysfunction, which impacts quality of life for patients.

It is a marker of disease severity and a source of residual pain, and physical dysfunction, which impact quality of life of patients.

There are approximately $1 6 million Psa of patients in the U S.

Speaker 4: There are approximately 1.6 million PSA patients in the U.S.

Speaker 4: And the 2022 PSA treatment market was valued at $8.8 billion globally and is estimated to grow to nearly $18 billion by 2030.

And the 2022 PSA treatment market was valued at $8 $8 billion globally and is estimated to grow to nearly $18 billion by 2030.

Speaker 4: Historically, PSA treatments have been more effective in the joints and skin, but not the harder-to-treat manifestations of the disease, such as emphysitis.

Historically PSA treatment have been more effective in the joints and skin, but not the harder to treat manifestations of the disease such as in the slides.

Rapid deeper and more durable resolution of disease across clinical measures is the key to improving overall quality of life, which is ultimately our goal for patients.

Speaker 4: Rapid, deeper, and more durable resolution of disease across clinical measures is the key to improving overall quality of life, which is ultimately our goal for our patients.

We have already shared results from a phase II placebo controlled trial of its kind of in PSA, which demonstrated a differentiated dose ordered responses as early as one month into treatment and increasing overtime.

Speaker 4: We have already shared results from a Phase II placebo-controlled trial of ischiava in PSA, which demonstrated differentiated dose-ordered responses as early as one month into treatment and increasing over time.

This included an ACR 50 response of 50% at week 12, or 44% placebo adjusted.

Speaker 4: This included an ACR 50 response of 50% at week 12, or 44% placebo adjustment.

Resolution identified us as measured by the leaves and beside of index was 82% at week eight.

Speaker 4: Resolution of emphysitis, as measured by the Leeds Emphysitis Index, was 82% at week 8 at our 80mg every other week dose.

At our 80 milligram every other week dose with.

<unk> 12 was not a protocol specified time point for this measure.

Yes, I read the resolution is a standard approach to reporting improvements for insights.

Speaker 4: That resolution is the standard approach to reporting improvements for NCI.

To enable comparison with recently reported emphasize data from one of the also TNF inhibitors. We also analyze subjects with Elliott of two plus at baseline with an improvement of two plus points at our rate versus the other agents data at week 12.

Speaker 4: To enable comparison with recently reported emphysitis data for one of the IL-17-AM...

Speaker 4: We also analyzed subjects with LEI of 2 plus at baseline with an improvement of 2 plus points at hour week 8 versus the other agent's data at week 9.

Speaker 4: This analysis showed a 100% response at week 8 in patients receiving 80mg of Inzokaivo versus 0% in patients receiving 1mg of Inzokaivo.

This analysis showed 100% response at week eight in patients receiving 80 milligrams per visit kind of versus zero percentage of placebo.

These results are relative to 71% reported at 120 milligrams for the IL 17, a S. H at 12 weeks without disclosure of a placebo as a reference for that agent.

Speaker 4: These results are relative to 71% reported at 120 milligrams for the IL-17AF agent at 12 weeks without disclosure of a placebo as a reference for that agent.

Okay.

Speaker 4: At UR, in June of 2022, we presented primary endpoint 16-week data, showing that Izakaya demonstrated clinically meaningful benefits across disease manifestations, including 52% ACR50 response, 85% POSI-75 response, and 88% resolution of emphysitis, which to our knowledge, is a level of resolution not previously reported for any other age group.

If you are in June 2022, we presented primary endpoint 16 week data showing that is the cause of demonstrated clinically meaningful benefits across disease manifestations, including 52% ACR 50 response, 85% policy 75 response at 88% reservation that the floods, which to our knowledge is the level of.

Resolution not previously reported for any other agent.

Speaker 4: These clinical benefits subsequently drove significant improvements in quality of life across all domains, and importantly, this included statistically significant improvements in pain, functional capacity, and sleep disturbance, as measured by the Psoriatic Arthritis Impact of Disease Questionnaire.

These clinical benefits benefits subsequently drove significant improvements in quality of life across all domains and importantly, this included statistically significant improvements at P functional capacity and sleep disturbance as measured by the Psoriatic arthritis impact of disease questionnaire, what he said.

Speaker 4: DSS is a validated psoriatic arthritis-specific patient-reported outcome.

The piece that is a validated psoriatic arthritis specific patient reported outcome measure.

Furthermore earlier this year, we were delighted to report initial long term efficacy from the same phase two trials that showed that with longer duration of treatment patients experience durable and deepening resolution of disease across clinical manifestations of PSA, meaning further improvements in quality of life as measured by the.

Speaker 4: Furthermore, earlier this year, we were delighted to report initial long-term efficacy from the same phase two trial that showed that with longer duration of treatment, patients experienced durable and deepening resolution of disease across clinical manifestations of PSA, leading to further improvements in quality of life as measured by.

He said.

Additional data demonstrating the increased duration of therapy continues to enhance resolution of disease will be presented at both poster and oral podium sessions, taking place next Monday during the upcoming American College of Rheumatology is convergence at San Diego.

Speaker 4: Additional data demonstrating that increased duration of therapy continues to enhance resolution

Speaker 4: will be presented in both poster and oral podium sessions taking place next Monday during the upcoming American College of Rheumatology's Convergence in San Diego.

Speaker 4: At 46 weeks of participants receiving Izakayevac 80mg every other week, 79% achieved ACR50 response, up from 52%.

At 46 weeks of participants receiving its caused US 80 milligrams every other week, 71% achieved ACR 50 response up from 52% and week 16 and ease.

Speaker 4: And even higher orders of clinicals of response in measures approximating resolution of disease were observed with 52% achieving ACR 70.

Hydro orders of clinical response in there just approximating resolution of disease were observed with 52% of teasing ACR 70, 71% achieving policy, 189% achieving episodic resolution.

Speaker 4: 71% achieving POSI-100, and 89% achieving emphysitis resolution.

Notably patients who switched from placebo to 80 milligrams every other week at week 16 responded quickly.

Speaker 4: Notably, patients who switched from placebo to 80 milligrams every other week at week 16 responded quickly.

With more than 60% of patients in both the switch fruit as well as the original 80 milligram every other week group achieving minimal disease activity plus the 46.

Speaker 4: with more than 60% of patients in both the switch group as well as the original 80 milligram every other week group, achieving minimal disease activity by week 40.

Speaker 4: Importantly, this efficacy was delivered with a safety profile consistent with previous isochybect experience and that of the IL-17A class as a whole, with no evidence of dose limitation.

Importantly, this efficacy was delivered with a safety profile consistent with previous gets a cut that experience and that of the IL 17, a class as a whole with no evidence of dose limiting toxicity.

Modeling from the phase two PSA data predicted the potential to increase response overtime as has been demonstrated with the 46, we didn't.

Speaker 4: Modeling from the phase two PSA data predicted the potential to increase response over time as has been demonstrated with the 46-week data. The modeling further predicts the potential for increased efficacy with higher doses over the 80 milligrams every other week utilized in the phase two trial.

The modeling trying to predict the potential for increased efficacy with higher doses over the 80 milligrams every other week utilized from a safety trial.

Speaker 4: To that end, the ongoing Phase 2B3 trial in PSA is evaluating both 160 milligrams weekly and every other week to continue to maximize potential responses for patients.

That is the ongoing phase two b III trial. The PSA is evaluating both the 160 milligrams weekly and every other week to continue to maximize potential responses for patients.

Aside from the higher doses.

Design of this trial is consistent with that of the phase two with a few notable exceptions.

Speaker 4: The design of this trial is consistent with that of the Phase II, with a few notable improvements.

Speaker 4: Firstly, this is a truly global study with 352 patients across 71 sites, including 40 in the U.S. and 30 internationally, to enable the potential for registration across geography.

Firstly this is a truly global study with 352 patients across 71 sites, including 40 in the U S and 30 internationally to enable the potential for registration across geographies.

In addition, there was an increased percentage of emphasize at baseline and an increased percentage of TNF failures. Many individuals who have had an inadequate response empowers intolerance or contra indication.

Speaker 4: In addition, there is an increased percentage of endocytes at baseline and an increased percentage of TNF failures, meaning individuals who have had an inadequate response, intolerance, or contraindication.

Speaker 4: These aspects all have the potential to impact the specific point estimates relative to phase 2, but are important in understanding the potential benefits of ISA-TIZUP for PSA patients.

Sex all have the potential to impact a specific point estimates relative to say as to what are important in understanding the potential benefits are tied up for PSA patients well.

Speaker 4: Both are important given the contribution of ensitis to severity of disease, including continued pain to disability.

Both are important given the contribution of that decided to severity of disease, including continued pain and disability.

Speaker 4: And also the increasing number of patients who have not simply been exposed to TNF inhibitors, but have demonstrated an inadequate clinical response.

And also the increasing number of patients who are not simply been exposed TNF inhibitors, but have demonstrated an inadequate clinical response.

Speaker 4: This Phase 2b-3 trial in PSA completed enrollment in the second quarter of 2020.

This seems to be three trial and P. S. A completed enrollment in the second quarter of 2023.

Speaker 4: Over 75% of patients have completed through the primary endpoint at week 16, and the discontinuation rate is 5.9%.

Over 75% of patients have completed through the primary endpoint at week 16, and the discontinuation rate is five 9%.

Topline data continues to be expected in the first quarter of 'twenty 'twenty four.

Speaker 4: Top line data continues to be expected in the first quarter of 2020.

Speaker 4: Now, we'll turn our attention to Hyderadonitis Suprativa, which continues to be an area of rapid evolution.

Now I will turn our attention to hidradenitis, Suppurativa, which continues to be an area of rapid evolution.

Speaker 4: Just last week, only the second treatment for HS, and the first new option for patients in almost a decade, was approved by the FDA.

Just last week only the second treatment for Hs is the first new option for patients in almost a decade was approved by the FDA.

Speaker 4: We have the great fortune at Acceleron of having members of our team who held important roles in the context of each of these approved therapies, and for all of us, it's always gratifying to see new treatment options for patients.

We have the great fortune of out of children of the members of our team who held important roles in the context of each of these approved therapies and for all of US It's always gratifying to see your treatment options for patients.

At the same time well the other 17, a safety profile is well established we have also seen especially recently our understanding of the safety profile target sub units beyond the IL 17, a continuous to move off and they become a more important consideration.

Speaker 4: At the same time, while the other 17A safety protocols are well established.

Speaker 4: We have also seen, especially recently, our understanding of the safety profile of targeting subunits beyond I-017A continues to evolve and may be.

Targeting both Ana speaks to dose responsive increases local exceptions. This.

Speaker 4: Targeting both ANF leads to dose-responsive increase in focal inception.

Speaker 4: This was seen in data from both agents targeting inhibition of IL-17A.

This was seen in data from both agents targeting inhibition of IL 17 a F.

After 24 weeks of treatment, one demonstrated an approximate doubling of fungal infection risk for 12 weeks, which increased to about 20% in the plant ups and almost 30% in their higher dose with the beginnings of reports of occurrence of these local infections in areas beyond just skin.

Speaker 4: After 24 weeks of treatment, one demonstrated an approximate doubling of fungal infection risk from 12 weeks, which increased to about 20% in the planned dose and almost 30% in their higher dose, with the beginnings of reports of recurrence of these fungal infections in areas beyond just.

Speaker 4: Additionally, the risk of suicidal ideation and behavior was noted in a recent label of an IL-17-AS.

Additionally, the risk of suicidal ideation and behavior was noted in a recent label of an IL 17 a M.

This has been noted previously in the label on the anti IL 17 receptor inhibitor, which was all of a sudden 17, including IL 17 a F.

Speaker 4: This has been noted previously in the label of an anti-IL-17 receptor inhibitor, which blocks all the subunits of IL-17.

Cumulative data from these two agents over the Registrational programs raises the question of relationship between inhibiting IL 17, more broadly than IL 17, a specifically the potential association with the inhibition of last 15 half.

Speaker 4: Accumulative data from these two ages, over the registration of programs, raises the question of relationship between inhibiting IL-17 more broadly than IL-17A, specifically the potential association with the inhibition of IL-17A.

Speaker 4: This recent label also noted the requirement for routine laboratory monitoring for liver toxicity, which is not previously.

This recent label also noted the requirement for routine laboratory monitoring for liver toxicity, which has not previously voted for the us of the sellers.

So the landscape because that's what's evolving in terms of balancing efficacy and safety hurdles for new treatments for Hs patients.

Speaker 4: So the landscape is actively evolving in terms of balancing efficacy and safety hurdles for new treatments for atrial fasciitis.

Speaker 4: We believe it is a type of potential in H.S. with roughly 25% of patients achieving high score 100 responses within 12 weeks, which means they rapidly achieve resolution of all abscesses and nodules without needing to go to the ER.

We believe it is the type of schedule.

With roughly 25% of patients achieving high school 100 responses within 12 weeks, which means they rapidly achieve resolution of all absent seasonal the tools without me Crazy times.

This is a level of responders achieved in half the time reported by others and without the safety or Tolerability considerations of targeting IL 17.

Speaker 4: This is a level of responders achieved in half the time reported by others and without the safety or tolerability considerations of targeting IL-17F in addition to IL-17A.

Addition to IL 17, a.

Speaker 4: As we've previously shared, both our Phase 2P3 and our ongoing Phase 3 trial are moving forward, and discussions with the FDA will help inform next steps to advance our registrational program.

As we've previously shared both our phase three and our ongoing phase II trial are moving forward and discussions with the FDA will help inform next steps toward Bachelor of Registrational program.

We expect to have an update by the end of this year or early next year.

Speaker 4: We expect to have an update by the end of this year or early next year.

And in addition to P. S N H S. We continue to explore the potential for it to catch up to make a meaningful difference for patients with both X Y Z items.

Speaker 4: And in addition to PSA and HS, we continue to explore the potential for enzocagum to make a meaningful difference for patients with both asthma and uveitis. Enzocytus.

Decided is a central feature of Xbox and he believes the rates within the slightest resolution as demonstrated in the phase two PSA trials suggest the potential for clinically meaningful differentiated benefits for patients with this disease.

Speaker 4: And we believe the rates of endocytous resolution demonstrated in the Phase 2 PSA trial suggest the potential for clinically meaningful differentiated benefits for patients.

Speaker 4: We will use the optimal dose from the PSA program to inform a planned future phase 3 program next fall.

We will use the optimal dose from the PSA program towards form of planned future phase III program in asphalt.

Speaker 4: We also continue to enroll our Phase II B3 clinical trial with this concept as a treatment for UBI.

We also continue to enroll our phase two phase three clinical trial of its kind of as a treatment for uveitis previously reported data for another IL 17 inhibitor delivered intravenously.

Speaker 4: Previously reported data for another IL-17A inhibitor delivered intravenously has validated the inhibition of IL-17A as potential therapeutic for UBI.

Validated the inhibition of IL 17, a potential therapeutic for uveitis.

Well, that's a card that this lead program in our portfolio. We have two other programs a lot of them up and sell rental iPhone seven which we are developing in thyroid eye disease and muscle for the diseases.

Speaker 4: While InstaKypeUp is the lead program in our portfolio, we have two other programs, Lawn-a-goop-map and Acceleron 517, which we are developing in thyroid eye disease and mast cell

Thyroid eye disease is a vision threatening progressive chronic autoimmune disease and similar to H S. The tech landscape is evolving rapidly.

Speaker 4: Thyroid disease is a vision-threatening progressive chronic autoimmune disease, and similar to HS, the TET landscape is evolving rapidly.

Speaker 4: Our team has deep experience in this indication, with many involved in developing the only currently approved

Our team has deep experience in this indication with many involved in developing the only currently approved treatment.

Speaker 4: Recent clinical data demonstrating the effectiveness of inhibiting IGF-1 receptor in chronic tests supports our approach to developing Lomagutumab, not just for acute disease, but also more treatments for chronic inflammatory autoimmune diseases.

Recent clinical data demonstrating the effectiveness of inhibiting IGF, one receptor and kratos supports our approach to developing a lot of it.

Not just for acute disease, but also more treatments for chronic inflammatory autoimmune diseases.

Speaker 4: This includes targeting greater depth and durability of response with longer-term dosing and the goal of achieving resolution.

This includes targeting greater depth and durability of response with longer term dosing is a goal of achieving resolution of disease.

Recent updates with the M. P H the warnings and precautions of the currently approved therapy also highlighted hearing impairment as a serious potentially permanent side effect of treatment.

Speaker 4: Recent updates from the FDA to the warnings and precautions of the currently improved therapy also highlight hearing impairment as a serious, potentially permanent fight.

We have not publicized this hearing as care, but may be directly related to the inhibition of the normal function of IGF one given its small in regenerative cells in the inner ear subsequent to routine auditory insults.

Speaker 4: We have hypothesized that hearing impairment may be directly related to the inhibition of the normal function of IGF-1, given its role in regenerating cells in the inner ear subsequent to routine auditory impairment.

Speaker 4: The unique characteristics of a lot of these maps may allow us to optimize efficacy by maintaining minimum drug levels needed to achieve improved depth and durability of response, limit safety liability, including hearing impairment, potentially associated with high maximum drug concentrations, and maximize patient convenience through subcutaneous therapy.

The unique characteristics of all yourself may allow us to optimize efficacy, while maintaining minimum drug levels needed to achieve improved depth and durability of response limits safety liability, it's getting hearing apparent potentially associated with high maximum drug concentrations and maximize patient convenience.

Through subcutaneous delivery.

The phase one two trial of monarch at Mt delivered subcutaneously took patients is ongoing.

Speaker 4: The Phase 1-2 trial of London Mutant Mouth, delivered subcutaneously in 10 patients, is ongoing.

Speaker 4: We anticipate initial proof of concept data, including proctosis response and clinical activity score by end of first quarter 2020.

We anticipate initial proof of concept data, including Proptosis response, and clinical activity score by end of first quarter 2024.

So on slide seven is a fully human highly potent IGT want monoclonal antibody directed against C kit with the potential to address muscle diseases.

Speaker 4: SLN517 is a fully human, highly potent IgG1 monoclonal antibody directed against C-Kid with the potential to address mass overpopulation.

We are conducting a phase <unk> proof of concept trial silver five oneself and expect topline results in the second half of 'twenty 'twenty four.

Speaker 4: We are conducting a Phase 1-2 proof-of-concept trial of Aceleron 517 and expect top-line results in the second half of the year.

With that overview of the portfolio, let me now turn the call over to Gil for a review of our financials Gil. Thank you Charlie for overview of our portfolio and good afternoon everyone.

Speaker 5: With that overview of the portfolio, let me now turn the call over to Gil for a review of our financials. Gil? Thank you, Shalini, for that overview of our portfolio, and good afternoon, everyone.

Speaker 5: As Shalini mentioned, we are fortunate to be operating from a strong financial position as we not only advance our portfolio of clinical stage programs, but also build our organizational capability and identify potential additional diamonds in the rough to add to our pipeline.

Sheldon you mentioned, we are fortunate to be operating from a strong financial position.

As we not only advance our portfolio of clinical stage programs, but also build our organizational capability and identify potential additional diamonds in the rough Torchmark board.

At September 32023, cash and cash equivalents and short term marketable securities totaled 780 844 million, which.

Speaker 5: At September 30, 2023, cash and cash equivalents and short-term marketable securities totaled $788.4 million, which we expect to fund operations through

Which we expect to fund operations through key value driving milestones across all three programs.

Speaker 5: value driving milestones across all three programs.

Research and development expenses were $74.6 million for the <unk>.

Speaker 5: Research and development expenses were $74.6 million for the third quarter as compared to $12.5 million for the same period in 2022.

Third quarter as compared to $12 5 million.

For the same period of 2022.

Speaker 5: Comparing 2023 to 2022, the company has undergone significant growth, including the expansion of the Isokaibat program across multiple indications, and the addition of two programs in 2023, both of which are now in clinical stage development.

Comparing 2023 to 2022 the company says are gone significant growth including expansion.

That program across multiple indications.

The addition of two programs of 2023.

Both of which are now a clinical stage development.

General and administrative expenses were 19 4 million.

Speaker 5: General and administrative expenses were $19.9 million for the third quarter as compared to $2.9 million for the same period in 2022.

For the third quarter as compared to 2.9 billion for the same period in 2022.

The quarter ended September 32023, including stock based compensation expense of $11 7 million.

Speaker 5: The quarter ended September 30, 2023, includes stock-based compensation expense of $11.7 million.

These increases in expenses were primarily a result of expanding our organizational capabilities to support the development of our broad portfolio of immunology product candidates. Finally, our net loss for the third quarter of 2023 totaled $83 9 billion.

Speaker 5: These increases in expenses were primarily a result of expanding our organizational capability to support the development of our broad portfolio of immunology product candidates.

Speaker 5: Finally, our net loss for the third quarter of 2023 totaled $83.9 million, or $0.87 per share, compared to $14.4 million, or $8.17 per share, for the third quarter of 2023.

87 cents per share compared to $14 4 million.

Or $8 17 per share for the third quarter of 2022.

Speaker 5: The total net loss for the current quarter includes stock-based compensation expense of $15.3 billion.

The total net loss for the current quarter includes stock based compensation expense of $15 3 billion.

Speaker 5: As you can see, we continue to carefully allocate capital across our robust clinical portfolio and we're delighted to have a strong financial position for which to continue our important work for patients. And now I will turn the

As you can see.

We continue to carefully allocate capital across our robust clinical portfolio.

We're delighted to have a strong financial position from which to continue our important for patients.

And now I will turn the call back to Xiaomi shortly.

Thanks Gil.

Speaker 4: As you've heard, we continue to make steady progress in our efforts to build a leading immunology company.

As you've heard we continue to make steady progress in our efforts to build a leading immunology company.

We feel fortunate to have an experienced team a robust pipeline and a strong financial position providing runway through multiple key milestones across all three clinical programs.

Speaker 4: a robust pipeline, and a strong financial position providing runway for multiple key milestones across all three clinical programs.

Speaker 4: We remain committed to our long-term vision to accelerate the development and commercialization of transformative medicines to address unmet medical needs and to deliver sustainable value to our shareholders, partners, and most importantly, to the patient.

We remain committed to our long term vision to accelerate the development and commercialization of transformative medicines to address unmet medical needs and to deliver sustainable value to our shareholders partners and most importantly to the patients we serve.

Speaker 4: In the ever-evolving landscape of our industry, we understand the importance of adaptability and resilience.

In the ever evolving landscape of our industry, we understand the importance of adaptability and resilience.

Speaker 4: We are committed to making data driven, disciplined decisions, as well as being responsible stewards of our human and financial resources in navigating challenges and embracing opportunities. Once again.

We are committed to making data driven disciplined decisions as well as being responsible stewards of our human and financial resources in navigating challenges and embracing opportunities.

Once again I. Thank you for your trust and support we look forward to your continued partnership as we journey ahead together.

Speaker 4: We look forward to your continued partnership as we journey ahead together. Operator, we are now ready.

Operator, we are now ready to open the call to questions.

Thank you.

Speaker 2: Thank you. We will now conduct the question and answer session.

We'll now conduct a question and answer session.

Speaker 2: To ask a question, please press star one one on your telephone and wait for your name to be announced.

To ask a question. Please press star one on your telephone and wait for your name to be announced.

Speaker 2: To withdraw your question, please press star 11 again. Please stand by while we.

To withdraw your question. Please press star one again.

Please stand by while we compile the Q&A roster.

Speaker 2: Our first question comes from Yasmin Rahimi from Piper Sandler. Please go ahead.

Our first question comes from.

He asked me right Amy.

Piper Sandler. Please go ahead.

Good afternoon team and thank you so much for all your really talked about hallmark for us.

Speaker 6: Good afternoon team and thank you so much for all your really thoughtful remarks for us.

Speaker 6: Team, as we're awaiting that PSA data early next year, could you maybe comment on sort of how soon post the second Phase IIB, Phase III would you be in a position to get ready and file for approval in PSA and whether the data would be sufficient on the heels of both of the results, if you could just provide color in that regard.

Team and we're awaiting that PSA data and early next year could you maybe comment on sort of how to post the second phase TBC would you be in a position to get.

Get ready to file for approval in PSA and whether the data would be sufficient on the health of both of the resolved. If you could just provide color in that regard.

Speaker 6: And then two, if you could just maybe comment on how you're tracking, you know, or have been tracking or are tracking currently like suicide ideation, liver enzyme abnormalities to the extent you can across all studies and I'll jump back into the queue. And thank you again.

And then two maybe you could just maybe comment on how you're tracking you know or have been tracking archrock concurrently.

To cite ideation liver enzyme abnormalities to the extend you can across all studies.

And I will jump back into the queue and thank you again.

Speaker 4: Thank you. This is Shelly. So with regards to PSA, we anticipate that registration will require both the ongoing Phase 2B3 that we hope to be part of that package, as well as a confirmatory study, which is standard for these indications.

Thank you, yes. This is shelly.

With regards to our PSA, we anticipate that registration will acquire.

The ongoing phase two b three that we hope to be part of that package as well as a confirmatory study with just standard.

For these indications we haven't yet provided guidance.

I think lead times post.

Speaker 4: time post, you know, sort of post this study readout relative to.

Sort of post this study read out relative to what we think that would be.

Speaker 6: But obviously, we'll move forward expeditiously, as expeditiously as possible. With regards to the signals that you've noted, really since the Bridalium experience with this group, these have been endpoints that have been followed across the IL-17 class and we're following the standard approaches there as well. Okay. Thank you. I'll jump back into the queue.

But obviously, we'll move forward expeditiously as expeditiously as possible with regard to the signals.

That you've noted you know really since the <unk> experience.

With his group.

Ben.

Endpoints that even the followed across the IL 17 class.

And we're following the standard.

Approaches there as well.

Okay. Thank you I'll jump back into the queue.

Thank you.

One moment for our next question.

Our next question comes from Tyler Van Buren from PV Cowen. Please go ahead.

Speaker 2: Our next question comes from Tyler Van Buren from TD Cowan, please go ahead.

Speaker 6: Hi, this is Beth on for Tyler. Thank you guys for taking our questions. We have 2 for you. So, 1st, looking forward to the top line PSA phase 2, 3, read out and 2, 1, how are you thinking about the bar for success given that the mechanism of phase 3 data and other recent competitor read out?

Hi, This is Stefan for Tyler. Thank you guys for taking our questions. We have two for you. So first of all looking forward to the topline PSA phase three readout in Q1, how are you thinking about the bar for success given the been the kid's mouth phase III data and other recent competitor readout.

Speaker 6: And then two for the long and good mad, mad head patient readout and Q1, how many patients worth of data might we see across the 3 to 4 dose cohorts and how the risking do you expect the early proctosis data to be as we think about efficacy in later stage trials. Thank you.

And then two for the moment good Mad Mad Ted patient readout in Q1, how many patients worth of data might we see across the three to four dose cohorts and how Derisking do you expect the early proptosis data to be as we think about efficacy and later stage trials. Thank you.

Super Thanks, Beth So your first question was about the upcoming PSA <unk> readout in first quarter of 'twenty four and the bar for success you know the way we think about this is that the phase two studies that we've already completed that went up to 80 milligrams and want to make sure those.

Speaker 4: Super. Thanks for that Beth. So your first question was about the upcoming PSA 2B3 readout in first quarter of 24 and the bar for

Speaker 4: You know, the way we think about this is that the phase 2 study that we've already completed that went up to 80 milligrams and we're going to share the long-term data, even additional measures of resolution of disease at the upcoming ACR meeting, we feel like that study already demonstrated the potential for differentiation with izakaibap, especially the top-dose 80 milligrams every other one.

Long term data you can even additional measures of resolution of disease at the upcoming ACR meeting, we feel like that study already demonstrated the potential for differentiation within Sky bet, especially the top dose of 80 milligrams every other week, we see top range results with regards to joints and skin.

Speaker 4: We've seen top-range results with regards to joints and skin at the week 16 primary endpoint and really outsized endocytosis results as we recap today within that time frame. And that just hasn't been seen before with other.

<unk> primary end point and really outsized emphasized as a result of the recap today.

Within that timeframe and in the future.

<unk> been seen before with other agents.

Speaker 4: And we've shared that at the 46-week time frame, we see, you know, sort of even continued deepening of those responses, again, as we've shared today with ACR 50s, or sorry, ACR 70s, up at above 50%, POSI 100 scores, up over 70%, and emphysitis still in the kind of 80s and 90s.

And we've shared that at 46 week timeframe, we see.

Even continued deepening of those responses.

Again, as we've shared today with ACR fifties Oh.

Or I'm, sorry use our seventy's up at above 50% pardon me 100 scores over 70% and emphasized is still in the kind of 80% to 90% range. So we're very very pleased with those results. We think that they fundamentally derisk. The TB three that are coming up.

Speaker 4: So we're very, very pleased with those results. We think that they fundamentally de-risk the 2B3 that's coming up. We conducted that 2B3 really because our modeling from that phase two suggested to us that we could get some additional efficacy out of additional pushing the exposure a bit more within the context.

<unk> conducted that television really because our modeling from that phase II suggested to us that we could get some additional.

Efficacy out of additional pushing the exposure a bit more within the context of the state and so that's the reason for the additional dose ranging the television portion if you will of the TB three that's upcoming.

Speaker 4: And so that's the reason for the additional dose ranging, the 2B portion, if you will, of the 2B3 that's upcoming. As a for instance, we know from our earlier psoriasis experience that moving from 80 every other week to 160 every other week in psoriasis did give us a bit of a bump with regards to efficacy. So at a minimum, we hope to recapitulate that. But already, we feel like we have a differentiated

And as a for instance, we know from our earlier thrives as experienced that moving from 80 every other week to 160 every other week in psoriasis.

With regards to efficacy or at a minimum we hope to recapitulate that but.

But already we feel like we have a differentiated.

Offering.

Speaker 4: And then your second question was about monoglutinab and how much data we would have moving forward and how de-risking that is, you know, sort of overall. I think what you can anticipate is that from a proof of concept, initial proof of concept perspective, you know, we'll have proof of, we'll have a number of patients that are very similar to what's been demonstrated previously for the Viridian and Immunivax sort of

And then your second question was about Manav, good map and how much data we would have moving forward and help you risking that is sort of overall I think what you can anticipate is that from a proof of call. It. The initial proof of concept perspective, we'll have.

Uh huh.

We will have a number of patients that are very similar to what's been demonstrated previously for the Caribbean and even if that.

Speaker 4: compounds on the order of, you know, six or so patients in those experiences have been sufficient to really demonstrate the potential for signal across the both proctosis as well as.

Compounds on the order of.

Six or so patients in those experiences have been sufficient to really demonstrate the potential for signal across both proptosis as well as clinical activity score. So we'll have those measures are within the context of 10 patients to evaluate we may have more patients than that.

Speaker 4: So we'll have those measures within the context of TED patients to evaluate. We may have more patients than that, but

You know as we move forward, we'll have a better better beat on that.

Speaker 4: As we move forward, we'll have a better beat on that. And because of the strong signal in terms of efficacy that we see with this axis, we anticipate it's not going to take much more than that to see a signal for these agents, again, as has been demonstrated already.

And.

Because of the strong signal in terms of the efficacy that we see with this axis.

We anticipate that's not going to take much more than that.

See a signal.

For for these agents again as has been demonstrated.

Already.

Yeah.

Thank you.

One moment for our next question.

Okay.

Speaker 2: Our next question comes from Vikram Pirohit from Morgan Stanley . Please go ahead.

Our next question comes from frequent peer Rohit.

From Morgan Stanley. Please go ahead.

Hi, everyone. This is golf ball on for Freedom, we have two questions regarding the PSA in Hs.

Speaker 7: Hi, everyone. This is Garth Paul on phone frequency. We have two questions regarding PSA and HS. So for PSA, I was wondering what the competitor data readout has data tells you, if anything, about the importance of molecule size for the treatment of PSA. And then in regards to HS, I was wondering, have you been able to further analyze the results to better understand the placebo response?

For PSA I was wondering.

I was wondering I was wondering what the competitor data readout.

No data tells you if anything about the importance of molecule size.

But it could meant of PSA and then in regards to it just I was wondering have you been able to further analyze the results to better understand the placebo response.

Speaker 7: and discontinuation rate observed? If so, did you currently see any read across to the ongoing PSA readout?

Discontinuation rates observed <unk>.

Did you currently see any read across to the ongoing Psa ever get out.

Speaker 7: and idea measures that have been put in place for that study to prevent similar issues from arising.

IBM measures that have been put in place for that study to prevent similar it seems like issue from horizon.

Thank you.

Thank you for that thoughtful.

Speaker 4: Thank you for that gospel. You know, maybe I'll start backwards a little bit to tie it back in, which is, you know, and I appreciate the question. Obviously, given our HS readout that we shared in September , we've been extraordinarily hyper vigilant with regards to putting in any measures such that we understand in real time, continue to understand and ensure that we are understanding in real time.

Maybe I'll start backwards, a little bit Uh huh.

Tied back in which is.

You know.

And I appreciate the question, obviously, given our H S meat out that we shared in September we've been extraordinarily hyper vigilant.

With regards to putting in any measures such that we understand real time.

Or else, we will continue to understand and ensure that we are understanding in real time any discontinuation as well as.

Speaker 4: as well as putting into place anything that could help from a placebo response perspective. We don't anticipate any read-through to our PSA, and we think that our sort of blinded, continued analysis haven't suggested anything.

Putting into place of anything that could help from a from a placebo response perspective, we don't anticipate any read through to our PSA and we think that are sort of blinded continued analysis haven't suggested to us any any issues in that regard. We have continued further deep dives with regards to the Hs dataset.

Speaker 4: issues in that regard. We have continued further deep dives with regards to the H.S. data set, and as I shared in our prepared remarks, we anticipate having more information with regards to that program by end of year, early next year, to share when we have relevantly compiled both our conversations with the health authorities as well as the deep dives that

And as I shared in our prepared remarks, we anticipate having.

More information with regards to that program by end of year early next year to share when we have relevant to be compiled both our conversations with the health authorities as well as the deep dives that that continue to be ongoing.

Speaker 4: So bottom line is H.S. continues to move forward with regards to the 2B3 study that ran out as primary as well as the ongoing phase 3 as planned as we had previously planned.

So bottom line is.

It just continues to move forward with regard to be three study that read out its primary as well as the ongoing phase III.

As planned as we have previously discussed.

Speaker 4: We don't anticipate a read-through to PSA, and from the PSA perspective, you know, we do think that there is importance still with regards to the molecule size and the potential for differentiation. We think our Phase II results, especially in emphysitis.

We don't anticipate at least with the PSA and from the PSA perspective.

We do things to that.

<unk> is important still with regards to the molecule size and the potential for differentiation, we think our phase two results, especially and emphasize a point to that.

Speaker 4: point to that, exactly where the threshold was for, you know, the size cutoff that could enable us to get into that dense, strong sort of polyvascular tissue relative to other molecules wasn't entirely clear. I, you know, I will say that the data more recently suggests that not only is the threshold between our 18 kilodaltons and the 150 or so for the marketed monoclons, but perhaps is even between the 18 and the 40.

Exactly where the threshold for.

<unk> cut off that could enable us to get into that dense strong sort of smaller poorly vascular tissue relative to.

Other molecules wasn't entirely clear I, you know I will say that the data more recently suggests that not only is the threshold between our 18 kilovolt ones and the ones you see yourself more towards the marketed monopoles.

But perhaps as is even between the 18 in the 40.

Speaker 4: That was be kiled on of recently.

We.

Recently released data.

Speaker 4: given the difference in endocytosis. I've shared with you today, in our prepared remarks, our best attempt at an apples-to-apples comparison, given the data that was presented, not with regards to LEI resolution, which we've shared previously, but with regards to LEI 2-plus at baseline, improving more than 2-plus points.

Given the difference in episodic like I've shared with you today.

In our prepared remarks, our best attempt at an apples to apples comparison.

Given the data that was presented.

With regards to the Eliott resolution, which we've shared previously but with regards to Elliot to.

Plus at baseline improving.

More than two points over the course of the study.

Speaker 4: over the course of the study, and recall that that was, for us, at week 8, an earlier time point because we didn't collect it in week 12, a 100% response for that degree of change or improvement versus a placebo of 0% relative to 71% without the placebo reporting.

And recall that that was up for us as we gained an earlier time point, because we didn't collect 12 Ah ha.

Percent.

For that degree of change and improvement.

Comparisons of placebo zero percent realm.

Relative to 71% without the placebo reported.

Okay.

Yeah.

Thank you.

One moment for our next question.

Our next question comes from.

Speaker 2: Our next question comes from Emily Botner from H.C. Wainwright, please go ahead.

<unk> partner.

From H C. Wainwright. Please go ahead.

Hi, Thanks for taking the question.

Speaker 6: Hi, thanks for taking the questions, um, kind of along the lines of some of the other questions on PSA. I was wondering if you can maybe discuss.

Kind of along the lines of the other questions on PSA I was wondering if you can maybe discuss what unacquainted metrics, but physicians are most looking to see an improved upon or where are they kind of feed the largest unmet need where you think you can differentiate I know you talked about empathy, that's already but are there.

Speaker 8: What endpoints or metrics that physicians are most looking to see improved upon or where they kind of see the largest unmet need where you think you can differentiate. I know you've talked about and decided already, but are there any other places where, where you kind of see the kinds of differentiating and maybe just on expenses. If you can.

Any other places where were you kind of see they'll probably go up to.

Differentiating.

And then maybe just on expenses if you can touch on.

Speaker 8: touch on. It looks like in 3Q, the expenses kind of doubled from the second quarter. So is that kind of a base level for you going forward or?

It looks like in three Q the expenses kind of doubled from the second quarter. So does that kind of a base level for you going forward or any guidance you can give out expenses for.

Speaker 8: any guidance you can give on expenses for the remainder of the year or next year. Thank you.

For the remainder of the year or next year.

Yeah. Thanks for that I believe maybe I'll start with PSA sort of disease state notifications et cetera, and I'll, let bill handle the second question.

Speaker 4: Yeah, thanks for that, Emily. Maybe I'll start with PSA, sort of disease state manifestations, et cetera, and I'll let Gil handle the second question.

Speaker 4: So, you know, with regards to where we think the field is going and what's important for patients, and therefore for our investigators as well, is that we really need to do better with regards to our treatment offerings for these patients. We've traditionally been talking about an ACR 50 response in the 50% sort of range. And, you know, what that means is that.

So with regards to where we think the field is going and what's important for patients and therefore for for our investigators and Kols as well is that we really need to do better with regards to our.

Treatment offerings for these patients we've traditionally been talking about on ACR 15 response of a 50% sort of range and you know.

What that means is that half the people, who will get 50% better with regards to their joint disease, which is.

Speaker 4: you know, half the people will get 50% better with regards to their joint disease, which is.

Speaker 4: know, a pretty low bar still if you think about how much better we should be able.

A pretty low bar still if you think about how much unmet need how much better we should be able to do so it seems like ACR 70.

Speaker 4: So things like ACR 70s are as close to remission as we've been able to have within the ACR scoring system. POSI 100s are sort of all clear skin. Encephalitis resolution means that I don't have any more encephalitis that I can measure, which is terrific. And so it's really the totality of all of the manifestations of this disease that, therefore, as you can imagine, impact most the overall quality of life of people.

Or as close to remission as we've been able to have within the ACR, scoring system pausing. One hundreds are sort of all clear skin emphasizes resolution means that I don't have any more insight that I can I can measure, which is terrific and so it's really the totality of all of the minutes manifestations of this disease.

Yes.

That therefore as you can imagine impact most the overall quality of life of patients. So it's important not just to hit the joints in the skin. Although of course, one once the infamous hardest one can really be able to talk about with mission of resolution ACR seventies and the.

Speaker 4: So it's important not just to hit the joints and the skin, although of course one wants to hit them as hard as one can, really be able to talk about remission or resolution, ACR 70s, and the majority of people achieving ACR 70s, the vast majority of people achieving POSI-100, and now we feel like we're in a time that the vast majority of people are achieving resolution of their emphysitis, which is again, a marker of severity of disease, of residual pain and dysfunction.

The majority of people achieving ACR 70 is the vast majority of people achieving pardon me 100, and now we feel like with this aside that the vast majority of people.

Teasing resolution of their emphasizing switches again.

Marker of severity of disease of residual pain and dysfunction for these patients that obviously adds up to <unk>.

Speaker 4: obviously adds up to the quality of life. And one of the measures of, you know, sort of this overarching

These license and one of the measures.

You know some of this overarching.

Speaker 4: resolution of disease is also minimal disease activity. And as we've shared, you know, both our switch from placebo to active in the phase two study as well as the 80 milligram from the get-go, those subjects are achieving about 60% minimal disease activity in the upcoming day.

Resolution of disease is also minimal disease activity.

And as we've shared both our switch from placebo to active in the phase two study as well as the 80 milligram, we get though those subjects are achieving about 60%.

Minimal disease activity.

In the upcoming dataset that will be presented so we're excited about this we think that the to be three gives us the potential to impact this even further.

Speaker 4: So we're excited about this. We think that the 2B3 gives us the potential to impact this even further. And we already know that the opportunity exists based on our existing data to do that from a skin.

And we already know that the opportunity exists based on our existing data to do that from a skinny.

Speaker 9: Granted, to the financial question, Emily, you know, as I said in my prepared remarks, we ended the quarter with over $788 million.

Phil great into the to the financial question. Emily You know as I said in my prepared remarks, we ended the quarter with over $788 million.

Cash on the balance sheet. So obviously, we're in a very strong financial position.

Speaker 9: cash on the balance sheet. So obviously we're in a very strong financial position where.

Speaker 9: have sufficient funding to go through catalysts across our pipeline.

Sufficient funding to go through kind of was across our pipeline.

Speaker 9: At this stage, we're not giving specific line item guidance, but I can tell you that we're thinking very carefully.

At this stage, we're not giving a specific line item guidance, but I can tell you that we're thinking very carefully about how we allocate capital stage appropriate we're scaling investments.

Speaker 9: about how we allocate capital stage appropriate.

Speaker 9: We're scaling the investments as we scale the trials. And so we're obviously in 2024 planning, and we're looking very closely at that and being prudent with our capital, but we're really pleased with where we are at this point.

Scale, but the trials.

So we are obviously in 2020 for planning and we're looking very closely at that and being prudent with our capital, but we're really pleased with where we are at this point.

Got it okay. Thank you.

Yeah.

As a reminder.

Speaker 2: As a reminder, if you would like to ask a question, please press star one one and wait for your name to be announced.

If you would like to ask a question. Please press star one one and wait for your name to be announced.

One moment for our next question.

Our next question comes from cash to here from Jefferies. Please go ahead.

Speaker 2: Our next question comes from Akash Tahiri from Jeffries. Please go ahead.

Hey, Thanks, so much for taking my question. So I remember as of September you had mentioned the blinded dropout rate for your upcoming Psoriatic arthritis trial was around 5% any color on what thats tracking through as we get into November and what level of drop out the claim with for this trial with your current powering assumptions and then I guess, maybe on the Hs can you go.

Speaker 10: Hey, thanks so much for taking my question. So I remember as of September , you had mentioned the blinded dropout rate for your upcoming psoriatic arthritis trial was around 5%.

Speaker 10: Any color on what that's tracking to as we get into November and what level of dropouts do you claim with for this trial with your current powering assumptions?

Speaker 10: And then, I guess, maybe on HS, can you go over precisely what your HS protocol deemed to be drug related or not? For example, in the circumstance by which a participant had an injection site reaction and also stop treatment.

Over precisely what Youre Hs protocol deemed to be drug related or not for example in the circumstance by which a participant had an injection site reaction and also stopped treatment how would you determine whether that was a drug related discontinuation or otherwise. Thanks. So much.

Speaker 10: How would you determine whether that was a drug-related discontinuation or otherwise? Thanks so much.

Speaker 4: Thanks, Akash. So, with regards to your first question about the PSA study that's about to weed out and discontinuation rates, so as I shared in our prepared remarks, we are at over 75% of patients within the context of that trial, having completed through the primary endpoint, and our discontinuation rate currently is 6.9%.

Thank you Josh.

So with regards to your first question about the PSA study, that's about to read out and Andrew and discontinuation rates.

So as I shared in our prepared remarks.

<unk>.

We're at over 75% of patients within the context of that trial, having completed through the primary endpoint.

Continuation rate currently and six 9%, so we feel well apologies five 9%.

Speaker 4: 5.9% and you know and it just speaks to my mindset with regard to my next comment which is really that anything below 10% is the usual threshold that we think about for clinical trials in general and if it bounces around within the context of that number but is below 10% we really aren't concerned. So we're feeling very good about where we are with that study at this juncture and as I said earlier to Emily's comments really don't feel like there's any read-through.

And.

And it just speaks to my mindset with regard to my next comment which is really not anything below 10%.

As usual threshold that we think about for clinical trials in general.

And if it bounces around within the context of that number but what is below 10%, we really aren't concerned. So we're feeling very good about where we are.

With that study at this juncture and as I said earlier to Emily's comments really don't feel like Theres any read through.

Speaker 4: That and we wouldn't have expected that

And we wouldn't have expected that but we don't think we're seeing that.

Speaker 4: that. Separately with regards to HS and scoring of ISRs and whether or not those are adverse events, we take that as reported to us.

Currently with regards to H S and X.

And scoring of ISR and whether or not those are adverse events.

We treat that as a as reported to us ISR and whether or not they were dropouts due to ISR.

Speaker 4: ISRs and whether or not they were dropouts due to ISRs, when we talk about our dropouts.

When we talk about our dropouts.

Speaker 4: As discontinuations, we were responders without adverse events, we actually went back through and didn't just take at face value whether or not it was reported to us as whether it was a loss to follow up or through consent, etc. We went back through the entire electronic database.

And discontinuation.

Responders without adverse events, we actually went back through and didn't just take at face value and whether or not it was reported to us as the weather was lost to follow up with you as concerns et cetera, We went back maybe entire electronic dataset.

Speaker 4: and evaluated for whether or not there was a pattern, including looking for ISRs that weren't necessarily reported.

And evaluated whether or not there was no pattern, including looking for ISR that weren't necessarily reported as an AE and that pattern also does not exist, which I think is probably your underlying question.

Speaker 4: And that pattern also does not exist, which I think is probably your underlying question.

Awesome. Thanks, so much.

Thank you.

Speaker 2: I am showing no further questions. I will now turn the conference over to Tyler Marciniak for closing remarks.

I am showing no further questions I will now turn the conference over to Tyler Mark <unk> for closing remarks.

Speaker 3: Thank you all for joining today's opportunity for us to share with you our third quarter financial results and corporate updates. As Shelley and Gil mentioned, thank you for your trust and support as we continue to build Celeron into a leading I&I company.

Okay.

Thank you all for joining today's opportunity for us to share with you our third quarter financial results and corporate updates.

Thank you for your trust and support because we continue to build a salary into a leading ini company.

Speaker 3: We look forward to engaging with you regularly and transparently, and in that vein, I would like to highlight once again our upcoming PSA data presentations at ACR and the several investment conferences we are attending in the coming weeks. We hope to see you in person soon and would encourage you to view the Fireside Chats and other resources we regularly post to our website. And of course, please feel free to contact our investor relations team at any time if we can be of service.

We look forward to engaging with you regularly and transparently.

I would like to highlight once again, our upcoming POC data presentation at ACR and several investment conferences. We are attending in the coming weeks. We don't see you in person soon I would encourage you to view the fireside chat and other resources, we regularly posted to our website.

Of course, please feel free to contact our Investor relations team at any time, if we can be of service to you.

Speaker 3: With that, we'll conclude our call for today. Thank you very much.

That will conclude our call for today.

You very much.

This concludes today's conference call. Thank you for participating you may now disconnect.

Speaker 2: This concludes today's conference call. Thank you for participating. You may now disconnect.

Yeah.

Okay.

[music].

[music].

Speaker 11: I.

[music].

Good day, and thank you for standing by.

Speaker 2: Good day and thank you for standing by.

Speaker 2: Welcome to the Celeron Q3 2023 Earnings Conference Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session.

Welcome to the seller in Q3 2023 earnings conference call.

At this time all participants are in listen only mode. After.

After the speaker's presentation, there will be a question and answer session.

Speaker 2: To ask a question during this session, you will need to press star one one on your telephone.

To ask a question during this session.

Need to press star one on your telephone.

You would then here an automated message advising your hand is raised to withdraw your question. Please press star one again.

Speaker 2: You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded.

Please be advised that today's conference is being recorded.

Speaker 2: I would now like to hand the conference over to Tyler Marciniak, Vice President of Investor Relations, Communications, and Corporate Operations. Please go ahead.

I would now like to hand, the conference over to Tyler <unk>, Vice President of Investor Relations Communications and corporate operations. Please go ahead.

Thank you operator.

Speaker 3: Thank you, operator. Good afternoon, everyone. And thank you for joining us before we begin. I'd like to remind the audience that this conference call will contain forward looking statements, such as those related to progress of our clinical trials and anticipated data readout our future financial and operating results and investments and our ability to commercialize our product candidates.

Afternoon, everyone and thank you for joining us before we begin I'd like to remind the audience that this conference call will contain forward looking statements such as those related to progress of our clinical trials and anticipate data readouts for future financial and operating results and investments and our ability to commercialize our product candidates.

Speaker 3: These forward-looking statements involve risks and uncertainties that could cause our actual results and events to differ materially. We urge you to review the risk factors section of our Form 10-Q for the quarter ended June 30, 2023, filed at the SEC, and also available on our website at aceleron.com, along with statements 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.

These forward looking statements involve risks and uncertainties that could cause our actual results and events to differ materially we urge.

Or would you to review the risk factors section of our Form 10-Q for the quarter ended June 32023 filed with the SEC and also available on our website at <unk> Dot com along with statements in today's press release, and our slide presentation, which identifies certain factors that could cause our actual results performance and events to differ materially.

Yeah.

Additionally, these statements are based on information available to US today November seven 2023, and we undertake no obligation to update them as circumstances may change.

Speaker 3: Additionally, these statements are based on information available to us today, November 7, 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 CEO and Gillman grocery our chief Financial Officer.

Speaker 3: Joining us on today's call are Dr. Xiaoli Lin, our founder and CEO , and Gilda Bruchery, our Chief Financial Officer. I will now turn the call over to Dr. Lin. Xiaoli? Thank you, Tyler.

I will now turn the call over to Dr. Linda <unk>.

Shelly.

Thank you Tom good.

Good afternoon, everyone.

Thank you for joining us for a solid third quarter update call.

Speaker 4: As we approach the end of 2023, we feel fortunate for the progress we have made throughout the course.

As we approached the end of 2023, we feel fortunate for the progress we have made throughout the course of the year.

Speaker 4: We began in January with the transformative expansion of our portfolio through the acquisition of another private I&I company.

It began in January and forward and expansion of our control.

The acquisition of another private company.

Speaker 4: And in May, we were pleased to close a successful IPO in a challenging market environment.

And in May we were pleased to close the successful IPO in a challenging market environment.

Okay.

Speaker 4: We are grateful to our investors for walking alongside with us in our journey as we remain focused on building a leading I&I company.

We are grateful to our investors for walking alongside with us.

As we remain focused on building a media company.

Speaker 4: and continuing to advance programs across multiple autoimmune and inflammatory diseases with the goal to deliver transformative medicines for patients.

Continuing to advance programs across multiple autoimmune and inflammatory diseases with the goal to deliver transformative medicines for patients.

Our strategy remains steadfast.

Speaker 4: To identify candidates we believe are diamonds in the rough, where based on molecule characteristics, our collective experience and expertise, and the evolving scientific

To identify candidates, we believe our guidance were based on molecule characteristics, our collective experience and expertise in the evolving scientific and medical understanding.

Speaker 4: We can establish a development plan to test our hypotheses around clinical differentiation and the potential benefit for patients.

We can establish development plan to test our hypothesis around clinical differentiation.

For patients.

We are advancing our portfolio of programs across multiple indications, including as kind of the next generation <unk> inhibitor <unk> being studied in multiple trials with registrational potential within the rheumatology dermatology and ophthalmology generics.

Speaker 4: We are advancing our portfolio of programs across multiple indications, including isekaiba, the next generation inhibitor of IL-17A, being studied in multiple trials with registrational potential within the rheumatology, dermatology, and ophthalmology settings.

Lot of good map, a subcutaneously delivered inhibitor of IGF one receptor.

Speaker 4: a subcutaneously-delivered inhibitor of IGF-1 receptor being developed for thyroid IgM.

Developed with thyroid eye disease.

Speaker 4: And SOM 517, an earlier stage program we are evaluating for allergy-related mast cell driven disease.

And so were 507 and earlier stage program, we are evaluating for allergy related mass cell driven diseases, such as contract attached.

In addition to our clinical progress we continue to build our organizational capability and capacity to support our portfolio.

Speaker 4: In addition to our clinical progress, we continue to build our organizational capability and capacity to support our portfolio.

Speaker 4: Most recently, we announced the appointment of Patricia Turney as our Chief Technical Operations Officer, responsible for overseeing technical operations, CMC regulatory, corporate quality, and...

Most recently, we announced the appointments of Patricia.

Chief Technical operations officer responsible for overseeing technical operations CMC regulatory corporate quality.

Patricia brings to account for 25 years of biopharmaceutical experience across R&D clinical and commercial supply management and expands our capacity for multi assets late stage manufacturing at a pivotal time as we have a robust portfolio.

Speaker 4: Patricia brings to a cell in more than 25 years of biopharmaceutical experience across R&D, clinical and commercial supply management, and expands our capacity for multi-asset late-stage manufacturing at a pivotal time as we advance a robust portfolio.

Speaker 4: with multiple large-scale clinical trials underway and prepare for potential regulatory filings and commercial launches.

Multiple large scale clinical trials underway and prepare for potential regulatory filings and commercial launches.

We also welcomed in September Dr shifts.

Our senior Vice President of development responsible for clinical development and translational Sciences.

Speaker 4: Our Senior Vice President of Development, responsible for clinical development and translational science.

Speaker 4: Shep brings more than 20 years of industry experience, including a long tenure at Novartis where he most recently served as Senior Vice President and Chief Medical Officer for Novartis G-Therapy.

Jeff brings more than 20 years of industry experience, including a long tenure at Novartis, where he most recently served as senior Vice President and Chief Medical Officer for large gene therapies.

Speaker 4: Prior to that, Shep was the global lead for Cetakinumab, where he advanced the product from early development through to multiple approvals across the indications, including psoriatic arthritis, or PSA, hyperadenitis subcutaneous, or HS.

Prior to that ship with the global lead for such Kitimat, where he advanced product from early development through multiple approvals across indications, including Psoriatic arthritis PSA hi.

Hi, Brad neither <unk> or Hs.

Speaker 4: uveitis, and axial spondyloarthritis, or AST.

<unk> and axial spondylarthritis for export.

His extensive experience will be key as we enhance our pipelines across many of the same disease states.

Speaker 4: His extensive experience will be key as we advance our pipeline across many of the...

Well Gilbert who will review our financials in greater detail later on the call I do want to underscore our strong financial position.

Speaker 4: While Gil will review our financials in greater detail later on the call, I do want to underscore our strong financial position.

Speaker 4: With nearly $800 million on our balance sheet, we can execute on our strategy over the coming months and years and achieve numerous key milestones across the entire portfolio of programs.

Nearly $800 million on our balance sheet, we can execute on our strategy over the coming months and years and achieved numerous key milestones across the entire portfolio of programs and indications.

Let's turn now to a review of our progress across the portfolio.

Speaker 4: Let's turn now to a review of our progress across the portfolio.

Speaker 4: As a recap, Ithacapep is a small protein therapeutic designed to inhibit IL-17A with a high potency through type-binding...

As a recap is it kind of is a small protein therapeutic designed to inhibit IL 17, a with a high potency through tight binding affinity. It has the potential for robust tissue penetration into a small molecular sides, which is about 110th the size of a monoclonal antibody and has an albumin binding domain that extends halfway.

Speaker 4: that has the potential for robust tissue penetration due to its small molecular size, which is about one-tenth the size of a monoclonal antibody, and has an albumin binding domain that extends half-life.

Speaker 4: We have hypothesized that the high potency and small size of Izakaika can lead to clinically meaningfully differentiated responses for patients across multiple indications where this mechanism of action has been validated and that this can be achieved with a safety profile consistent with that of the IL-17A class as has been demonstrated by the currently marketed monoclonal antibodies that begin available.

We are called the size that the high potency of small size. It is and how that can lead to clinically meaningfully differentiated responses for patients across multiple indications where this mechanism of action has been validated and that this can be achieved with a safety profile consistent with that with the IL 17 class as has been demonstrated by the currently marketed one.

So could you do that.

Any changes in that.

Speaker 4: IL-17A, as a target, has not demonstrated dose-limiting toxicity over 10 years of post-marketing and millions of patient years of safety.

Okay.

And the target has not demonstrated dose limiting toxicity over 10 years of post marketing a million patient years of safety experience. This will be important as we discuss what appears to be an evolving understanding around targeting the IL 17 assets more broadly and then selectively targeting IL 17.

Speaker 4: This will be important as we discuss what appears to be an evolving understanding around targeting the IL-17 axis more broadly than selectively targeting IL-17A.

Let me begin with Psoriatic arthritis, which is our most advanced program. It represents the largest potential indication for <unk>.

Speaker 4: It's our most advanced program and represents the largest potential indication for IZAKOTA. Psoriatic arthritis is a chronic condition.

Psoriatic arthritis is a chronic inflammatory disease with multiple clinical manifestations, including arthritis, psoriasis spondylitis that device and importantly, emphasize which is an inflammation of the strong dense poorly vascular tissues that anchor our ligaments and tendons.

Speaker 4: multiple clinical manifestations, including arthritis, psoriasis, spondylitis, dactylitis, and importantly, emphysitis, which is an inflammation of the...

Speaker 4: poorly vascular tissues that anchor our ligaments and tendons to fall.

Mr Ball.

Speaker 4: the majority of moderate to severe psoriatic arthritis patients, and has been historically very difficult.

It's a sinus impacts the majority of moderate to severe psoriatic arthritis patients. It has been historically very difficult to treat.

It is a marker of disease severity and a source of residual pain, and physical dysfunction, which impact quality of life for patients.

Speaker 4: is a marker of disease severity and a source of residual pain and physical dysfunction, which impacts quality of life for patients.

Speaker 4: There are approximately 1.6 million PSA patients in the U.S.

There are approximately $1 6 million PSA patients in the U S.

Speaker 4: And the 2022 PSA treatment market was valued at $8.8 billion globally and is estimated to grow to nearly $18 billion by 2030.

And the 2022 PSA treatment market was valued at $8 8 billion globally and is estimated to grow to nearly $18 billion by 2030.

Speaker 4: Historically, PSA treatments have been more effective in the joints and skin, but not the harder-to-treat manifestations of the disease, such as emphysitis.

Historically PSA treatments have been more effective in the joints and skin, but not the harder to treat manifestations of the disease such as in the slides.

Rapid deeper and more durable resolution of disease across clinical measures is the key to improving overall quality of life, which is ultimately for patients.

Speaker 4: Rapid, deeper, and more durable resolution of disease across clinical measures is the key to improving overall quality of life, which is ultimately our goal for patients.

Speaker 4: We have already shared results from a Phase II placebo-controlled trial of this type of NPSA, which demonstrated differentiated dose-ordered responses as early as one month into treatment and increasing over time.

We have already shared results from a phase II placebo controlled trial of its kind of in PSA, which demonstrated a differentiated dose ordered responses as early as one month into treatment and increasing over time.

This included in the ACR 50 response of 50% at week 12, or 44% placebo adjusted.

Speaker 4: This included an ACR-50 response of 50% at week 12, or 44% placebo dose.

Resolution of episodic as measured by believes emphasizes index was 82% at week eight.

Speaker 4: Resolution of emphysitis, as measured by the Leeds Emphysitis Index, was 82% at week 8, at our 80 mg every other week dose.

At our 80 milligram every other week dose week 12, without a protocol specified time point to this session.

Yes, Scott.

Speaker 4: SDI resolution is a standard approach to reporting improvements for NCI.

Resolution is the standard approach to reporting improvements for insights.

To enable comparison with recently reported emphasize data from one of the IL 17, Aaas inhibitors. We also analyzed subjects with <unk> of two plus at baseline with an improvement of two plus points are right.

Speaker 4: To enable comparison with recently reported emphasized data for one of the IL-17-AM...

Speaker 4: We also analyzed subjects with LEI of 2 plus at baseline with an improvement of 2 plus.

Speaker 4: at our week eight versus the other agents' data at...

<unk> versus the other agents data at week 12.

Speaker 4: This analysis showed a 100% response at week 8 in patients receiving 80mg of Inzokyboprotein versus 0% in patients receiving 1mg of Inzokyboprotein.

This analysis showed 100% response at week, eight and patients receiving 80 milligrams visit kind of versus zero percent placebo.

These results are relative to 71% reported at 120 milligrams for the IL Seventeens Aaas agent at 12 weeks without disclosure of a placebo as a reference for the agents.

Speaker 4: These results are relative to 71% reported at 120 milligrams for the IL-17AF agent at 12 weeks without disclosure of a placebo as a reference for that.

Okay.

Speaker 4: At UR, in June of 2022, we presented primary endpoint 16-week data showing that Izakaya demonstrated clinically meaningful benefits across disease manifestations, including 52% ACR50 response, 85% POSI-75 response, and 88% resolution of emphysitis, which, to our knowledge, is a level of resolution not previously reported for any other age group.

And you are in June 2022, we presented primary endpoint 16 week data showing that as a cause I've demonstrated clinically meaningful benefits across disease manifestations, including 52% ACR response, 85% policy 75 response, and 88% resolution that the slides, which to our knowledge is <unk>.

Level of resolution not previously reported for any other agents.

Speaker 4: These clinical benefits subsequently drove significant improvements in quality of life across all domains. And importantly, this included statistically significant improvements in pain, functional capacity, and sleep disturbance, as measured by the Psoriatic Arthritis Impact of Disease Questionnaire.

These clinical benefits subsequently drove significant improvements in quality of life across all domains and importantly, this included statistically significant improvements at P functional capacity and sleep disturbance as measured by the Psoriatic arthritis impact of disease questionnaire, what he said.

Speaker 4: The thesis is a validated psoriatic or arthritis-specific patient-reported outcome.

<unk> is a validated psoriatic arthritis specific patient reported outcome measure.

Furthermore earlier this year, we were delighted to report initial long term efficacy from the same phase II trials that showed that with longer duration of treatment patient experienced durable and deepening resolution of disease across clinical manifestations of PSA leading to further improvements in quality of life as measured.

Speaker 4: Furthermore, earlier this year we were delighted to report initial long term efficacy from the same phase 2 trial that showed that with longer duration of treatment, patients experienced durable and deepening resolution of disease across clinical manifestations of PSA, leading to further improvements in quality of life as measured by the study.

On the PC.

Additional data demonstrating the increased duration of therapy continues to enhanced resolution of disease will be presented at both poster and oral podium session taking place next Monday during the upcoming American College of Rheumatology convergence in San Diego.

Speaker 4: Additional data demonstrating that increased duration of therapy continues to enhance resolution

Speaker 4: will be presented in both poster and oral podium sessions taking place next Monday during the upcoming American College of Rheumatology Convergence in San Diego.

At 46 weeks of participants receiving its kind of at 80 milligrams every other week, 71% achieved ACR 50 response up from 52% and week 16, and even higher orders of clinical response in measured approximating resolution of disease were observed with 52% achieving ACR 70.

Speaker 4: At 46 weeks of participants receiving Izakayevac 80mg every other week, 79% achieved ACR50 response, up from 52% in the last year.

Speaker 4: And even higher orders of clinical response in measures approximating resolution of disease were observed with 52% exceeding ACR 70.

Speaker 4: 71% achieving POSI-100, and 89% achieving emphysitis resolution.

71%, achieving causing 189% achieving episodic resolution.

Notably patients who switched from placebo to 80 milligrams every other week at week 16 responded quickly.

Speaker 4: Notably, patients who switched from placebo to 80 milligrams every other week at week 16 responded quickly.

Speaker 4: With more than 60% of patients in both the switch group, as well as the original 80 milligram every other week group, achieving minimal disease activity by week 40.

With more than 60% of patients in both the Switzerland as well as the original 80 milligram every other week group achieving minimal disease activity by week 46.

Speaker 4: Importantly, this efficacy was delivered with a safety profile consistent with previous physical experience and that of the IL-17A class as a whole, with no evidence of dose limiting.

Importantly, this efficacy was delivered with a safety profile consistent with previous experience and that is the IL 17 class as a whole with no evidence of dose limiting toxicity.

Speaker 4: Modeling from the Phase II PSA data predicted the potential to increase response over time as has been demonstrated with the 46-week data. The modeling further predicts the potential for increased efficacy with higher doses over the 80 milligrams every other week utilized in the Phase II trials.

Modeling from the phase two PSA data predicted the potential to increase response over time as has been demonstrated with 46 week data.

The modeling trying to predict the potential for increased efficacy with higher doses over the 80 milligram every other week utilized in the phase two trial.

Speaker 4: To that end, the ongoing Phase 2b3 trial in PSA is evaluating both 160 milligrams weekly and every other week to continue to maximize potential responses for patients.

So that is the ongoing phase <unk> trial. The PSA is evaluating both 160 milligrams weekly and every other week to continue to maximize potential responses for patients.

Aside from the higher doses.

Speaker 4: The design of this trial is consistent with that of the Phase II, with a few notable improvements.

Design of this trial is consistent with that of the phase III with a few notable exceptions.

Firstly this is a truly global study with 352 patients across 71 sites, including 40 in the U S and 30 internationally to enable the potential for registration across geographies.

Speaker 4: Firstly, this is a truly global study with 352 patients across 71 sites, including 40 in the U.S. and 30 internationally, to enable the potential for registration across geography.

Speaker 4: In addition, there is an increased percentage of endocytes at baseline, and an increased percentage of TNF failures, meaning individuals who have had an inadequate response, intolerance, or contraindication.

In addition, there was an increased percentage of emphasize at baseline and an increased percentage of TNF failures. Many individuals who have had an inadequate response empowers intolerance or contra indicated.

These aspects all have the potential to impact a specific point estimates relative to phase two but are important in understanding the potential benefits of <unk>.

Speaker 4: These aspects all have the potential to impact the specific point estimates relative to phase 2, but are important in understanding the potential benefits of ISATIZE-UP for PSA patients.

Patients.

Speaker 4: Both are important given the contribution of ensitis to severity of disease, including continued pain and disability.

Both are important given the contribution of inside of severity of disease, including continued pain and disability.

And also the increasing number of patients who are not simply been exposed TNF inhibitors, but have demonstrated an inadequate to clinical response.

Speaker 4: And also the increasing number of patients who have not simply been exposed to TNF inhibitors, but have demonstrated an inadequate clinical response.

Speaker 4: This Phase 2b3 trial in PSA completed enrollment in the second quarter of 2020.

This phase <unk> trial in PSA completed enrollment in the second quarter of 2023.

Speaker 4: Over 75% of patients have completed through the primary endpoint at week 16, and the discontinuation rate is 5.9%.

75% of patients have completed through the primary endpoint at week 16, and the discontinuation rate is five 9%.

Speaker 4: Top line data continues to be expected in the first quarter of 2020.

Topline data continues to be expected in the first quarter of 2024.

Speaker 4: Now we'll turn our attention to Hyderadonitis Suprativa, which continues to be an area of rapid evolution.

Now I will turn our attention to hidradenitis, Suppurativa, which continues to be an area of rapid evolution.

Speaker 4: Just last week, only the second treatment for HS and the first new option for patients in almost a decade was approved by the FDA.

Last week only the second treatment for Hs is the first new option for patients in almost a decade was approved by the FDA.

Speaker 4: We have the great fortune at Accelerin of having members of our team who held important roles in the context of each of these approved therapies. And for all of us, it's always gratifying to see new treatment options for patients.

We have the great fortune of Epsilon or have some members of our team who held important roles in the context of each of these approved therapies and for all of US, It's always gratifying to see new treatment options for patients.

At the same time, well the honest 17, a safety profile is well established we have also seen especially recently our understanding of the safety profile targeting sub units beyond the IL 17, a continuous football that may become a more important consideration.

Speaker 4: At the same time, while the other 17A safety profile as well as that.

Speaker 4: We have also seen, especially recently, our understanding of the safety profile of targeting subunits beyond I-017A continues to evolve and may be.

Speaker 4: Targeting both ANF leads to those responsive increase in focal inception.

Targeting both Ana speaks to dose responsive increases in fungal infections.

Speaker 4: This was seen in data from both agents targeting inhibition of IL-17A.

This will see the data from both agents targeting inhibition of IL 17 a F.

Speaker 4: After 24 weeks of treatment, one demonstrated an approximate doubling of fungal infection risk from 12 weeks, which increased to about 20% in the planned dose and almost 30% in their higher dose, with the beginnings of reports of recurrence of these fungal infections in areas beyond just.

After 24 weeks of treatment, one demonstrated an approximate doubling of fungal infection risk for 12 weeks, which increased to about 20% in the planters and almost 30% in their higher dose with the beginnings of reports of occurrence of this local infections in areas beyond just skin.

Speaker 4: Additionally, the risk of suicidal ideation and behavior was noted in a recent label of an IL-17 AF.

Additionally, the risk of suicidal ideation and behavior was noted in our recent label of an IL 17 a M.

This has been noted previously in the label of an anti IL 17 receptor inhibitor, which was all of a sudden clio 17, including IL 17.

Speaker 4: This has been noted previously in the label of an anti-IL-17 receptor inhibitor, which blocks all the subunits of IL-17.

Cumulative data from these two agents over the Registrational programs raises the question of relationship between inhibiting IL 17, more broadly than iOS SDK, specifically the potential association with the inhibition of <unk>.

Speaker 4: Cumulative data from these two ages over the registrational programs raises the question of relationship between inhibiting IL-17 more broadly than IL-17A, specifically the potential association with the inhibition of IL-17A.

This recent label also noted the requirement for routine laboratory monitoring for liver toxicity, which has not previously voted for the <unk> inhibitors.

Speaker 4: This recent label also noted the requirement for routine laboratory monitoring for liver toxicity, which has not previously been noted.

So the landscape does that cause evolving in terms of balancing efficacy and safety hurdles for new treatments for Hs patients.

Speaker 4: So the landscape is actively evolving in terms of balancing efficacy and safety hurdles for new treatments for HSBC.

Speaker 4: We believe it is a type of potential in H.S. with roughly 25% of patients achieving high score 100 responses within 12 weeks, which means they rapidly achieve resolution of all abscesses and nodules without needing to go to the ER.

We believe it is the type of schedule NHS with roughly 25% of patients achieving high score 100 responses within 12 weeks, which means they rapidly achieve resolution of all asset season nodules without nutrient tons.

Speaker 4: This is a level of responders achieved in half the time reported by others and without the safety or tolerability considerations of targeting IL-17F in addition to IL-17C.

This is a level of responders achieved in half the time reported by others and without the safety or Tolerability considerations of targeting IL 17.

To IL 17 a.

Speaker 4: As we previously shared, both our Phase 2P3 and our ongoing Phase 3 trial are moving forward, and discussions with the FDA will help inform next steps to advance our registrational program.

As we've previously shared both our phase III and our ongoing phase III trials are moving forward and discussions with the FDA will help inform next steps towards answer a registrational program.

Speaker 4: We expect to have an update by end of this year or early next

We expect to have an update by end of this year or early next year.

And in addition to P. S N H S. We continue to explore the potential for it to cause us to make a meaningful difference for patients with both X Y Z items.

Speaker 4: And in addition to PSA and HS, we continue to explore the potential for enzocagum to make a meaningful difference for patients with both asthma and uveitis. Enzocytus.

<unk> is a central feature of lifestyle and we believe the rates are at the slightest resolution as demonstrated in the phase II PSA trials suggest the potential for clinically meaningful differentiated benefits for patients with this disease.

Speaker 4: And we believe the rates of emphysitis resolution demonstrated in the PHASE II PSA trial suggest the potential for clinically meaningful differentiated benefits for patients.

Speaker 4: We will use the optimal dose from the PSA program to inform a planned future phase 3 program next fall.

We will use the optimal dose from the PSA program to inform a planned future phase III program next fall.

Speaker 4: We also continue to enroll our Phase II, V, and III clinical trial with this concept as a treatment for uveitis.

We also continue to enroll our phase <unk> clinical trial of its kind of as a treatment for uveitis previously reported data for another IL 17 inhibitor delivered intravenously has validated the inhibition of IL 17, a potential therapeutic for uveitis.

Speaker 4: Previously reported data for another IL-17A inhibitor delivered intravenously has validated the inhibition of IL-17A as potential therapeutic for UBI.

Well, that's a card that this lead program in our portfolio. We have two other programs slotted to map and similar in 2007, which we are developing a thyroid eye disease and vessels of the diseases.

Speaker 4: While InstaKybep is the lead program in our portfolio, we have two other programs, Lonagut, MAP, and Acceleron 517, which we are developing in thyroid eye disease and mast cell

Thyroid eye disease is a vision threatening progressive chronic autoimmune disease and similar to Hs the tech landscape is evolving rapidly.

Speaker 4: Thyroid disease is a vision-threatening progressive chronic autoimmune disease, and similar to HS, the TET landscape is evolving rapidly.

Speaker 4: Our team has deep experience in this indication, with many involved in developing the only currently approved

Our team has deep experience in this indication with many involved in developing the only currently approved treatment.

Speaker 4: Recent clinical data demonstrating the effectiveness of inhibiting IGF-1 receptor in chronic tests supports our approach to developing London HootMap, not just for acute disease, but also more treatments for chronic inflammatory autoimmune diseases.

Recent clinical data demonstrating the effectiveness of inhibiting IGF, one receptor and chronic supports our approach to development.

Not just for acute disease, but also more treatments for chronic inflammatory autoimmune diseases.

Speaker 4: This includes targeting greater depth and durability of response with longer-term dosing and the goal of achieving resolution.

This includes target greater depth and durability of response with longer term dosing in the <unk>.

Goal of achieving resolution of disease.

Recent updates from the FDA to the warnings and precautions of the currently approved therapy also highlighted hearing impairment as a serious potentially permanent side effect of treatment.

Speaker 4: Recent updates from the FDA to the warnings and precautions of the currently improved therapy also highlight hearing impairment as a serious, potentially permanent side effect.

Speaker 4: We have hypothesized that hearing impairment may be directly related to the inhibition of the normal function of IGF-1, given its role in regenerating cells of the inner ear subsequent to routine auditory impairment.

We haven't publicized this hearing of care, but may be directly related to the inhibition of the normal function of IGF one given its small in regenerate itself.

So quick to routine auditory insults.

The unique characteristics of audience now allow us to optimize efficacy by maintaining minimum drug levels needed to achieve improved depth and durability of response limits safety liability, excluding hearing impairment potentially associated with high maximum drug concentrations and maximize patient convenience.

Speaker 4: The unique characteristics of autoimmune therapy may allow us to optimize efficacy by maintaining minimum drug levels needed to achieve improved depth and durability of response, limit safety liability, including hearing impairment, potentially associated with high maximum drug concentrations, and maximize patient convenience through subcutaneous therapy.

<unk> through subcutaneous delivery.

Speaker 4: The Phase 1-2 trial of Lundegut-MAP, delivered subcutaneously in 10 patients, is ongoing.

The phase one two trial of monetizing that delivered subcutaneously in patients is ongoing.

Speaker 4: We anticipate initial proof of concept data, including proptosis response and clinical activity score by end of first quarter 2020.

We anticipate initial proof of concept data, including Proptosis response, and clinical activity score by end of first quarter 2024.

Speaker 4: Epsilon 517 is a fully human, highly potent IgG1 monoclonal antibody directed against C-Kid with the potential to address mass overpopulation.

So on slide seven is a fully human highly potent IGT want monoclonal antibody directed against C kit with the potential to address muscle diseases.

Speaker 4: We are conducting a Phase I-II proof-of-concept trial of SELRN 517 and expect top-line results in the second half of the year.

We are conducting a phase <unk> proof of concept trial of silver five one zone and expect topline results in the second half of 'twenty 'twenty four.

With that overview of the portfolio, let me now turn the call over to Gil for a review of our financials Gil. Thank you Charlie for overview of our portfolio and good afternoon everyone.

Speaker 5: With that overview of the portfolio, let me now turn the call over to Gil for a review of our financials. Gil? Thank you, Shali, for that overview of our portfolio, and good afternoon, everyone.

Speaker 5: As Shalini mentioned, we are fortunate to be operating from a strong financial position as we not only advance our portfolio of clinical stage programs, but also build our organizational capability and identify potential additional diamonds in the rough to add to our pipeline.

Shelby you mentioned, we are fortunate to be operating from a strong financial position.

As we not only advance our portfolio of clinical stage programs, but also build our organizational capability.

<unk> potential additional diamonds in the rough to add to our pipeline.

Speaker 5: At September 30, 2023, cash and cash equivalents and short term marketable securities totaled $788.4 million, which we expect to fund operations through

At September 32023, cash and cash equivalents and short term marketable securities totaled 780, $844 million, which we expect to fund operations through key value driving milestones across all three programs.

Speaker 5: value driving milestones across all three programs.

Speaker 5: Research and development expenses were $74.6 million for the third quarter as compared to $12.5 million for the same period in 2022.

Research and development expenses were $74 6 million for the third quarter as compared to $12 5 million for the same period in 2000, it's way too.

Speaker 5: Comparing 2023 to 2022, the company has undergone significant growth, including the expansion of the Isochibat program across multiple indications, and the addition of two programs in 2023, both of which are now in clinical stage development.

Comparing to 2023 months of 2022.

<unk> has all gone significant growth including expansion.

Program across multiple indications.

The addition of two programs in 2023, both of which are now a clinical stage development.

General and administrative expenses were $19 9 million for the third quarter as compared to $2 9 million for the same period in 2022.

Speaker 5: General and administrative expenses were $19.9 million for the third quarter as compared to $2.9 million for the same period in 2022.

The quarter ended September 32023.

Speaker 5: The quarter ended September 30, 2023, includes stock-based compensation expense of $11.7 million.

Stock based compensation expense of $11 7 million.

These increases in expenses were primarily a result of expanding our organizational capabilities to support the development of our broad portfolio of immunology product candidates.

Speaker 5: These increases in expenses were primarily a result of expanding our organizational capability to support the development of our broad portfolio of immunology product candidates.

Speaker 5: Finally, our net loss for the third quarter of 2023 totaled $83.9 million, or $0.87 per share, compared to $14.4 million, or $8.17 per share, for the third quarter of 2023.

Finally, our net loss for the third quarter of 2023 totaled $83 9 million or <unk> 87 per share compared to $14 4 million or $8 17 per share for the third quarter of 2022.

Speaker 5: The total net loss for the current quarter includes stock-based compensation expense of $15.3 billion.

The total net loss for the current quarter includes stock based compensation expense of $15 3 billion.

As you can see we continue to carefully allocate capital across our robust clinical portfolio.

Speaker 5: As you can see, we continue to carefully allocate capital across our robust clinical portfolio, and we're delighted to have a strong financial position from which to continue our important work for patients. And now I will turn the

Delighted to have a strong financial position from which to continue our important work for patients.

And now I will turn the call back to Shelley shortly.

Thanks Gil.

Speaker 4: As you've heard, we continue to make steady progress in our efforts to build a leading immunology company.

As you've heard we continue to make steady progress in our efforts to build a leading immunology company.

We feel fortunate to have an experienced team.

Speaker 4: a robust pipeline, and a strong financial position providing runway for multiple key milestones across all three clinical programs.

Robust pipeline and a strong financial position, providing runway through multiple key milestones across all three clinical programs.

We remain committed to our long term vision to accelerate the development and commercialization of transformative medicines to address unmet medical needs and to deliver sustainable value to our shareholders partners and most importantly to the patients we serve.

Speaker 4: We remain committed to our long-term vision to accelerate the development and commercialization of transformative medicines to address unmet medical needs and to deliver sustainable value to our shareholders, partners, and most importantly, to the patient.

Speaker 4: In the ever-evolving landscape of our industry, we understand the importance of adaptability and resilience.

In the ever evolving landscape of our industry, we understand the importance of adaptability and resilience.

We are committed to making data driven disciplined decisions as well as being responsible stewards of our human and financial resources in navigating challenges and embracing opportunities.

Speaker 4: We are committed to making data-driven, disciplined decisions, as well as being responsible stewards of our human and financial resources in navigating challenges and embracing opportunities.

Once again I. Thank you for your trust and support.

Speaker 4: We look forward to your continued partnership as we journey ahead together. Operator, we are now ready.

Look forward to your continued partnership as we journey ahead together.

Operator, we are now ready to open the call to questions.

Thank you.

Speaker 2: Thank you. We will now conduct the question and answer session.

We will now conduct a question and answer session.

Speaker 2: To ask a question, please press star one one on your telephone and wait for your name to be announced.

To ask a question. Please press star one on your telephone and wait for your name to be announced.

Speaker 2: To withdraw your question, please press star one, one again, please stand by while we come

To withdraw your question. Please press star one again.

Please standby, while we compile the Q&A roster.

Speaker 2: Our first question comes from Yasmin Rahimi from Piper Sandler. Please go ahead.

Our first question comes from Jasmine.

He asked me right.

From Piper Sandler. Please go ahead.

Speaker 6: Good afternoon team and thank you so much for all your really thoughtful remarks for us.

Good afternoon, Stephen Thank you so much for all your really talked about hallmarks for us.

Speaker 6: Team, as we're awaiting that PSA data early next year, could you maybe comment on sort of how soon post the second phase 2B, phase 3, would you be in a position to get ready and file for approval in PSA and whether the data would be sufficient on the heels of both of the results, if you could just provide color in that regard.

Team as we're awaiting that PSA data.

Early next year could you maybe comment on sort of how to post the second phase <unk> would you be.

In a position to get.

Get ready to file for approval in PSA and whether the data would be sufficient on the health of both of the results. If you could just provide color in that regard.

Speaker 6: And then two, if you could just maybe comment on how you're tracking, you know, or have been tracking or tracking currently, like, suicide ideation, liver enzyme abnormalities to the extent you can across all studies and I'll jump back into the queue. And thank you again.

And then two if you could just maybe comment on how you're tracking you know or have been tracking archrock concurrently.

Two sided ideation liver enzyme abnormality to the extent you can across all studies.

And I'll jump back into the queue and thank you again.

Speaker 4: Thank you. This is Shelly. So with regards to PSA, we anticipate that registration will require both the ongoing Phase 2B3 that we hope to be part of that package, as well as a confirmatory study, which is standard for these indications.

Yes.

This is shelly.

So with regards to PSA, we anticipate that registration acquire.

The ongoing phase <unk> three that we hope to be part of that package as well as a confirmatory study, which is standard for these indications we haven't yet provided guidance.

Typically the time post.

Speaker 4: time post, you know, sort of post this study readout relative to.

Sort of post the study read out relative to what we think that will be.

Speaker 12: But obviously, we'll move forward expeditiously, as expeditiously as possible. With regards to the signals that you've noted, really since the Bridalium experience with this group, these have been endpoints that have been followed across the I-17 class and we're following the standard approaches there as well. Okay. Thank you. I'll jump back into the queue.

But obviously, we'll move forward expeditiously as expeditiously as possible with regard to the signals.

That you've noted you know really since the prevailing in that experience.

This group.

That's it.

Endpoints that followed across the 70 class.

And we are following the standard.

Approaches there as well.

Okay. Thank you I'll jump back into the queue.

Thank you.

One moment for our next question.

Our next question comes from Tyler Van Buren from Cowen. Please go ahead.

Speaker 2: Our next question comes from Tyler Van Buren from TD Cowan. Please go ahead.

Hi, This is Stefan for Tyler. Thank you guys for taking our questions. We have two for you. So first looking forward to the topline PSA phase two three read out in Q1, how are you thinking about the bar for success given that then the kids' mouths phase III data and other recent competitor read off.

Speaker 6: Hi, this is Beth on for Tyler. Thank you guys for taking our questions. We have 2 for you. So, 1st, looking forward to the top line PSA phase 2, 3, read out and Q. 1. how are you thinking about the bar for success? Given the data and other recent competitor read out.

Speaker 6: And then 2 for the long and good mad, mad head patient readout and Q1, how many patients worth of data might we see across the 3 to 4 dose cohorts and how the risking do you expect the early proctosis data to be as we think about efficacy in later stage trials. Thank you.

Then to for the long and good Matt Matt Ted patient read out in Q1, how many patients worth of data might we see across the three to four dose cohorts and how Derisking do you expect the early proptosis data to be as we think about efficacy and later stage trials. Thank you.

Speaker 4: Super. Thanks for that, Beth. So your first question was about the upcoming PSA 2B3 readout in first quarter of 24 and the bar for

Super Thanks, Beth So your first question was about the.

Upcoming PSA TV three readout in first quarter of 'twenty, four and the bar for success.

Speaker 4: You know, the way we think about this is that the phase two study that we've already completed that went up to 80 milligrams and we're going to share the long-term data, even additional measures of resolution of disease at the upcoming ACR meeting. We feel like that study already demonstrated the potential for differentiation with Izakai VEF, especially the top-dose 80 milligrams every other one.

The way we think about this is that the phase two study that we've already completed that went up to 80 milligrams and we're going to share those.

Long term data, even even additional measures of resolution of disease. The ACR meeting, we feel like that study already demonstrated the potential for differentiation, which is the cutback, especially the top dose of 80 milligrams every other week, we see top range results with regards to joints and skin.

Speaker 4: We've seen top-range results with regards to joints and skin at the WSIS-16 primary endpoint and really outsized emphysitis results, as we recap today, within that time frame. And that just hasn't been seen before with other.

<unk> primary endpoint it really outsized emphasized as a result of the recap today.

Within that timeframe.

It hasn't been seen before with other agents.

Speaker 4: And we've shared that at the 46-week time frame, we see, you know, sort of even continued deepening of those responses, again, as we've shared today, with ACR 50s, or sorry, ACR 70s, up at above 50%, POSI 100 scores up over 70%, and emphysitis still in the kind of 80s,

And we shared that at 46 week timeframe, we see sort.

Even continued deepening of those responses.

Again, as we've shared today with ACR fifties.

Or sorry, ECR seventies up at above 50% pardon me 100 scores well over 70% and emphasized is still in the kind of 80% to 90% range. So we're very very pleased with those results, we think that they fundamentally derisk. The TB three that's coming up.

Speaker 4: So we're very, very pleased with those results. We think that they fundamentally de-risk the 2B3 that's coming up. We conducted that 2B3 really because our modeling from that phase two suggested to us that we could get some additional efficacy out of additional pushing the exposure a bit more within the context.

We conducted that TB, three really because our plumbing from that phase II suggested to us that we could get some additional.

Efficacy out of additional pushing the exposure a bit more within the context of the state and so that's the reason for the additional dose ranging with TV portion. If you will of the Tvs readouts upcoming.

Speaker 4: And so that's the reason for the additional dose ranging, the 2B portion, if you will, of the 2B3 that's upcoming. As a for instance, we know from our earlier psoriasis experience that moving from 80 every other week to 160 every other week in psoriasis did give us a bit of a bump with regards to efficacy. So at a minimum, we hope to recapitulate that. But already, we feel like we have a differentiated

And as a for instance, we know from our earlier psoriasis experience that moving from 80 every other week to 160 every other week and thrive.

Yes.

With regards to efficacy at a minimum we hope to recapitulate that.

But already we feel like we have a differentiated.

Offering.

Speaker 4: And then your second question was about monoglutinab and how much data we would have moving forward and how de-risking that is, you know, sort of overall. I think what you can anticipate is that from a proof of concept, initial proof of concept perspective, you know, we'll have proof of, we'll have a number of patients that are very similar to what's been demonstrated previously for the Viridian and Immunodad sort of

And then your second question was about <unk> and how much data we would have moving forward and help you risking that is sort of overall I think what you can anticipate is that.

Cause initial proof of concept perspective.

Uh huh.

We will have a number of patients that are very similar to what's been demonstrated previously for the Caribbean and human events.

Speaker 4: compounds on the order of, you know, six or so patients in those experiences have been sufficient to really demonstrate the potential for signal across both proctosis as well as.

<unk> on the order of.

Six or so patients in those experiences have been sufficient to really demonstrate the potential for signal across both proptosis as well as clinical activity score. So we will have those measures within the context of 10 patients.

Speaker 4: So, we'll have those measures within the context of TED patients to evaluate. We may have more patients than that, but, you know, as we move forward, we'll have a better beat on that. And, you know, because of the strong signal in terms of efficacy that we see with this axis, we anticipate it's not going to take much more than that to see a signal for these agents, again, as has been demonstrated already.

Valuations may have more patients than that.

You know as we move forward, we will have a better better beat on that.

Yes.

Because of the strong signal in terms of the efficacy that we see with this axis.

We anticipate it's going to take much more than that.

We see a signal.

For for these agents again as has been demonstrated.

Already.

Okay.

Thank you.

One moment for our next question.

Our next question comes from Vikram period.

Speaker 2: Our next question comes from Vikram Pirohit from Morgan Stanley . Please go ahead.

Morgan Stanley. Please go ahead.

Hi, everyone. This is Scott on for Freedom, we have two questions regarding the PSA in Hs.

Speaker 7: Hi, everyone. This is Gaspo on Fort Frickin. We have two questions regarding PSA and HS. So for PSA, I was wondering what the competitor data readout has to note. Data tells you, if anything, about the importance of molecule size for the treatment of PSA. And then in regards to HS, I was wondering, have you been able to further analyze the results to better understand the placebo response?

<unk> PSA I was wondering.

I was wondering I was wondering what the competitor data readout.

The data tells you if anything about the importance of <unk> size.

For the treatment of PSA on that in regards to it says I was wondering have you been able to further analyze the results to better understand the placebo response.

Speaker 7: and discontinuation rate observed? If so, did you currently see any read across to the ongoing PSA readout?

Im discontinuation rates observed.

If so do you currently see any read across to the ongoing PSA figured out.

Speaker 7: and idea measures that have been put in place for that study to prevent similar issues from arising.

And I do have measures that have been put in place for that study to prevent similar similar issues arising.

Thank you for that thoughtful.

Speaker 4: Thank you for that. You know, maybe I'll start backwards a little bit to tie it back in, which is, you know, and I appreciate the question. Obviously, given our HS readout that we shared in September , we've been extraordinarily hyper vigilant with regards to putting in any measures such that we understand in real time, continue to understand and ensure that we are understanding in real time.

Maybe I'll start backwards a little bit.

To tie back in which is.

You know.

And I appreciate the question, obviously, given our H S readout that we shared in September we've been extraordinarily hypervigilant.

With regards to putting in any measure such that we understand real time.

Or else, we will continue to understand and ensure that we are understanding in real time any discontinuation as well as.

Speaker 4: as well as putting into place anything that could help from a placebo response perspective. We don't anticipate any read-through to our PSA, and we think that our sort of blinded, continued analysis haven't suggested anything.

Putting into place of anything that could help from a triple placebo response perspective, we don't anticipate any read through to our PSA and we think that our blinded continued analysis haven't suggested to us any any issues in that regard. We have continued further deep dives with regards to the Hs dataset.

Speaker 4: issues in that regard. We have continued further deep dives with regards to the HS data set and as I shared in our prepared remarks, we anticipate having more information with regards to that program by end of year, early next year to share when we have relevantly compiled both our conversations with the health authorities as well as the deep dives that

And as I shared in our prepared remarks, we anticipate having more information with regards to that program by end of year early next year to share when we have relevant to be compiled both our conversations with the health authorities as well as the deep dives that that continue to be ongoing.

Speaker 4: So bottom line is H.S. continues to move forward with regards to the 2B3 study that ran out as primary, as well as the ongoing phase 3, as planned as we had previously planned.

So bottom line is.

It just continues to move forward with regard to the T V. Three study that read out its primary as well as the ongoing phase III as planned as we have previously discussed.

Speaker 4: We don't anticipate a read-through to PSA, and from the PSA perspective, you know, we do think that there is importance still with regards to the molecule size and the potential for differentiation. We think our Phase II results, especially in emphysitis.

We don't anticipate at least with PSA and from the PSA perspective.

We do think too that.

There is important still with regards to the.

A molecule size and the potential for differentiation, we think our phase two results, especially and emphasize a point to that.

Speaker 4: point to that, exactly where the threshold was for, you know, the size cutoff that could enable us to get into that dense, strong sort of polyvascular tissue relative to other molecules wasn't entirely clear. I, you know, I will say that the data more recently suggests that not only is the threshold between our 18 kilodaltons and the 150 or so for the marketed monoclonals, but perhaps is even between the 18 and the 40.

Exactly where the threshold for.

The five cut off that could enable us to get into that dense strong sort of thought poorly vascular tissue relative to <unk>.

Other molecules wasn't entirely clear.

I will say that the data more recently suggests that not only is the threshold between our 18 kilovolt ones and the ones you see yourself more towards the market in multiples.

But perhaps is even between the 18 in the 40 that will kill.

Recently released data.

Given the difference in emphasize what I've shared with you today.

Our.

In our prepared remarks, our best attempt at an apples to apples comparison.

The data that was presented.

With regards to the Eliott resolution, which we've shared previously but with regards to Elliot to plus at baseline improving.

More than two points over the course of the study.

And recall that that was up for us as we gained an earlier time point, because we didn't collect 12.

3rd% response.

That degree of change and improvement.

Versus the placebo zero percent realm.

Relative to 71% without the placebo reported.

Yes.

Right.

Thank you.

One moment for our next question.

Our next question comes from <unk>.

<unk> partner.

<unk> from H C. Wainwright. Please go ahead.

Hi, Thanks for taking the questions.

Kind of along the lines of some of the other questions on PSA I was wondering if you can maybe discuss what endpoints or metrics that physicians are most looking to see an improved upon or where are they kind of feed the largest unmet need where you think you can differentiate I know you talked about anthracite us already but are there.

Any other places where were you kind of see that type of up.

Differentiating.

And then maybe just on expenses if you can touch on.

It looks like in three Q, the expenses kind of doubled from the second quarter.

Is that kind of a base level for you going forward or any guidance you can give on expenses.

For the remainder of the year next year. Thank you.

Yeah. Thanks for that I believe maybe I'll start with PSA sort of disease state notifications et cetera, and I'll, let bill handle the second question.

So with regards to where we think the field is going and what's important for patients and therefore for them for our investigators and Kols as well is that we really need to do better with regards to our.

Treatment offerings for for these patients we've traditionally been talking about on ACR 15 responses of 50% sort of range and.

What that means is that half the people, who will get 50% there with regards to their joint disease, which is.

A pretty low bar still if you think about how much unmet need how much better we should be able to do so it seems like ECR seventies.

Or as close to remission as we've been able to have within the ACR, scoring system pausing one hundreds are sort of all clear skin.

Besides resolution means that I don't have any more insight that I can I can measure.

Which is terrific and so it's really the totality of all of the minutes manifestations of this disease.

And that therefore as you can imagine impact most the overall quality of life of participation. So it's important not just to hit the joints in the skin. Although of course once they hit the hardest one can really be able to talk about with mission of resolution ACR seventies.

The majority of people achieving ACR seventies.

Majority of people achieving pardon me 100, and now we feel like we just decided that the vast majority of people achieving resolution of their emphasizes which is again a marker of severity of disease of residual pain and dysfunction for these patients and obviously adds up to the quality of life and one of the measures.

Some of this overarching.

Resolution of disease is also minimal disease activity.

And as we've shared both our switch from placebo to active in the phase III study as well as the 80 milligram, we get though those subjects are achieving about 60%.

<unk> disease activity.

In the upcoming dataset presented so we're excited about this we think that the to be three gives us the potential to.

<unk> two impact this even further.

We already know that the opportunity exists based on our existing data to do that from a skin improvement perspective.

Great into the to the financial question Emily.

As I said in my prepared remarks, we ended.

Quarter with over $788 million.

Cash on the balance sheet. So obviously, we're in a very strong financial position.

Sufficient funding to go through kind of was across our pipeline.

This stage, we're not giving a specific line item guidance, but I can tell you that we're thinking very carefully.

How we allocate capital stage appropriate.

We're scaling the investments as we scale the trials.

So we are obviously in 2020 core plan and we're looking very closely at that and being prudent with our capital, but we're really pleased with where we are at this point.

Got it okay. Thank you.

As a reminder.

If you would like to ask a question. Please press star one one and wait for your name to be announced.

One moment for our next question.

Our next question comes from a cash to here from Jefferies. Please go ahead.

Hey, Thanks, so much for taking my question. So I remember as of September you had mentioned the blinded dropout rate for your upcoming Psoriatic arthritis trial was around 5% any color on what thats tracking too as we get into November and what level of drop out do you plan with for the trial with your current powering assumptions and then I guess, maybe on the Hs can you go.

Precisely what Youre Hs protocol deemed to be drug related or not for example in the circumstance by which a participant had an injection site reaction and also stopped treatment how would you determine whether that was a drug related discontinuation or otherwise. Thanks. So much.

Thank you Josh.

With regards to your first question about the PSA study, that's about to read out and draw and discontinuation rates.

So as.

As I shared in our prepared remarks.

<unk>.

We're at over 75% of patients within the context of that trial, having completed through the primary endpoint and are introduced.

The continuation rate currently six 9%, so we feel Oh apologies five 9% and the.

And it just speaks to my mindset with regard to my next comment which is really not anything below 10%.

Unusual threshold that we think about.

Clinical trials in general.

It bounces around within the context of that number, but let's use the low 10%, who really aren't concerned. So we're feeling very good about where we are with that study at this juncture Ed as I said earlier to Anthony's comments really don't feel like Theres any read through that and we wouldn't have expected that but we don't think we're seeing that.

Separately with regards to Hs.

And.

And scoring of ISR and whether or not those are adverse events.

Take that as a as reported to us ISR is and whether or not they would drop outs do the ISR.

Hmm.

When we talk about our dropouts.

<unk> discontinuation.

Sponsors without adverse events, we actually went back through and didn't just take at face value, whether or not it was reported to us.

Whether it was lost to follow up with you as consents etcetera, we went back through the entire electronic dataset.

And evaluated whether or not there was no pattern, including looking for ISR that weren't necessarily reported as an AE and that pattern also does not exist, which I think is probably your underlying question.

Awesome. Thanks, so much.

Thank you.

I am showing no further questions I will now turn the conference over to Tyler <unk> for closing remarks.

Thank you all for joining today's opportunity for us to share with you our third quarter financial results and corporate updates shall we didn't kill bench and thank you for your trust and support because we continue to build a salary into a leading ini company.

We look forward to engaging with you regularly and transparently.

I would like to highlight once again, our upcoming POC data presentations at ACR and the several investment conferences, we are testing in the coming weeks.

I'll see you in person soon I would encourage you to view the fireside chat and other resources, we regularly post to our website.

And of course, please feel free to contact our Investor relations team at any time, if we can be of service to you.

With that we'll conclude our call for today. Thank you very much.

This concludes today's conference call. Thank you for participating you may now disconnect.