Q2 2024 Acelyrin Inc Earnings Call and Business Update
It.
This conference call is being recorded today August 13, 2024, I would now like to turn the conference call over to Tyler My Senior Vice President of Investor Relations and corporate Affairs Tyler.
Tyler: Thank you Carmen and good afternoon, everyone and thank you for joining us before we begin I'd like to remind you that this conference call may contain forward looking statements such as those related to progress of our clinical trials and anticipated data readouts, our future financial and operating results and our projected cash runway and our ability to.
Tyler: Commercialize our product candidates.
Tyler: These forward looking statements involve risks and uncertainties that could cause our actual results and events to differ materially.
Tyler: We would urge you to review the risk factors section of our Form 10-Q for the quarter ended June 32024, and additional form 8-K that we filed with the SEC both of which are also available on our website at <unk> Dot com along with today's press release and our slide presentation.
Tyler: Additionally, these statements are based on information available to us today August 13th 2024.
Tyler: And we undertake no obligation to update them as circumstances may change.
Speaker Change: The agenda for today's call is on the screen, we will review the corporate strategy updates announced in our press release as well as positive topline data from the phase III trial of <unk> in Hidradenitis Suppurativa.
Speaker Change: We will also provide an update on the lot a good amount of program and Ted and close with our financial update highlighting our projected three year cash runway covering multiple anticipated milestones.
Speaker Change: Joining us on today's call are Mena, Kim our Chief Executive Officer, Dr. Sharron, <unk>, our Chief Medical Officer, and Gil <unk>, Our Chief Financial Officer, and Chief Business Officer.
Speaker Change: I will now turn the call over to Nina.
Nina: Thanks, Tyler and thanks, everyone for joining us today.
Speaker Change: Earlier today, we announced positive phase III results for <unk> in Hidradenitis, Suppurativa as well as details of our refocused pipeline strategy and plan designed to extend our cash runway to mid 2027, we'd like to provide more details on that call.
Speaker Change: First we're very pleased to have achieved a positive phase III readout for Isaac high Def in Hs <unk>.
Speaker Change: The primary endpoint of high 475, and are especially pleased with the compelling response rates in high school or 90, and 100 within 12 weeks of treatment.
Speaker Change: And in fact, we believe has not been previously observed by other agents.
Speaker Change: While the primary endpoint was measured at 12 weeks, we continue dosing patients in our placebo controlled manner through week 16.
Speaker Change: We have data from two thirds of the trial participants who completed week 16, and these preliminary data further demonstrate deepening of responses over time.
Speaker Change: These data follow the positive PSA phase <unk> readout, we announced earlier this year and which were presented in a late breaking session at <unk> in June.
Speaker Change: Collectively the data in Hs and PSA further validate our longstanding view that <unk> has the potential to be an effective therapy that is approvable in multiple indications.
Speaker Change: As we have previously stated we will make disciplined in capital conscious decisions.
We have determined that a program of this breadth and size that's brought to market by our larger organization with more resources in an existing footprint in the therapeutic areas of interest.
Speaker Change: Over the past several months, we've been evaluating where to prioritize investments to maximize the success of our pipeline, including Lana good at math.
Speaker Change: Which we believe has the potential to improve upon the clinical response and convenience versus the standard of care in thyroid eye disease.
Speaker Change: We plan to complete the ongoing trials advisor Kaibab, an H F and PSA, but we will not start new trials in these indications.
Speaker Change: We do plan to continue the ongoing phase <unk> trial in uveitis through to its primary endpoint with topline data expected in the fourth quarter of 2024.
Speaker Change: There is high unmet need and uveitis and a compelling scientific rationale for the IL 17 access.
Speaker Change: Should the upcoming phase <unk> data be positive we anticipate one additional phase III trial of roughly 200 to 250 patients would be required for registration and the.
Speaker Change: The ongoing trial is fully enrolled with approximately 100 patients.
Speaker Change: In addition to these items tied up updates, we decided to stop internal development of SLR and <unk> seven are early anti ticket program.
Speaker Change: Data from healthy volunteers demonstrated molecular activity, but we have made the decision to de prioritize this program.
Speaker Change: Finally, this refocused pipeline also requires a different organizational structure.
Speaker Change: And we are executing and approximately 33% reduction in force.
Speaker Change: I wanted to take a moment to pause and thank our colleagues who were impacted by the restructuring.
Speaker Change: They've played an important role in our growth and I wish them, the very best in the future.
Speaker Change: While these decisions are difficult we are confident that they are the right ones to enable a salary and long term success.
Speaker Change: We remain committed to high quality execution that disciplined capital conscious these program decisions as well as the organizational restructuring enable us to move forward aggressively to development of <unk> and extend our cash runway to mid 2027.
Speaker Change: By focusing future capital investment on <unk>, we will be well positioned to fund our ongoing and planned trials through the BLA submission.
chef: Chef will review, our overall strategy and ongoing activity for <unk> in a moment, but I didn't want to make a few comments on the program.
chef: In terms of development strategy. The original plan had included a phase <unk> III, but with the additional dose ranging that we're completing in patients in the ongoing phase II trial, we will be able to go directly into a phase III program potentially with concurrent trials.
We're currently planning to start the phase III program in the first quarter of 2025.
chef: Additionally, we plan to meet with the FDA later this year and then hosted an investor presentation to provide additional phase II data and details for the planned phase III program.
Speaker Change: With that I'd like to turn the call over to shop.
Shon: Thank you Dina and.
Shawn: Hello, everyone I'm very pleased to share with you today positive phase III data of ICL kebab in hidradenitis Suppurativa.
Shon: Sure.
Speaker Change: And provide a program update on lending could come up in Paradise disease, let.
Speaker Change: Let me start with <unk>.
Speaker Change: This regulated interleukin 17 activity plays a pivotal role in hidradenitis Suppurativa pathogenesis multi domain disease resolution is under achieved with available current therapies.
Sales for the planned phase III program.
phase 2 data and details for the planned phase 3 program. With that, I'd like to turn the call over to Shep.
Speaker Change: An unmet need exists for therapies demonstrating efficacy.
Shep: Thank you, Meena, and hello, everyone. I'm very pleased to share with you today positive phase 3 data of Isocubib in Hydradenitis Suprativa, or HS, and provide a program update on learning GUTMAP in thyroid eye disease. Let me start with HS.
Speaker Change: Across multiple disease manifestations, including upset inflammatory nodules and draining tunnels.
Speaker Change: <unk> is a small protein therapeutic designed to selectively inhibit <unk> with high potency through tight binding affinity the <unk>.
Speaker Change: Dysregulated interleukin-17A activity plays a pivotal role in hydradenitis supertiva pathogenesis.
Speaker Change: Molecular size of ICU beds.
Speaker Change: <unk> the size of a monoclonal antibody may enable tissue penetration.
Speaker Change: Multi-domain disease resolution is underachieved with available current therapies.
Speaker Change: It's our opinion binding domain prolong this half life.
Speaker Change: An unmet need exists for therapies demonstrating efficacy across multiple disease manifestations, including abscess, inflammatory nodules, and draining tunnels.
Speaker Change: In may enhance targeting to sites of inflammation in Hs.
Speaker Change: Yes, Youll see the design of our global Phase III trial of ICL, Kebab, and Hs, which we expect will be the first of the two pivotal trials needed for registration in this indication.
Speaker Change: Izoquibab is a small protein therapeutic designed to selectively inhibit interleukin-17A with high potency through tight binding affinity.
Speaker Change: 258 patients were randomized one to one to receive either <unk> hundred 60 milligram weekly or placebo.
Speaker Change: The small molecular size of azocubans attains the size of a monoclonal antibody, may enable tissue penetration, and its albumin-binding domain prolongs its half-life.
Speaker Change: The inclusion criteria and design is similar to other phase III studies.
Speaker Change: With the primary endpoint here for the first time in a phase III of highest concern to five at week 12.
Speaker Change: and may enhance targeting to sites of inflammation in HS.
Speaker Change: Here you see the design of our global phase 3 trial of isocipab in HS, which we expect will be the first of the two pivotal trials needed for registration in this indication.
Speaker Change: At week 16, placebo patients with switch to receive <unk>.
Speaker Change: 160 milligram weekly in the active treatment blinded period.
Speaker Change: As <unk> mentioned two thirds of trial participants if available week 16 data and we will present those preliminary data today as well.
Speaker Change: 258 patients.
Speaker Change: We randomized one-to-one to receive either Isocubib 160 mg weekly or placebo. The inclusion criteria and design is similar to other Phase III studies.
Speaker Change: Yes, we see patient demographics, and baseline characteristics, which were well balanced between I look at the treatment group and placebo typical of a patient population with moderate to severe hs and comparable to other global phase III pivotal trials.
Speaker Change: with a primary endpoint here for the first time in FS3 of high score 75 at week 12.
Speaker Change: At week 16, placebo patients were switched to receive isocupep 160 milligram weekly in the active treatment blinded period.
Speaker Change: 103 patients on <unk> and.
Speaker Change: <unk> hundred 12 patients in the placebo arm.
Speaker Change: As Mina mentioned, two-thirds of trial participants have available Week 16 data, and we'll present those preliminary data today as well.
Speaker Change: Completed the study through week 12, thus hedging approximately 20% when I look at that.
Speaker Change: Approximately 13% on placebo discontinuing treatment with a delta of around 7% between two groups. Please.
Mina: Here we see patient demographics and baseline characteristics.
Mina: which were well-balanced between isochiped treatment group and placebo, typical of a patient population with moderate to severe HS and comparable to other global phase 3 pivotal trials.
Speaker Change: Please note the most common reasons, leading to discontinuation on I look a bit where mild aes.
Speaker Change: And there were no notable differences between <unk> and placebo in terms of loss to follow up and withdrawal of consent rates.
Speaker Change: 103 patients on the isotope arm and 112 patients in the placebo arm completed the study through week 12.
In this trial <unk> had a rapid onset of action associated with clear evidence of improvement within two weeks achieving statistical significance as early as week four as mentioned the study met its primary endpoint with 33% of patients achieving a.
Speaker Change: Thus, having approximately 20% on isocubep arm and approximately 13% on placebo arm discontinued treatment with a delta of around 7% between the two groups.
Speaker Change: Please note the most common reasons leading to discontinuation on Isocubep were mild AEs.
Speaker Change: <unk> response that is 75% reduction in upset in inflamed mergers this is 21% for placebo.
Speaker Change: And there were no notable differences between izokibeb and placebo in terms of loss to follow-up and withdrawal of consent rates.
Speaker Change: Looking at the two thirds of patients with the week 16 data.
Speaker Change: We cannot zev and increase in response up to 40% on ISO cubit versus 20% on placebo.
Speaker Change: In this trial, iZokibeb had a rapid onset of action associated with clear evidence of improvement.
Speaker Change: When we look at higher orders of response.
Speaker Change: within two weeks.
Speaker Change: Achieving statistical significance as early as week 4, as mentioned, the study met its primary end point.
Speaker Change: Looking at high School 90 in high school hundreds as occupancy again achieved statistically significant responses at week 12 versus placebo with approximately one in four patients when I look at them achieving these deeper responses versus placebo.
Speaker Change: with 33% of eye-occupied patients.
Speaker Change: achieving a high-score 75 response. That is a 75% reduction in abscess and inflamed nodules, less than 21% for placebo.
Speaker Change: Notably the Delta So high school 19, hundreds were maintained at week 16.
Speaker Change: Looking at the two-thirds of patients worth of week 16 data, we can observe an increase in response up to 40% on isocubets versus 20% on placebo.
Speaker Change: Yes, you'll see the response across the continuum of highest call 50 to 100 is depicted from left to right on this slide.
Speaker Change: When we look at higher orders of response,
Speaker Change: As expected, we observe a consistent trend with placebo response decreasing as the efficacy ahead with increases at week 12.
Speaker Change: looking at high school 90 and high school 100.
Speaker Change: ISOCQ-IPAP again achieved statistically significant responses.
Speaker Change: at week 12 versus placebo. With approximately one in four patients.
Speaker Change: Clinical meaningful reductions in skin pain and improvements in <unk> were seen observed versus placebo at week 12, and also at week 16.
Speaker Change: on Isocubep achieving these deeper responses versus placebo. Notably, the deltas for high score 90 and 100 were maintained at week 16.
Speaker Change: The safety findings of I look at that were consistent with those observed in previous trials with the most common adverse events being mild to moderate injection site reactions in around 65% of patients on <unk> versus 8% in the placebo arm.
Speaker Change: Here you see the response across the continuum of high score 50 to 100 as depicted from left to right on the slide. As expected, we observe a consistent trend with placebo response decreasing as the efficacy threshold increases at week 12.
Speaker Change: You'll also note not much differences for other.
Speaker Change: Clinical meaningful reductions in skin pain and improvements in DLQI were seen observed versus placebo at week 12 and also at week 16.
Speaker Change: Events like headache happening in 10% this is 9% and 7% in.
Speaker Change: NASA pharyngitis in both.
Speaker Change: Notably there were no cases of Canada on <unk> with only three cases showing in placebo there.
Speaker Change: The safety findings of iZoKiBab were consistent with those observed in previous trials with the most common adverse events.
Speaker Change: There was no IBD liver toxicity, suicidal ideation and behavior in the <unk> treatment.
Speaker Change: being mild to moderate injection site reaction.
Speaker Change: In conclusion.
Speaker Change: in around 65% of patients on a Zikebab versus 8% in the placebo arm. You also note not much differences for other events like headache happening in 10% versus 9% and 7% of nasopharyngitis.
Speaker Change: Zaki bit safety is in line with our past experience.
Speaker Change: It appears to have the optimal to offer deep clinical responses across multiple domains, including skin pain in patient reported outcomes we.
Speaker Change: We are very pleased to have successfully delivered this positive phase III trial for ISO Tibetan Hs, which builds on the phase III data released in PSC earlier this year.
Speaker Change: in both arms.
Speaker Change: Notably, there were no cases of candida on izokibeb, with only three cases showing in placebo. There was no IBD, liver toxicity, suicidal ideation behavior in the izokibeb treatment arm.
Now turning our attention to <unk>, which we are developing as a subcutaneous treatment for thyroid eye disease.
Speaker Change: In conclusion...
Speaker Change: iZocupep's safety is in line with our past experience, and iZocupep appears to have the optimal to offer deep clinical responses across multiple HS domains, including skin pain and patient-reported outcomes.
Speaker Change: Thyroid eye diseases, and autoimmune disorder characterized by progressive inflammation that can lead to irreversible damage to tissues around the eye.
Speaker Change: Threatening vision patients present, with Proptosis diplopia, and a variety of disabling symptoms.
Speaker Change: We are very pleased to have successfully delivered this positive Phase III trial for Isocubib in HS, which builds on the Phase III data released in PSA earlier this year.
Speaker Change: Fix greater than 100000 patients in the U S.
Speaker Change: A high unmet need persist and thyroid eye disease, a multifaceted disease was impact extends beyond the well recognized visual disfigurement patient quality of life is markedly impacted by Ted.
Speaker Change: Now, turning our attention to Lonigutmab, which we are developing as a subcutaneous treatment for thyroid eye disease.
Speaker Change: Thyroid eye disease is an autoimmune disorder characterized by progressive inflammation that can lead to irreversible damage to tissues around the eye, threatening vision. Patients present with proptosis, diplopia, and a variety of disabling eye symptoms.
Speaker Change: A therapy that provides the rapids deeper disease modifying effects that are durable across 10 months gestation and result, and improve patient quality of life.
Speaker Change: Safety and convenience will be important for patients.
Speaker Change: It affects greater than 100,000 patients in the U.S.
Speaker Change: Lonnie good map is the next generation recombinant humanized <unk>, one monoclonal antibodies against human IGF, one receptor being developed to treat severe manifestations of <unk> <unk>.
Speaker Change: A high unmet need persists in thyroid eye disease, a multifaceted disease whose impact extends beyond the well-recognized visual disfigurement. Patient quality of life is markedly impacted by TED.
<unk> in the middle cartoon on slide <unk>.
Speaker Change: <unk> binds IGF one hour on the unique binding site.
Speaker Change: A therapy that provides rapid, deeper disease-modifying effects that are durable across third-month gestation and results in improved patient quality of life, safety, and convenience will be important for patients.
Speaker Change: Which we call an epitope and does not compete with IGF one binding.
Speaker Change: It does this with high affinity with a kilo delta affinity measured are unfettered, picomolar and specificity, which triggers a rapid internalization and degradation within minutes of the IGF one receptor thus.
Speaker Change: Lonigutmav is a next-generation recombinant humanized IgG1 monoclonal antibodies against human IgF1 receptor being developed to treat severe manifestations of TEDS, as shown in the middle cartoon on the slide.
Speaker Change: Eliminating it from the surface of the IGF, one expressing sales with potential to maintain IGF one within homeostatic levels.
Speaker Change: Lonnie Goodman binds IGF-1-ARA on a unique binding site.
Speaker Change: Jeff One IRA internalization prevent downstream signaling an orbital fibroblast from patients with Ted and has been associated with therapeutic benefit into.
Speaker Change: which we call an epitope, and does not compete with IGF-1 binding.
Speaker Change: It does this with high affinity, with a kilo-delta affinity measured around 30 picomolar, and a specificity which triggers rapid internalization and degradation within minutes of the IGF-1 receptor.
Speaker Change: The rapid and efficient suppression of IGF, one receptor signaling and Ted with loans, good map could potentially improve clinical outcomes for patients by providing lower doses of exposure to achieve robust clinical response as we saw in our proof of.
Speaker Change: thus eliminating it from the surface of the IGF-R1-expressing cells with potential to maintain IGF-1 within homeostatic levels.
Speaker Change: Yet with 40 milligrams Q3 W. Hedging responses at early time points when we assessed at three weeks after a single dose.
Speaker Change: IGF-1RI internalization prevents downstream signaling in orbital fibroblasts from patients with TED and has been associated with therapeutic benefit in TED.
Speaker Change: There is potential for deep and durable responses with chronic dosing and ability to minimize safety risk by choosing an optimal convenient dose regimen.
Speaker Change: the rapid and efficient suppression of IGF-1 receptor signaling.
Speaker Change: in TED with Lonnie Goodman could potentially improve clinical outcomes.
Speaker Change: As I mentioned, we completed the phase one proof of concept portion of our ongoing.
Speaker Change: for patients by providing lower doses of exposure.
Speaker Change: Trial earlier this year and we are now embarking on a dose ranging phase II portion.
Lonnie Goodman: to achieve robust clinical response as we saw in our proof of concept with 40 milligrams Q3W having responses at early time points when we assessed at three weeks after a single dose.
Speaker Change: Across four dose groups levels as you can see depicted on the right part of this slide projected.
Speaker Change: The phase two trial was designed with the flexibility to test multiple dose levels and regimens in order to number one is tablet <unk>, what we call a minimum effective dose.
Lonnie Goodman: There's potential for deep and durable responses with chronic dosing and ability to minimize safety risks by choosing an optimal, convenient dose regimen.
Lonnie Goodman: As I mentioned, we completed the Phase 1 proof of concept.
Speaker Change: When we are focusing on assessing the C mean.
Lonnie Goodman: portion of our ongoing learning group trial earlier this year.
Speaker Change: And number two to enable establishment of an optimal dose selection for phase III program.
Lonnie Goodman: And we are now embarking on a dose ranging phase two portion across four dose group levels, as you can see depicted on the right part of the slide projected.
Speaker Change: We think the optimal therapeutic window.
Speaker Change: Can see labeled on the Y axis on the left part of this slide.
Lonnie Goodman: The Phase II trial was designed with the flexibility to test multiple dose levels and regimens in order to, number one, establish what we call a minimum effective dose.
Speaker Change: And making sure that we don't have a CE marks that results in over exposure and therefore really calibrating an opportunity.
Speaker Change: To minimize safety, which might be associated with high and.
Speaker Change: when we are focusing on assessing the sea mine.
Speaker Change: Over exposure.
Speaker Change: And number two, to enable establishment of an optimal dose selection for phase 3 program.
Speaker Change: We are using the totality of this data to calibrate to an optimal dose level and convenient dose regiment. We recently initiated the final dose group with a dose level of 70 milligrams administered every three to four weeks in this phase III trial to confirm the dose will take to phase III with.
Speaker Change: within the optimal therapeutic window that you can see labeled on the y-axis on the left part of the slide.
Speaker Change: And making sure that we don't have a C-max that results in overexposure and therefore really calibrating an opportunity to minimize safety which might be associated with high and overexposure.
Speaker Change: Believe our phase III approach is unique and that is patient centric designed comprehensively to address the ongoing unmet needs of thyroid eye disease patients and really balance benefit risk to define an optimal dose level and a regimen that profiles, our robust therapeutic impact.
Speaker Change: We are using the totality of this data to calibrate to an optimal dose level and convenient dose regimen.
Speaker Change: Across the multi faceted aspects of Ted we are currently planning to start the phase III trial in the first quarter of 2025.
Speaker Change: We recently initiated the final dose group with a dose level of 70 milligrams administered every 3 to 4 weeks.
Gil: As <unk> mentioned, we are looking forward to meeting with the FDA later this year and sharing more information about the Registrational program in its future and Vista event now turn over to Gil.
Speaker Change: in this phase two trial to confirm the dose we will take to phase three.
Speaker Change: We believe our Phase II approach is unique in that it's patient-centric, designed comprehensively to address the ongoing and met needs of thyroid eye disease patients.
Gil: Thank you Chuck and good afternoon, everyone.
Gil: Today I'm going to make a few comments on financial highlights from the quarter ended June 32024.
Speaker Change: and really balance benefit-risk to define an optimal dose level and a regimen that profiles a robust therapeutic impact across the multifaceted aspects of TED.
Gil: And then discuss some of the financial implications of the refocused pipeline and restructuring initiatives, we announced today.
Speaker Change: We are currently planning to start the Phase 3 trial in the first quarter of 2025. And as Mina mentioned, we are looking forward to meeting with the FDA later this year and sharing more information about the registration program in TED at a future investor event.
Gil: The key milestones ahead for us.
And also provide year end cash guidance.
Gil: We are fortunate to be in a strong financial position.
Gil: At June 30, our cash position was approximately $635 million.
Gail: Now turn over to Gail.
Gil: For Q2, our R&D expense was $76 4 million as compared to $30 million for the same period in 2023.
Gail: Thank you, Shep, and good afternoon, everyone.
Gail: Today, I'm going to make a few comments on financial highlights from the quarter ended June 30, 2024. Thank you.
Gail: and then discuss some of the financial implications of the refocused pipeline and restructuring initiatives we announced today, the key milestones ahead for us, and also provide year-end cash guidance.
Gil: A substantial majority of our R&D expense approximately 75% is related to the <unk> program, where we have been executing three phase III programs, this year, and PSA Hs and uveitis.
Gail: We are fortunate to be in a strong financial position.
Gil: General and administrative expenses were $16 6 million for the second quarter.
Gail: At June 30th, our cash position was approximately $635 million.
Gil: As compared to $12 7 million for the same period in 2023.
Gail: For Q2, our R&D expense was $76.4 million, as compared to $30 million for the same period in 2023.
Gil: R&D and G&A expense includes stock based compensation expense of $10 2 million.
Gail: A substantial majority of our R&D expense, approximately 75%, is related to the Isochibet program where we have been executing three phase three programs this year in PSA, HS, and uveitis.
Gil: Which increased from $8 5 million for the same quarter in 2023.
Gil: Today.
Gil: We made the difficult decision to rightsize our organization in line with our refocused pipeline strategy.
Gil: I wanted to make a few comments on the financial implications of this decision.
Gail: General and administrative expenses were $16.6 million for the second quarter as compared to $12.7 million for the same period in 2023.
Gil: We expect to incur approximately 4.4.
Gil: $4 5 million in cash based restructuring charges related to the workforce reduction.
Gail: R&D and G&A expense includes stock-based compensation expense of $10.2 million, which increased from $8.5 million for the same quarter in 2023.
Gil: Our estimate for the costs associated with the completion of the ongoing with the Ida study Hs.
Gil: PSA studies is expected to range between 30 and $35 million.
Gail: Today we made the difficult decision to right-size our organization in line with our refocused pipeline strategy.
Gil: With respect to the ongoing <unk> CMC activities and commitments we.
Gail: I wanted to make a few comments on the financial implications of this decision.
Gil: We expect to incur between 55% and $85 million.
Gail: We expect to incur approximately $4.5 million in cash-based restructuring charges related to the workforce reduction.
Gil: We are actively working with our manufacturing partners with the goal to mitigate these costs.
Gil: From a financial point of view.
Gil: Our focus will be on efficiently and effectively executing this refocused pipeline strategy and associated restructuring.
Gail: Our estimate for the cost associated with the completion of the ongoing uveitis study, HS, and PSA studies is expected to range between $30 and $35 million.
Gil: Remaining disciplined and risk aware with our operational spend.
Gil: And significantly extending our cash runway out approximately three years to mid 2027 through multiple value enhancing catalyst.
Gail: with respect to the ongoing ISO-CIIBAP-CMC activities and commitments.
Gail: We expect to incur between $55 and $85 million.
Gail: We are actively working with our manufacturing partners with a goal to mitigate these costs.
Gil: This long range financial guidance includes adding an additional dose arm to our on going Monica Mab phase II trial as ship just reviewed.
Gail: From a financial point of view.
Gail: Our focus will be on efficiently and effectively executing this refocused pipeline strategy and associated restructuring.
Gil: Funding two phase III trials for water, Guten, Mab and BLA, enabling activities for that program.
Gail: remaining disciplined and risk-aware with our operational spend.
Gil: In addition.
Gil: Please note that our cash runway guidance does not include any proceeds related to additional financing or partnering.
Gail: and significantly extending our cash runway out approximately three years to mid-2027 through multiple value enhancing catalysts.
Gil: We are very excited about the milestones ahead for our sellers and we remained focused on our core mission to accelerate the development and delivery of transformative medicines in immunology.
Gail: This long-range financial guidance includes adding an additional dose arm to our ongoing Montegut MAP Phase 2 trial, as Shep just reviewed.
On this slide we have outlined some of the important milestones for our development programs and related timing windows.
Shep: Funding to phase 3 trials for one, a good map and enabling activities for that program.
Gil: Following our end of phase II meeting with the FDA on a lot of good map program.
Shep: In addition, please note that our cash runway guidance does not include any proceeds related to additional financing or partnering.
Gil: We plan to hold an investor event focused on the unmet need for thyroid eye disease patients the detailed rationale underpinning dose selection.
Speaker Change: We are very excited about the milestones ahead for Accelerin. We remain focused on our core mission to accelerate the development and delivery of transformative medicines and immunology.
Gil: I'll come at the end of Phase II meeting with the FDA.
Gil: Additional data from the ongoing phase III.
Gil: And the design of our phase III development program.
Speaker Change: On this slide, we have outlined some of the important milestones for our development programs and related timing windows.
Gil: In addition, we also continue to project.
Gil: That we will have top line results from the ISO <unk>.
Gil: <unk> III trial in <unk> before year end.
Speaker Change: Following our end of phase two meeting with the FDA on the Lana Goodman program.
Gil: We anticipate rapidly advancing lot of good map into late stage development with the start of the phase III program before the end of Q1 2025.
Speaker Change: We plan to hold an investor event focused on the unmet need for thyroid eye disease patients. The detailed rationale underpinning dose selection.
Gil: We expect the first top line readout from the registration program in 2026.
Speaker Change: The outcome of the end of Phase 2 meeting with the FDA, additional data from the ongoing Phase 2.
Gil: And to file a potential BLA thereafter.
Speaker Change: And the design of our phase 3 development program.
Gil: We look forward to sharing more details on our plans to block a lot of good map program at our upcoming investor events.
Speaker Change: In addition, we also continue to project.
Speaker Change: that we'll have top-line results from the ISO QIVEP phase 2b3 trial in uveitis before year-end.
Gil: Now turning to forward looking financial guidance.
Gil: We currently project our 2024 at year end cash position will range between 420 and $450 million.
Speaker Change: We anticipate rapidly advancing Lana-Guten-MAP into late-stage development with the start of the Phase III program before the end of Q1 2025.
Gil: We expect our cash used in operations to increase substantially in the second half of 2024 remember in the first half of 2024, we received $37 million from a one time vendor credit and licensing payments Conversely.
Speaker Change: We expect the first top-line readout from the registration program in 2026.
Speaker Change: and to file a potential BLA thereafter.
Speaker Change: We look forward to sharing more details on our plans for the Lotta Good Map program at our upcoming investor event.
Gil: In the second half of 2024, we expect to pay a $31 million option payment related to achieving proof of concept with <unk> and.
Speaker Change: Now, turning to forward-looking financial guidance.
Speaker Change: We currently project our 2024 year-end cash position will range between $420 million and $450 million.
Gil: Nonrecurring payment for costs related to the restructuring and exiting certain isocheim commitments.
Gil: As I mentioned earlier, we now project our cash runway to mid 2027, which we anticipate will fully fund the <unk> development program through BLA filing while also preserving capital for selective pipeline expansion.
Speaker Change: We expect our cash used in operations to increase substantially in the second half of 2024. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit and licensing payments. We expect our cash used in operations to increase substantially in the second half of 2024. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit and licensing payments. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit
Speaker Change: Conversely, in the second half of 2024, we expect to pay a $31 million option payment related to achieving proof of concept with Lana Guttenmab and non-recurring payment for costs related to the restructuring and actually inserting ISO-CIBA commitments.
Gil: And as I stated earlier, our cash runway guidance does not include any proceeds related to it additional financing or partnering.
Gil: And now I'll turn the call back over to Nina.
Nina: Thank you Galen shop, and thank you all for joining us on today's call. The decisions, we announced today about our go forward strategy position us to execute online and get them out from a position of strength.
Speaker Change: As I mentioned earlier, we now project our cash runway to mid-2027.
Speaker Change: which we anticipate will fully fund the Wanagut and MADD development program through BLA filing while also preserving capital for selective pipeline expansion.
Speaker Change: By suspending new investment for either kind of NPSA in Hs discontinuing SLR and $5 seven and the difficult decision to right size. Our organization. We can now focus on rapidly developing <unk> as a potential therapy for thyroid eye disease.
Speaker Change: And, as I stated earlier, our cash runway guidance does not include any proceeds related to additional financing or partnering.
Nina: We have an outstanding team.
Nina: Physician to deliver high quality execution of the pivotal program.
Speaker Change: And now I'll turn the call back over to Nina.
Nina: Thank you, Gil and Shep, and thank you all for joining us on today's call. The decisions we announced today about our Go Forward strategy position us to execute on Montegutamab from a position of strength.
Speaker Change: And we now have the cash runway to take our program through both pivotal trials. We're excited by the opportunity to serve the unmet needs of 10 patients.
Speaker Change: Since taking on the CEO role a few months ago I've had the opportunity to meet with many probably more than 100 of our investors and I appreciate the opportunity to provide this update today.
Speaker Change: By suspending new investment for izakibab and PSA and HF, discontinuing SLRN 517, and the difficult decision to right-size our organization, we can now focus on rapidly developing lanagutamab as the potential best therapy for thyroid eye disease.
Speaker Change: We look forward to providing regular updates on our progress and I Hope you will join us for our Investor event. After our FDA meeting, where we will provide an in depth and comprehensive overview of the full one a good amount of opportunity and the many reasons fiber. So excited to move this program forward. Thank you for joining us today and operator with that we can open up to <unk>.
Speaker Change: We have an outstanding team. We're positioned to deliver high-quality execution of the pivotal program. And we now have a cash runway to take the program through both pivotal trials. We're excited by the opportunity to serve the unmet needs of TED patients.
Speaker Change: Austin.
Operator: Thank you so much and as a reminder to our audience press star one one to get in the queue and wait for your name to be announced to remove yourself from the queue Press star one again.
Speaker Change: Since taking on the CEO role a few months ago, I've had the opportunity to meet with many, probably more than 100 of our investors, and I appreciate the opportunity to provide this update today.
Speaker Change: Please standby for our first question.
Speaker Change: We look forward to providing regular updates on our progress and I hope you will join us for our investor event after our FDA meeting where we will provide an in-depth and comprehensive overview of the full Wanagooda Map opportunity and the many reasons why we're so excited to move this program forward.
Speaker Change: And he comes from the line of Derek <unk> with Wells Fargo. Please proceed.
Derek <unk>: Hey, thanks for taking the questions.
Speaker Change: Three quick ones from Us I guess first.
Derek <unk>: What's the rationale for adding a 70 milligram dose in the ongoing facing for a long ago to map also the every three week dosing arm as well.
Speaker Change: Thanks for joining us today and operator with that we can open up to questions.
Speaker Change: Thank you so much and as a reminder to our tele audience, press star 11 to get in the queue and wait for your name to be announced. To remove yourself from the queue, press star 11 again. Please stand by for our first question.
Speaker Change: Just wanted to also figure out whether this is kind of leading to potentially.
Speaker Change: A loading dose.
Speaker Change: In phase III. So that's the first question second question just for I guess is the plan to partner this asset right now or is it just going on the shelf I just wanted to clarify in terms of the comments you made around uveitis is that something you would plan to move forward by yourself if that data looks good.
Speaker Change: And it comes from the line of Derek Archela with Wells Fargo. Please proceed.
Derek Archela: Hey, thanks for taking the questions just three quick ones from us. I guess first What's the rationale for adding the 70 milligram dose?
And then third.
Speaker Change: In terms of the kind of as we expand our cash runway and opportunity potentially to expand the pipeline I guess is that a near term priority and I guess, what stage of development would you be looking for in terms of assets. Thanks.
Speaker Change: and the ongoing phase two for long to go to map. Also the every three week dosing arm as well.
Speaker Change: Just want to also figure out, you know, whether this is kind of leading to potentially, you know, a loading dose in phase three.
Hi, Derik thanks for the questions. There's a lot in there I think I'm going to take them in order.
Speaker Change: So, that's the first question. Second question, just for Izzo, I guess, is the plan to partner this asset right now, or is it just going on the shelf? I just wanted to clarify in terms of the comments you made around UV-itis, is that something you would plan to move forward by yourself if that data looks good?
Speaker Change: Maybe to start with ISO right and the partnering question and then what are we going to do with you would be or how do we think about uveitis.
Speaker Change: I would say with respect to partnering and this is what we've been saying we're going to do what's best for the program right. We're open to all options and fundamentally we want to see Hs and TSA right bring benefit to patients that might be with a larger organization that has existing capabilities and infrastructure right. So again, we will do well.
Speaker Change: And then third, you noted in terms of kind of the expanded cash runway and opportunity potentially to expand the pipeline, I guess, is that a near-term priority, and I guess what stage of development would you be looking for in terms of assets? Thanks.
Speaker Change: Yeah. Hi, Derek. Hey, thanks for the questions. There's a lot in there, so I'm going to take them in order.
Speaker Change: All the options and we'll do what's best for the program.
Speaker Change: I do want to note and reemphasize something that Gail said, which is we have not included any financing proceeds our proceeds from our partnership and our cash runway guidance right. So that that excludes any contribution from a potential partnership.
Speaker Change: Hey, maybe to start with right in the partnering question and then what are we going to do with or, you know, how do we think about, you know, what I say with respect to partnering and this is what we've been saying we're going to do what's best for the program.
Speaker Change: So I think that the.
Speaker Change: The response on the EIS, though any of the other questions with respect to potential BD going forward look I mean, we are always going to look at opportunities, we'll be opportunistic and as Gil said, we have assumed right that there could be some pipeline expansion and we have the funding for that.
Speaker Change: Right, we're open to all options and, you know, fundamentally, we want to see bring benefit to patients and that might be with a larger organization that has existing capabilities and infrastructure.
Speaker Change: Yeah.
Speaker Change: Right. So again, you know, we'll do we'll look at all the options and we'll do what's best for the program
Speaker Change: I do want to note and reemphasize something that Gail said, which is we have not included any financing proceeds or proceeds from a partnership in our cash runway guidance, right? So that excludes any contribution from a potential partnership.
Speaker Change: We believe right I would say that right now it's important for us to have focus on line in <unk> and high quality execution on that program and that is the focus for now and so any additional BD you know I don't think were in a hurry.
Speaker Change: So, I think that's the response on the ISO and uveitis questions with respect to potential BD going forward.
Speaker Change: And it's a high bar, but we certainly will consider any opportunistic opportunities right over time.
Speaker Change: Look, I mean, we're always going to look at opportunities will be opportunistic. And as Gil said, we have assumed.
Speaker Change: And then I think you had questions around.
Speaker Change: That design right of the longitude of Mab development program and maybe it's helpful to frame that up a little bit right. Just stepping back. We have spent the last few months evaluating the entire development program really with two goals. One is how do we derisk the phase III program.
Gil: right, that there could be some pipeline expansion and we have the funding for that, we believe.
Gil: Right, I would say though, right now, it's important for us to focus on long and good map and high quality execution on that program. And that is the focus for now.
Speaker Change: And the other is can we do that at the same time as we try to accelerate the program and we have been trying to balance both of those things. We do think that adding this additional guest cohort into the phase two program helps us achieve that first it allows us to complete dose exploration in the phase III trial rather than.
Speaker Change: And so any additional BD, you know, I don't think we're in a hurry, and it's a high bar, right? But we certainly will consider any, you know, opportunistic opportunities, right, over time.
Speaker Change: And then I think you had questions around the design, right, of the Lana Gudumab development program, and maybe it's helpful to frame that up a little bit.
<unk> three as originally planned and what that does is it allows us to move directly into a phase III program and potentially run two phase III trials concurrently.
Speaker Change: Right, just stepping back, you know, we have spent the last few months evaluating the entire development program. Really with 2 goals 1 is how do we de-risk the phase 3 program.
Speaker Change: Rather than sequentially, which obviously has the potential to accelerate that program.
Speaker Change: Right, and the other is, can we do that at the same time as we try to accelerate the program? And we have been trying to balance both of those things.
Speaker Change:
Speaker Change: And we've added the 70 know Nick dose we are looking at it in those three weeks right and four weeks right to confirm the dose that we're going to take into the pivotal program I would say I think it's important to note. We think we have our dose right, but regimen is also important and again, we want confidence around that dose we take into the program.
Speaker Change: We do think that adding this additional dose cohort into the PHEAS-2 program helps us achieve that.
Speaker Change: First, it allows us to complete dose exploration in the Phase 2 trial rather than in a 2B3 as originally planned.
Speaker Change: And what that does is it allows us to move directly into a phase 3 program and potentially run 2 phase 3 trials concurrently. Right, rather than sequentially, which obviously has the potential to accelerate that program.
Speaker Change: And the ability to do that in the phase two right is we think potentially both derisking and hopefully does allow us to go more quickly into that phase III program.
Speaker Change: You know, and we've added the 70 mil dose. We are looking at it in both 3 weeks, right? And 4 weeks, right? To confirm the dose that we're going to take into the pivotal program. I would say, I think it's important to know. We think we have our dose.
Speaker Change: Understood I guess, just a follow up there in terms of again is that being examined for potential loading dose or the loading dose is going to be figured into the phase III program.
Speaker Change: I mean thats not something we are contemplating now I mean, we do think there's 70 is our dose.
Speaker Change: Right, but regimen is also important. And again, we want confidence around that dose. We take into the program and the ability to do that in the face. To write is, we think, potentially both the risking and hopefully does allow us to go more quickly into that phase 3 program.
Speaker Change: Understood. Thank you.
Eric: Thanks, Eric.
Speaker Change: Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed.
Speaker Change: Hey, guys. Thanks for the updates it's encouraging to see the rationalization of the pipeline.
Speaker Change: Wanted to ask about the phase III uveitis trial readout, so what would compelling data.
Speaker Change: Understood. I guess just just to follow up there in terms of like, again, is that being examined for potential loading dose or the loading dose going to be figured into the phase 3 program?
From that trial look like later this year that would lead you to pursue another trial for registration.
Speaker Change: No, I mean, that's not something we're contemplating now. I mean, we do think the 70 is our dose.
Speaker Change: And the second question is what are your latest thoughts on the market size for uveitis.
Speaker Change: Understood. Thank you.
Speaker Change: Yeah, So maybe I'll start and then I'll turn it over to the team I mean.
Eric: Thanks, Eric.
Speaker Change: Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed. Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen.
Speaker Change: We're going to evaluate uveitis in the same way that we have all of our other programs right. We're going to look at the totality of the data the market the unmet need what I would say maybe.
Speaker Change: Hey, guys, thanks for the updates. It's encouraging to see the rationalization of the pipeline. I want to ask about the phase 3 uveitis trial readout. So, what would compelling data
Speaker Change: To start is there is very high unmet need right in uveitis and so we like that opportunity right to address the unmet needs of patients.
Speaker Change: from that trial look like later this year that would lead you to pursue another trial for registration. And the second question is, what are your latest thoughts on the market size for uveitis?
Speaker Change: There is obviously very limited Theyre very limited options for those patients and that will also factor into it.
Speaker Change: In terms of the trial design and sort of what are the endpoints.
Speaker Change: Yeah, so maybe I'll start and then I'll turn it over to the team. I mean, you know, I think we're going to evaluate in the same way that we have all of our other programs, right? We're going to look at the totality of the data, you know, the market, the unmet need.
Speaker Change: Turn it over to shop, maybe Todd just walk you through that yes, no. Thanks Nina.
Todd: Our trial is designed the same as the mirror trial, which is the only large phase III study that was done in <unk>, we have patients receiving steroids at baseline and then having a regimen to decrease them over 15.
Speaker Change: What I would say maybe to start is there is very high unmet need, right, in uveitis. And so we like that opportunity, right, to address the unmet needs of patients.
Speaker Change: And we have a primary efficacy endpoint at week 24, where we will be looking at full parameters Sim is your mirror deed looking at inflammation in the back of the eye quarterly original inflammation and then looking at inflammation within the eye.
Speaker Change: There is obviously, you know, very limited, there are very limited options for those patients and that will also factor into it.
Shaf: In terms of the trial design and sort of what are the end points, I'll turn it over to Shaf, maybe to just walk you through that. Yeah, no, thanks, Mina. Our trial is designed the same as the Yomira trial, which is the only large phase 3 study that was done in UPI.
Speaker Change: Looking at the vitreous haze anterior chamber as well and then best corrected visual acuity. So thats the treatment failure. So we'll be looking at a compelling data set that showcases there are more patients on placebo versus drug that achieved this endpoint.
Shaf: We have patients receiving
Shaf: steroid baseline, and then having a regimen to decrease them over 15.
Shaf: And we have a primary FCAS endpoint at week 24, where we'll be looking at four parameters same as Jumeirah did.
Speaker Change: Tyler.
Shaf: looking at inflammation in the back of the eye, coronary retinal inflammation, and then looking at inflammation within the eye, looking at the vitreous, haze, anterior chamber as well, and then best...
Speaker Change: Yes. Good. Thank you. Thank you one moment for our next question.
Speaker Change: And our next question comes from the line of Yasmin Rahimi with Piper Sandler. Please proceed.
Shaf: corrected visual acuity. So that's the treatment failure. So we'll be looking at a compelling data set that showcases there are more patients on placebo versus drug that achieve this end point.
Yasmin Rahimi: Thank you so much team for sharing this difficult decisions with us and walking us through the rationale.
Yasmin Rahimi: Tim I guess could you maybe talk about cohort three cohort four has just begun.
Speaker Change: [inaudible]
Yasmin Rahimi: What do you I'm Shannon.
Yasmin Rahimi: Have you seen from that dose cohorts, so far when should we be expecting data from that and then I guess.
Speaker Change: Tyler?
Speaker Change: And then and then as we think about phase III design, just maybe parts of the you alluded to some innovative approaches, but maybe maybe walk us through who would be the ideal patient.
Speaker Change: And our next question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed.
Yasmeen Rahimi: Thank you so much, team, for sharing these difficult decisions with us and walking us through the rationale. Team, I guess, could you maybe talk about Cohort 3? Cohort 4 has just begun.
Speaker Change: It also seems like pet studies have become quite competitive in terms of enrollment.
Speaker Change: We should also color and ensuring being able to deliver top line data in an efficient manner, sorry, there was too many questions in there, but I guess.
Speaker Change: at what junction, at what have you seen from that dose cohort so far? When should we be expecting data from it? And then...
Speaker Change: Cohort three and yeah.
Speaker Change: I appreciate color on that thank you, sorry, but yeah no for sure. So let's start with cohort three and then.
Speaker Change: I guess, um...
Speaker Change: And then as we think about phase 3 design, just maybe parts of the – you alluded to some innovative approaches.
Speaker Change: If we Miss anything just yeah, just just to remind us just prompt us.
Speaker Change: but maybe walk us through who would be the ideal patient.
Speaker Change: Okay.
Speaker Change: Like I would just add in.
Speaker Change: In our prepared remarks, we are thinking about that phase III program right Holistically. We think it's most useful to read out the data from that phase III program. After we've met with the FDA later this year right. When we can give a more complete picture and that more complete picture would be additional data rate includes.
Speaker Change: It also seems like...
Speaker Change: TET studies have become quite competitive in terms of enrollment.
Color: So, I appreciate also Color and ensuring, you know, being able to deliver top-line data in an efficient manner. Sorry, there were too many questions in there, but I guess, cohort three, and, yeah, I appreciate Color on that. Thank you. Sorry about that.
Speaker Change: <unk> from cohort three in a really from the totality of that.
Speaker Change: No, for sure. So, let's start with cohort 3 and then if we miss anything, just. Just just remind us, just prompt us, you know, like, I.
Across the Phase III program and also how we're thinking about the phase III program. So I think thats, a little bit at the timing and we would expect that to be later this year or potentially early next year right, but really when we got a more complete picture to share with you all and we think that that is most useful.
Speaker Change: Like, I just said, and, you know, in our prepared remarks, we are thinking about that phase 2 program, right? Holistically.
Speaker Change: We think it's most useful to read out the data from that phase two program after we've met with the FDA later this year, right? When we can give a more complete picture.
Speaker Change: So I think that that's kind of a design in terms of the patients that we can potentially serve we do think that there continues to be very high unmet need right.
Speaker Change: And that more complete picture would be additional data, right, including from, you know, cohort three, you know, really from the totality of that across the phase two program.
Speaker Change: And Ted patients.
Speaker Change: And I think we've talked about this before we are particularly interested in the ability to think about chronic dosing right. This is a disease that can flare or regress or however, you want to describe that and there is an ongoing need for those patients right across many different end points and so we.
Speaker Change: And also how we're thinking about the, the phase 3 program. So, you know, I think that's a little bit of the timing and we would expect that to be later this year or potentially early next year. Right? But really, when we've got a more complete picture to share with you, well, we think that that's most useful.
Speaker Change: Really want to optimize the dose and a regimen right to try to address the totality of the disease. So we think that there again continues to be unmet need and we are very interested in exploring that chronic population.
Speaker Change: So I think that's kind of the design. In terms of the patients that we can potentially serve, we do think that there continues to be very high unmet need.
Speaker Change: Right in Ted patients, and, you know, I think we've talked about this before. We are particularly interested in the ability to think about chronic dosing.
Speaker Change: That is what did I Miss yes, and no no no just yes, that's an enrollment timing just because of competitive like with full confidence too.
Speaker Change: Right, this is a disease that, you know, can flare or regress or, you know, however, you want to describe that. And there is an ongoing need for those patients right across many different endpoints. And so we really want to optimize sort of the dose and the regimen.
Speaker Change: Now just because now several.
Speaker Change: Touch studies will be ongoing concurrently in phase three.
Speaker Change: I appreciate it.
Speaker Change: Color there.
Speaker Change: to try to address the totality of the disease. So we think that there, again, continues to be unmet need and we are very interested in exploring that chronic population.
Speaker Change: Yeah, and look we feel good about that I mean, obviously, we're rolling patients right now right into the phase two and we think that that's.
Speaker Change: We feel good about that experience and confident going into the phase III trial.
Speaker Change: Thank you. What did I miss? Yes. No, no, no. Just, just, yeah, that's an enrollment timing just because it's competitive, like, we feel confident to.
Speaker Change: Somewhat based on that experience so understand that there are more trials going on that we feel good about that.
Speaker Change: Thank you so much I'll jump back in the queue.
Speaker Change: You know, just because now several test studies will be ongoing concurrently in Phase 3, it would precate some color there.
Speaker Change: Thank you.
Our next question comes from the line of our cash to worry with Jefferies. Please proceed.
Speaker Change: Yeah, and look, we feel good about that. I mean, obviously, we're rolling patients right now right into the phase two and, you know, we think that that's.
Hi, This is <unk> on for Kash. Thank you for taking our question. So I guess more on uveitis are you targeting more refractory patients like those who are on or after prior biologic use and Additionally will you be IFC considered an orphan indication and could you potentially get orphan pricing of around.
Speaker Change: We feel good about that experience and confident going into the phase 3 trials, you know, somewhat based on that experience. So, you know, understand that there are more trials going on, but we feel good about that.
Speaker Change: 200000 per year, and Lithification I imagine there might be some pushback from parents for orphan drug pricing given humira is already approved for uveitis and a much cheaper with just some color on that would be helpful.
Speaker Change: Thank you so much. I'll jump back in the queue.
Speaker Change: Thank you. Our next question comes from the line of Akash Tiwari with Jeffries. Please proceed.
Speaker Change: Yeah, great. Thanks for the question. This is Gil as <unk> was saying earlier.
Speaker Change: Hi, this is Phoebe on for Akash. Thank you for taking our questions.
Speaker Change: Any indication there is still a very high unmet need there's really only a couple of treatment options essentially steroids.
Phoebe: So, I guess more on uveitis, are you targeting more refractory patients, like those who are on or after prior biologic use? And additionally, will uveitis be considered an orphan indication, and could you potentially get orphan pricing of around $10,000?
Speaker Change: And Humira and the current standard of care is really only modestly effective.
Speaker Change: So we really think there's an opportunity here to drive additional benefits to patients whether that.
Speaker Change: 200,000 per year in this indication. I imagine there might be some pushback from payers for orphan drug pricing given Humira is already approved for uveitis and is much cheaper, so just some color around that would be helpful.
Speaker Change: At any line of this we also think that.
Speaker Change: With the limited therapeutic options.
Speaker Change: As a therapy like ISO may come in here that will also have an opportunity to expand the market in the diagnosis of this this condition.
Speaker Change: Yeah, great. Thanks for the question. This is Gil. You know, as Mina was saying earlier, you know, this is an interesting indication There's still a very high unmet need. There's really only a couple treatment options essentially steroids
Speaker Change: I think in terms of.
In terms of the pricing question, that's a little early to say, but certainly something that we can.
Speaker Change: and Humira. And the current standard of care is really only modestly effective. So we really think there's an opportunity here to drive additional benefits to patients, whether that's at any line of this. We also think that
Speaker Change: Think about it.
Speaker Change: As we go in but it's a little early to speculate on pricing in the indication.
Speaker Change: Yes on patients that are coming into the study these are patients with <unk>.
Speaker Change: Active non infectious uveitis, there will be patients who also have been previously exposed to other by other biologics, except those biologics that are on the IL 17 pathway.
Speaker Change: With the limited therapeutic options, you know, as a therapy, like Iso may come in here, they'll also have an opportunity to expand the market and diagnosis of this condition.
Speaker Change: Understood. Thank you.
Speaker Change: I think in terms of the pricing question, you know, that's a little early to say, but certainly something that we think about as we go in, but it's a little early to speculate on pricing and the indication.
Speaker Change: Thank you.
Emily <unk>: Our next question comes from the line of Emily <unk> with HC Wainwright. Please proceed.
Speaker Change: Alright, thanks for taking the questions I guess, one of the clarifying question and the 70 Meg wanted.
Speaker Change: Yeah, and on patients that are coming in to study, these are patients with
Speaker Change: active, non-infectious UBITs.
Speaker Change: Are you enrolling <unk> patients in total across the three weekly and four weekly regimen or the APE per regimen.
Speaker Change: There will be patients who also have been previously exposed to other biologics, except those biologics that are on the IL-17 pathway.
Speaker Change: And then kind of a follow up to Bob do you think about the sufficient number of patients to kind of get an idea if that's the appropriate dose to take into phase III.
Speaker Change: Understood. Thank you.
Speaker Change: And then lastly, if you can kind of confirm that you haven't seen any cases of hearing impacts from any of the cohorts so far okay.
Speaker Change: Thank you.
Speaker Change: Our next question comes from the line of Emily Botnar with H.C. Wainwright. Please proceed.
Speaker Change: Yeah. Thanks, Let me, let me start and maybe I'll turn it over to shop on that they're hearing the way that this this final cohort is set up it has eight patients and allows us to try the 70 Megs Q3 and Q4. It also gives us the flexibility to go up to 16 patients.
Emily Botnar: Hi, thanks for being the questions. I guess some of the clarifying question and the 70 Meg Lonnie does. Are you.
Emily Botnar: enrolling 8 patients in total across the 3-weekly and 4-weekly regimens, or the 8 per regimen? And kind of follow up to that, do you think that's a sufficient number of patients to kind of get an idea of if that's the appropriate dose to take into phase 3?
Speaker Change: You know in our cohorts. So it is built with some flexibility obviously those are small numbers, but in totality right across the phase III program right. We will have seen in patient data across multiple doses and regimens and we think that that's going be bakery again useful for us.
Speaker Change: And then, lastly, if you can kind of confirm that you haven't seen any cases of hearing impacts from any of the cohorts so far. Thank you.
Speaker Change: Yeah, thanks. Let me start, and maybe I'll turn it over to Shep on the hearing. The way that this final cohort is set up, it has eight patients and allows us to try the 70 mg Q3 and Q4.
Speaker Change: And a way to Derisk that phase III program.
Speaker Change: Right.
Speaker Change: I'll, let <unk> address that the hearing question.
Speaker Change: Thanks for the response.
Speaker Change: It also gives us the flexibility to go up to 16 patients.
Speaker Change: Hearing all.
Speaker Change: Dose groups that we have been exploring the dose range that <unk> done at baseline and throughout the course of the study none of the patients in any of the dose.
Shep: Uh, you know, in that cohort, so it is built with some flexibility, you know, obviously, those are small numbers, but in totality, right across this phase 2 program, right? We will have seen inpatient data. Across multiple doses and regimens, and we think that that's going to be very again useful for us and a way to de risk that phase 3 program.
Speaker Change: Most groups have developed any notable hearing impairment or sense in your hearing loss. We did report in March in our topline data that there were three patients in one of the cohorts that hit tons into new tests that resolved and none of those patients that are <unk>.
Shep: Right, and maybe I'll let Chet address the hearing question.
Speaker Change: <unk> and audio ground. So so far no major changes pertaining to audio chrome changes.
Chet: Yeah, no, thanks for that response. And for hearing all our dose groups that we have been exploring in the dose range have audiograms done at baseline and throughout the course of the study. None of the patients in any of the dose.
Speaker Change: In all of our cohorts.
Speaker Change: Okay, great. Thanks for taking the questions.
Speaker Change: Thank you. Thank you.
Vikram <unk>: Our next question comes from the line of Vikram <unk> with Morgan Stanley. Please proceed.
Chet: those groups have developed any notable hearing impairment or sensorineural hearing loss. We did report in March in our top-line data that there were three patients in one of the cohorts that it
Speaker Change: Hi, good afternoon, Thank you for taking our questions.
Vikram <unk>: You had two so first on $501 seven which just curious what you might have seen in the early stage of development for that molecule to <unk>.
Chet: transient tinnitus that resolved and none of those patients that changes in audiogram. So, so far no major changes pertaining to audiogram changes in all of our cohorts.
Speaker Change: Decided to stop.
Pursuing that any further and then secondly.
For the end of Phase II meeting with the FDA. Just curious what are the main questions. You are hoping to have answered about the phase III development program through.
Speaker Change: Okay, great. Thanks for being the question.
Speaker Change: Okay
Speaker Change: Thank you. Thank you. Our next question comes from the line of Vikram Purohit with Morgan Stanley. Please proceed.
Speaker Change: That meeting with the agency.
Speaker Change: Yeah, maybe I'll start with that with $5 seven as I said on the call. We did do a healthy volunteer study and actually some of that data is up on our website. If you want to take a look at that.
Vikram Purohit: Hi, good afternoon. Thank you for taking our questions. We had two. So first on 517, I was just curious.
Speaker Change: Hmm.
Speaker Change: You know.
Vikram Purohit: What you might have seen in the early stage of development for that molecule to decide to stop pursuing that any further. And then secondly.
Speaker Change: Really we've made a again a strategic sort of prioritization decision and a program decision and so that's you know we are not going to continue development of that program internally, but if you can do you want to see the data it is up on the website.
Speaker Change: For the end of phase 2 meeting with the FDA, just curious, what are the main questions you're hoping to have answered about the phase 2 development program through that meeting with the agency?
Okay, and then I guess on the second question.
Shob: With respect to the end of phase two meeting, maybe I'll turn that over to shop.
Speaker Change: Yeah, maybe I'll start with that with 517 as I said on the call, you know, we did do a healthy volunteer study and actually some of that data is up on our website. If you want to take a look at that, you know, I, I think.
Shao: Thank you for that question our end of Phase II meeting is principally a traditional end of phase two where we would sit with the regulator FDA to explore what we have done to date and agree.
Speaker Change: You know, in really, we made a, again, a strategic sort of prioritization decision and a program decision. And so that's, you know, we are not going to continue development of that program internally.
Speaker Change: On the benefit risks that we are showcasing as.
Speaker Change: As was discussed dose and obviously importantly, the study designs will be at that point in time.
Speaker Change: But if you do want to see the data, it is up on the website.
Speaker Change: Wanting to proceed with in Phase III.
Speaker Change: Okay, and then I guess on the 2nd question with with.
Speaker Change: With respect to the end of phase two meeting, maybe I'll turn that over to Shaf.
Speaker Change: Understood. Thank you and then a quick follow up then just I apologize. If this was discussed and we missed it but the cash runway guidance through 'twenty seven exactly what does that contemplate with regards to future future.
Shaf: Yeah, no, thank you for that question. Our end of phase two meeting is principally a traditional end of phase two Where we would sit with the regulator FDA to explore what we have done to date
Speaker Change #100: Future development in uveitis.
Speaker Change #101: Yes, so the cash runway guidance Vikram we included.
Shaf: and agree on the benefit-risk that we are showcasing as was discussed, DOS, and obviously importantly, the study designs will be at that point in time wanting to proceed with in phase three.
Speaker Change #102: The completion of the ongoing <unk> study as well as the Hs NPSA. We have included the completion of the phase two.
Speaker Change #101: Graham and lot of good Mab.
Speaker Change #103: Two phase III programs, two phase III trials in the Registrational program.
Speaker Change: Understood. Thank you. And then a quick follow-up, then just apologies if this was discussed and we missed it, but the cash runway guidance through 27, exactly what does that contemplate with regards to future development in UV-ITIS? Okay.
Speaker Change #104: For a lot of Nab as well as potential BLA, enabling activities.
Speaker Change #105: Okay understood. Thank you.
Speaker Change: Yeah, so the cash fundraise guidance, Vikram, we have included
Speaker Change #105: Thank you.
Speaker Change #106: And our last question is coming from the line of Symantec Salman Khan with Citi. Please proceed.
Speaker Change: The completion of the ongoing uveitis study, as well as the HS and PSA, we have included the completion of the Phase II program in Lana Guttmach.
Speaker Change #107: Hi, good afternoon, and thanks for taking the questions I just have a couple on money.
Speaker Change #108: And your corporate deck, you have I think maybe a new slide just a bit more detail on the tinnitus that you've seen and you have several Gulf of cases from cohort one.
Speaker Change: Two phase three programs, two phase three trials in the registrational program for a lot of good map as well as, you know, potential enabling activities.
Speaker Change #109: So the question is why do you think that might be the case why is it only in cohort one.
Speaker Change: Okay, understood. Thank you.
Speaker Change #110: The cohort two patients so far or is there something common between these three patients, whereas perhaps the loading strategy loading dose strategy export in cohort two do you think that's driving the difference the difference with just love any thoughts you could provide there.
Speaker Change: Thank you.
Speaker Change: And our last question is coming from the line of Samantha Semenkov with Citi. Please proceed.
Samantha Semenkov: Hi, good afternoon, and thanks for taking the questions. I just have a couple on Lonnie. I see in your corporate deck you have, I think, what's maybe a new slide, just a bit more detail on the tinnitus that you've seen, and you've observed all three cases from just cohort one.
Speaker Change #111: Yeah look maybe I would just start with what.
Speaker Change #112: What we are showing is what we saw in cohort two and I would note that there were none in <unk>.
Speaker Change #112: Cohort one sorry, there were none in cohort two.
Shaf: And then maybe I will turn it over to shop for some more detail yeah no. Thanks for the question Samantha.
Speaker Change: So the question is, why do you think this might be the case? Why is it only in cohort one and none in the cohort two patients so far? Is there something common between these three patients?
Speaker Change #114: Number one we have not seen any.
Speaker Change #115: Reason why these patients with tinnitus and that court. If you specifically look at the narrative for each respective patients you will notice that this was <unk> that was transient in the majority of those three patients and resolved if anything I can comment on one of the patients who had seen.
Speaker Change: Or is perhaps the loading strategy, loading dose strategy, exporting cohort 2, do you think that's driving the difference? But just love any thoughts you could provide there.
Speaker Change: Yeah, look, maybe I would just start with, you know, what we are showing is what we saw in Cohort 2, and I would note that there were none in Cohort 1, sorry, there were none in Cohort 2, and then maybe I will turn it over to Shep for some more detail.
Speaker Change #116: It has 24 hours after the first injection in 24 hours it resolved.
It happened the same remember cohort one hit to injection that we zero in week three so no relationship to any aspect pertaining to the patient characteristics and I think not seeing anything in court to give us the confidence that.
Shep: Yeah, I know. Thanks for the question, Samantha.
Shep: Number one, we have not seen any.
Shep: Reason why this patient's a tinnitus in that court if you
Shep: specifically look at the narratives for each respective patient.
Speaker Change #116: This is not related to any dose exposure and.
Shep: you will notice that.
Shep: This was tinnitus that was transient.
Speaker Change #116: And therefore this was just something that happened within the study and as I mentioned all patients are having audiogram that baseline over time and to date, we have not seen anything that speaks to since then you're hearing loss or impairment.
Shep: in the majority of those three patients and resolved.
Shep: If anything, I can comment on one of the patients who had tinnitus at 24 hours after the first injection and 24 hours it resolved.
Shep: and it happened the same. Remember, cohort one only had two injections at week zero and week three. So no relationship to any aspect pertaining to the patient characteristics.
Speaker Change #116: Great. Thanks, so much for taking the question.
Speaker Change #116: Thank you and with no further questions in the queue I will turn it back to Tyler Martinez for his concluding comments.
Speaker Change: And I think not seeing anything in court to give us the confidence that this is not related to any dose exposure.
Tyler Martinez: Thank you Carmen and thank you all for joining today's call for the opportunity to share with you. These exciting corporate updates from our seller and as noted in the press release, we look forward to sharing more information about our plans for a lot of good amount with you during the upcoming Investor event, and our management will also participate in multiple webcasts and presentations and one on one meetings at upcoming Investor.
Speaker Change: And therefore, this was just something that happened within the study. And as I mentioned, all patients are having audiograms at baseline over time. And to date, we have not seen anything that speaks to sensorineural hearing loss or impairment.
Speaker Change #118: Conferences. So please visit our website regularly for our latest IR calendar and of course, please feel free to contact me in the 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.
Speaker Change: Great. Thanks so much for taking the question.
Speaker Change: Thank you. And with no further questions in the queue, I will turn it back to Tyler Marciniak for his concluding comments.
Tyler Marciniak: Thank you, Carmen. Thank you all for joining today's call, for the opportunity to share with you these exciting corporate updates from Aceleron.
Speaker Change #119: Thank you all who participated in today's conference you may now disconnect.
Speaker Change: As noted in the press release, we look forward to sharing more information about our plans for Lana Gudumab with you during the upcoming investor event. And our management will also participate in multiple webcasted presentations and one-on-one meetings at upcoming investor conferences.
Speaker Change: So, please visit our website regularly for our latest IR calendar. And of course, please feel free to contact me and the 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.
Speaker Change: And thank you all who participated in today's conference. You may now disconnect.
Speaker Change: Dr. Paret, Dr. Paret, Dr. Semenkow, Dr. Semenkow, Dr. Paret
Speaker Change: Good afternoon and welcome to the Accelerin, Inc. conference call to discuss the company's second quarter 2024 financial results and other corporate updates. This conference call is being recorded today, August 13, 2024.
Speaker Change: I would now like to turn the conference call over to Tyler Marciniak, Vice President of Investor Relations and Corporate Affairs. Tyler?
Tyler Marciniak: Thank you, Carmen. Good afternoon, everyone, and thank you for joining us.
Speaker Change: Before we begin, I'd like to remind you that this conference call may contain forward-looking statements, such as those related to progress of our clinical trials and anticipated data readouts, our future financial and operating results and projected cash runway, and our ability to commercialize our product candidates.
Speaker Change: These forward-looking statements involve risks and uncertainties that could cause our actual results and events to differ materially.
Speaker Change: We would urge you to review the risk factor section of our Form 10-Q for the quarter ended June 30, 2024 and additional Form 8-K that we filed with the SEC, both of which are also available on our website at aceleron.com, along with today's press release and our slide presentation.
Speaker Change: Additionally, these statements are based on information available to us today, August 13, 2024.
Speaker Change: And we undertake no obligation to update them as circumstances may change.
Speaker Change: The agenda for today's call is on the screen. We will review the corporate strategy updates announced in our press release as well as positive top-line data from the Phase 3 trial of Isocaibit and Hydrodinitis Suprativa.
Speaker Change: We will also provide an update on the Lana Gudemev program in TED and close with a financial update highlighting our projected three-year cash runway covering multiple anticipated milestones.
Speaker Change: Joining us on today's call are Mina Kim, our Chief Executive Officer, Dr. Shep Mpofu, our Chief Medical Officer, and Gil Labroucherie, our Chief Financial Officer and Chief Business Officer.
Speaker Change: I will now turn the call over to Mina.
Speaker Change: Thanks, Tyler, and thanks everyone for joining us today. Earlier today, we announced positive phase 3 results for Isochibab and Hydronida supertiva. As well as details of a refocus pipeline strategy. And plan designed to extend our cash runway to mid 2027.
Speaker Change: We'd like to provide more details on this call. First, we're very pleased to have achieved a positive phase 3 readout for Isaac Haibab in H.S. H.S.
Speaker Change: We met the primary endpoint of high score 75 and are especially pleased with a compelling response rates in high score 90 and 100 within 12 weeks of treatment.
Speaker Change: And in fact, we believe has not been previously observed by other agents.
Speaker Change: While the primary endpoint was measured at 12 weeks, we continued dosing patients in a placebo-controlled manner through week 16.
Speaker Change: We have data from two-thirds of the trial participants who completed Week 16, and these preliminary data further demonstrate deepening of responses over time.
Speaker Change: These data follow the positive PSA Phase 2B3 readout we announced earlier this year, and which were presented in a late-breaking session at ULAR in June.
Speaker Change: Collectively, the data in HS and PSA further validate our long-standing view that Izakaiten has the potential to be an effective therapy that is approvable in multiple indications.
Speaker Change: As we have previously stated, we will make disciplined and capital conscious decisions.
Speaker Change: We've determined that a program of this breadth and size is best brought to market by a larger organization with more resources and an existing footprint in the therapeutic areas of interest.
Speaker Change: Over the past several months, we've been evaluating where to prioritize investments to maximize the success of our pipeline, including Lonegood and Bass.
Speaker Change: which we believe has the potential to improve upon clinical response and convenience versus the standard of care in thyroid eye disease.
Speaker Change: We plan to complete the ongoing trials of Isaac Hi-Bev in HS and PSA, but we will not start new trials of these indications.
Speaker Change: We do plan to continue the ongoing phase 2B3 trial in uveitis through to its primary endpoint with top line data expected in the 4th quarter of 2024.
Speaker Change: There's high unmet need in uveitis and a compelling scientific rationale for the IL-17 axis.
Speaker Change: Should the upcoming Phase 2b3 data be positive, we anticipate one additional Phase 3 trial of roughly 200 to 250 patients would be required for registration.
Speaker Change: The ongoing trial is fully enrolled with approximately 100 patients.
Speaker Change: In addition to these iZotopibab updates, we've decided to stop internal development of SLRN 517, our early anti-TKIT program.
Speaker Change: Data from healthy volunteers demonstrated molecular activity, but we have made the decision to deprioritize this program.
Speaker Change: Finally, this refocus pipeline also requires a different organizational structure.
Speaker Change: and we are executing an approximately 33% reduction in force.
Speaker Change: I want to take a moment to pause and thank our colleagues who were impacted by this restructuring.
Speaker Change: They played an important role in our growth, and I wish them the very best in the future.
Speaker Change: While these decisions are difficult, we're confident that they are the right ones to enable Accelerin's long-term success.
Speaker Change: We remain committed to high-quality execution that's disciplined and capital conscious. These program decisions, as well as the organizational restructuring, enable us to move forward aggressively to develop Montegutimab and extend our cash runway to mid-2027.
Speaker Change: By focusing future capital investment on Lonagutamab, we will be well-positioned to fund our ongoing and planned TED trials through the BLA submission.
Speaker Change: Shep will review our overall strategy and ongoing activity for Lonaguta MAP in a moment, but I did want to make a few comments on the program.
Shep Mpofu: In terms of development strategy, the original plan had included a phase 2b3, but with the additional dose ranging that we are completing in patients in the ongoing phase 2 trial, we will be able to go directly into a phase 3 program, potentially with concurrent trials.
Shep Mpofu: We're currently planning to start the phase 3 program in the 1st quarter of 2025.
Shep Mpofu: Additionally, we plan to meet with the FDA later this year and then host an investor presentation to provide additional phase 2 data and details for the planned phase 3 program.
Shep Mpofu: With that, I'd like to turn the call over to Shep.
Shep Mpofu: Thank You Mina and hello everyone. I'm very pleased to share with you today positive phase 3 data of isocubib in hydradenitis superativa or HS and provide a program update on learning good map in thyroid eye disease.
Shep Mpofu: Let me start with HS.
Shep Mpofu: Dysregulated interleukin-17A activity plays a pivotal role in hydradenitis supertiva pathogenesis.
Shep Mpofu: Multi-domain disease resolution is underachieved with available current therapies.
Shep Mpofu: An unmet need exists for therapies demonstrating efficacy across multiple disease manifestations, including abscess, inflammatory nodules, and draining tunnels.
Shep Mpofu: Isocubab is a small protein therapeutic designed to selectively inhibit interleukin-17A with high potency through tight binding affinity.
Shep Mpofu: The small molecular size of azocubate attains the size of a monoclonal antibody, may enable tissue penetration, and its albumin-binding domain prolongs its half-life, and may enhance targeting to sites of inflammation in HS.
Shep Mpofu: Here you see the design of our global phase 3 trial of isocipab in HS, which we expect will be the first of the two pivotal trials needed for registration in this indication.
Shep Mpofu: 258 patients.
Shep Mpofu: We randomized one-to-one to receive either isocubib 160 mg weekly or placebo. The inclusion criteria and design is similar to other phase 3 studies.
Shep Mpofu: with a primary endpoint here for the first time in FS3 of high score 75 at week 12.
Shep Mpofu: At week 16, placebo patients were switched to receive isocupep 160 milligram weekly in the active treatment blinded period.
Shep Mpofu: As Mina mentioned, two-thirds of trial participants have available Week 16 data and we will present those preliminary data today as well.
Mina Kim: Here we see patient demographics and baseline characteristics, which were well balanced between isochiped treatment group and placebo, typical of a patient population with moderate to severe HS, and comparable to other global phase 3 pivotal trials.
Speaker Change: 103 patients on the isotope arm and 112 patients in the placebo arm completed the study through week 12.
Speaker Change: Thus, having approximately 20% on Isocubep arm and approximately 13% on placebo arm discontinued treatment with a delta of around 7% between the two groups.
Speaker Change: Please note the most common reasons leading to discontinuation on Isocubep were mild AEs.
Speaker Change: And there were no notable differences between izokibeb and placebo in terms of loss to follow-up and withdrawal of consent rates.
Speaker Change: In this trial, iZoki Beb had a rapid onset of action associated with clear evidence of improvement.
Speaker Change: Within two weeks, achieving statistical significance as early as week four, as mentioned, the study met its primary endpoint.
Speaker Change: with 33% of eyes occupied patients.
Speaker Change: achieving a high-score 75 response. That is a 75% reduction in abscess and inflamed nodules, versus 21% for placebo.
Speaker Change: Looking at the two-thirds of patients worth of week 16 data.
Speaker Change: We can observe an increase in response up to 40% on isocubits versus 20% on placebo.
Speaker Change: When we look at higher orders of response,
Speaker Change: looking at high score 90 and high score 100. iZoCupeb again achieved statistically significant responses at week 12 versus placebo, with approximately one in four patients on iZoCupeb achieving these deeper responses versus placebo.
Speaker Change: Notably, the deltas for high score 90 and 100 were maintained at week 16.
Speaker Change: Here you see the response across the continuum of high score 50 to 100 as depicted from left to right on the slide.
Speaker Change: As expected, we observe a consistent trend with placebo response decreasing as the efficacy head will increase at week 12.
Speaker Change: Clinical meaningful reductions in skin pain and improvements in DLQI were seen observed versus placebo at week 12 and also at week 16.
Speaker Change: The safety findings of Isocubet were consistent with those observed in previous trials with the most common adverse event
Speaker Change: being mild to moderate injection-site reactions.
Speaker Change: in around 65% of patients on azethicibab versus 8% in the placebo arm. You also note not much differences for other events like headache happening in 10% versus 9% and 7% of nasopharyngitis in both arms.
Speaker Change: Notably, there were no cases of candida on izokibeb with only three cases showing in placebo. There was no IBD, liver toxicity, suicidal ideation behavior in the izokibeb treatment arm.
Speaker Change: In conclusion, iZocupep safety is in line with our past experience, and iZocupep appears to have the optimal to offer deep clinical responses across multiple HS domains, including skin pain and patient-reported outcomes.
Speaker Change: We are very pleased to have successfully delivered this positive phase 3 trial for Isocubep in HS, which builds on the phase 3 data released in PSA earlier this year.
Speaker Change: Now, turning our attention to Lonigutumab, which we are developing as a subcutaneous treatment for thyroid eye disease.
Speaker Change: Thyroid eye disease is an autoimmune disorder characterized by progressive inflammation that can lead to irreversible damage to tissues around the eye, threatening vision.
Speaker Change: Patients present with proctosis, diplopia, and a variety of disabling eye symptoms.
Speaker Change: It affects greater than 100,000 patients in the U.S.
Speaker Change: A high unmet need persists in thyroid eye disease, a multifaceted disease whose impact extends beyond the well-recognized visual disfigurement.
Speaker Change: Patient quality of life is markedly impacted by TIRD.
Speaker Change: A therapy that provides rapid, deeper disease-modifying effects that are durable across 10-month gestation and results in improved patient quality of life, safety, and convenience will be important for patients.
Lonnie Goodman: Lonnie Goodman is a next-generation recombinant humanized IgG1 monoclonal antibodies against human IgF1 receptor being developed to treat severe manifestations of TED. As shown in the middle cartoon on the slide.
Lonnie Goodman: Lonnie Goodman binds IGF-1-ARA on a unique binding site.
Lonnie Goodman: which we call an epitope, and does not compete with IGF-1 binding.
Lonnie Goodman: It does this with high affinity, with a kilo-delta affinity measured around 30 picomolar, and a specificity which triggers rapid internalization and degradation within minutes of the IGF-1 receptor.
Lonnie Goodman: thus eliminating it from the surface of the IGFR1-expressing cells with potential to maintain IGF1 within homeostatic levels.
Lonnie Goodman: IGF-1RI internalization prevents downstream signaling in orbital fibroblasts from patients with TED and has been associated with therapeutic benefit in TED.
Lonnie Goodman: the rapid and efficient suppression of IGF-1 receptor signaling
Lonnie Goodman: in TED with Lonnie Goodmap could potentially improve clinical outcomes.
Lonnie Goodman: for patients by providing
Lonnie Goodman: lower doses of exposure.
Lonnie Goodman: to achieve robust clinical response.
Lonnie Goodman: as we saw in our proof of concept.
Lonnie Goodman: with 40 milligrams Q3W having responses at early time points when we assessed at three weeks after a single dose.
Lonnie Goodman: There is potential for deep and durable responses with chronic dosing and ability to minimize safety risks by choosing an optimal, convenient dose regimen.
Lonnie Goodman: As I mentioned, we completed the phase one proof of concept.
Speaker Change: portion of our ongoing Lonely Boot Math trial earlier this year.
Speaker Change: And we are now embarking on a dose ranging phase two portion across four dose group levels, as you can see depicted on the right part of the slide projected.
Speaker Change: The Phase II trial was designed with the flexibility to test
Speaker Change: multiple dose levels and regimens in order to, number one, establish what we call a minimum effective dose when we are focusing on assessing the C mean.
Speaker Change: And number two, to enable establishment of an optimal dose selection for phase 3 program within the optimal therapeutic window that you can see labeled on the y-axis on the left part of the slide.
Speaker Change: And making sure that we don't have a C-max that results in overexposure and therefore really calibrating an opportunity to minimize safety which might be associated with high and overexposure.
Speaker Change: We are using the totality of this data to calibrate to an optimal dose level and convenient dose regimen.
Speaker Change: We recently initiated the final dose group with a dose level of 70 milligrams administered every three to four weeks in this phase two trial to confirm the dose we will take to phase three.
Speaker Change: We believe our Phase II approach is unique in that it's patient-centric, designed comprehensively to address the ongoing and met needs of thyroid eye disease patients.
Speaker Change: and really balance benefit-risk to define an optimal dose level and a regimen that profiles a robust therapeutic impact across the multifaceted aspects of TED.
Speaker Change: We are currently planning to start the Phase 3 trial in the first quarter of 2025. And as Mina mentioned, we are looking forward to meeting with the FDA later this year and sharing more information about the registration program in TED at a future investor event.
Gail: Now turn over to Gail.
Speaker Change: Thank you, Shep, and good afternoon, everyone.
Gail: Today, I'm going to make a few comments on financial highlights from the quarter ended June 30, 2024. Thank you.
Gail: And then discuss some of the financial implications of the refocused pipeline and restructuring initiatives we announced today, the key milestones ahead for us, and also provide year-end cash guidance.
Gail: We are fortunate to be in a strong financial position.
Gail: At June 30th, our cash position was approximately $635 million.
Gail: For Q2, our R&D expense was $76.4 million, as compared to $30 million for the same period in 2023.
Gail: A substantial majority of our R&D expense, approximately 75%, is related to the Isochibet program where we have been executing three phase three programs this year in PSA, HS, and uveitis.
Gail: General and administrative expenses were $16.6 million for the second quarter as compared to $12.7 million for the same period in 2023.
Gail: R&D and G&A expense includes stock-based compensation expense of $10.2 million, which increased from $8.5 million for the same quarter in 2023.
Gail: Today, we made the difficult decision to right-size our organization in line with our refocused pipeline strategy.
Gail: I wanted to make a few comments on the financial implications of this decision.
Gail: it
Gail: We expect to incur approximately $4.5 million in cash-based restructuring charges related to the workforce reduction.
Gail: Our estimate for the cost associated with the completion of the ongoing uveitis study, HS, and PSA studies is expected to range between $30 and $35 million.
Gail: With respect to the ongoing ISO-CIIBAP-CMC activities and commitments,
Gail: We expect to incur between $55 and $85 million.
Gail: We are actively working with our manufacturing partners with a goal to mitigate these costs.
Gail: From a financial point of view,
Gail: Our focus will be on efficiently and effectively executing this refocused pipeline strategy and associated restructuring.
Gail: remaining disciplined and risk-aware with our operational spend.
Gail: and significantly extending our cash runway out approximately three years to mid-2027 through multiple value enhancing catalysts.
Gail: This long-range financial guidance includes adding an additional dose arm to our ongoing Montegut MAP Phase 2 trial, as Shep just reviewed.
Shep Mpofu: Funding to phase three trials for one acute map and enabling activities for that program.
Shep Mpofu: In addition, please note that our cash runway guidance does not include any proceeds related to additional financing or partnering.
Speaker Change: We are very excited about the milestones ahead for Accelerin. We remain focused on our core mission to accelerate the development and delivery of transformative medicines and immunology.
Speaker Change: On this slide, we have outlined some of the important milestones for our development programs and related timing windows.
Speaker Change: Following our end of phase 2 meeting with the FDA on the Lana Goodman program.
Speaker Change: We plan to hold an investor event focused on the unmet need for thyroid eye disease patients. The detailed rationale underpinning dose selection.
Speaker Change: The outcome of the end of Phase 2 meeting with the FDA, additional data from the ongoing Phase 2.
Speaker Change: And the design of our phase 3 development program.
Speaker Change: In addition, we also continue to project.
Speaker Change: that we'll have top-line results from the IsoQiVap Phase 2b3 trial in uveitis before year-end.
Speaker Change: We anticipate rapidly advancing Lana-Guten-MAP into late-stage development with the start of the Phase III program before the end of Q1 2025.
Speaker Change: We expect the first top-line readout from the registration program in 2026.
Speaker Change: and to file a potential BLA thereafter.
Speaker Change: We look forward to sharing more details on our plans for the Lonegood MAP program at our upcoming investor event.
Speaker Change: Now, turning to forward-looking financial guidance.
Speaker Change: We currently project our 2024 year-end cash position will range between $420 million and $450 million.
Speaker Change: We expect our cash used in operations to increase substantially in the second half of 2024. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit and licensee payments. We expect our cash used in operations to increase substantially in the second half of 2024. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit and licensee payments. Remember, in the first half of 2024, we received $37 million from a one-time vendor credit
Speaker Change: Conversely, in the second half of 2024, we expect to pay a $31 million option payment related to achieving proof of concept with Lana Guttenmabb and non-recurring payment for costs related to the restructuring and actually in certain ISO-CIFA commitments.
Speaker Change: As I mentioned earlier, we now project our cash runway to mid-2027, which we anticipate will fully fund the Lawn and Goose Mat development program through BLA filing, while also preserving capital for selective pipeline expansion.
Speaker Change: And, as I stated earlier, our cash runway guidance does not include any proceeds related to additional financing or partnering.
Speaker Change: And now I'll turn the call back over to Mina.
Mina Kim: Thank you, Gail and Shep, and thank you all for joining us on today's call. The decisions we announced today about our Go Forward strategy position us to execute on Lonagutamab from a position of strength.
Mina Kim: By suspending new investment for izakibab and PSA and HF, discontinuing SLRN 517 and the difficult decision to right-size our organization, we can now focus on rapidly developing lanagutamab as the potential best therapy for thyroid eye disease.
Mina Kim: We have an outstanding team. We're positioned to deliver high quality execution of the pivotal program. And we now have a cash runway to take the program through both pivotal trials. We're excited by the opportunity to serve the unmet needs of Ted patients.
Speaker Change: Since taking on the CEO role a few months ago, I've had the opportunity to meet with many, probably more than 100 of our investors, and I appreciate the opportunity to provide this update today.
Speaker Change: We look forward to providing regular updates on our progress and I hope you will join us for our investor event.
Speaker Change: After our FDA meeting, where we will provide an in depth and comprehensive overview of the full want to go to map opportunity. And the many reasons why we're so excited to move this program forward. Thanks for joining us today and operator with that, we can open up to questions.
Speaker Change: Thank you so much and as a reminder to our tele audience, press star 11 to get in the queue and wait for your name to be announced. To remove yourself from the queue, press star 11 again.
Speaker Change: Please stand by for our first question.
Speaker Change: And it comes from the line of Derek Archilla with Wells Fargo. Please proceed.
Derek Archilla: Hey, thanks for taking the questions just three quick ones from us. I guess first What's the rationale for adding the 70 milligram dose?
Speaker Change: in the ongoing phase two for long-aguda map. Also the every three week dosing arm as well.
Speaker Change: Just want to also figure out, you know, whether this is kind of leading to potentially a, you know, a loading dose in phase 3. So that's the 1st question.
Speaker Change: Second question, just for Izzo, I guess, is the plan to partner this asset right now or is it just going on the shelf? I just wanted to clarify in terms of the comments you made around uveitis, is that something you would plan to move forward by yourself if that data looks good?
Speaker Change: And then third, you noted in terms of kind of the expanded cash runway and opportunity potentially to expand the pipeline, I guess, is that a near-term priority, and I guess what stage of development would you be looking for in terms of assets? Thanks.
Izzo: Yeah. Hi, Derek. Hey, thanks for the questions. There's a lot in there, so I'm going to take them in order. Hey, maybe to start with ISO, right? And the partnering question, and then what are we going to do with UV? Or, you know, how do we think about UV? You know, what I say with respect to partnering and this is what we've been saying. We're going to do what's best for the program.
Izzo: Right, we're open to all options and, you know, fundamentally, we want to see and right bring benefit to patients and that might be with a larger organization that has existing capabilities and infrastructure.
Izzo: So again, we'll look at all the options and we'll do what's best for the program.
Speaker Change #100: I do want to note and reemphasize something that Gail said, which is we have not included any financing proceeds or proceeds from a partnership in our cash runway guidance, right? So that excludes any contribution from a potential partnership.
Speaker Change #100: So I think that's the response on the ISO and uveitis questions with respect to potential BD going forward.
Speaker Change #101: Look, I mean, we're always going to look at opportunities will be opportunistic and as Gil said, we have assumed.
Speaker Change #102: right, that there could be some pipeline expansion and we have the funding for that, we believe.
Gil Labroucherie: Right, I would say though, right now, it's important for us to focus on long and good map and high quality execution on that program. And that is the focus for now.
Speaker Change #104: And so any additional BD, you know, I don't think we're in a hurry, and it's a high bar, right? But we certainly will consider any, you know, opportunistic opportunities, right, over time.
Speaker Change #104: And then I think you had questions around the design, right, of the Lana Gutamad development program. And maybe it's helpful to frame that up a little bit. Right, just stepping back, you know, we have spent the last few months evaluating the entire development program. Really with 2 goals.
Speaker Change #104: One is how do we de-risk the phase three program?
Speaker Change #104: Right? And the other is, can we do that at the same time as we try to accelerate the program? And we have been trying to balance both of those things.
Speaker Change #104: We do think that adding this additional dose cohort into the PHEAS-2 program helps us achieve that.
Speaker Change #104: First, it allows us to complete dose exploration in the phase 2 trial rather than in a 2B3 as originally planned. Next slide. And... Next slide.
Speaker Change #104: And what that does is it allows us to move directly into a phase 3 program and potentially run two phase 3 trials concurrently, right? Rather than sequentially, which, you know, obviously has the potential to accelerate that program.
Speaker Change #105: Um, you know, and and we've added the 70 mil dose. We are looking at it in both 3 weeks. Right? And 4 weeks, right? To confirm the dose that we're going to take into the pivotal program.
Speaker Change #105: I would say, I think it's important to know we think we have our dose right? But regimen is also important. And again, we want confidence around that dose. We take into the program in the ability to do that in the face to write is we think.
Speaker Change #105: Potentially both de-risking and hopefully does allow us to go more quickly into that phase three program.
Speaker Change #106: I guess just to follow up there in terms of like, again, is that being examined for potential loading dose or is the loading dose going to be figured into the Phase 3 program?
Speaker Change #107: No, I mean, that's not something we're contemplating now. I mean, we do think the 70 is our dose.
Speaker Change #108: Understood. Thank you.
Eric: Thanks, Eric.
Speaker Change #109: Thank you. Our next question comes from the line of Tyler Van Buren with TD Cowen. Please proceed.
Speaker Change #110: Hey, guys, thanks for the updates. It's encouraging to see the rationalization of the pipeline. I want to ask about the phase 3 uveitis trial readout. So, what would compelling data
Speaker Change #111: from that trial look like later this year that would lead you to pursue another trial for registration. And the second question is, what are your latest thoughts on the market size for uveitis?
Speaker Change #112: Yeah, so maybe I'll start and then I'll turn it over to the team. I mean, you know, I think we're going to evaluate in the same way that we have all of our other programs, right? We're going to look at the totality of the data, you know, the market, the unmet need.
Speaker Change #112: What I would say maybe to start is there is very high unmet need, right, in uveitis and so we like that opportunity, right, to address the unmet needs of patients.
Speaker Change #112: There is obviously, you know, very limited, there are very limited options for those patients and that will also factor into it.
Shaq: In terms of the trial design and sort of what are the end points, I'll turn it over to Shaq, maybe to just walk you through that. Yeah, no, thanks, Mina. Our trial is designed the same as the Yomira trial, which is the only large phase 3 study that was done in UPI.
Shaq: We have patients receiving
Shaq: steroids at baseline and then having a regimen to decrease them over 15 days.
Speaker Change #114: And we have a primary ESCAS endpoint at week 24, where we'll be looking at four parameters, same as Jumeirah did, looking at inflammation in the back of the eye, corneal-retinal inflammation, and then looking at inflammation within the eye.
Speaker Change #114: looking at the vitreous haze, anterior chamber as well, and then best corrected visual acuity. So that's the treatment failure. So we'll be looking at a compelling data set that showcases there are more patients on placebo versus drug that achieve this endpoint.
Speaker Change #114: Tyler?
Tyler Marciniak: Yep, all good. Thank you. Thank you. One moment for our next question.
Speaker Change #115: And our next question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed.
Yasmeen Rahimi: Thank you so much, team, for sharing these difficult decisions with us and walking us through the rationale. Team, I guess, could you maybe talk about Cohort 3? Cohort 4 has just begun.
Speaker Change #116: at what junction, at what have you seen from that dose cohort so far? When should we be expecting data from it? And then.
Speaker Change #117: I guess, um...
Speaker Change #118: And then as we think about phase 3 design, just maybe parts of the – you alluded to some innovative approaches.
Speaker Change #118: but maybe walk us through who would be the ideal patient.
Speaker Change #118: It also seems like...
Speaker Change #119: TET studies have become quite competitive in terms of enrollment.
Color: So, I appreciate also Color and ensuring, you know, being able to deliver top-line data in an efficient manner. Sorry, there were too many questions in there, but I guess cohort three and, yeah, I appreciate Color on that. Thank you. Sorry about that.
Speaker Change #120: No, for sure. So let's start with cohort 3 and then if we miss anything, just just just remind us just prompt us, you know, like, I.
Speaker Change #121: Like, I just said, and, you know, in our prepared remarks, we are thinking about that phase 2 program, right? Holistically.
Speaker Change #122: We think it's most useful to read out the data from that phase two program after we've met with the FDA later this year, right? When we can give a more complete picture.
Speaker Change #122: And that more complete picture would be additional data, right, including from, you know, cohort three, you know, really from the totality of that across the phase two program.
Speaker Change #122: And also how we're thinking about the, the phase 3 program. So, you know, I think that's a little bit of the timing and we would expect that to be later this year or potentially early next year. Right? But really, when we've got a more complete picture to share with you all, we think that that's most useful.
Speaker Change #122: So I think that's kind of the design. In terms of the patients that we can potentially serve, we do think that there continues to be very high unmet need.
Speaker Change #122: Right in Ted patients and, you know, I think we talked about this before. We are particularly interested in the ability to think about chronic dosing.
Speaker Change #122: Right? This is a disease that, you know, can flare or regress or, you know, however you want to describe that. And there is an ongoing need for those patients, right, across many different endpoints. And so we really want to optimize sort of the dose and the regimen.
Speaker Change #122: to try to address the totality of the disease. So we think that there, again, continues to be unmet need and we are very interested in exploring that chronic population.
Speaker Change #123: Thank you. What did I miss? Yes. No, no, no. Just, just, yeah. That's an enrollment tithing just because it's competitive. Like, we feel confident to.
Speaker Change #123: You know, just because now several test studies will be ongoing concurrently in Phase 3, I appreciate some color there.
Speaker Change #124: Yeah, and look, we feel good about that. I mean, obviously, we're rolling patients right now right into the phase two and, you know, we think that that's.
Speaker Change #124: We feel good about that experience and confident going into the phase three trial, you know, somewhat based on that experience. So, you know, understand that there are more trials going on, but we feel good about that.
Speaker Change #125: Thank you so much. I'll jump back in the queue.
Speaker Change #126: Thank you. Our next question comes from the line of Akash Tiwari with Jeffries. Please proceed.
Speaker Change #127: Hi, this is Phoebe on for Akash. Thank you for taking our question.
Phoebe: So, I guess more on uveitis, are you targeting more refractory patients, like those who are on or after prior biologic use? And additionally, will uveitis be considered an orphan indication, and could you potentially get orphan pricing of around $10,000?
Speaker Change #128: $200,000 per year in this indication. I imagine there might be some pushback from payers for orphan drug pricing, given Humira is already approved for UV artists and it's much cheaper. So just some color around that would be helpful.
Speaker Change #128: Yeah. Great. Thanks for the question. This is Gil. You know, as Mina was saying earlier, you know, this is an interesting indication. There's still a very high unmet need. There's really only a couple treatment options, essentially steroids.
Speaker Change #128: and Humira, and the current standard of care is really only modestly effective. So, we really think there's an opportunity here to drive additional benefits to patients, whether that's at any line of this. We also think that
Speaker Change #129: With the limited therapeutic options, you know, as a therapy, like Iso may come in here. They'll also have an opportunity to expand the market and diagnosis of this condition.
Speaker Change #130: I think in terms of the pricing question, you know, that's a little early to say, but certainly something that we think about as we go in, but it's a little early to speculate on pricing and the indication.
Speaker Change #131: Yeah, and on patients that are coming in the study, these are patients with active non-infectious uveitis. There will be patients who also have been previously exposed to other biologics, except those biologics that are on the IL-17 pathway.
Speaker Change #132: Understood. Thank you.
Speaker Change #132: Thank you.
Speaker Change #132: Our next question comes from the line of Emily Botnar with HC Wainwright. Please proceed.
Emily Botnar: Hi, I think to the end of the questions, I guess some of the clarifying question and the 70 Meg long a dose. Are you.
Emily Botnar: enrolling eight patients in total across the three-weekly and four-weekly regimens, or the eight per regimen? And then kind of follow up to that, do you think that's a sufficient number of patients to kind of get an idea of that's the appropriate dose to take into phase three?
Speaker Change #133: And then, lastly, if you can kind of confirm that you haven't seen any cases of hearing impacts from any of the cohorts so far, thank you.
Speaker Change #134: Yeah, thanks. Let me start, and maybe I'll turn it over to Shep on the hearing. The way that this final cohort is set up, it has eight patients and allows us to try the 70 mg Q3 and Q4.
Speaker Change #134: It also gives us the flexibility to go up to 16 patients.
Shep Mpofu: You know, in that cohort, so it is built with some flexibility, you know, obviously, those are small numbers, but in totality right across this phase 2 program.
Shep Mpofu: We will have seen inpatient data across multiple doses and regimens, and we think that that's going to be very, again, useful for us and a way to de-risk that phase 3 program.
Shep Mpofu: Right and maybe I'll let Shep address the hearing question.
Shep Mpofu: Thanks for that response and for hearing all our dose groups that we have been exploring in the dose range have audiograms done at baseline and throughout the course of the study. None of the patients in any of the dose.
Shep Mpofu: dose groups have developed any notable hearing impairment or sensorineural hearing loss. We did report in March in our top-line data that there were three patients in one of the cohorts that had
Shep Mpofu: transient tinnitus that resolved, and none of those patients had changes in audiogram. So, so far, no major changes pertaining to audiogram changes in all of our cohorts.
Speaker Change #135: Okay, great. Thanks for being the question.
Speaker Change #136: Thank you. Thank you.
Speaker Change #137: Our next question comes from the line of Bikram Purohit with Morgan Stanley. Please proceed.
Bikram Purohit: Hi, good afternoon. Thank you for taking our questions. We had two. So first on 517, I was just curious.
Bikram Purohit: What you might have seen in the early stage of development for that molecule to decide to stop pursuing that any further. And then secondly.
Speaker Change #139: For the end of phase 2 meeting with the FDA, just curious, what are the main questions you're hoping to have answered about the phase 2 development program through that meeting with the agency?
Speaker Change #140: Yeah, maybe I'll start with that with 517. Um, as I said on the call, you know, we did do a healthy volunteer study and actually some of that data is up on our website. If you want to take a look at that, you know, I, I think, um.
Speaker Change #140: You know, in really, we made a, again, a strategic sort of prioritization decision and a program decision. And so that's, you know, we are not going to continue development of that program internally.
Speaker Change #140: But if you do want to see the data, it is up on the website.
Speaker Change #140: Okay, and then I guess on the 2nd question with with.
Speaker Change #140: With respect to the end of phase two meeting, maybe I'll turn that over to chef
chef: Yeah, no, thank you for that question. Our end of phase two meeting is principally a traditional end of phase two Where we would sit with the regulator FDA to explore what we have done to date
Speaker Change #142: and agree on the benefit-risk that we are showcasing as was discussed, DOS, and obviously, importantly, the study designs will be, at that point in time, wanting to proceed within phase three.
Speaker Change #143: Understood. Thank you. And then a quick follow-up, then just apologies if this was discussed and we missed it, but the cash runway guidance through 27, exactly what does that contemplate with regards to future development in UV-ITIS?
Speaker Change #143: Yeah, so the cash runway guidance, Vikram, we have included
Speaker Change #144: The completion of the ongoing uveitis study, as well as the HS and PSA, we have included the completion of the Phase II program in Lana Guttmach.
Speaker Change #145: 2 phase 3 programs, 2 phase 3 trials in the registrational program. For a lot of good math as well as potential enabling activities.
Speaker Change #146: Okay, understood. Thank you.
Speaker Change #147: Thank you. Thank you.
Speaker Change #147: And our last question is coming from the line of Samantha Semenkov with Citi. Please proceed.
Samantha Semenkov: Hi, good afternoon and thanks for taking the questions. I just have a couple on Lonnie. I see in your corporate deck you have I think what's maybe a new slide just a bit more detail on the tinnitus that you've seen.
Speaker Change #148: And you've observed all three cases from just cohort one.
Speaker Change #149: So the question is, why do you think this might be the case? Why is it only in Cohort 1 and none in the Cohort 2 patients so far? Is there something common between these three patients?
Speaker Change #150: Or is perhaps the loading strategy, loading dose strategy, exporting cohort two, do you think that's driving the difference, but just love any thoughts you could provide there.
Speaker Change #150: Yeah, look, maybe I would just start with, you know, what we are showing is what we saw in cohort 2, and I would note that there were none in cohort 1, sorry, there were none in cohort 2. And then maybe I will turn it over to Shep for some more detail.
Shep Mpofu: Yeah, I know. Thanks for the question, Samantha.
Shep Mpofu: Number one, we have not seen any.
Shep Mpofu: Um,
Shep Mpofu: reason why these patients with tinnitus in that cohort, if you
Shep Mpofu: specifically look at the narratives for each respective patient.
Shep Mpofu: you will notice that.
Shep Mpofu: This was tinnitus that was transient.
Shep Mpofu: in the majority of those three patients and resolved.
Speaker Change #151: If anything, I can comment on one of the patients who had tinnitus at 24 hours after the first injection and 24 hours it resolved.
Speaker Change #151: and it happened the same. Remember, cohort one only had two injections at week zero and week three.
Speaker Change #151: So, no relationship to any aspect pertaining to the patient characteristics.
Speaker Change #152: And I think not seeing anything in court to give us the confidence that this is not related to any dose exposure.
Speaker Change #152: And therefore, this was just something that happened within the study. And as I mentioned, all patients are having audiograms at baseline over time, and to date we have not seen anything that speaks to sensorineural hearing loss or impairment.
Speaker Change #152: Great, thanks so much for taking the question.
Speaker Change #152: Thank you. And with no further questions in the queue, I will turn it back to Tyler Marciniak for his concluding comments.
Tyler Marciniak: Thank you, Carmen. Thank you all for joining today's call for the opportunity to share with you these exciting corporate updates from Accelerin.
Speaker Change #153: As noted in the press release, we look forward to sharing more information about our plans for Lanagutamab with you during the upcoming investor event. And our management will also participate in multiple webcasted presentations and one-on-one meetings at upcoming investor conferences.
Speaker Change #154: So, please visit our website regularly for our latest IR calendar. And of course, please feel free to contact me and the 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. And thank you all who participated in today's conference. You may now disconnect.