Q2 2024 Amylyx Pharmaceuticals Inc Earnings Call

Camille: Good morning. My name is Camille and I will be your conference operator for today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals second quarter 2024 earnings conference call.

Camille: All participants will be on a listen-only mode. After today's presentation, there will be an opportunity to ask questions.

Camille: To ask a question, please press star 1 on your telephone keypad. To withdraw your question, please press star 2.

Camille: Please limit your questions to one, with one follow-up. If you have additional questions, you may rejoin the queue.

Camille: Please be advised that this call is being recorded at the company's request.

Camille: I would now like to turn the call over to Lindsey Allen, Head, Investor Relations and Communications. Please proceed.

Lindsey Allen: Good morning, and thank you all for joining us today to discuss our second quarter 2024 financial results.

Speaker Change: With me on the call today are Josh Cohen and Justin Klee, our co-CEOs.

Speaker Change: Dr. Camille Bedrosian, our Chief Medical Officer, and Jim Frates, our Chief Financial Officer.

Speaker Change: Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are based on our current beliefs.

Speaker Change: plans and expectations and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Speaker Change: These statements include, but are not limited to, our expectations with respect to Avexitide, AMX 35, and AMX 114.

Speaker Change: Statements regarding regulatory and clinical developments and the impact thereof and the expected timing thereof, and statements regarding our cash runway.

Speaker Change: Actual events and results could differ materially from those expressed or implied by any forward-looking statements.

Speaker Change: You are cautioned not to place any undue reliance on these forward-looking statements, and Amylyx disclaims any obligation to update such statements unless required by law. Now, I will turn the call over to Justin.

Justin Klee: Good morning and thank you all for joining us today. As an organization, we have made significant progress over the past few months as part of our continued mission and our goal to deliver important treatment options to the neurodegenerative, neuroendocrine, and endocrine communities we serve.

Justin Klee: Most notably, last month, we expanded our late-stage pipeline with our acquisition of Avexitide, and now have three assets targeting orphaned indications.

Justin Klee: Avexatide is a Phase III ready asset with FDA breakthrough therapy designation in diseases with no approved treatment options.

Unknown Executive: Avexitide is a GLP-1 receptor antagonist with orphan drug designation for hyperinsulinemic hypoglycemia. The GLP-1 receptor is one of the key regulators of the glucose-insulin response, and an imbalance in this response leads to hyperinsulinemic hypoglycemia, which underlies several conditions and diseases. The first indication, PVH, is a significant but orphaned condition that affects a subpopulation of people who have undergone bariatric surgery. People living with PBH could benefit from a treatment that helps stabilize glucose levels, particularly the dangerously low crashes in blood glucose associated with PBH. In the second quarter, we largely completed our restructuring.

Unknown Executive: Oxytide is a GLP-1 receptor antagonist with orphan drug designation for hyperinsulinemic hypoglycemia. The GLP-1 receptor is one of the key regulators of the glucose-insulin response, and an imbalance in this response leads to hyperinsulinemic hypoglycemia, which underlies several conditions and diseases.

Justin Klee: Avexatide is a GLP-1 receptor antagonist with orphan drug designation in hyperinsulinemic hypoglycemia.

Justin Klee: The GLP-1 receptor is one of the key regulators of the glucose-insulin response, and an imbalance in this response leads to hyperinsulinemic hypoglycemia, which underlies several conditions and diseases.

Unknown Executive: So far, vexatide has been studied in two indications characterized by hyperinsulinemic hypoglycemia, post-bariatric hypoglycemia (PBH), and congenital hyperinsulinism. The first indication, PVH, is a significant but orphaned condition that affects a subpopulation of people who have undergone bariatric surgery. Now, let me elaborate a little further on the market opportunity ahead.

Justin Klee: So far, Avexitide has been studied in two indications characterized by hyperinsulinemic hypoglycemia, post-bariatric hypoglycemia, or PBH, and congenital hyperinsulinism.

Justin Klee: The first indication, PBH, is a significant but orphaned condition that affects a subpopulation of people who have undergone bariatric surgery.

Justin Klee: Now, let me elaborate a little further on the market opportunity ahead.

Unknown Executive: Despite the introduction of GLP-1 receptor agonists for weight loss, more than 200,000 new bariatric procedures are performed every year, and this number has continued to grow on an annual basis. In the past 10 years, approximately 2 million people in the United States have undergone the two most common types of weight loss surgery, Roux-en-Y gastric bypass and sleeve gastrectomy. Experts expect surgery to remain a cornerstone of weight loss therapy, given the procedure is highly effective and results in substantial and sustained weight loss, particularly for people with higher BMIs.

Justin Klee: Despite the introduction of GLP-1 receptor agonists for weight loss, more than 200,000 new bariatric procedures are performed every year, and this number has continued to grow on an annual basis.

Unknown Executive: Evidence also suggests that bariatric surgery reduces the risk of cardiovascular events and the severity of metabolic dysfunction associated with liver disease. Turning to PPH, this persistent condition can develop in people who have received bariatric surgery one to three years prior, and in some cases, even longer post-surgery. We estimate that approximately 8% of the 2 million people I referenced, or 160,000 people in the U.S. today, have symptomatic PBH. Symptomatic PBH is characterized by hypoglycemic events associated with brain glucose starvation, known as neuroglycopenia, including impaired cognition, loss of consciousness, and seizures, as well as activation of the autonomic nervous system, presenting as hunger, sweating, tingling, tremors, palpitations, and anxiety.

Justin Klee: Over the past 10 years, approximately 2 million people in the United States have undergone the two most common types for weight loss, Roux-en-Y gastric bypass and sleeve gastrectomy.

Justin Klee: Experts expect surgery to remain a cornerstone of weight loss therapy given the procedure is highly effective and results in substantial and sustained weight loss, particularly for people with higher BMIs.

Justin Klee: Evidence also suggests that bariatric surgery reduces the risk of cardiovascular events and the severity of metabolic dysfunction associated liver disease.

Justin Klee: Turning to PPH, this persistent condition can develop in people who had received bariatric surgery one to three years prior and in some cases even longer post-surgery.

Speaker Change: We estimate that approximately 8% of the 2 million people I referenced, or 160,000 people in the U.S. today, have symptomatic PBH.

Justin Klee: Symptomatic PBH is characterized by hypoglycemic events associated with brain glucose starvation known as neuroglycopenia.

Speaker Change: including impaired cognition, loss of consciousness, and seizures, as well as activation of the autonomic nervous system, presenting as hunger, sweating, tingling, tremors, palpitations, and anxiety.

Unknown Executive: People living with PBH could benefit from a treatment that helps stabilize glucose levels, particularly the dangerously low crashes in blood glucose associated with PBH. Camille will discuss our plans for the Phase 3 development program for Avexitide, which we expect to initiate in the first quarter of next year. There is agreement with FDA on the primary outcome for the pivotal phase 3 study for PDH. The outcome, reduction in the composite of level 2 and level 3 hypoglycemia events, is clearly linked to GLP-1 receptor antagonism and was already met in the phase 2 and phase 2b clinical trials of Avexitide and PBH with high significance.

Speaker Change: People living with PBH could benefit from a treatment that helps stabilize glucose levels, particularly the dangerously low crashes in blood glucose associated with PBH.

Speaker Change: Camille will discuss our plans for the Phase 3 development program for Avexitide, which we expect to initiate in the first quarter of next year.

Camille Bedrosian: There is agreement with FDA on the primary outcome for the pivotal phase 3 study for PDH.

Camille Bedrosian: The outcome, reduction in the composite of level 2 and level 3 hypoglycemia events, is clearly linked to GLP-1 receptor antagonism, and was already met in the phase 2 and phase 2b clinical trials of Avexitide and PBH with high significance.

Camille Bedrosian: Camille will also recap the key data, including the statistically significant and clinically meaningful reductions in hypoglycemic events.

Unknown Executive: Camille will also recap the key data, including the statistically significant and clinically meaningful reductions in hypoglycemic events. We are highly encouraged by the greater than 50% reductions in level 1, 2, and 3 hypoglycemic events that have been demonstrated by Avexatide, and Exetide has the potential to be the first-in-class GLP-1 receptor antagonist.

Camille Bedrosian: We are highly encouraged by the greater than 50% reductions in level I, II, and III hypoglycemic events that have been demonstrated by Avexatide.

Camille Bedrosian: Avexitide has the potential to be the first-in-class GLP-1 receptor antagonist.

Unknown Executive: Before I turn it over to Camille, I would like to quickly touch on our cash runway. In the second quarter, we largely completed our restructuring. We expect our cash runway to take us into 2026. Jim will provide additional context. I will now turn the call over to Camille.

Speaker Change: Before I turn it over to Camille, I would like to quickly touch on our cash runway.

Speaker Change: In the second quarter, we largely completed our restructuring.

Camille Bedrosian: We expect our cash runway to take us into 2026. Jim will provide additional context.

Camille: Thanks, Justin. Now, I will briefly review each of our four programs. Vexotide and hyperinsulinemic hypoglycemia, including post-bariatric hypoglycemia or PBH. AMX0035 in Wolfram syndrome and in progressive supranuclear palsy or PSP, and AMX0114 in ALS. Avexitide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose flow. Avexitide has been studied in five clinical trials in PBA.

Speaker Change: I will now turn the call over to Camille.

Camille Bedrosian: Thanks Justin. Now I will briefly review each of our four programs.

Camille Bedrosian: Avexatide and hyperinsulinemic hypoglycemia, including post-bariatric hypoglycemia or PBH.

Unknown Executive: AMX0035 in Wolfram syndrome and in progressive supranuclear palsy or PSP, and AMX0114 in ALS. Avecetide has been studied in five clinical trials in TBH. Data from these trials demonstrated highly significant reductions in hypoglycemic events. Based on these data, we are actively planning and are on track to initiate a Pivotal Phase III program in PBH in Q1 of next year. For those of you who are not familiar with PBH, the condition affects people who have undergone bariatric surgery.

Camille Bedrosian: AMX0035 in Wolfram Syndrome and in Progressive Supernuclear Palsy or PST and AMX0114 in ALS.

Speaker Change: Avexatide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels.

Camille Bedrosian: Avesatide has been studied in five clinical trials in TBH.

Camille: Data from these trials demonstrated highly significant reductions in hypoglycemic events. Most notably, the 90 milligram dose, which we intend to study in phase three, showed a 66% reduction in level 3 hypoglycemic events in a phase 2b trial with a p-value of 0.0003, and a 53% reduction in level 2 hypoglycemic events with a p-value of 0.004. The primary efficacy outcome of our Phase 3 program will be a reduction in the composite of Level 2 and Level 3 hypoglycemic events.

Camille Bedrosian: Data from these trials demonstrated highly significant reductions in hypoglycemic events.

Camille Bedrosian: Most notably, the 90 milligram dose, which we intend to study in phase 3.

Camille Bedrosian: showed a 66% reduction in level 3 hypoglycemic events in a phase 2b trial with a p-value of 0.0003.

Camille Bedrosian: and a 53% reduction in level 2 hypoglycemic events.

Camille Bedrosian: with a p-value of 0.004.

Camille Bedrosian: The primary efficacy outcome of our Phase 3 program will be the reduction in the composite of Level 2 and Level 3 hypoglycemic events.

Camille: The FDA has agreed on this primary efficacy outcome. Furthermore, these data were achieved while demonstrating a favorable safety profile. The benefit of Avexitide is further supported by four additional trials in PBH, which reproducibly showed glucose stabilization and decreased insulin levels with statistically significant p-values. We reviewed these data in depth during our conference call last month.

Camille Bedrosian: The FDA has agreed on this primary efficacy outcome.

Camille Bedrosian: Furthermore, these data were achieved while demonstrating a favorable safety profile.

Camille Bedrosian: The benefit of Avexatide is further supported by four additional trials in PBH which reproducibly showed glucose stabilization and decreased insulin levels with statistically significant p-values.

Camille Bedrosian: We reviewed these data in depth during our conference call last month.

Camille: Based on these data, we are actively planning and are on track to initiate a Pivotal Phase III program in PBH in Q1 of next year. For those of you who are not familiar with PBH, the condition affects people who have undergone bariatric surgery. Symptomatic PBH can have disabling effects on quality of life and ability to live independently, especially the neuroglycopenic symptoms. Imagine you are driving and your blood sugar drops without you realizing it, and you have a seizure.

Camille Bedrosian: Based on these data, we are actively planning and are on track to initiate a Pivotal Phase III program in PBH in Q1 of next year.

Camille: As a result, your license could be suspended, or because you could potentially faint and lose consciousness at any time, you have to move in with a friend or relative so they can provide immediate assistance or call 9-1-1 if you fall and injure yourself.

Camille Bedrosian: For those of you who are not familiar with PDH, the condition affects people who have undergone bariatric surgery.

Unknown Executive: Symptomatic PBH can have disabling effects on quality of life and ability to live independently, especially the neuroglycopenic symptoms. Imagine you are driving and your blood sugar drops without you realizing it, and you have a seizure. As a result, your license could be suspended, which can create very problematic health, social, and economic issues despite their best efforts with dietary modifications and off-label use of other medications. At the International Society for Pediatric and Adolescent Diabetes Conference this fall, including promising data on Glycemic as well as Optic and Global Impressions of Change Outcomes presented in April.

Camille Bedrosian: Symptomatic PBH can have disabling effects on quality of life and ability to live independently, especially the neuroglycopenic symptoms.

Camille Bedrosian: Imagine you are driving and your blood sugar drops without you realizing it and you have a seizure. As a result, your license could be suspended.

Camille Bedrosian: Or, because you could potentially faint and lose consciousness at any time, you have to move in with a friend or relatives so they can provide immediate assistance or call 911 if you fall and injure yourself.

Camille: Imagine being forced to retire mid-career because you have impaired cognition due to sustained low glucose. These examples are experiences that individuals living with PBH have shared. This is the reality for the 160,000 people that we estimate are currently living with symptomatic PBH. These individuals could benefit from a therapy that might mitigate unexpected or current drops in blood glucose, which can create very problematic health, social, and economic issues despite their best efforts with dietary modifications and off-label use of other medications.

Camille Bedrosian: Imagine being forced to retire mid-career because you have impaired cognition due to sustained low glucose.

Camille Bedrosian: These examples are experiences that individuals living with PDH have shared.

Camille Bedrosian: This is the reality for the 160,000 people that we estimate are currently living with symptomatic PBH.

Camille Bedrosian: These individuals could benefit from a therapy that might mitigate unexpected or current drops in blood glucose.

Camille Bedrosian: which can create very problematic health, social, and economic issues despite their best efforts with dietary modifications and off-label use of other medications.

Camille: We believe the significant unmet need, coupled with the robust exercise clinical data in PBH, contribute to the excitement about our PBH program among endocrinologists. We will work to enroll participants in our Phase 3 program as promptly as possible, such that we will be in a position to share top-line data from the program in 2020. Now, turning to the Wolfram Syndrome Program.

Speaker Change: We believe the significant unmet need, coupled with the robust of exercise clinical data in PBH, contribute to the excitement about our PBH program among endocrinologists.

Unknown Executive: At this time, I would like to welcome everyone to the Amalix Pharmaceuticals 2nd quarter, 2024 Earnings Conference call. All participants will be on a listen only mode. After today's presentation, there will be an opportunity to ask questions. To ask a question, please press star one on your telephone keypad. To withdraw your question, please press star two. Please limit your questions to one, with one follow-up. If you have additional questions, you may rejoin the queue.

Camille Bedrosian: We will work to enroll participants in our Phase III program as promptly as possible, such that we will be in a position to share top-line data from the program in 2026.

Speaker Change: Now, turning to the Wolfram Syndrome Program.

Camille: We look forward to presenting the top line data for all 12 participants in the Helios trial at week 24, including longer term data available for participants who have reached their week 36 or week 48 visit at that time, at the International Society for Pediatric and Adolescent Diabetes Conference this fall. We are engaging with stakeholders, including the FDA, and planning for a single phase three clinical trial, and we'll provide more details once the trial is finalized.

Camille Bedrosian: We look forward to presenting the top-line data for all 12 participants in the Helios trial at Week 24, including longer-term data available for participants who have reached their Week 36 or Week 48 visits at that time.

Unknown Executive: Please be advised that this call is being recorded at the company's request.

Lindsey Allen: I would now like to turn the call over to Lindsey Allen, head investor relations and communications. Please proceed.

Camille Bedrosian: at the International Society for Pediatric and Adolescent Diabetes Conference this fall.

Justin Klee: Good morning, and thank you all for joining us today to discuss our 2nd quarter, 2024 financial results.

Camille Bedrosian: We are engaging with stakeholders, including the FDA, and planning for a single Phase III clinical trial, and will provide more details once finalized.

Justin Klee: With me on the call today are Josh Cohen and Justin Klee, our co-CEO's Dr. Camille Vajrogian, our chief medical officer and Jim Freides, our chief financial officer. Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are based on our current beliefs, plans and expectations and are made pursuant to the safe harbor provisions of the private securities litigation reform act of 1995.

Camille: As a reminder, AMX0035 has shown highly significant benefits in glycemic control in the in vivo WFS1 knockout mouse model of Wolfram syndrome. These glycemic results were recapitulated and extended in our clinical trial of Wolfram, including promising data on glycemic as well as optic and global impressions of change outcomes presented in April. Recall that Wolfram syndrome is a progressive neurodegenerative disease.

Camille Bedrosian: As a reminder, AMX0035 has shown highly significant benefits in glycemic control in the in vivo WFS1 knockout mouse model of Wolfram Syndrome.

Camille Bedrosian: These glycemic results were recapitulated and extended in our clinical trial of Wolfram.

Speaker Change: including promising data on Glycemic as well as Optic and Global Impressions of Change Outcomes presented in April .

Justin Klee: These statements include but are not limited to our expectations with respect to a vexatide AMX 35 and AMX 114 statements regarding regulatory and clinical developments and the impact thereof and the expected timing thereof and statements regarding our cash runway.

Camille Bedrosian: Recall that Wolfram syndrome is a progressive neurodegenerative disease.

Camille: While we had anticipated slowing this progression, in fact, the data suggested stabilization or even improvement across these outcomes. Now turning to the Orion PSP program, and Raman in the study, things are going well. As we have described previously, we intend to conduct an interim analysis of Orion and share data in mid-2025. I would like to describe the planned analysis in a bit more detail. We have introduced an operationally seamless Phase 2b3 study design.

Camille Bedrosian: While we had anticipated slowing of this progression, in fact, the data suggested stabilization or even improvement across these outcomes.

Camille Bedrosian: Now turning to the Orion PSP program.

Justin Klee: Actual events and results could differ materially from those expressed or implied by any forward-looking statements. You were cautioned not to place any and do reliance on these forward-looking statements and AMX disclaims any obligation to update such statements unless required by law.

Unknown Executive: As we have described previously, we intend to conduct an interim analysis of Orion and share data in mid-2025. The goal of this analysis is to inform a go-no-go decision. As a reminder, AMX0035 has shown highly significant reductions of tau in CSF in a randomized placebo-controlled study in Alzheimer's patients. As we have previously discussed, PSP is a tauopathy with a highly significant genetic link between variance in tau and the disease and with clear tau pathology in human samples.

Camille Bedrosian: and roman in the study is going well

Camille Bedrosian: As we have described previously, we intend to conduct an interim analysis of Orion and share data in mid-2025.

Camille Bedrosian: I would like to describe the plant analysis in a bit more detail.

Justin Klee: Now I will turn the call over to Justin. Good morning and thank you all for joining us today. As an organization, we have made significant progress over the past few months as part of our continued mission and our goal to deliver important treatment options to the neurodegenerative, neuroendocrine and endocrine communities we serve. Most notably last month we expanded our late stage pipeline with our acquisition of the vexatide and now have three assets targeting orphan indications.

Camille Bedrosian: We have introduced an operationally seamless Phase 2b3 study design.

Camille: The first part will include approximately 100 people living with PSP. In mid-2025, we plan to conduct an unblinded analysis of top line data through week 24 for these participants. In addition, the available data on participants who have proceeded beyond 24 weeks will also be analyzed. The goal of this analysis is to inform a go-no-go decision. Strong data will encourage us to move seamlessly into the second portion of the study, whereas mixed or negative data will allow us to reprioritize our research.

Camille Bedrosian: the first part will include approximately one hundred people living with p

Camille Bedrosian: Mid-2025, we plan to conduct an unblinded analysis of topline data through week 24 for these participants.

Camille Bedrosian: In addition, the available data on participants who have proceeded beyond 24 weeks also will be analyzed.

Camille Bedrosian: The goal of this analysis is to inform a go-no-go decision.

Camille Bedrosian: strong data will encourage us to move seamlessly into the second portion of the study whereas mixedora negative data will allow us to reprioritize our resources

Justin Klee: A vexatide is a phase three ready asset with FDA breakthrough therapy designation in diseases with no approved treatment options. A vexatide is a GLP1 receptor antagonist with orphan drug designation in hyperinflenemic hypoglycemia. The GLP1 receptor is one of the key regulators that the glucose insulin response and an imbalance in this response leads to hyperinflenemic hypoglycemia which underlies several conditions and diseases. So far, a vexatide has been studied in two indications characterized by hyperinflenemic hypoglycemia, postbariatric hypoglycemia or PBH and congenital hyperinflenism. The first indication PBH is a significant but orphan condition that affects the subpopulation of people who have undergone bariatric surgery.

Camille: As a reminder, AMX0035 has shown highly significant reductions of tau in CSF in a randomized placebo-controlled study in Alzheimer's patients. As we have previously discussed, PSP is a tauopathy with a highly significant genetic link between variance in tau and the disease and with clear tau pathology in human samples. AMX0035 is believed to affect intracellular tau, and we believe it is the first agent to be studied in a large trial with the potential to impact intracellular tau pathology.

Speaker Change: As a reminder, AMX0035 has shown highly significant reductions of tau in CSF in a randomized placebo-controlled study in Alzheimer's disease.

Speaker Change: As we have previously discussed, PST is a tauopathy with a highly significant genetic link between variance in tau and the disease, and with clear tau pathology in human samples.

Camille Bedrosian: AMX0035 is believed to affect intracellular tau, and we believe it is the first agent to be studied in a large trial with the potential to impact intracellular tau pathology.

Camille: Finally, our AMX 0114 program remains on track, and we plan to begin clinical testing before the end of the year. AMX 0114 is an antisense oligonucleotide, or ASO, designed specifically to inhibit calpain-2, a protein involved in axonal degeneration and neurofilament biology. We are planning to study this agent in a multiple ascending dose placebo-controlled study in ALF to evaluate the safety and the biological activity of AMX0114. At Amylyx, our goal is to significantly impact diseases of unmet need, and with these four programs, we believe we are on track to do so. I will now turn over the call to Jim. Okay?

Camille Bedrosian: Finally, our AMX 0114 program remains on track.

Camille Bedrosian: We plan to begin clinical testing before the end of the year.

Justin Klee: Now, let me elaborate a little further on the market opportunity ahead. Despite the introduction of GLP-1 receptor agonist for weight loss, more than 200,000 new bariatric procedures are performed every year, and this number has continued to grow on an annual basis. Over the past ten years, approximately 2 million people in the United States have undergone the two most common types of weight loss, ruin why gastric bypass, and sleeve gastrectomy. Experts expect surgery to remain a cornerstone of weight loss therapy given the procedure is highly effective and results in substantial and sustained weight loss, particularly for people with higher BMI's.

Camille Bedrosian: AMX 0114 is an antisense oligonucleotide, or ASO, designed specifically to inhibit Calpain-2, a protein involved in axonal degeneration and neurofilament biology.

Speaker Change: We are planning to study this agent in a multiple ascending dose placebo-controlled study in ALS to evaluate the safety and the biological activity of AMX0114.

Camille Bedrosian: At Amylyx, our goal is to significantly impact diseases of unmet need, and with these four programs, we believe we are on track to do so.

Speaker Change: I will now turn over the call to Jim. Jim?

Justin Klee: Evidence also suggests that bariatric surgery reduces the risk of cardiovascular events and the severity of metabolic dysfunction associated liver disease. Turning to PBH, this persistent condition can develop in people who had received bariatric surgery one to three years prior, and in some cases even longer post-surgery. We estimate that approximately 8% of the two million people I referenced, or 160,000 people in the U.S, today, have symptomatic PBH. Symptomatic PBH is characterized by hypoglycemic events associated with brain glucose starvation known as neural glycopenia, including impaired cognition, loss of consciousness, and seizures, as well as activation of the autonomic nervous system, presenting as hunger, sweating, tingling, tremors, palpitations, and anxiety. People living with PBH could benefit from a treatment that helps stabilize glucose levels, particularly the dangerously low crashes in blood glucose associated with PBH.

Jim: Following Phoenix's top-line results, we restructured quickly, which placed us in a strong cash position and enabled us to focus on our meaningful near-term clinical milestones. We ended Q2 with $309.8 million in cash and investments. As a reminder, we acquired Avexitide in early Q3 for a purchase price of $35.1 million. Since the acquisition, we have targeted our budget to focus on our major clinical programs. As a result of this work, we believe our cash will take us into 2026, and we will work to manage the company through meaningful clinical data readouts.

Jim Frates: Thanks, Camille. Following Phoenix's top-line results, we restructured quickly, which placed us in a strong cash position and enabled us to focus on our meaningful near-term clinical milestones.

Unknown Executive: We ended Q2 with $309.8 million in cash and investment. Now, I turn to other details of our financial results. We do not expect any material changes moving forward.

Jim Frates: We ended Q2 with $309.8 million in cash and investments. As a reminder, we acquired Avexitide in early Q3 for a purchase price of $35.1 million.

Jim Frates: Since the acquisition, we have targeted our budget to focus on our major clinical programs. As a result of this work, we believe our cash will take us into 2026, and we will work to manage the company through meaningful clinical data readouts, namely…

Jim: Namely, data readout from our Phase II Helios trial in Wolfram syndrome, the interim readout from our PSP program, interim clinical data from our AMX 114 program, and the readout of top-line data from the Avexitide Phase III program.

Jim Frates: the data readout from our Phase 2 Helios trial in Wolfram syndrome, the interim readout from our PSP program, interim clinical data from our AMX 114 program, and the readout of top-line data from the Avexitide Phase 3 program.

Jim: Now, I turn to other details of our financial results. Net product revenue was negative $1 million for the second quarter due to adjustments to our gross to net revenue reserve estimates. This was mainly driven by adjustments to our estimates for returns once we stopped our sales. Cost of sales was $7.4 million for Q2, compared to $5.6 million for the same period in 2023. Cost of sales this quarter was primarily related to estimated losses on firm commitments under Commercial Manufacturing and Supply Agreements for Rolivrio and Albrioza that were established for future production prior to the results from Phoenix. We do not expect any material changes moving forward.

Jim Frates: Now, turn into other details of our financial results.

Speaker Change: Net product revenue was negative $1 million for the second quarter due to adjustments to our gross to net revenue reserve estimates.

Camille Vajrogian: Camille will discuss our plans for the Phase 3 Development Program for Avexatide, which we expect to initiate in the first quarter of next year. There is agreement with FDA on the primary outcome for the pivotal Phase 3 study for PBH. The outcome, reduction in the composite of Level 2 and Level 3 hypoglycemia events, is clearly linked to GLP-1 receptor antagonism, and was already met in the Phase 2 and Phase 2 B clinical trials of Avexatide and PBH with high significance.

Speaker Change: This was mainly driven by adjustments to our estimates for returns once we stopped our sales.

Speaker Change: Cost of sales were $7.4 million for Q2, compared to $5.6 million for the same period in 2023.

Speaker Change: Cost of sales this quarter were primarily related to estimated losses on firm commitments under commercial manufacturing and supply agreements for Relivrio and Albrioza that were established for future production prior to the results from Phoenix.

Speaker Change: We do not expect any material COGs moving forward.

Camille Vajrogian: Camille will also recap the key data, including the statistically significant and clinically meaningful reductions in hypoglycemic events. We are highly encouraged by the greater than 50% reductions in Level 1, 2, and 3 hypoglycemia events that have been demonstrated by Avexatide. Avexatide has the potential to be the first-in-class GLP-1 receptor antagonist.

Unknown Executive: Research and development expenses were $23.3 million for the quarter, compared to $29 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel-related costs and a decrease in consulting and professional services. Restructuring expense was $22.9 million in the quarter, compared to zero for the same period in 2023. Finally, in the second quarter, we recorded a net loss of $72.7 million, or $1.07 per share, including restructuring. I'll now turn the call over to Josh to make some closing remarks.

Jim: Research and development expenses were $23.3 million for the quarter, compared to $29 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel-related costs as a result of our restructuring and a decrease in clinical expenses due to the outcome of the Phoenix trial. Felling General and Administrative Expenses were $21.6 million for Q2, compared to $43.4 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel-related costs and a decrease in consulting and professional services following our decision to voluntarily discontinue the marketing of Relivrio and Eldrio.

Jim Frates: Research and development expenses were $23.3 million for the quarter, compared to $29 million for the same period in 2023.

Jim Frates: The decrease was primarily due to a decline in payroll and personnel-related costs as a result of our restructuring and a decrease in clinical expense due to the outcome of the Phoenix trial.

Justin Klee: Before I turn it over to Camille, I would like to quickly touch on our cash runway. In the second quarter, we largely completed our restructuring.

Speaker Change: Belling General and Administrative expenses were $21.6 million for Q2.

Speaker Change: compared to $43.4 million for the same period in 2023.

Justin Klee: We expect our cash runway to take us into 2026. Jim will provide additional context.

Speaker Change: The decrease was primarily due to a decline in payroll and personnel-related costs, and a decrease in consulting and professional services, following our decision to voluntarily discontinue the marketing of Relivrio and Albrioza.

Camille Vajrogian: I will now turn the call over to Camille. Thanks, Justin. Now, I will brief and review each of our four programs. Avexatide and hyper-insulinemic hypoglycemia, including post-bariatric hypoglycemia or PBH. AMX-0035 and Wolfram Syndrome and in Progressive Supernuclear Prawl of the ERPST and AMX-0114 in ALF. Avexatide is designed to bind to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels.

Jim: Restructuring expense was $22.9 million in the quarter, compared to zero for the same period in 2023. The majority of this charge is related to employee severance and termination-related benefits that were paid in Q2, and our restructuring plan was largely completed this quarter. Consistent with our prior expectations, as we move into 2025, we expect total combined spend on R&D and SG&A to be in the range of $30 to $40 million in cash per quarter.

Speaker Change: Restructuring expense was $22.9 million in the quarter, compared to zero for the same period in 2023.

Speaker Change: The majority of this charge is related to employee severance and termination-related benefits that were paid in Q2, and our restructuring plan was largely completed this quarter.

Speaker Change: Consistent with our prior expectations as we move into 2025, we expect total combined spend on R&D and SG&A will be in the range of $30 to $40 million in cash per quarter.

Jim: Finally, in the second quarter, we recorded a net loss of $72.7 million, or $1.07 per share, including restructuring. Overall, we're in a solid financial position and believe in our ability to deliver on the clinical milestones that we outlined today. I'll now turn the call over to Josh to provide some closing remarks.

Speaker Change: Finally, in the second quarter, we recorded a net loss of $72.7 million, or $1.07 per share, including the restructuring charges.

Camille Vajrogian: Avexatide has been studied in five clinical trials in TBH, data from these trials demonstrated highly significant reductions in hypoglycemic events. Most notably, the 90 milligram dose, which we intend to study in phase 3, showed a 56 percent reduction in level 3 hypoglycemic events in a phase 2B trial, with a p-value of 0.003, and a 53 percent reduction in level 2 hypoglycemic events, with a p-value of 0.004. The primary efficacy outcome of our phase 3 program will be the reduction in the composite of level 2 and level 3 hypoglycemic events.

Speaker Change: Overall, we're in a solid financial position and believe in our ability to deliver on the clinical milestones that we outlined today.

Speaker Change: I'll now turn the call over to Josh to provide some closing remarks.

Josh: In closing, we are excited about our four pipeline programs, upcoming milestones, and path ahead. Avexitide has both FDA breakthrough therapy designation and orphan drug designation and is poised to advance into phase three development in PBH beginning in the first quarter of 2025. In Wolfram syndrome, we expect top-line data from Helios in the fall for all 12 participants at week 24, including longer-term data available for participants who have reached their week 36 or 48 visit at that time.

Josh Cohen: Thank you, Jim. In closing, we are excited about our four pipeline programs, upcoming milestones, and path ahead.

Unknown Executive: Avexitide has both FDA breakthrough therapy designation and orphan drug designation and is poised to advance into phase three development in PBH beginning in the first quarter of 2025. We will provide more details on the trial once the design is finalized. AMX 114 is on track to be studied in people living with ALS later this year. Thank you.

Josh Cohen: Avexatide has both FDA breakthrough therapy designation and orphan drug designation and is poised to advance into Phase III development in PBH beginning in the first quarter of 2025.

Speaker Change: In Wolfram Syndrome, we expect the top-line data from Helios in the fall for all 12 participants at week 24, including longer-term data available for participants who have reached their week 36 or 48 visit at that time.

Camille Vajrogian: The FDA has agreed on this primary efficacy outcome. Furthermore, these data were achieved while demonstrating a favorable safety profile. The benefit of avexatide is further supported by four additional trials in TBH, which reproducibly showed glucose stabilization and decreased insulin levels with statistically significant p-values. We reviewed these data and deaths during our conference call last month. Based on these data, we are actively planning and are on track to initiate a pivotal phase 3 program in TBH in Q1 of next year.

Josh: We are engaging the FDA and other stakeholders and planning for a single phase three clinical trial. We will provide more details on the trial once the design is finalized. The Orion trial of AMX-35 and PSP is recruiting well, and we continue to expect data from an interim analysis mid-next year. AMX 114 is on track to be studied in people living with ALS later this year. And we believe we have the team and resources in place to deliver on four meaningful clinical data readouts ahead.

Speaker Change: We are engaging the FDA and other stakeholders and planning for a single phase 3 clinical trial.

Speaker Change: we will provide more details on the trial once that design'is finalized

Speaker Change: The Orion trial of AMX-35 and PSP is recruiting well, and we continue to expect data from interim analysis mid-next year.

Speaker Change: AMX 114 is on track to be studied in people living with ALS later this year.

Speaker Change: And, we believe we have the team and resources in place to deliver on four meaningful clinical data readouts ahead.

Camille Vajrogian: For those of you who are not familiar with TBH, the condition affects people who have undergone bariatric surgery. Symptomatic p-bh can have disabling effects on quality of life and ability to live independently, especially the neuro glycopenic symptoms. Imagine you are driving and your blood sugar drop without you realizing it, and you have a seizure as a result your license could be suspended. Or because you could potentially faint and lose consciousness at any time, you have to move in with a friend or relative so they can provide immediate assistance or call 911 if you fall and injure yourself.

Josh: We look forward to keeping you updated as we build upon our critical work in orphan neurodegenerative, neuroendocrine, and endocrine diseases of high unmet need. Now, I would like to open the call up for Q&A. Thank you.

Speaker Change: We look forward to keeping you updated as we build upon our critical work in orphan neurodegenerative, neuroendocrine, and endocrine diseases with high unmet need.

Speaker Change: Now I would like to open the call up for Q&A.

Operator: Thank you. We will now begin the Q&A session. To ask a question, please press star 1 on your telephone keypad. To withdraw your question, press the pound key or star 2.

Speaker Change: Thank you. We will now begin the Q&A session. To ask a question, please press star 1 on your telephone keypad. To withdraw your question, press the pound key or star 2.

Operator: Please limit your question to one with one follow-up. If you have additional questions, you may rejoin the call.

Operator: Please limit your question to one, with one follow-up. If you have additional questions, you may rejoin the call. At this time, we will pause momentarily to assemble our roster. Your first question comes from the line of Charlie Yang from Bank of America. Please go ahead.

Speaker Change: Please limit your question to one, with one follow-up. If you have additional questions, you may rejoin the queue.

Camille Vajrogian: Imagine being forced to retire mid-career because you have impaired cognition due to sustained low glucose. These examples are experiences that individuals living with TBH have shared. This is the reality for the 160,000 people that we estimate are currently living with symptomatic p-bh. These individuals could benefit from the therapies that might mitigate unexpected or current drops in blood glucose, which can create very problematic health, social and economic issues despite their best efforts with dietary modifications and off-label use of other medications.

Speaker Change: At this time, we will pause momentarily to assemble our roster.

Speaker Change: Your first question comes from the line of Charlie Yang from Bank of America. Please go ahead.

Charlie Yang: Great, thanks for taking my questions. I just wanted to ask about the PSP data in mid next year in terms of the county expectation over there and then, you know, I'm assuming if there's a signal observed, is there, I guess, is there a path to make an adjustment to a number of patients as needed to further amplify the potential success of this trial? At the end, we go. Yeah.

Charlie Yang: Great, thanks for taking my questions. I just wanted to ask about the PSP data in mid next year, in terms of the county expectation over there, and then, you know, I'm assuming if there's a signal observed, you know, is there, I guess,

Unknown Caller: Is there a way to make an adjustment to a number of patients as needed to further amplify the potential success of this trial?

Speaker Change: Is there a path to make an adjustment to a number of patients as needed to further kind of amplify the potential success of this trial?

Camille Vajrogian: We believe the significant unmet need coupled with the robust of exotite clinical data in TBH contribute to the excitement about our p-bh program among endocrinologists. We will work to enroll participants in our FA3 program as promptly as possible. Cable, such that we will be in a position to share top-line data from the program in 2026.

Camille Bedrosian: Thank you, Charlie. This is Camille.

Camille: Thank you, Charlie. This is Camille.

Speaker Change: at the final readout.

Speaker Change: Thank you, Charlie. This is Camille. As we indicated in our prepared remarks, the first part of the study of the Phase 2b, where we will analyze about 100 participants,

Camille: As we indicated in our prepared remarks, the first part of the study in Phase 2b, where we will analyze about 100 participants, unblinded AMX0035 versus placebo and do a full-on analysis at 24 weeks, and for those who have gone beyond 24 weeks, to look at their longer-term data as well. And based on that result, we will then, if positive and strong, proceed seamlessly into the phase three portion of the study. And based on those data, the final sample size.

Camille Bedrosian: As we indicated in our prepared remarks, the first part of the study in Phase 2B, where we will analyze about 100 participants, unblinded AMX0035 versus placebo and do a full-on analysis at 24 weeks and for those who have gone beyond 24 weeks to look at their longer-term data as well. And based on that result, we will then, if positive and strong, proceed seamlessly into the phase three portion of the study. And based on those data, the final sample size.

Speaker Change: I'm blinded, AMX 0035 versus placebo.

Camille Vajrogian: Now, turning to the Wolfram syndrome program.

Speaker Change: and do a full-on analysis at 24 weeks.

Camille Vajrogian: We look forward to presenting the top-line data for all 12 participants in the Helios trial at week 24, including longer-term data available for participants who have reached their week 36 or week 48 visits at that time. At the International Society for Pediatric and Adolescent Diabetes Conference, this fall.

Speaker Change: And for those who have gone beyond 24 weeks to look at their longer term data as well.

Speaker Change: And based on that result, we will then, if positive and strong, we will proceed seamlessly into the phase three portion of the study. And based on those data, the final sample size will be determined.

Camille: Great, thanks. And maybe just one quick follow-up, just in terms of global firm opportunity in Europe, how does that compare to the US?

Speaker Change: Great, thanks. And maybe just one quick follow-up, just in terms of the World Firm opportunity in Europe , how does that compare to the US? Thank you.

Camille Vajrogian: We are engaging with stakeholders including the FDA and planning for a single-phase three clinical trial and will provide more details once finalized. As a reminder, AMX0035 has shown highly significant benefits in glycemic controls in the INVIVO-WSS1 knockout mouth model of Wolfram syndrome. These glycemic results were recapitulated and extended in our clinical trial at Wolfram, including promising data on glycemic, as well as optic and global impressions of change outcomes presented in April. Recall the Wolfram syndrome is a progressive neurodegenerative disease. While we had anticipated slowing of this progression, in fact, the data suggested stabilization or even improvement across these outcomes.

Unknown Executive: Yes, so we are certainly aware of endocrinologists who are familiar with wolfram and have a large, large, relatively speaking, wolfram population. So, but right now, we are focusing on the U.S. And so we do, yeah. So more to come on that as we do more research. But I would add that, you know, wolfram being a monogenic disease.

Camille: Yes, so we are certainly aware of endocrinologists who are familiar with wolfram and have a large, large, relatively speaking, wolfram population. So, but right now, we are focusing on the U.S., and so we do, yeah. So, more to come on that as we do more research. But I would add that, you know, Wolfram being a monogenic disease, we do see people with Wolfram syndrome all around the world. So it is very much a global unmet need.

Speaker Change: Yes, so we are certainly aware of endocrinologists who are familiar with wolfram and have a large, large, relatively speaking, wolfram population.

Speaker Change: So, but right now we are focusing on the U.S. and so we do, yeah, so more to come on that as we do more research.

Speaker Change: But I would add that, you know, Wolfram being a monogenic disease, we do see people with Wolfram syndrome all around the world. So it is very much a global unmet need.

Corinne Johnson: Your next question comes from the line of Corinne Johnson from Goldman. Please go ahead.

Speaker Change: Thank you.

Speaker Change: Your next question comes from the line of Corrine Johnson from Goldman. Please go ahead.

Palak: Hi, good morning. This is Palak on behalf of Corinne.

Camille Vajrogian: Now, turning to the Orion PSP program. Enrollment in the study is going well. As we have described previously, we intend to conduct an interim analysis of Orion and share data in mid-2025.

Palak: Hi, good morning. This is Palak on for Corinne. Two from us on the PSP front. The first thing, what do prior studies in PSP suggest for placebo and natural history population at the 24-week time point?

Camille: Two from us on the PSP front. The first thing is, what do prior studies in PSP suggest for the placebo and natural history population at the 24-week time point? And then the second question is, what are you thinking about in terms of the threshold for futility at the 24-week end point in the interim analysis? Thank you.

Camille Vajrogian: I would like to describe the planned analysis in a bit more detail. We have introduced an operationally seamless SAIS-2B3 study design. The first part will include approximately 100 people living with PSP. Mid-2025, the planning-aduct and unblinded analysis of top-line data through week 24 for these participants. In addition, the available data on participants who have proceeded beyond 24 weeks also will be analyzed. The goal of this analysis is to inform a go-no-go decision. Strong data will encourage us to move seamlessly into the second portion of the study, whereas mixed or negative data will allow us to re-prioritize our resources.

Speaker Change: And then the second was, what are you thinking about in terms of the threshold for futility at the 24-week end point in the interim analysis? Thank you.

Camille: Yep, so as you are alluding, in fact, the progression of the disease is actually quite reproducible. There were three relatively large phase three studies in PSP, unfortunately, none of which showed a benefit of the active ingredient or active drug. But it did show that there was reproducible deterioration, and it's at a relatively similar rate. So we do use that as a basis for understanding and looking at the data coming in. And, you know, as your other question to me on the threshold for

Unknown Executive: Yep, so as you are alluding, in fact,

Speaker Change: So, as you are alluding, in fact, the.

Speaker Change: Progression of the disease is actually quite reproducible. There were three

Speaker Change: relatively large phase 3 studies in PSP.

Speaker Change: Unfortunately, none of which showed a benefit of the active drug, but it did show that there was reproducible deterioration.

Speaker Change: And it's at a relatively similar rate. So we do use that as a basis for understanding and looking at the data coming up.

Camille: And as for your other question, too, on the threshold for futility, this is not a formal futility analysis. We're doing a full evaluation of the data, so we'll be looking at kind of a full top-line release, essentially a Phase IIb release when we do that interim analysis. And just highlighting Camille's point as well, when you look at the past larger randomized placebo-controlled studies that have been conducted in PSP, the placebo rate is actually quite strikingly consistent, usually at just under a point.

Camille Vajrogian: As a reminder, AMX0035 has shown highly significant reductions of TAL and CSF and are randomized to see the control study in alphymus disease. As we have previously discussed, PSP is a TAL opacy, with a highly significant genetic link between variants in TAL and the disease and with clear TAL pathology in human samples. AMX0035 is believed to affect intracelular TAL and we believe it is the first agent to be studied in a large trial with the potential to impact intracelular TAL pathology.

Speaker Change: And, you know, as your other question, too, on the threshold for futility, this is not a, you know, formal futility analysis. We're doing a full evaluation of the data. So we'll be looking at, you know, kind of a full top-line release, you know, essentially a Phase IIB release.

Camille Bedrosian: When we do that interim analysis, and just, you know, highlighting Camille's point as well, when you look at the past larger randomized placebo-controlled studies that have been conducted in PSP, the placebo rate is actually, you know, quite strikingly consistent, you know, usually at just under a point a month.

Umer Raffat: Thank you. Your next question comes from the line of Umer Raffat from Evercore. Please go ahead.

Speaker Change: Understood, thank you.

Camille Vajrogian: Finally, our AMX00114 program remains on track.

Speaker Change: Thank you. Your next question comes from the line of Umer Raffat from Evercore. Please go ahead.

Camille Vajrogian: We plan to begin clinical testing before the end of the year. AMX00114 is an anti-sense oligonucleotide or ASO, designed specifically to inhibit calpane 2, a protein involved in exonal degeneration and neurofilament biologists.

Chen Xiang: Hi, good morning. This is Chen Xiang from Umer.

Speaker Change: Hi, good morning. This is Chun-Hsian Ong from OMER. Thanks for taking our questions.

Camille: Thanks for taking our questions. Firstly, for the Wolfram Syndrome Phase 3 trial, does it need to be placebo-controlled? And secondly, for 0114, are you planning to give incremental data updates as it progresses? Maybe the timing between the Phase 2 Wolfram trial data this fall and the Phase 3 PSP interim next year? Right, so thank you for the answer.

Chun-Hsian Ong: I guess firstly, for Wolfram Syndrome Phase 3 trial, does it need to be placebo-controlled? And secondly, for 0114, are you planning to give incremental data updates as it progresses, maybe the timing between Phase 2 Wolfram trial data this fall and the Phase 3 PSB interim next year?

Camille Vajrogian: Technology. We are planning to study this agent in a multiple ascending dose with SIBO-controlled study in ALF to evaluate the safety and the biological activity of AMX-0114. At AMOX, our goal is to significantly impact diseases of unmet needs, and with these four programs, we believe we are in track to do so.

Camille: Regarding Wolfram, as we indicated in our prepared remarks, we are engaging with stakeholders that include, of course, the FDA, and once our plans are finalized, we'll share those with you. Just as a reminder, later this fall, we will share data on all 12 participants through 24 weeks and additional longer-term data for those individuals who have gone through weeks 36 and 48. So we're looking forward to those readouts as well.

Camille: Right, so thank you for the question. This is Camille.

Unknown Executive: Right, so thank you for that.

Speaker Change: Right, so thank you for the questions. This is Camille. Regarding Wolfram, as we indicated in our prepared remarks, we are engaging with stakeholders that include, of course, the FDA, and once our plans are finalized, we'll share those with you. Just as a reminder, later this fall, we will share, you know,

Jim Freides: I will now turn over the call to Jim. Jim, Thanks, Camille. Following Phoenix top-line results, we restructured quickly, which placed us in a strong cash position, and enabled us to focus on our meaningful near-term clinical milestones. We ended Q2 with $309.8 million in cash and investments. As a reminder, we acquired a vexatide in early Q3 for a purchase price of $35.1 million. Since the acquisition, we have targeted our budget to focus on our major clinical programs.

Speaker Change: data on alsotwelve participants to twenty-four weeks and

Speaker Change: Additional longer-term data for those individuals who have gone

Camille: And then regarding 0114, as we indicated, we are planning to initiate our multiple ascending dose study in individuals with ALS by the end of the year. And as the study progresses, we'll be able to provide more detailed timing and types of data we'll be sharing through 2025. Thank you. Your next question...

Speaker Change: through week 36 and 48.

Speaker Change: So we're looking forward to those readouts as well.

Speaker Change: And then regarding 0114, as we indicated, we are planning to initiate our multiple ascending dose study in individuals with ALS by the end of the year.

Jim Freides: As a result of this work, we believe our cash will take us into 2026, and we will work to manage the company through meaningful clinical data readouts. Namely, the data readout from our Phase 2 Helios trial and Wolfram Syndrome, the interim readout from our PSP program, interim clinical data from our AMX-114 program, and the readout of top-line data from the vexatide Phase 3 program.

Speaker Change: And as the study progresses, we'll be able to provide more details.

Speaker Change: Timing and types of data we'll be sharing through 2025.

Graig Suvannavejh: Thank you. Your next question comes from the line of Graig Suvannavejh from Mizuho Financial Group.

Speaker Change: Alright, thank you.

Speaker Change: Thank you. Your next question comes from the line of Graig Suvannavejh from Mizuho Financial Group. Please go ahead.

Charles Wayne: Please go ahead. Morning, everyone. This is Charles Wayne and Alfred Gregg. Thanks for taking our question. We were wondering what type of data you would present.

Charles Wainoffer: Good morning, everyone. This is Charles Wainoffer, Graig. Thanks for taking our question. We were wondering what type of data will you present at the updated data presentation for Helios? Should we expect it to be similar to the interim readout earlier this year? Thanks.

Jim Freides: Now, turn into other details of our financial results. That product revenue was negative $1 million for the second quarter due to adjustments to our growth to net revenue reserve estimates. This was mainly driven by adjustments to our estimates for returns once we stopped our sales.

Camille: Yep, thank you. This is Camille again.

Camille Bedrosian: Yep, thank you. This is Camille again. Indeed, so we do intend to provide longer term data for those individuals about whom we reported in April of this year, as well as data through 24 weeks for all 12 participants.

Jim Freides: Cost of sales were $7.4 million for Q2 compared to $5.6 million for the same period in 2023. Cost of sales this quarter were primarily related to estimated losses on firm commitments under commercial manufacturing and supply agreements for Relidrio and Albrioza that were established for future production prior to the results from Phoenix. We do not expect any material cogs moving forward.

Camille: Indeed, we do intend to provide longer-term data for those individuals about whom we reported in April of this year, as well as data through 24 weeks for all 12 participants. It's top-line data, primary endpoints, and key secondary endpoints, and we look forward to sharing those details with you at the upcoming international meeting.

Speaker Change: It's top-line data, primary endpoints, and key secondary endpoints, and we look forward to sharing those details with you at the upcoming international meeting.

Jim Freides: Research and development expenses were $23.3 million for the quarter, compared to $29 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel-related costs as a result of our restructuring and a decrease in clinical expense due to the outcome of the Phoenix trial.

Mark Goodman: Your next question comes from the line of Mark Goodman from Leering Partners. Please go ahead.

Graig: Thank you, Graig.

Speaker Change: Your next question comes from the line of Mark Goodman from Leering Proctors. Please go ahead.

Rudy: Hi, thanks for taking my question. This is Rudy on the line for Mark.

Rudy: Hi, thanks for taking my question. This is Rudy on the line for Mark. Can you talk about R&D expenses going into 2025? What is your strategy to build a pipeline going forward with both internal and external assets?

Rudy: Hi, thanks for taking my question. This is Rudy on the line from Mark. Can you talk about R&D expenses going into 2025? What is your strategy to build a pipeline going forward with both internal and external assets? Thanks.

Joel Beatty: Can you talk about R&D expenses going into 2025? What is your strategy to build a pipeline going forward with both internal and external resources? Thanks.

Jim Freides: Felling general and administrative expenses were $21.6 million for Q2 compared to $43.4 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel-related costs and a decrease in consulting and professional services following our decision to voluntarily discontinue the marketing of Relidrio and Albrioza.

Jim: Yeah, thank you. It's Jim. Good morning.

Jim: Thanks. Yeah, thanks you. It's Jim. Good morning.

Charles Wainoffer: Yeah, thank you. It's Jim. Good morning.

Jim: You know, I think one of the things that is happening on our R&D line, right, as our restructuring has occurred and as the large Phoenix Phase 3 winds down, and you can find some detail on those expenses historically in our queues, that really opens up room for some of the new spending that we have going on. And, you know, currently, the Wolfram study is ongoing. The PSP study is starting to move into a range where that, you know, that's going to be consistent as opposed to really growing.

Jim Frates: You know, I think one of the things that is happening on our R&D line, right, as our restructuring has occurred and as the large Phoenix Phase III winds down, and you can find some detail on those expenses historically in our queues,

Jim Freides: Restructuring expense was $22.9 million in the quarter, compared to $0 for the same period in 2023. The majority of this charge was related to employee severance and termination-related benefits that were paid in Q2 and our restructuring plan was largely completed this quarter.

Speaker Change: That really opens up room for some of the new spending that we have going on. And, you know, currently the Wolfram study is ongoing.

Speaker Change: The PSP study is starting to move up into a range where that's going to be consistent as opposed to really growing, and so that leaves us room as we move forward to spend on the 1.1.4 study and the new Avexitide program.

Jim Freides: Consistent with our prior expectations as we move into 2025, we expect total combined spend on R&D and SG&A will be in the range of $30 to $40 million in cash per quarter.

Jim: And so that leaves us room as we move forward to spend on the 1.1.4 study and the new Avexitide program. And then just overall, as we outlined, we expect cash expense, now that's excluding non-cash comp, to be in the range of $30 million to $40 million a quarter for both R&D and SG&A. So that's how some of the moving parts are going into 2020.

Joel Beatty: Thank you. Your next question comes from the line of Joel Beatty from Baird. Please go ahead.

Rudy: And then just overall, as we outlined, we expect cash expense, now that's excluding non-cash comp, to be in the range of $30 to $40 million a quarter for both R&D and SG&A. So that's how some of the moving parts are going into 2025.

Jim Freides: Finally, in the second quarter, we recorded a net loss of $72.7 million or $1.7 per share including the restructuring charges. Overall, we're in a solid, tenantial position and believe in our ability to deliver on the clinical milestones that we outlined today.

Speaker Change: Very helpful. Thanks.

You're welcome.

Operator: comes from the line of Joel Beatty from Baird. Please go ahead.

Joshua Cohen: I'll now turn the call over to Josh to provide some closing remarks. Thank you, Jim. In closing, we are excited about our four pipeline programs upcoming milestones and path ahead.

Speaker Change: Thank you. Your next question comes from the line of Joel Biatti from Baird. Please go ahead.

Joel Beatty: Hi, thanks for taking the questions. For the PSP interim analysis to get data around mid-2025, does that mean completing enrollment around the end of this year? And what gives you confidence in the trial completing enrollment around that time frame?

Joel Beatty: Hi, thanks for taking the questions. For the PSP interim analysis, to get data around mid-2025, does that mean completing enrollment around the end of this year? And what gives you confidence on the trial completing enrollment around that time frame?

Joshua Cohen: At Exitide has both FDA breakthrough therapy designation and orphan drug designation and has poised to advance into phase three development in PBH beginning in the first quarter of 2025. In Wolfram Syndrome, we expect the top-line data from Helios in the fall for all 12 participants at week 24 including longer-term data available for participants who have reached their week 36 or 48 visit at that time. We are engaging the FDA and other stakeholders and planning for a single phase three clinical trial.

Camille: Yes, hi Joel. This is Camille. We are enrolling quite well, as I indicated in our prepared remarks, and we're tracking toward having data by mid-2025. We'll give more information as we march toward that time frame.

Operator: Yes, hi Joel, this is Camille. We are enrolling quite well as I indicated in our prepared remarks and we're tracking toward having data mid-2025.

Unknown Executive: remarks, and we're tracking toward having data by mid 2025. We'll give more information as we march toward that time.

Unknown Executive: We'll give more information as we march toward that time frame.

Unknown Executive: Okay, great. And then, as a follow-up question, do you anticipate any more acquisitions after the recent acquisition of ExoTide?

Joel Beatty: Okay, great. And then, as a follow-up question, do you anticipate any more?

Speaker Change: Okay, great. And then as a follow-up, do you anticipate any more acquisitions after the recent acquisition of ExoTide?

Joshua Cohen: We will provide more details on the trial once the design is finalized. The Orion trial of AMX 35 and PSP is recruiting well and we continue to expect data from interim analysis mid next year. AMX 114 is on track to be studied in people living with ALS later this year and we believe we have the team and resources in place to deliver on four meaningful clinical data readouts ahead. We look forward to keeping you updated as we build upon our critical work in orphan neuro generative neuroendocrine and endocrine diseases with high on that need.

Speaker Change: Yeah, you know, I'll say we wouldn't, you know, we've had a process ongoing for some time where we're evaluating, you know, many assets for, you know, that, that, you know, whether they fit well into our pipeline and have the requisite, you know, scientific and clinical and commercial, you know, path forward. Today, we're very excited about the assets we, you know, have today and that's our focus.

Speaker Change: But, you know, we're always looking and I'd say we wouldn't rule out, you know, adding additional things in.

Speaker Change: Thank you.

Unknown Executive: Thank you. There are no further questions at this time. I'll turn the call back to Mr. Klee.

Unknown Executive: Now I would like to open the call up for Q&A. Thank you.

Speaker Change: Thank you for joining us today on today's call to discuss our second quarter 2024 financial results. Have a great day.

Unknown Executive: We will now begin the Q&A session. To ask a question, please press star one on your telephone keypad. To withdraw your question, press the power key or start two.

Unknown Executive: Please limit your question to one with one follow-up. If you have additional questions, you may rejoin the queue.

Speaker Change: Thank you for joining today's call.

Speaker Change: Please disconnect your line. Thank you.

Unknown Executive: At this time, we will pause momentarily to assemble our roster.

Charlie Yang: Your first question comes from the line of Charlie Yang from Bank of America. Please go ahead. Great. Thanks for taking my questions. I just wanted to ask about the PSP data in mid next year in terms of the kind of expectation over there and then I was assuming if it is a signal observed, you know, is there, I guess, is there a path to make a adjustment to a number of pages as needed to further amplify the potential success of this trial at the final readout? Yep. Thank you, Charlie.

Camille Vajrogian: This is Camille. As we indicated in our prepared remarks, we will, the first part of the study is the phase 2v where we will analyze about 100 participants. I'm blinded, and at 0035 versus placebo, and do a full-on analysis at 24 weeks. And for those who have gone beyond 24 weeks to look at their longer-term data as well. And based on that result, we will then, if positive and strong, we will proceed seamlessly into the phase 3 portion of the study, and based on those data in the final sample size, with the determined.

Camille Vajrogian: Great, thanks. And maybe just one quick follow-up just in terms of the world from opportunity in Europe. How does that come compared to the US? Thank you. Yes, so we are certainly aware of endocrinologist who are familiar with world from and have a large large, relatively speaking, world from population. So, but right now we are focusing on the US and so we do, yeah. So, more to come on that is we do more research. But I would add that, you know, we're from being a monogenic disease. We do see people with who are from syndrome all around the world. So, it is very much a global underneath.

Unknown Executive: Thank you.

Karine Johnson: Your next question comes from the line of Karine Johnson from Goldman. Please go ahead. Hi, good morning. This is Pollock on for Corinne. Two from us on the PSP front. The first being what to prior studies in PSP suggests for placebo and natural history population at the 24-week time point. And then the second was what are you thinking about in terms of the threshold for futility at the 24-week endpoint in the internal analysis?

Karine Johnson: Thank you. Yep, so as you are alluding, in fact, the progression of the disease is actually quite reproducible. There were three relatively large phase three studies in PSP, unfortunately none of which were showed a benefit of the active drug. But it did show that there was reproducible deterioration at a relatively similar rate. So we do use that as a basis for understanding and looking at the data coming up. And as your other question too on the threshold for futility, this is not a formal futility analysis.

Karine Johnson: We're doing a full evaluation of the data. So we'll be looking at kind of a full-top line release, essentially a phase two being released when we do that in term analysis. And just highlighting Camille's point as well, when you look at the past in a larger randomized placebo controlled studies that have been conducted in PSP, the placebo rate is actually quite strikingly consistent, usually at just under a point of a month. Understood, thank you. Thank you.

Umar Raffat: Your next question comes from the line of Umar Raffard from Evercore. Please go ahead. Hi, good morning.

Camille Vajrogian: This is Transjan Alvaro Umar. Thanks for taking our questions. I could firstly, for Wolfram's Syndrome phase three trial, that didn't need to be placebo controlled. And secondly, for zero one month four, are planning to give incremental data updates as it progresses? Maybe the timing between phase two Wolfram from data this fall and the phase three gets to be interim next year?

Camille Vajrogian: Right, so thank you for the questions. This is Camille. Regarding Wolfram, as we indicated out prepared remarks, we are engaging with stakeholders that include, of course, the FDA. And once our plans are finalized, we'll share those with you. Just as a reminder, later this fall, we will share data on all 12 participants through 24 weeks and additional longer term data for those individuals who have gone through week 36 and 48. So we're looking forward to those readouts as well.

Camille Vajrogian: And then regarding zero one one four, as we indicated, we are planning to initiate our multiple-less sending dose study and individuals with ALS by the end of the year. And as the study progresses, we'll be able to provide more detailed timing and types of data we'll be sharing through 2025. Thank you.

Greg Suvannavejh: Your next question comes from the line of Greg Suvannavejh from Izouho Financial Group. Please go ahead. Morning everyone. This is Charles Wayne, Alfred Greg. Thanks for taking our question. We were wondering what type of data will you present at the updated data presentation for Helios? Should we expect it to be similar to the interim readout earlier this year? Thanks. Yep. Thank you. This is Camille again. Indeed. So we do intend to provide longer term data for those individuals who about whom we reported in April of this year, as well as data through 24 weeks for all 12 participants. It's top line data, primary endpoint, and key secondary endpoints, and we look forward to sharing those details with you at the upcoming international meeting. Thank you, Graig.

Mark Goodman: Your next question comes from the line of Mark Goodman from Learing Brothers. Please go ahead. Thanks for taking the question.

Jim Freides: This is Judy on the line for Mark. Can you talk about R&D expenses going into 2025? What is your strategy to view the pipeline going forward with both internal and external assets? Thanks. Yeah. Thank you. It's Jim. Good morning. You know, I think one of the things that is happening on our R&D line right as our restructuring is occurred and as the large phoenix phase three winds down and you can find some detail on those expenses historically in our cues.

Jim Freides: That really opens up room for some of the new spending that we have going on. And you know, currently the Wolfram study is ongoing. The PSP study is starting to move up into a range where that, you know, that's going to be consistently consistent as opposed to really growing. And so that leaves us room as we move forward to spend on the 114 study and the new of exotide program. And then just overall as we outlined, we expect cash expense.

Jim Freides: Now, that's excluding non cash comp to be in the range of 30 to 40 million a quarter for both R&D and SG&A. So that's how some of the moving parts are going into 2025. Very helpful. Thanks. You're welcome. Thank you.

Joel Beatty: Your next question comes from the line of Joel Beatty from Beard.

Camille Vajrogian: Please go ahead. Hi, thanks for taking the questions for the PSP interim analysis to get data around mid 2025. Does that mean completing enrollment around the end of this year? And what gives you confidence on the trial, completing enrollment around that time frame?

Camille Vajrogian: Yes, hi Joel. This is Camille. We are enrolling quite well as I indicated in our prepared remarks. And we're tracking toward having data mid 2025. We'll give more information as we march toward that time frame.

Camille Vajrogian: Okay. And then as a follow-up, do you anticipate any more acquisitions after the recent acquisition of the exotide? Yeah, you know, also, we wouldn't, you know, we've had a process on going for some time or evaluating, you know, many assets for, you know, that, that, you know, whether they fit well into our pipeline and have the requisite, you know, scientific and clinical and commercial, you know, path forward. Today, we're very excited about the assets we, you know, have today and that's our focus, but, you know, we're always looking and I'd say we wouldn't rule out, you know, adding additional things in.

Unknown Executive: Thank you.

Unknown Executive: There are no further questions at this time.

Justin Klee: I'll turn the call back to Mr. Klee.

Justin Klee: Thank you for joining us today on today's call to discuss our second quarter, 2024 financial results. Have a great day. Thank you for joining today's call.

Unknown Executive: Please disconnect your line.

Unknown Executive: Thanks.