Q2 2024 Wave Life Sciences Ltd Earnings Call

August 8, 2024

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Operator: Good morning, and welcome to the WAVE Life Sciences second quarter 2024 financial results conference call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Rausch, Vice President, Investor Relations, and Corporate Affairs. Please go ahead.

Operator: Good morning, and welcome to the WAVE Life Sciences 2nd Quarter 2024 Financial Results Conference Call. At this time, all participants are in a listen-only mode. As a reminder, this call is being recorded and webcast. I'll now turn the call over to Kate Rausch, Vice President, Investor Relations, and Corporate Affairs. Please go ahead.

Kate Rausch: Thank you, operator. Good morning, and thank you for joining us today to discuss our recent business progress and review WAVE's second quarter 2024 financial results. Joining me today were prepared remarks from Dr. Paul Bolno, President and Chief Executive Officer, Ann Marie Lee Quichung, Chief Development Officer, and Kyle Moran, Chief Financial Officer. Eric Engelsen, Chief Scientific Officer, Chandra Vargeese, Chief Technology Officer, and Jenny Yang, SPP of Translational Medicine, will also be available for questions following the call.

Speaker Change: Thank you operator, good morning, and thank you for joining us today to discuss our recent business progress and review with second quarter 2024 financial results joining.

Kate Rausch: Joining me today with prepared remarks are Dr. Paul Bolno, President and Chief Executive Officer, Anne-Marie Lee-Kwai Chung, Chief Development Officer, and Kyle Moran, Chief Financial Officer. Eric Ingleson, Chief Scientific Officer, Chandra Vargeese, Chief Technology Officer, and Jenny Yang, SVP of Translational Medicine, will also be available for questions following the call.

Speaker Change: Joining me today with prepared remarks are Dr. Pagano, President and Chief Executive Officer, and really quite Chang Chief Development Officer, and Paul Moran, Chief Financial Officer, Eric Engel, Chief Scientific Officer, Saundra, Varghese, Chief Technology Officer, and Jerry Yang SVP of translational Medicine will also be available for questions.

Kate Rausch: The press release issued this morning is available on the investor section of our website, www.wavelifesciences.com. Before we begin, I would like to remind you that the discussions during this conference call will include forward-looking statements. These statements are subject to several risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filing. We undertake no obligation to update or revise any forward-looking statement for any reason. I'd now like to turn the call over to Paul.

During the call.

Release issued this morning is available on the investors section of our website at Www Dot wave life Sciences Dot com.

Kate Rausch: The press release issued this morning is available in the investor section of our website, www.wavelifesciences.com. Before we begin, I would like to remind you that the discussions during this conference call will include forward-looking statements. These statements are subject to several risks and uncertainties that could cause our actual results to differ materially from those described in these forward-looking statements. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings. We undertake no obligation to update or revise any forward-looking statement for any reason. I'd now like to turn the call over to Paul.

Paul Bolno: A highlight of the second quarter was the positive results from the SelectHD clinical trial for WVE-003 in Huntington's disease. And I'll begin today with some remarks on this program and the progress we've made since the announcement.

Before we begin I would like to remind you that discussions during this conference call will include forward looking statements. These statements are subject to several risks and uncertainties that could cause our actual results to differ materially from those described in these forward looking statements. The factors that could cause actual results to differ are discussed in the press release issued today and in our SEC filings.

Speaker Change: We undertake no obligation to update or revise any forward looking statement for any reason I'd now like to turn the call over to Paul.

Paul Bolno: Thank you. Good morning, and thank you all for joining us on today's call. We have made incredible progress throughout the first half of this year, both in demonstrating the continued translation of our unique novel platform in the clinic and advancing our high-impact RNA medicines pipeline across modalities. A highlight of the second quarter was the positive results from the SELECT-HD clinical trial for WVE-003 in Huntington's disease. And I'll begin today with some remarks on this program and the progress we've made since the announcement.

Paul: Thanks, Keith Good morning, and thank you all for joining us on today's call.

Paul: We have made incredible progress throughout the first half of this year both in demonstrating the continued translation of our unique novel platform in the clinic and advancing our high impact already medicine pipeline across modalities.

Paul: A highlight of the second quarter with the positive results from the select HD clinical trial for <unk> for Huntington's disease.

Speaker Change: I'll begin today with some remarks on this program and progress we've made since the announcement.

Paul Bolno: The clinical data, which we announced in June, serve as a testament to our best-in-class chemistry capabilities, where our proprietary PN and stereochemistry enabled WVE003 to achieve potent and durable mutant protein lowering while attaining exquisite specificity with wild-type preservation. This also led to a statistically significant correlation between mutant Huntington lowering and slowing of caudate atrophy, a potential clinical endpoint for accelerated approval. HD is a devastating disease affecting more than 200,000 patients across all stages of disease in the U.S. and Europe. HD is compared to having Alzheimer's disease, Parkinson's disease, and ALS combined.

Paul Bolno: The clinical data, which we announced in June, serve as a testament to our best-in-class chemistry capabilities, where our proprietary PN and Soviet chemistry enabled WVE-003 to achieve potent and durable mutant-coating lowering while attaining exquisite specificity with wild-type preservation. This also led to a statistically significant correlation between mutant Huntington lowering and slowing of caudate atrophy, a potential clinical endpoint for accelerated HD is a devastating disease affecting more than 200,000 patients across all stages of disease in the U.S. and Europe. HD is compared to having Alzheimer's disease, Parkinson's disease, and ALS combined.

The clinical data, which we announced in June serve as a testament to our best in class chemistry capabilities, where our proprietary pn and stereochemistry enabled WV 003 to achieved potent and durable protein lowering while attaining exquisite specificity with wild type preservation.

Paul: It also led to a statistically significant correlation between mutant Huntington lowering in slowing of cardiovascular being a potential clinical endpoint for accelerated approval.

HD is a devastating disease affecting more than 200000 patients across all stages of disease in the U S. Europe.

Paul: As can be compared to having all timers disease Parkinson's disease ALS combined patients are faced with extremely limited treatment options and there are no disease modifying therapies currently available.

Paul Bolno: Patients are faced with extremely limited treatment options, and there are no disease-modifying therapies currently available. WVE003 was designed to selectively knock down the mutant Huntington protein while preserving the healthy wild-type Huntington protein, which is critical to the health and function of neurons, in addition to symptomatic HD patients. As we look at the current treatment paradigm in therapies and development for DMD, there remains a significant scientific gap between the functional benefits of micro or mini dystrophin, as well as durability.

Paul Bolno: Patients are faced with extremely limited treatment options, and there are no disease-modifying therapies currently available. WVE-003 was designed to selectively knock down the mutant Huntington protein while preserving the healthy wild-type Huntington protein, which is critical to health and function. With the first ever clinical demonstration of allele selective silencing in patients, 003 is uniquely positioned to address the larger pre-syptomatic patient population. In addition to symptomatic HD patients, since announcing our SelectHD results, we have submitted our opt-in package to our partner, Takeda. If Takeda exercises this option right, our HD program, including potential additional SNPs, shifts to a 50-50 R&D and profit split. Ticata pays an opt-in payment, and WAVE is eligible for development and commercial milestones don't pay.

Speaker Change: <unk> was designed to selectively knock down the mutant Huntington protein, while preserving the healthy wild type Huntington protein, which is critical to the health and function of neurons.

Paul: With the first ever clinical demonstration of allele selective silencing in patients over three is uniquely positioned to address the larger pre symptomatic patient population.

Speaker Change: In addition to symptomatic HD patients.

Paul: Since announcing our select HD results, we have submitted our opt in package to our partner Takeda.

Speaker Change: <unk> exercised adoption rate, our HD program, including potential additional slips shift to a 50 50, R&D and profit split.

Speaker Change: Takeda pays an opt in payment and wave is eligible for development and commercial milestone payments. Our team has also initiated engagement with regulators on our clinical development path for <unk> that could support accelerated approval, we look forward to providing an update on regulatory feedback as well as an update on indicators decision by the end of the year.

Paul Bolno: Our team has also initiated engagement with regulators on a clinical development path for O03 that could support accelerated approval. We look forward to providing an update on regulatory feedback, as well as an update on Takeda's decision by the end of the year. Turning to DMD, our next expected clinical data. With WVE N531, our exon skipping candidate for patients amenable to exon 53 skipping, we are looking to achieve dystrophin expression greater than 5% with consistency across patients, which would provide a meaningful best-in-class new option. As we look at the current treatment paradigm in therapies and development for DMD, there remains a significant scientific gap between the functional benefits of micro or mini dystrophin, as well as durability.

Speaker Change: Turning to DMD, our next expected clinical data update with WV and 531 are exon skipping candidate for patients amenable to exon 53, skipping, we're looking to achieve dystrophin expression greater than 5% with consistency across patients, which would provide a meaningful best in class new option as we.

Paul: Look at the current treatment paradigm and therapies in development for DMD. There remains a significant scientific gap in the functional benefit of micro or mini dystrophin as well as durability.

Paul Bolno: And when paired with the unknown safety risks associated with AAV gene therapies, there's an urgent need to deliver better therapeutic options to patients. Importantly, these tissue concentration levels are approximately 20 times higher than the top levels reported by ExxonSkipping Technologies leveraging muscle delivery conjugates in DMD patients. Despite low and inconsistent dystrophin data, exon skipping therapeutics are standard of care for DMD and recorded approximately $1 billion in sales last year, primarily in the US, for therapeutics that address approximately 29% of the population.

Paul Bolno: And when paired with the unknown safety risks associated with AAV gene therapies, there's an urgent need to deliver better therapeutic options to patients. As a reminder, in our Part A study of N531, following just three doses administered every other week, we achieved industry-leading exon skipping and unprecedented muscle concentration. Importantly, these tissue concentration levels are approximately 20 times higher than the top levels reported by ExxonSkipping Technologies leveraging muscle delivery conjugates in

Paul: When paired with unknown safety risks associated with AAV gene therapy, there is an urgent need to deliver better therapeutic option to patients.

Speaker Change: As a reminder, in our part a study of <unk> 531, following just III doses administered every other week, we achieved industry, leading exon skipping an unprecedented muscle concentrations importantly, these tissue concentration levels are approximately 20 times higher than the cap levels reported by exon skipping technology leveraging muscle.

Speaker Change: Deliberate conjugate in DMD patients.

Paul Bolno: Despite low and inconsistent dystrophin data, exome skipping therapeutics are standard of care for DMD and recorded approximately $1 billion in sales last year, primarily in the US, for therapeutics that address approximately 29% of the population. Positive data with N531 would unlock the totality of our Exxon skipping programs, which would enable us to address up to 40% of the population, representing an opportunity to provide differentiated, Moving to RNA editing, WVE 006, our first-in-class galnec RNA editing candidate for AATD, aims to correct the AATD-causing mutations to increase circulating levels of wild site or MAAAT protein and reduce mutant VA There are an estimated 200,000 homozygous PIZZ patients in the U.S. and Europe.

Paul: Despite low and inconsistent dystrophin data exon skipping therapeutics are standard of care for DMD and recorded approximately $1 billion.

Paul: Last year, primarily in the U S for therapeutics that address approximately 29% of the population.

Paul Bolno: Positive data with N531 would unlock the totality of our Exxon skipping programs, which would enable us to address up to 40% of the population, representing an opportunity to provide differentiated therapeutic portfolios to patients. Moving to RNA editing, WPE006, our first-in-class GalNeck RNA editing candidate for AADD, aims to correct the AADD-causing mutation to increase circulating levels of wild type, or M-AAT protein, and reduce mutant Z-AAT protein aggregation in the liver, thereby treating patients with lung manifestations, liver manifestations, or both. There are an estimated 200,000 homozygous PIZZ patients in the U.S. and Europe.

Paul: Positive data with <unk> hundred one would unlock the totality of our exon skipping programs, which would enable us to address up to 40% of the population representing an opportunity to provide differentiated therapeutic portfolio of the patients.

Paul: Moving to RNA editing <unk> 006, our first in class <unk> RNA editing candidate for ACD aimed to correct. The AED, causing mutation to increase circulating levels of wild type or M protein and reduce mutant <unk>.

Paul: Protein aggregation in the liver, thereby treating patients with lung manifestations liver manifestations or both.

Paul: There are an estimated 200000 homozygous <unk> patients in the U S and Europe.

Paul Bolno: Treatment today is limited to weekly IV augmentation therapy for lung disease, while no therapies address AATD liver disease. siRNA treatments in development are confined to treating only liver disease and could exacerbate lung injury. By editing RNA, 006 differs from DNA editing technologies, which rely on hyperactive, exogenously delivered artificial enzymes that can result in irreversible collateral bifederas and 006 contains a GalNet conjugate, a highly specific and elegant delivery tool that is well validated with multiple approved silencing therapeutics on the market.

Paul Bolno: Treatment today is limited to weekly IV augmentation therapy for lung disease, while no therapies address AATD liver disease. siRNA treatments in development are confined to treating only liver disease and could exacerbate lung injury. By editing RNA, 006 differs from DNA editing technologies, which rely on hyperactive, exogenously delivered artificial enzymes that can result in irreversible collateral bifederas and delts. 006 contains a GalNet conjugate, a highly specific and elegant delivery tool that is well validated with multiple approved silencing therapeutics on the market.

Paul: Treatment today is limited to weekly IV augmentation therapy for lung disease, while no therapy, the drop HDD liver disease.

Speaker Change: Sorry, RNA treatments in development are confined to treating only liver disease and could exacerbate lung injury.

Speaker Change: By editing RNA <unk> differs from DNA editing technologies, which rely on hyperactive exogenously delivered artificial enzymes that can result in the irreversible collateral by better themselves.

Speaker Change: There are there are six contains a <unk> conjugate a highly specific and elegant delivery tool that is well validated with multiple approved silencing therapeutics on the market.

Paul Bolno: GALNEC enables the ease and convenience of subcutaneous dosing, effective and selective delivery to hepatocytes, as well as a high degree of confidence in preclinical to clinical translation since the entire dose delivered is reliably sent to the target organ, unlike lipid nanoparticles. In preclinical studies, our proprietary chemistry has enabled 006 to effectively recruit endogenous ADAR enzymes and achieve potent and durable editing. We've shown AET protein levels that exceed the threshold for both MZ and healthy MM populations and have confirmed this functionality with neutrophil elastase inhibition.

Paul Bolno: GalNet enables the ease and convenience of subcutaneous dosing, effective and selective delivery to hepatocytes, as well as a high degree of confidence in preclinical to clinical translation since the entire dose delivered is reliably sent to the target organ, unlike lipid nanoparticles. In preclinical studies, our proprietary chemistry has enabled 006 to effectively recruit endogenous ADAR enzymes and achieve potent and durable editing. We've shown AET protein levels that exceed the threshold for both MZ and healthy MM populations and have confirmed this functionality with neutrophil elastase inhibition.

Speaker Change: <unk> enables the ease and convenience of subcutaneous dosing effective and selective delivery to our site as well as a high degree of confidence of preclinical to clinical translation since the entire dose delivered as reliably to the target organ unlike lipid nanoparticles.

Speaker Change: In preclinical studies, our proprietary chemistry has enabled <unk> to effectively recruit endogenous adar enzymes and achieved potent and durable editing.

Paul: We've shown AEP protein levels that exceed the threshold for both <unk> and healthy population and have confirmed that functionality with neutrophil elastase inhibition assay.

Paul Bolno: Additionally, OLO6 decreased globular inflammation, reduced liver aggregates, and prevented increases in mitosis, indicating improved hepatocyte survival in preclinical models. These data would not only meaningfully derisk our ATD program, but would also serve as proof of concept for a growing pipeline of wholly owned editing candidates, which are designed to either correct or upregulate mRNA in both rare and prevalent diseases. WVE-006 is part of our ongoing collaboration with GSK, and development and commercialization responsibilities transfer to GSK at their sole cost after we complete our Restoration II study. Under the collaboration, there are $525 million in total milestones related to OO6, and WAVE is eligible for double-digit tiered royalties as a percentage of net sales up to the high team.

Paul Bolno: Additionally, OLO6 decreased globular inflammation, reduced liver aggregates, and prevented increases in mitoses, indicating improved hepatocyte survival in preclinical models. Dosing and our restoration to trial initiated in the third quarter, and we expect to deliver proof of mechanism data in the fourth quarter. These data would not only meaningfully de-risk our ATD program but would also serve as proof of concept for a growing pipeline of wholly owned editing candidates, which are designed to either correct or upregulate mRNA in both rare and prevalent diseases.

Paul: Additionally, <unk> decreased globular inflammation reduce liver aggregates and prevented increases in mitosis, indicating improved survival.

Paul: Survival in preclinical models.

Speaker Change: Dosing in a restoration to trial initiated in the third quarter and we expect to deliver proof of mechanism data in the fourth quarter of this year. These data would not only meaningfully derisk. Our HDD program, but would also serve as proof of concept for our growing pipeline of wholly owned editing candidates, which are designed to either correct or up regulate mrna in both rare.

Paul: <unk> and prevalent diseases.

Paul Bolno: WVE-006 is part of our ongoing collaboration with GSK, and development and commercialization responsibilities transfer to GSK at their sole cost after we complete our Restoration II study. Under the collaboration, there are $525 million in total milestones related to OO6, and WAVE is eligible for double-digit tiered royalties as a percentage of net sales up to the high team.

Paul: <unk> is part of our ongoing collaboration with GSK in development and commercialization responsibilities transfer to GSK at their sow cost after we complete our restoration to study.

Paul: Under the collaboration there are $525 million in total milestones related to our <unk> and wave is eligible for double digit tiered royalties as a percentage of net sales up to the high teens.

Paul Bolno: I'll next give an update on our GalNeck siRNA inhibiting program, which is now called WVE007. Obesity is a public health epidemic impacting approximately 175 million adults in the U.S. and Europe. Increasingly, it is being recognized that reduction of weight and fat mass is linked to improved health outcomes, including reduced risk of many diseases. With 007, we are advancing a completely novel approach to aid weight loss.

Paul Bolno: On Next, I will give an update on our GALNEC SIRNA and HIVENE program, which is now called WVE-007. Obesity is a public health epidemic impacting approximately 175 million adults in the U.S. and Europe. Increasingly, it is being recognized that reduction of weight and fat mass is linked to improved health outcomes, including reduced risk of many diseases. With 007, we are advancing a completely novel approach to weight loss. Enabled by our best-in-class siRNA technology, we believe this molecule has the potential to unlock the next frontier in obesity treatment and address millions impacted by the disease. This program is supported by Human Genetics.

Paul: And let's give an update on our <unk> inhibitor program, which is now called <unk> seven.

Paul: Obesity is a public health epidemic impacting approximately 175 million adults in the U S and Europe increase.

Paul: Increasingly it is being recognized that reduction of weight and fat mass are linked to improved health outcomes, including reduced risks of many diseases.

Paul: With <unk>, we are advancing a completely novel approach to weight loss enabled by our best in class <unk> RNA technology. We believe this molecule has the potential to unlock the next frontier in obesity treatment and address million impacted by the disease.

Paul Bolno: Enabled by our best-in-class siRNA technology, we believe this molecule has the potential to unlock the next frontier in obesity treatment and address millions impacted by the disease. This program is supported by Human Genetics. Inhibin-E loss-of-function heterozygous carriers have a favorable cardiometabolic profile, including reduced abdominal obesity and reduced odds of type 2 diabetes and coronary arteries. One could think of this target as the PCSK9 of obesity Inhibin E mRNA is expressed in the liver, and its corresponding receptor is on adipocytes, which control fat storage.

Paul: This program is supported by human genetics, and hip any loss of function heterozygous carriers have a favorable cardio metabolic profile, including reduced abdominal obesity and reduce odds of type two diabetes and coronary artery disease.

Paul Bolno: Inhibin-E loss-of-function heterozygous carriers have a favorable cardiometabolic profile, including reduced abdominal obesity and reduced odds of type 2 diabetes and coronary artery disease. One can think of this target as the PCSK9 of obesity. Inhibin E mRNA is expressed in the liver, with its corresponding receptor on adipocytes, which control fat storage.

Paul: One can think of the target as the PCF canine of obesity.

Paul: And have any mrna is expressed in the liver with its corresponding receptor on adequate sites, which control fat storage.

Paul Bolno: We designed 007 to silence the inhibin-E gene transcript, thereby recapitulating the cardiometabolic protection of carriers of inhibin-E loss of function mutations. However, while GLP-1s have become the current standard of care for weight loss, their impact is often limited by frequent dosing, loss of muscle mass, poor tolerability, and high discontinuation rates. We see three key areas of opportunity to address obesity with 007; as a frontline monotherapy in combination with GLP-1s for further improvement in weight loss or to reduce the doses of GLP-1s or as a maintenance therapy following cessation of GLP-1s therapy.

Paul Bolno: We designed 007 to silence the inhibin-E gene transcript, thereby recapitulating the cardiometabolic protection of carriers of inhibin-E loss-of-function mutations. While GLP-1s have become the current standard of care for weight loss, their impact is often limited by frequent dosing, loss of muscle mass, poor tolerability, and high discontinuation rates. Thus, we see three key areas of opportunity to address obesity with 00 As a frontline monotherapy, in combination with GLP-1s, or further improvement of weight loss, or to reduce the doses of GLP-1s, or as a maintenance therapy, following cessation of GLP-1s, First, our inhibitory E siRNA, we have demonstrated highly potent and durable silencing with an ED50 of less than one milligram per kilogram, supporting dosing intervals of just once or twice a

Paul: We designed <unk> to filing the <unk> gene transcript, thereby recapitulated, the cardio metabolic protection of carriers of inhibiting <unk> loss of function mutations.

Speaker Change: While <unk> have become the current standard of care for weight loss. Their impact is often limited by frequent dosing lots of muscle mass or tolerability and high discontinuation rates.

Paul: We see three key areas of opportunity to address obesity with double 11.

Paul: As a frontline monotherapy in.

Paul: In combination with <unk> or further improvement of weight loss or to reduce the doses of <unk> one four as a maintenance therapy following cessation of GOP ones.

Paul Bolno: First, with our inhibin E siRNA, we have demonstrated highly potent and durable silencing with an ED50 of less than one milligram per kilogram, supporting dosing intervals of just once or twice a year. Preclinically, our inhibiny siRNA also led to weight loss similar to semaglutide and reductions in fat mass with a preferential effect on visceral fat, all with no loss of muscle. As a reminder, the mechanism of inhibin-E silencing is distinct from GLP-1s, opening an exciting opportunity for use in combination following weight loss induction.

Speaker Change: First our inhibitor <unk> SA RNA, we've demonstrated highly potent and durable silencing with an <unk> of less than one milligram per kilogram supporting dosing intervals of just once or twice a year.

Paul Bolno: Preclinically, our inhibiny siRNA also led to weight loss similar to semibutyl and reductions in fat mass with a preferential effect on visceral fat, all with no loss of muscle. As a reminder, the mechanism of inhibin-E silencing is distinct from GLP-1s, opening an exciting opportunity for use in combination following weight loss induction. New results from an ongoing study underscore the potential for this use. Specifically, when administered in combination with semaglutide, a single dose of our inhibitor-E GalNeck siRNA doubled the weight loss observed with semaglutide alone, and this effect was sustained throughout the duration of the study. As we described previously, treatment with our Antibany S.I.R.A. upon cessation of semi-glutenants also curtails expected rebound weight gain.

Paul: Pre clinically are inhibiting S. Irna also lead to weight loss similar to Semgroup and reductions in fat mass with a preferential effect on visceral fat all with no loss of muscle mass.

Paul: As a reminder, the mechanism of inhibiting silencing is distinct from GOP, one opening an exciting opportunity for using combination following weight loss reduction.

Paul Bolno: New results from an ongoing study underscore the potential for this use. Specifically, when administered in combination with semaglutide, a single dose of our inhibin-E GalNeck sRNA doubled the weight loss observed with semaglutide alone, and this effect was sustained throughout the duration of the study. As we described previously, treatment with our inhibin-E siRNA upon cessation of semiglutide also curtailed expected rebound weight gain. We are very excited about the broad potential of this program in obesity and look forward to sharing more data at our annual R&D day. Looking ahead, we believe we can demonstrate clinical proof of concept with just a single dose of our inhibin E sRNA in a study of healthy overweight volunteers.

Paul: New results from an ongoing study underscore the potential for this use specifically when administered in combination with <unk> a single dose of our inhibitor <unk> doubled the weight loss observed with <unk> alone and this effect was sustained throughout the duration of the study.

Paul: As we described previously treatment with our inhibiting S. Irna upon cessation of Semgroup title also curtailed expected rebound weight gain we are very excited about the broad potential of this program in obesity and look forward to sharing more data at our annual R&D day.

Paul: Looking ahead, we believe we can demonstrate clinical proof of concept with just a single dose of our inhibitor <unk> in a study of healthy overweight volunteers, we remain on track to file a cta for <unk> 7 million as early as the end of year and initiate a clinical trial in the first quarter of next year.

Anne-Marie Lee-Kwai Chung: We remain on track to file a CTA for 007 as early as the end of the year and initiate a clinical trial in the first quarter of next year. We have a vast opportunity ahead of us to deliver differentiated therapies to millions of patients in areas of high unmet need. We are poised to deliver on multiple important catalysts in the second half of the year, which would unlock and de-risk additional programs. Additionally, at our annual R&D Day this fall, we expect to give an update on our emerging pipeline, including our wholly owned RNA editing program. Now, to discuss our clinical programs in more detail, I'll turn the call over to Anne-Marie. Thank you, Paul.

Paul Bolno: We have a vast opportunity ahead of us to deliver differentiated therapies to millions of patients in areas of high need. We are poised to deliver on multiple important catalysts in the second half of the year, which would unlock and de-risk additional programs. Additionally, at our annual R&D Day this fall, we expect to give an update on our emerging pipeline, including our wholly owned RNA editing program. Now, to discuss our clinical programs in more detail, I'll turn the call over to Anne-Marie. Thank you, Paul.

Paul: We have a vast opportunity ahead of us to deliver differentiated therapy to millions of patients in areas of high unmet need we are poised to deliver a multiple important catalysts in the second half of the year, which would unlock and derisk additional programs. Additionally, at our annual R&D Davis fall, we expect to give an update.

Paul: On our emerging pipeline, including our wholly owned RNA editing programs now.

Speaker Change: Now to discuss our clinical programs in more detail I'll turn the call over to Anne Marie <unk>.

Ann Marie Lee Quichung: Thank you, Paul. It's certainly been a busy year thus far, and I'm excited to share an update on our clinical program. I'll begin with H.D., and I'll read some clinical results. I'll read some clinical results, I'll read some clinical results, I'll read some clinical results. Our Select HD clinical trial was designed to demonstrate safety and tolerability, PK and mutant Huntington silencing over 30%, with healthy wild-type Huntington preservation with multiple doses of WAVE-003. In this multi-dose cohort, where we tested 30 milligrams dosed intratically every eight weeks, we saw excellent translation of our preclinical modeling with potent and durable mutant hunting and reductions of up to 46 percent plus preservation of wild-type hunting. Multidosing was generally safe and well-tolerated, with mild to moderate adverse events and no serious adverse events.

Anne-Marie Lee-Kwai Chung: Thank you, Paul. It's certainly been a busy year thus far, and I'm excited to share an update on our clinical program. I'll begin with HD and our recent clinical results. Our SelectHD clinical trial was designed to demonstrate safety and tolerability, PK, and mutant huntington silencing over 30%, with healthy wild-type huntington preservation with multiple doses of WAVE-003. In this multidose cohort, where we tested 30 milligrams dosed intrathecally every eight weeks, we saw excellent translation of our preclinical modeling, with potent and durable mutant Huntington reductions of up to 46 percent, plus preservation of wild-type Huntington. Multidosing was generally safe and well-tolerated, with mild to moderate adverse events and no serious adverse events.

Anne Marie: Thank you Paul has certainly been a busy year, thus far and I'm excited to share an update on our clinical programs.

Anne-Marie Lee-Kwai Chung: Further, this cohort showed a statistically significant correlation between mutant Huntington reductions and slowing of chordate atrophy, a known imaging biomarker that is predictive of clinical outcomes. This was also the first ever demonstration of such a correlation in the clinic, reinforcing the potential benefits of allele-selective mutant Huntington-lowering therapy. Since sharing these data, we have been connecting with KOLs and patient groups who are excited about the Mutip Huntington knockdown and, most of all, the first potential therapeutic option that preserves healthy wild-type hunting.

Anne Marie: I'll begin with HD and our recent clinical results also that's HTS clinical trial was designed to demonstrate safety and Tolerability PK and mutant Huntington financing over 30% with healthy Wild type Huntington preservation with multiple doses of <unk> III.

Anne Marie: And this multi dose cohort, where we tested that two milligrams dosed intravenously every eight weeks, we saw excellent translation of preclinical modeling with potent and durable mutant Huntington reductions of up to 46% plus preservation of wild type Huntington.

Anne Marie: Multi dosing was generally safe and well tolerated with mild to moderate adverse events and no serious adverse events.

Ann Marie Lee Quichung: Further, this cohort showed a statistically significant correlation between mutant Huntington reductions and slowing of chordate atrophy, a known imaging biomarker that is predictive of clinical outcomes. This was also the first ever demonstration of such a correlation in the clinic, reinforcing the potential benefits of allele-selective mutant Huntington-lowering therapy. Since sharing these data, we have been connecting with KOLs and patient groups who are excited about the Mutip Huntington knockdown and, most of all, the first potential therapeutic option that preserves healthy wild-type hunting.

Anne Marie: So that this cohort showed a statistically significant correlation between mutant Huntington reductions and slowing of quota at USA and then imaging biomarker that is predictive of clinical outcomes.

Anne Marie: This was also the first ever demonstration of such a correlation in the clinic reinforcing the potential benefit of allele selective mission Huntington Larry.

Anne Marie: Since sharing this data we have been connecting with Kols and patient groups, who are excited about the mutant Huntington knockdown and most of all the SaaS potential therapeutic option that preserves healthy wild type Huntington.

Ann Marie Lee Quichung: We'll be sharing these previously announced results with the Board of HD community at the annual meeting of the European Huntington's Disease Network, or EHDN, taking place on the 12th and 14th of September in Strasbourg, France. One thing that's been clear to me in my conversations with HD patients, families, and physicians who have experienced challenges with large and long placebo-controlled studies is that there is a pressing need for novel biomarkers to enable a more efficient path to registration.

Anne-Marie Lee-Kwai Chung: We'll be sharing these previously announced results with the broader HD community at the annual meeting of the European Huntington's Disease Network, or EHDN, taking place on the 12th and 14th of September in Strasbourg, France. One thing that's been clear to me in my conversations with HD patients, families, and physicians who have experienced challenges with large and long placebo-controlled studies is that there is a pressing need for novel biomarkers to enable a more efficient path to registration.

Anne Marie: We will be sharing these previously announced results with the board of H D community at the annual meeting of the European Huntington's disease, <unk> HTS, taking place on the 12 to 14 to September and stressful fronts.

Speaker Change: One thing Thats been kits may in my conversations with H D patients families and physicians, who have experienced challenges with large and long placebo controlled studies. There was a question need for novel Biomarkers to enable a more efficient path to registration.

Ann Marie Lee Quichung: For accelerated approval, we know regulators are looking for biomarkers with biological relevance for the disease in question. Chordate is one of the primary areas where HD manifests in the brain. At the point of clinical diagnosis, patients have marked brain atrophy compared to controls, typically having lost more than 40% of their chordate at the time of first symptom onset and clinical diagnosis.

Anne-Marie Lee-Kwai Chung: For accelerated approval, we know regulators are looking for biomarkers with biological relevance for the disease in question. Chordate is one of the primary areas where HD manifests in the brain. At the point of clinical diagnosis, patients have marked brain atrophy compared to controls, typically having lost more than 40% of their chordate at the time of first symptom onset and clinical diagnosis.

Anne Marie: For accelerated approval, we know regulators are looking for biomarkers with biological relevance for the disease in question.

Anne Marie: Good day is one of the primary areas, where H D manifest in the brain.

Speaker Change: At the point of clinical diagnosis patients half of market, Brian ACH bank compared to controls typically haven't lost more than 40% of that call date at the time, the first symptom onset and clinical diagnosis.

Ann Marie Lee Quichung: Since loss of caudate manifests many years before diagnosis and continues to be lost at a rate of about 2-4% a year, there are clear correlations between caudate loss and clinical outcomes, giving it the potential to be used to design a clinical development path to accelerated approval. Just last month, we attended the Critical Path Institute's Critical Risk Meeting, where the consortium and FDA discussed the urgency of disease-modifying therapies in Huntington's disease and ways to enable more efficient trial designs, including the use of endpoints reasonably likely to predict clinical outcomes.

Anne-Marie Lee-Kwai Chung: Since loss of caudate manifests many years before diagnosis and continues to be lost at a rate of about 2-4% a year, there are clear correlations between caudate loss and clinical outcomes, giving it the potential to be used to design a clinical development path to accelerated approval. Just last month, we attended the Critical Path Institute's Critical Risk Meeting, where the consortium and FDA discussed the urgency of disease-modifying therapies in Huntington's disease and ways to enable more efficient trial designs, including the use of endpoints reasonably likely to predict clinical outcomes.

Anne Marie: Since last quarter manifest many years before diagnosis and continues to be lost as the rates of about 2% to 4%.

Anne Marie: Correlations between quote at loss on clinical outcomes, giving it the potential to be used to design the clinical development path to accelerated approval.

Speaker Change: Just last month, we attended the critical path Institute critical risks meeting, where the consortium and FBI engaged on the urgency for disease modifying therapies in huntington's disease and ways to enable more efficient trial designs, including the use of endpoints reasonably likely to predict clinical outcomes.

Ann Marie Lee Quichung: Given our focus on caudate atrophy, we are pleased to announce that we have joined the Huntington Disease Image Harmonization Consortium and are working in conjunction with CHDI and ICHSECO to advance the data sets needed to support establishment of caudate atrophy as an endpoint reasonably likely to predict clinical outcomes.

Anne-Marie Lee-Kwai Chung: Given our focus on caudate atrophy, we are pleased to announce that we have joined the Huntington's Disease Image Harmonization Consortium and are working in conjunction with CHDI and ICSICO to advance the data sets needed to support establishment of caudate atrophy as an end point reasonably likely to predict clinical outcomes.

Anne Marie: Given our focus on quota.

Anne Marie: We are pleased to announce that we have joined the Huntington's disease image harmonization consortium and are working in conjunction with CACI and execute it to advance the datasets needed to support establishment of Cotai atrophy, as an endpoint reasonably likely to predict clinical outcomes.

Ann Marie Lee Quichung: In tandem, we've engaged regulators on our clinical development pathway, including the potential for accelerated approval, and expect feedback by year end. The SelectHD trial is now complete, and all future steps will be informed by this regulatory feedback. In addition, as Paul mentioned, we've submitted our opt-in package to Takeda. We'd like to sincerely thank the patients, families, and sites who participated in SelectHD. None of this research would be possible without

Anne-Marie Lee-Kwai Chung: In tandem, we've engaged regulators on our clinical development pathway, including the potential for accelerated approval, and expect feedback by year end. The SelectHD trial is now complete, and all future steps will be informed by this regulatory feedback. In addition, as Paul mentioned, we've submitted our opt-in package to Takeda. We'd like to sincerely thank the patients, families, and sites who participated in SelectHD. None of this research would be possible without

Anne Marie: In tandem we've engaged regulators on our clinical development pathway, including the potential for accelerated approval and expect feedback by yearend.

Anne Marie: Select H D trial is now complete and all future steps will be informed by this regulatory feedback.

Anne Marie: In addition, as Paul mentioned, we have submitted our opt in package to Takeda.

Speaker Change: I'd like to sincerely. Thank the patients families and sites, who participated in select tasty. None of this research will be possible without them.

Ann Marie Lee Quichung: Turning to DMD, we are advancing our open-label Forward 53 trial of WAVE N531 for boys with exon 53 amenable DMD. We are on track to deliver 24-week distribution data later this year. The preclinical and clinical data we've observed thus far with WAVE N531 bolster our confidence and excitement to deliver a potential transformative new therapeutic option for patients. In Part A of our clinical trial, N531 demonstrated industry-leading mean 53% exon skipping, which was driven by muscle tissue concentrations of 42,000 nanograms per gram, which is far above what other exon skipping companies have reported.

Anne-Marie Lee-Kwai Chung: Turning to DMD, we are advancing our open-label Forward 53 trial of WAVE N531 for boys with exon 53 amenable DMD. We are on track to deliver 24-week distribution data later this month. The preclinical and clinical data we've observed thus far with WAVE N531 bolster our confidence and excitement to deliver a potential transformative new therapeutic option for patients. In Part A of our clinical trial, N531 demonstrated industry-leading mean 53% exon skipping, which was driven by muscle tissue concentrations of 42,000 nanograms per gram, which is far above what other exon skipping companies have reported.

Anne Marie: Turning to DMD.

Anne Marie: We are advancing our open label $4 53 trial of wave advisory one for boys with exon 53 amenable Dnb.

Ann Marie Lee Quichung: Also, in Part A, we observed clinical evidence of myogenic stem cell or satellite cell uptake of N531. This is particularly notable, as myogenic stem cells are the progenitor cells for new myoblasts, and we are not aware of any other clinical data for Exxon skippers or gene therapy that has been able to demonstrate myogenic stem cell. [inaudible] Preclinically, we've shown N531 concentrations in the heart and diaphragm exceed that of skeletal muscle, which could speak to the promise of addressing what remains a huge unmet need in DMD, respiratory and cardiac function. As a reminder, in addition to having a safe and tolerable profile, we are focused on what we believe will be the key to success for next-generation exon skippers

Anne-Marie Lee-Kwai Chung: Also, in Part A, we observed clinical evidence of myogenic stem cell or satellite cell uptake of N531. This is particularly notable as myogenic stem cells are the progenitor cells for new myoblasts, and we are not aware of any other clinical data for exon skippers or gene therapy that have been able to demonstrate myogenic stem cell uptake. Preclinically, we've shown N531 concentrations in the heart and diaphragm exceed that of skeletal muscle, which could speak to the promise of addressing what remains a huge unmet need in DMD, respiratory and cardiac function. As a reminder, in addition to having a safe and tolerable profile, we are focused on what we believe will be the key to success for next-generation exon skippers.

Anne Marie: We are on track to deliver 24 week dystrophin data later this quarter.

Anne Marie: The preclinical and clinical data, we've observed thus far with <unk> bolster our confidence and excitement to deliver a potential transformative new therapeutic option for patients.

Anne Marie: In pace of our clinical trials at trial, and 531 demonstrated industry, leading 53% excellent skipping, which was driven by muscle tissue concentrations of 42000 nanograms per Gram, which is far revival of exon skipping companies have reported.

Anne Marie: Also in pace, we observe clinical evidence of myogenic stem cell or satellite cell uptake of advisory was this.

Speaker Change: This is particularly notable as monogenic stem cells are the progenitor cells. When you my boss and we are not aware of any other clinical data for exon skip those all gene therapy, but have been able to demonstrate myogenic stem cell uptake.

Anne Marie: Pre clinically we have shown in slide 31 concentrations and Houghton diaphragm exceed that of skeletal muscle, which could speak to the promise of addressing what remains a huge unmet need in DMD respiratory and cardiac function.

Speaker Change: As a reminder, in addition to having a safe and tolerable profile. We are focused on what we believe will be the key for success for next generation exon skippers. Firstly of course is increasing the quantity of dystrophin available to provide a better life for him profile of greater than 5%, which would exceed that.

Anne-Marie Lee-Kwai Chung: Firstly, of course, is increasing the quantity of dystrophin available to provide a Becker-like dystrophin profile of greater than 5%, which would exceed the current standard of care. Secondly, delivering high-quality functional dystrophin through exon skipping, which is distributed and produced through exon skipping includes important regions that are absent from mini or micro distributions. Lastly, consistency of response.

Ann Marie Lee Quichung: Firstly, of course, is increasing the quantity of dystrophin available to provide a Becker-like dystrophin profile of greater than 5%, which would exceed the current standard of care. Secondly, delivering high-quality functional dystrophin through exon skipping, which is distributed and produced through exon skipping includes important regions that are absent from mini or micro distributions. Lastly, consistency of response.

Anne Marie: Current standard of care.

Anne Marie: Secondly, delivering high quality functional dystrophin exon skipping.

Anne Marie: Just to help produce the exon skipping increase importantly, gents, but absent from mini or micro dystrophin lastly.

Ann Marie Lee Quichung: We know prior therapies have provided highly variable and inadequate responses as a patient. Despite there being approved therapies in the market, when we speak to KOLs and patients, we hear a need for more and better treatment options about the treatment options available. Coupled with extending dosing intervals to once or twice a month, N531 could provide meaningful benefit to patients and their families currently needing weekly infusions. We are well poised to provide a meaningful new therapeutic option for the treatment of DMD.

Anne-Marie Lee-Kwai Chung: We know prior therapies have provided highly variable and inadequate responses in patients. Despite there being approved therapies in the market, when we speak to KOLs and patients, we hear a need for more and better treatment options about the treatment options available. Coupled with extending dosing intervals to once or twice a month, N531 could provide meaningful benefit to patients and their families currently needing weekly infusions. We are well poised to provide a meaningful new therapeutic option for the treatment of DMD.

Anne Marie: Lastly, consistency of response, we have price rfps have provided highly variable and inadequate response at the patient level.

Anne Marie: Despite that being approved therapies in the market when we speak to Kols on patients, we have a need for more and better treatment options.

Anne Marie: About the treatment options available.

Anne Marie: Coupled with extending dosing intervals to once or twice a month and 531 could provide meaningful benefit to patients and their families. Currently meeting weekly infusion.

Anne Marie: We are well poised to provide a meaningful therapeutic option for the treatment of DMD.

Ann Marie Lee Quichung: If positive, Distrofin data would support our plans to file for accelerated approval of N531 in the U.S. and would accelerate our clinical development plans to build a multi-Exon DMD franchise beyond Exon 53. We've generated data on compounds that would all together address up to 40% of the DMD, And importantly, these programs continue to demonstrate skipping and protein restoration in pre-clinical studies, but on a par with or exceeds With WAVE 006, we are rapidly advancing our restoration clinical program for AATD, the first RNA editing program in the clinic.

Anne-Marie Lee-Kwai Chung: If positive, Distrofin data would support our plans to file for accelerated approval of N531 in the U.S. and would accelerate our clinical development plans to build a multi-Exon DMD franchise beyond Exon 53. We've generated data on compounds that would all together address up to 40% of the DMD, And importantly, these programs continue to demonstrate skipping and protein restoration in preclinical studies that's on a par with or exceeds With WAVE 006, we are rapidly advancing our restoration clinical program for AATD, the first RNA editing program in the clinic.

Anne Marie: If positive dystrophin data with support our plans to file for accelerated approval of AB 531 in the U S and would accelerate our clinical development plans to build a multi exxon DMD franchise beyond exon 53.

Anne-Marie Lee-Kwai Chung: We have generated data on compounds that would all together address up to 40% of the DMD patients.

Anne Marie: Fortunately these programs continued to demonstrate skipping and protein restoration in preclinical studies.

Anne Marie: With or exceeds <unk> 31.

Anne-Marie Lee-Kwai Chung: With <unk>, we are rapidly advancing our restoration clinical program for AIG TD. The first RNA editing program in the clinic.

Ann Marie Lee Quichung: This clinical program is comprised of Restoration 1, a dose escalation study in healthy volunteers, and Restoration 2, a Phase 1b-2a open-label study with single and multiple ascending dose portions that's designed to evaluate the safety, controllability, pharmacodynamics, and pharmacokinetics of 0.6 and patients with AATD who have the homozygous PISUZ mutate. Restoration 1 continues to dose escalate, Utilising our pharmacokinetic data from healthy volunteers, as well as our robust pre-clinical data, we identified a dose level expected to engage targets.

Anne-Marie Lee-Kwai Chung: This clinical program is comprised of Restoration 1, a dose escalation study in healthy volunteers, and Restoration 2, a Phase 1b-2a open-label study with single and multiple ascending dose portions that's designed to evaluate the safety, tolerability, pharmacodynamics, and pharmacokinetics of 006 in patients with AATD who have the homozygous PIZZ mutation. Restoration 1 continues to dose escalate, and Utilising our pharmacokinetic data from healthy volunteers, as well as our robust preclinical data, we identified a dose level expected to engage targets.

Anne-Marie Lee-Kwai Chung: This clinical program is comprised of frustration one a dose escalation study in healthy volunteers and restoration to a phase <unk> open label study with single and multiple ascending dose portions that's designed to evaluate the safety Tolerability pharmacogenomics and pharmacokinetics of <unk> six.

Speaker Change: <unk> with ITD have homozygous TICC mutation.

Anne-Marie Lee-Kwai Chung: Restoration, one continues to dose escalate and pharmacokinetic data are translating as expected for a gallon that conjugated oligonucleotides.

Anne-Marie Lee-Kwai Chung: <unk>, all pharmacokinetic data from healthy volunteers as well as outright robust preclinical data, we identify the dose level expected to engage target.

Ann Marie Lee Quichung: In the third quarter of 2024, we will commence dosing in AATD patients in the first single dose cohort in restoration. Throughout the dose cohort, we will be taking multiple assessments to measure the potential presence of wild-type healthy MAAT protein in the serum. As a reminder, ZZ patients do not produce any MAAT protein, so detection of MAAT protein would be the first ever clinical demonstration of RNA editing in humans. The trial is progressing, and we expect to announce proof of mechanism in the fourth quarter of 2020.

Anne-Marie Lee-Kwai Chung: In the third quarter of 2024, we will commence dosing in AATD patients in the first single dose cohort in restoration. Throughout the dose cohort, we will be taking multiple assessments to measure the potential presence of wild-type healthy MAAT protein in the serum. As a reminder, ZZ patients do not produce any MAAT protein, so detection of MAAT protein would be the first ever clinical demonstration of RNA editing in humans. The trial is progressing, and we expect to announce proof of mechanism in the fourth quarter of 2021.

Anne Marie: In the third quarter of 2024, we commenced dosing in <unk> patients.

Anne-Marie Lee-Kwai Chung: Patients in the first single dose cohort in restoration too.

Anne-Marie Lee-Kwai Chung: Throughout dose cohorts, we will be taking multiple assessments to measure the potential questions a wild type healthy MAA protein in the serum.

Anne-Marie Lee-Kwai Chung: As a reminder, Z patients do not produce any MAA protein. So detection of MAA protein would be the first ever clinical demonstration of RNA editing in humans.

Anne-Marie Lee-Kwai Chung: The trial is progressing and we expect to announce proof of mechanism in the fourth quarter of 2024.

Ann Marie Lee Quichung: Beyond that, we have the flexibility to adjust both dose level and frequency in Restoration 2 as we look ahead to delivering a medicine that can bring AATDZZ patients to a healthier MZ phenotype with total serum AAT protein levels above the anticipated therapeutic threshold of 11 micromolar. With that, I'd like to turn our call over to our CFO, Kyle Moran, to provide an update on our financials.

Anne-Marie Lee-Kwai Chung: Beyond that, we have the flexibility to adjust both dose level and frequency in Restoration 2 as we look ahead to delivering a medicine that can bring AATDZZ patients to a healthier MZ phenotype with total serum AAT protein levels above the anticipated therapeutic threshold of 11 micromolar. With that, I'd like to turn our call over to our CFO, Kyle Moran, to provide an update on our financials.

Anne-Marie Lee-Kwai Chung: Beyond that we have the flexibility to adjust both dose level and frequency and restoration case as we look ahead to delivering a medicine that can bring 80 days easy patients to a healthier MZ phenotype with total serum.

Anne-Marie Lee-Kwai Chung: Protein levels above the anticipated therapeutic threshold of 11 micro molar.

Kyle Moran: We recognize collaboration revenue of $19.7 million in the second quarter of 2024 as compared to $22.1 million in the prior year quarter. This slight decrease in revenue reflects typical variations in recognition of collaboration revenue. Research and development expenses were $40.4 million in the second quarter of 2024, as compared to $33.3 billion in the prior year quarter. This increase was primarily driven by spending in our INBD program, along with AATD and DMD programs, and early stage pipeline initiatives.

Anne-Marie Lee-Kwai Chung: With that I'd like to turn our call to our CFO, Colorado to provide an update on our financials.

Kyle Moran: Our G&A expenses were $14.3 million in the second quarter of 2024 as compared to $12.3 million in the prior year quarter. As a result, our net loss was $32.9 million for the second quarter as compared to $21.1 million for the prior year quarter.

Kyle Moran: Thanks Anne Marie.

Kyle Moran: We recognize collaboration revenue of $19.7 million in the second quarter of 2024, as compared to $22.1 million in the prior year quarter. This slight decrease in revenue reflects typical variations in recognition of collaboration revenue. Research and development expenses were $40.4 million in the second quarter of 2024, as compared to $33.3 million in the prior year quarter. This increase was primarily driven by spending in our InBD program, along with AATD and DMD programs, and early stage pipeline initiatives.

Kyle Moran: We recognized collaboration revenue of $19 $7 million in the second quarter of 2024 as compared to $22 $1 million in the prior year quarter.

Kyle Moran: This slight decrease in revenue reflects typical variations in recognition of collaboration revenue.

Kyle Moran: Research and development expenses were $40 4 million in the second quarter of 2024.

Kyle Moran: As compared to $33 3 million in the prior year quarter.

Kyle Moran: This increase was primarily driven by spending in our M&A program, along with ATB DMD program and early stage pipeline initiatives.

Kyle Moran: Our G&A expenses were $14 3 million for the second quarter of 2024 as compared to $12 $3 million in the prior year quarter.

Kyle Moran: As a result, our net loss was $32 $9 million for the second quarter as compared to $21 $1 million in the prior year quarter.

Paul Bolno: We ended the second quarter with $154 million in cash and cash equivalents. We expect our current cash and cash equivalents will be sufficient to fund operations into the fourth quarter of 2025. It is important to note that we do not include any future milestones or opt-in payments under our CSK or CICADA collaboration in our cash runway, but we do have the potential to receive meaningful near-term milestone payments this year and beyond. I'll now turn the call back over to Paul for closing remarks.

Paul Bolno: We ended the second quarter with $154 million in cash and cash equivalents. We expect that our current cash and cash equivalents will be sufficient to fund operations into the fourth quarter of 2025. It is important to note that we do not include any future milestones or opt-in payments under our CSK or CICADA collaboration in our cash runway, but we do have the potential to receive meaningful near-term milestone payments this year and beyond. I'm now turning the call back over to Paul for closing remarks.

Kyle Moran: We ended the second quarter with $154 million in cash and cash equivalents.

Paul Bolno: We expect that our current cash and cash equivalents will be sufficient to fund operations into the fourth quarter of 2025.

Speaker Change: It is important to note that we do not include a future milestone and opt in payments under our GSK Takeda.

Paul Bolno: Collaborations in our cash runway.

Paul Bolno: We do have the potential to receive meaningful near term milestone payments this year and beyond.

Paul Bolno: Now I'll turn the call back over to Paul for closing remarks.

Operator: Kyle, it is an incredibly exciting time for WAVE as we are poised to sustainably translate new human genetic insights into breakthrough medicine. With ongoing validation of our platform and several important program milestones ahead, our confidence and conviction in the promise of our pipeline have never been stronger. In this half of 2024, we expect to provide updates across each of our clinical programs, including district and data this quarter, as well as advance our obesity program into clinical development with the submission of the CTA.

Operator: It is an incredibly exciting time for WAVE as we are poised to sustainably translate new human genetic insights into breakthrough medicine. With ongoing validation of our platform and several important program milestones ahead, our confidence and conviction in the promise of our pipeline have never been stronger. In this half of 2024, we expect to provide updates across each of our clinical programs, including district and data this quarter, as well as advance our obesity program into clinical development with the submission of a CTA.

Paul Bolno: Thank you Kyle it is an incredibly exciting time for wave as we are poised to sustainably translate new human genetic insight into breakthrough medicines with ongoing validation of our platform and several are important program milestones ahead, our confidence and conviction in the promise of our pipeline has never been stronger.

Operator: In this half of 2024, we expect to provide updates across each of our clinical programs, including dystrophin data this quarter as well as advance our obesity program into clinical development with the submission of the Cta.

Operator: We are also planning an R&D day this fall to share new preclinical data on our wholly-owned portfolio, including our WVE-007 inhibitory program. We look forward to keeping you updated on our progress along the way. In closing, I would like to thank our teams that are working tirelessly to advance our programs, deliver our clinical results, and are preparing to initiate new clinical studies. Additionally, I would like to express our deepest gratitude to the patients and families participating in our studies and all who inspire us at WAVE. With that, I'll turn it over to the operator for Q&A. Operator? Thank you. Ciao.

Operator: We are also planning an R&D day this fall to share new preclinical data on our wholly owned portfolio, including our WVE-007 inhibitory program. We look forward to keeping you updated on our progress along the way. In closing, I would like to thank our teams that are working tirelessly to advance our programs, deliver our clinical results, and are preparing to initiate new clinical studies. Additionally, I would like to express our deepest gratitude to the patients and families participating in our studies and all who inspire us at WAVE. And with that, I'll turn it over to the operator for Q&A. Operator? Thank you.

Operator: We are also planning an R&D day. This followed the share new preclinical data on our wholly owned portfolio, including our <unk> inhibitor program. We look forward to keeping you updated on our progress along the way in closing I would like to thank our team that are working tirelessly to advance our program deliver our clinical results in our <unk>.

Operator: Pairing to initiate new clinical studies. Additionally, I would like to express our deepest gratitude to the patients and families participating in our studies and all who inspire us at wave and with that I'll turn it over to the operator for Q&A operator.

Operator: Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, press star 11 again. One moment while we compile the Q&A roster. And our first question will come from the line of Joon Lee with Truist. Your line is open.

Speaker Change: Thank you to ask a question. Please press star one one on your telephone and wait for your name to be announced so withdraw your question Press Star One again, one moment, while we compile the Q&A roster.

Operator: And our first question will come from the line of Joon Lee with <unk>. Your line is open.

Joon Lee: Congratulations on the progress, and I'm looking forward to a lot of data readouts in the next five months. I'm glad to hear that you have submitted the opt-in package to Takeda with a decision by year end. Regarding the conversations with regulators, is Takeda involved in those conversations, or is it just between you and the FDA? And what has been the feedback so far on the possibility of using imaging as a circuit biomarker? Thank you. And I have a quick follow-up.

Joon Lee: Congratulations on the progress and looking forward to a lot of data we'd out to the next five months. Glad to hear that you have submitted the opt-in package to Takeda with a decision by year end. Regarding the conversations with regulators, is Takeda involved in those conversations, or is it just between you and the FDA? And what has been the feedback so far on the possibility of using an image in the circuit by Martha? Thank you. I have a quick follow-up.

Joon Lee: Okay. Congrats on the progress and looking forward to a lot of data readouts over the next five years.

Speaker Change: Five months.

Joon Lee: Glad to hear that you have submitted the opt in package to Takeda with decision by year end.

Joon Lee: The conversations with regulators is to get involved in those conversations or is it just between you and the FDA and what has been the feedback so far on the possibility of using imaging of the circuit biomarker. Thank you and I have a quick follow up.

Paul Bolno: Thank you, Joon. Obviously, we don't comment on specific regulatory interactions at this point in time, but yes, Takeda is involved in our interaction.

June: Thank you June.

Speaker Change: Obviously, we don't comment on specific regulatory interactions point in time, but yes, Takeda is involved in our interactions.

Joon Lee: Great. And on DMV, just looking at the approved accidents, all of those in DMV, about 42% exon skipping for the 53 from Vilpepso leads to around 4.8% dischiffen. So would you say the bar for N531 is around 5%? Is there some internal bar for efficacy you'd like to see in the forthcoming data? Thank you.

Joon Lee: Great. And I'm DMV, just looking at the approved access for all of those in DMV, about 42% tax on skipping for the 53 from Bill Pepso, leading to around 4.8% this year's end. So would you say the bar for N-531 is around 5%? Is there some internal bar for SKC's like seeing the forthcoming data? Thank you.

Paul Bolno: Great.

Joon Lee: DMD just looking at the approved access all of those in DMD about 42% exon skipping for the 53.

Speaker Change: Bill touched so retail round, 548% discipline. So would you say the bar for <unk> is around 5% is there some internal bar for efficacy like seen before coming data. Thank you.

Paul Bolno: Yeah, thank you for the question, June. I mean, as we think about dystrophin expression and our guidance to 5% or more, right, greater than 5%, I think we look at this as the 42% you were citing from Biltepso was after six months of dosing. So what's encouraging to us is the 53% that we were seeing after three doses at six weeks. So again, getting the machinery of dystrophin production going earlier with a protein that has a high rate of stability.

Paul Bolno: Yeah, thank you for the question, June. I mean, as we think about dystrophin expression and our guidance to 5% or more, right, greater than 5%, I think we look at this as the 42% you were citing from Diltepso was after six months of dosing. So what's encouraging to us is the 53% that we were seeing after three doses at six weeks. So again, getting the machinery of dystrophin production going earlier with a protein that has a high rate of stability.

Speaker Change: Yes. Thank you for the question John I mean, as we think about dystrophin expression in our guidance to 5% or more right greater than 5% I think we look at this as the 42% you were citing from build cap. So with after six months of dosing. So what's encouraging to US is the 53% that we were seeing after three doses at <unk>.

Paul Bolno: Six weeks, so again getting the machinery of dystrophin production going earlier with a protein that is the high rate of stability I think as we think about that conversion, where you said that 42% to four 8% also important as we looked at those data sets from the clinic out at six months that really that four 8% is being driven by two outliers there with them.

Paul Bolno: I think as we think about that conversion where you said that 42% to 4.8%, it's also important as we looked at those data sets from the clinic out at six months that really that 4.8% was being driven by two outliers. So, as Anne-Marie mentioned, the consistency of response, which we saw earlier, is something we'll be looking for in this study. And if you remove those outliers, it was actually somewhere around 3%, just slightly above 3% dystrophin.

Paul Bolno: We mentioned the consistency of response, which we saw early is something we'll be looking for in this study and if you remove those outliers it was actually somewhere around 3% just slightly above 3% dystrophin. So again the production that we see of high quality high quantities of greater than 5% and consistency, we think will drive a differentiated profile.

Paul Bolno: So, again, the production that we see of high quality, high quantity, so greater than 5% and consistency, we think will drive a differentiated profile. I do think, as Anne-Marie said, getting back to your first question, I was reflecting on a lot of the work that's been happening over the course of this year in clinical surrogate endpoints, both through the HD Risk Consortium and work that's being done to evaluate the CHD track And I do think it is highly encouraging the work that's being done on CAUD8 imaging. I don't know, Emery, if there's any additional insights you want to reflect on back on the first question.

Paul Bolno: So, again, the production that we see of high quality, high quantity, so greater than 5% and consistency, we think will drive a differentiated profile. I do think, as Anne-Marie, getting back to your first question, I was reflecting on a lot of the work that's been happening. Over the course of this year, in clinical surrogate endpoints, both through the HD Risk Consortium, work that's being done to evaluate the CHD-TRACK HD data, and I do think it is highly encouraging the work that's being done on CAUD8 imaging.

Paul Bolno: Phil.

Paul Bolno: I do think as Emory getting back to your first question I was reflecting on a lot of the work that's been happening over.

Paul Bolno: Over the course of this year and clinical surrogate endpoints both through the HD risk consortium work, that's being done to evaluate the CIC track HD data and I do think it is highly encouraging the work that's being done on cardiac imaging I don't know if im right that any additional insights you want to reflect on back on the first question.

Paul Bolno: I don't know, Emory, if there's any additional insights you want to reflect on back on the first question.

Anne-Marie Lee-Kwai Chung: Yes, I think FDA is highly engaged with the community in general and with the HD risk consortium in particular. And as I mentioned in the recent meeting we had, they're absolutely aligned in the intent of trying to find more efficient ways to bring therapies to people with HD and also supporting endpoints. I think that's why we've entered into the consortium, the imaging consortium, to start collating and providing the data set that will be necessary to establish caudate atrophy as an endpoint reasonably likely to predict a clinical outcome. So it's all very encouraging.

Ann Marie Lee Quichung: Yes, I think FDA is highly engaged with the community in general and with the HD risk consortium in particular. And as I mentioned in the recent meeting we had, they're absolutely aligned in the intent of trying to find more efficient ways to bring therapies to people with HD and also supporting endpoints. I think that's why we've entered into the consortium, the imaging consortium, to start collating and providing the data set that will be necessary to establish caudate atrophy as an endpoint reasonably likely to predict a clinical outcome. So it's all very encouraging.

Paul Bolno: Yes.

Anne-Marie Lee-Kwai Chung: I think FDA is highly engaged.

Anne-Marie Lee-Kwai Chung: With the community in general and with the HD risk consortium in particular and as I mentioned in the recent meeting we had.

Anne-Marie Lee-Kwai Chung: That absolutely aligned in the intent of trying to find more efficient ways spring therapies to people with H D.

Anne-Marie Lee-Kwai Chung: And and also supporting.

Anne-Marie Lee-Kwai Chung: Endpoints.

Anne-Marie Lee-Kwai Chung: Reasonably likely to predict clinical outcome and that's why it's really important that we've entered into the consortium.

Anne-Marie Lee-Kwai Chung: The imaging consortium.

Anne-Marie Lee-Kwai Chung: <unk>.

Anne-Marie Lee-Kwai Chung: Placing them, providing the data set that will be necessary to establish could I atrophy as an endpoint reasonably likely to predict clinical outcomes.

Anne-Marie Lee-Kwai Chung: So very encouraging.

Paul Bolno: Great, thank you. I'm looking forward to the R&D event in the fall.

Anne-Marie Lee-Kwai Chung: Great. Thank you and looking forward to the R&D back in the fall.

Speaker Change: Thank you.

Operator: Thank you. One moment for our next question, and that will come from the line of Salim Syed with Mizzou. Your line is open.

Speaker Change: Thank you one moment for our next question.

Speaker Change: And that will come from the line of Salim Sayed with Mizuho. Your line is open.

Salim Syed: Great. Good morning, guys, and congrats on the progress.

Salim Syed: Great. Good morning, guys, and congrats on the progress. Paul, wanted to follow up a little bit on the Takeda stuff that we're going to get this year. So can you just clarify for us, is this, are you anticipating that the feedback we're going to get on the street, on the street, is there going to be one event or two events? In other words, are we supposed to expect regulatory feedback?

Salim Syed: Great. Good morning, guys and congrats on the progress Paul I wanted to follow up a little bit on the Takeda.

Paul Bolno: Paul, wanted to follow up a little bit on the Takeda stuff that we're going to get this year. So can you just clarify for us, is this, are you anticipating that the feedback we're going to get on the street, is there going to be one event or two events? In other words, are we supposed to expect regulatory feedback as one event and Takeda as the Takeda decision as another event? Are these two things linked?

Speaker Change: With Takeda.

Salim Syed: Stuff that we're going to get this year so.

Salim Syed: Could you just clarify for US is this are you anticipating that the feedback we're going to get to the street is it going to be one event or two events. In other words are we supposed to expect the regulatory feedback.

Salim Syed: As one event and Takeda as the Takeda decision as another event, are these two things linked? And then also, just what is the disclosure format, if you can just clarify for us, are we going to get that sometime as it happens, or are you going to wait for the quarterly, the next quarterly call? And then, just lastly, just related to that, as you're considering financing the company, just given DMD as a third quarter event and the feedback from the regulatory body in Takeda, Thank you.

Speaker Change: That's one event and Takeda as the Takeda decision is another event are these two things Ling.

Paul Bolno: And also, just what is the disclosure format, if you can just clarify for us, are we going to get that sometime as it happens, or are you going to wait for the quarterly, the next quarterly call? And then, just related to that, as you're considering financing the company, just given DMD as a third-quarter event and the feedback from the regulatory body in Takeda, Thank you.

Salim Syed: And then also just what are the disclosure format. If you can just clarify for US are we going to get that sometime as it happens or are you going to wait for the quarterly.

Speaker Change: The next quarterly call.

Salim Syed: And and then just lastly, just related to that.

Speaker Change: But youre considering financing.

Salim Syed: Company, just given DMD.

Salim Syed: Third quarter event.

Speaker Change: Feedback from the regulatory body and Takeda.

Salim Syed: It would be potentially a <unk> event would you would you wait for that to occur or would you be willing to finance on DMD given your your runway is now at $4 25. Thank you.

Paul Bolno: Thank you, Salim. And I'll take these in reverse order.

Paul Bolno: Thank you, Salim, and I'll take these in reverse order. So as it relates to, you know, when and where potential financings occur, again, besides just the Decatur opt-in, there are also continued milestones through the GSK collaboration, which we announced even in the first quarter. We received a $12 million payment for work that was happening under the research collaboration. So we do anticipate milestones through 2024 and 2025. As it relates to your first question, in terms of disclosures, it's important to think about these as two independent events. The Decatur opt-in decision is not predicated on regulatory feedback.

Speaker Change: Thank you so I will take these in reverse order so as it relates to when and where potential financings occur again. Besides just the Takeda opt and Theres also continued milestones through the GSK collaboration, which we announced even in the first quarter, we received a $12 million payment for work that was happening under the research.

Paul Bolno: Operations. So we do anticipate milestones through 2024 and 2025 as it relates to your first question in terms of disclosures. It's important to think about these as two independent events that Takeda often decision is not predicated on regulatory feedback that based on the data from the prior studies. So as we said on the call. The submission of the package was driven.

Paul Bolno: So as it relates to, you know, when and where potential financings occur, again, besides just the DECADA opt-in, there are also continued milestones through the GSK collaboration, which we announced even in the first quarter. We received a $12 million payment for work that was happening under the research collaboration. So we do anticipate milestones through 2024 and 2025. As it relates to your first question in terms of disclosures, it's important to think about these as two independent events.

Paul Bolno: It's based on the data from the prior study. So, as we said on the call, the submission of the package was driven by the data that met the threshold for us to submit that package. Now, those two pieces that are happening simultaneously towards the end of the year, there are interactions between what's happening across both of those, the regulatory feedback and the ongoing discussion with Decatur. So we do view those as well as two separate, distinct opportunities to provide feedback.

Paul Bolno: <unk> the data that met the threshold for us to submit that package now those two pieces that are happening simultaneously towards the end of the year.

Paul Bolno: The DECADA opt-in decision is not predicated on regulatory feedback; it's based on the data from the prior study. So, as we said on the call, the submission of the package was driven by the data that met the threshold for us to submit that package. Now, those two pieces that are happening simultaneously towards the end of the year; there are interactions between what's happening across both of those, the regulatory feedback and the ongoing discussion with DECADA.

Paul Bolno: Are there our interactions of what's happening across both of those the regulatory feedback and the ongoing discussions with Takeda. So we do view those as two separate distinct opportunities to provide feedback obviously anytime we cross the material threshold an opt in decision that shifted the nature of the program into not just.

Paul Bolno: So we do view those as well as the two separate distinct opportunities to provide feedback. Obviously, anytime we cross a material threshold and an opt-in decision that shifts the nature of the program into not just a cash infusion but also importantly, a shift in the HD program to a 50-50 profit split and a 50-50 R&D split is material. And so those updates would happen as they occur. And again, the timeline for these takes us back to 2024, by the end of the year. So these two events could be introduced distinctly as two separate events. Got it.

Paul Bolno: Obviously, any time we cross the material threshold and opt-in decision that shifts the nature of the program into not just a cash infusion but also, importantly, a shift in the HD program to a 50-50 profit split and a 50-50 R&D split is material. And so those updates would happen as they occur. And again, the timeline for these takes us to by the end of the year. So these two events could be introduced distinctly, as two separate events. I got it.

Paul Bolno: Our cash infusion, but also and importantly, a shift in the HD program. So that 50 50 profit, but at a 50 50 R&D split is material and so those update would happen as they occur and again the timeline for the use cases.

Paul Bolno: Two by the end of the year. So these two events could be introduced.

Paul Bolno: At two separate events.

Salim Syed: Got it. Thanks so much, Paul.

Paul Bolno: Got it thanks, so much Paul.

Speaker Change: Thank you Sir.

Operator: Thank you. One moment for our next question, and that will come from the line of Luca Issi with RBC. Your line is open.

Speaker Change: Thank you one moment our next question.

Luca Issi: And that will come from the line of Luca <unk> with RBC. Your line is open.

Lisa Walter: Oh, great. Thanks so much for taking our questions. This is Lisa on behalf of Luca.

Operator: Oh, great. Thanks so much for taking our questions. This is Lisa on behalf of Luca.

Operator: Oh, great. Thanks, so much for taking our questions. This is Lisa on for Luka.

Lisa Walter: First, on the Takeda opt-in, just wondering, should Takeda ultimately choose not to opt-in, what are your options for the program if that happens? And secondly, on Inhibi, given the target can potentially reduce fat and maintain muscle, wondering if you are thinking about any ways to assess muscle preservation in the clinic?

Lisa: First on the Takeda opt in just just wondering.

Lisa Walter: First, on the Takeda opt-in, just wondering, should Takeda ultimately choose not to opt-in? Just wondering, what are your options for the program if that happens? And secondly, on Inhibi, given the target can potentially reduce fat and maintain muscle, wondering if you are thinking about any ways to assess muscle preservation in the clinic?

Lisa Walter: Should takeda ultimately choose.

Lisa Walter: Not to opt in just wondering what are your options for the program if that happens.

Speaker Change: And secondly on in heavy given.

Lisa Walter: Given the target can potentially reduce fat and maintain muscle wondering if you are thinking about any ways to assess muscle preservation in the clinic any color there would be helpful. Thank you so much.

Paul Bolno: Any color there would be helpful. Thank you so much.

Paul Bolno: Sure, thank you, Lisa. So, for your first question, if Takeda makes the decision not to opt in, I mean, obviously, we're not waiting for that decision. So, one of the benefits of full data disclosure, which we've had, is inbound interest and questions from other strategics asking whether or not Takeda is planning on opting in to these data sets and whether or not we'd be interested in having conversations. Obviously, Takeda is a wonderful partner, and we're engaged with them.

Paul Bolno: Sure, thank you, Lisa. So, for your first question, if Takeda makes the decision not to opt-in, I mean, obviously, we're not waiting for that decision. So, one of the benefits of full data disclosure, which we've had, is inbound interest and questions from other strategics asking whether or not Takeda is planning on opting in to these datasets and whether or not we'd be interested in having conversations. Obviously, Takeda is a wonderful partner, and we're engaged with them.

Speaker Change: Sure. Thank you Lisa so for your first question if Takeda makes the decision not to opt in I mean, obviously, we're not waiting for that decision. So one of the benefits of a full data disclosure, which we've had.

Paul Bolno: Is inbound interest and questions from other strategics, asking whether or not Takeda is planning on opting in on these datasets.

Paul Bolno: But at the same time, given that these data sets are publicly disclosed, we are allowed to have discussions with others relative to the HD space and these data. And we are going to put ourselves in the best position to assure that this program should align with regulators around the path to accelerated registration, be aligned, and that this has a supportive path to continue to go to patients. In addition, we've also had discussions with folks who want to potentially fund the asset and step in financially to help Takeda's decision.

Paul Bolno: But at the same time, given that these datasets are publicly disclosed, we are allowed to have discussions with others relative to the HD space and these data, and we are going to put ourselves in the best position to assure that this program should align with regulators around the path to accelerated registration.

Paul Bolno: And whether or not we'd be interested in having conversations obviously takeda is a wonderful partner and we're engaged with them, but at the same time given that these datasets are publicly disclosed we are allowed to have discussions with others relative to the HD space and these data and we were going to put ourselves in the best position to assure that this program should alignment with regulators.

Paul Bolno: The path to accelerated registration.

Speaker Change: The align that this has a supportive path to continue to go to patients. In addition, we've also had discussions from balance.

Speaker Change: Folks who want to potentially fund the asset step in financially in the dedicated division. So we are in parallel to the ongoing.

Paul Bolno: So we are, in parallel to the ongoing discussions with Takeda, making sure that we put the program in the best light, and the best foot forward to assure that there is a disease-modifying treatment for patients if the FDA aligns with us on a path to accelerated registration. As it relates to the profile for inhibin-E, which we're incredibly excited about, given where we think it differentiates itself from the existing standard of care in obesity, to your point on both fat loss and being able to spare muscle, and the fact that we can design not just what we saw in the DIO mouse model but a clinical study in healthy overweight volunteers to recapitulate that phenotype, yes, we will be embedding I don't know, Eric, if you want to add anything additionally, or Anne-Marie, on terms of the clinical trial design.

Speaker Change: Gotcha, but takeda, making sure that we put the program in the best light best foot forward to assure that there is a disease modifying treatment for patients.

Speaker Change: <unk> aligned with us on a path to accelerated registration.

Speaker Change: As it relates to the profile for inhibitor <unk>, which we are incredibly excited about given where we think it differentiates itself from the existing standard of care in obesity to your point on both backlog and being able to spare muscle and the fact that we can design that does what we saw in the DIR mouse model, but a clinical study in healthy overweight volunteers to recapitulate that.

Eric: Phenotype, Yes, we will be embedding in the study have the opportunity to look at both fat and muscle up I don't know, Eric if you want to add anything Additionally, or Anne Marie on terms of the clinical trial design that we plan to not really.

Paul Bolno: Not really. Again, as Paul said, we see in the human genetics data, we see muscle sparing, we see a profound effect on fat distribution, and we replicate that in our preclinical studies. We haven't shared the design of the first clinical study yet. It will be in the Healthy Overweight Volunteers, and we will measure different measures of fat distribution and muscle, but we haven't shared the details of that yet. I mean, interestingly enough, just for those who aren't aware.

Paul Bolno: Again, we as Paul said, we see in the human genetics data, we see muscle sparing we see a.

Speaker Change: Profound effects on the fast distribution and we replicate that in our preclinical studies, we haven't shared yet but the design of the first clinical study it will be in a healthy overweight volunteers, but they are and we will measure different measures of past distribution and muscle, but we haven't shared the details of that yet.

Paul Bolno: I mean, interestingly enough, just for those who aren't aware, we know that as we go into new spaces of looking at ways to determine that, there are tests that are very good, whether that's DEXA, MRI, the SOMA signal test. So there are ways for us to embed in the clinical trial the ability to really differentiate and distinguish the profile of the program. But we'll obviously get more updates on that as we get closer to the regulatory filing and the beginning of the clinical trial.

Speaker Change: Interestingly enough just for those who aren't aware we know that.

Speaker Change: Go into new spaces of looking at ways to determine that there are tests that are very good weather.

Speaker Change: Alright, Thats somewhat signal test. So there are ways for us to embed in the clinical trial.

Paul Bolno: To really differentiate and distinguish the profile of the program, but we would obviously give more updates on that as we get closer to the regulatory filing at the beginning of the clinical trial.

Operator: Thank you. One moment for our next question, and that will come from the line of Steve Seedhouse with Raymond James. Your line is open.

Speaker Change: Thank you one moment for our next question.

Steve <unk>: And that will come from the line of Steve <unk> with Raymond James Your line is open.

Steven Seedhouse: Hi. Thank you for the question. This is Nick. I'm on behalf of Steve.

Operator: Hi, thank you for the question. This is Nick on behalf of Steve.

Nick: Hi, Thank you for the question. This is Nick on for Steve just wanted to clarify for the restoration to update in Q4 do you plan to show changes in AEP protein concentration or do you plan to only show.

Speaker Change: Proportion of corrected.

Speaker Change: <unk> versus <unk>.

Speaker Change: And as a quick follow up will be initial readout include data from the multi sending dose callable only single ascending dose cohorts. Thank you.

Nicholas Econom: Just wanted to clarify for the Restoration 2 update in Q4, do you plan to show changes in AAT protein concentration, or do you plan to only show the proportion of corrected M-AAT versus Z-AAT? And as a quick follow-up, will the initial readout include data from the multi-ascending dose cohort or only single ascending dose cohorts? Thank you.

Paul Bolno: Yeah, so the initial proof of mechanism data is not tied to either a single or multi-dose threshold; it's tied to exactly the first part of your question about profile. And so we'll be evaluating and assessing as part of that total protein and protein in combination. And the key driver of that is your point about being able to assess for the first time in humans the principle of RNA editing and, therefore, the translation from what we've seen in the Serpent A1 model and how that's translating now into humans.

Speaker Change: Yes. So the initial proof of mechanism data is not tied to either a single or multi dose thresholds tied to exactly the first part of your question our profile and so we will be evaluating and assessing as part of that total.

Speaker Change: Total protein and protein.

Speaker Change: In combination and the key driver of that is to your point to really be able to assess for the first time in humans. The principle of RNA editing and therefore the translation from what we've seen in the <unk>, one model and how thats translating now into humans, but we will be assessing both M protein totaled.

Speaker Change: Thank you.

Operator: One moment for our next question, and that will come from the line of Joseph Schwartz, with Learing Partners. The line is open.

Speaker Change: One moment for our next question.

Joseph Schwartz: And that will come from the line of Joseph Schwartz with Leerink Partners. Your line is open.

Joseph Schwartz: Hi Jenny, thanks for taking your questions Jenny on for Joe. I was just wondering if you could give us a little more insight into the data that's been generated so far to support caudate asphyxia and what will be needed to establish that biomarker as reasonably likely to predict benefit. And can you tell us kind of what you're expecting, how soon you might see meaningful changes in this biomarker, and if the proposed study design might include some interim analogies? Thank you.

Operator: I just wanted to clarify for the Restoration 2 update in Q4, do you plan to show changes in AAT protein concentration, or do you plan to only show the proportion of corrected M-AAT versus Z-AAT? And as a quick follow-up, will the initial readout include data from the multi-ascending dose cohort or only single ascending dose cohorts? Thank you.

Jamie: Hi, Thanks for taking our question is Jamie on for Joe I was just wondering if you could give us a little more insight into the data that's been generated so far to support coding Ashby.

Speaker Change: What will be needed to establish that biomarker.

Speaker Change: Reasonably likely to predict benefit.

Operator: Hi. Thanks for taking your questions, Jenny, on behalf of Joe.

Operator: And can you tell us kind of what youre expecting how soon you might see meaningful changes in this biomarker and if the proposed study design might include some interim analysis. Thank you.

Paul Bolno: So thank you for the question, and I'll start and then I'll turn it over to Anne-Marie. But there is a lot of data emerging over time, and Anne-Marie can speak to that, both in the consortium that we're engaged with and looking at the large data that's coming off of TRACK-HD to assess MRI changes on CAUTI. We do think going forward, as we've shared before, that there is the possibility to achieve that within 12 to 18 months.

Speaker Change: So thank you for the question and.

Speaker Change: Start and then I'll turn it over to Anne Marie but there is a lot of data emerging over time and Emory can speak to that both of the consortium that we're engaged with and looking at the large data that's coming off the track HD to assess MRI changes on caught it we do think going forward as we've shared before that we do think there is the possibility to image that within.

Paul Bolno: Obviously, the design of that study has to be agreed to with regulators. But the benefit of this is that imaging can see that over reasonably short periods of time with much smaller patient populations than what has been done before in HD with large clinical outcome studies. Anne-Marie, do you want to reflect on CAUTI atrophy and some of the imaging data coming?

Murray: 12 to 18 months, obviously the design of that study has to be agreed to with regulators, but the benefit of that is that there are the ability with imaging to see that over a reasonably short periods of time with much smaller patient population than what has been done before in HD with large clinical outcome studies and Murray I think do you want to.

Speaker Change: Reflect on the caudate atrophy and some of the imaging data coming.

Operator: I was just wondering if you could give us a little more insight into the data that's been generated so far to support caudate asphyxia and what will be needed to establish that biomarker as reasonably likely to predict benefit. And can you tell us kind of what you're expecting, how soon you might see meaningful changes in this biomarker, and if the proposed study design might include some interim abnormalities? Thank you.

Ann Marie Lee Quichung: I'm happy to. So one way in which we're very lucky in the HD environment is that there's a lot of natural history data available that's being collected prospectively by the community. That includes databases called Track and Predict HD. This means there are rich data sets available that would allow us to establish the predictive relationship between caudate change and clinical outcomes. And that is one of the first things that you need to establish an endpoint that's reasonably likely to predict a clinical outcome.

Speaker Change: I'm happy to so.

Operator: One way in which we're very lucky in the H D.

Speaker Change: Environment is that there is some.

Speaker Change: A lot of natural history data available that's being collected prospectively by the community.

Speaker Change: And that includes databases cold track and predict H D and this means that rich datasets available that would allow us to establish the predict chips.

Anne-Marie Lee-Kwai Chung: I'm happy to. One way in which we're very lucky in the HD environment is that there's a lot of natural history data available that's being collected prospectively by the community, and that includes databases called Track and Predict HD. And this means there are rich data sets available that would allow us to establish the predictive relationship between CORD-H change and clinical outcomes. And that is one of the first things that you need to establish an endpoint that's reasonably likely to predict a clinical outcome.

Speaker Change: Relationship between crude H change and clinical outcomes and that is one of the first things that you need to establish an endpoint. This recent beat likely to predict clinical outcome. So the consortium that we mentioned the Huntington's disease image harmonization consortium.

Anne-Marie Lee-Kwai Chung: So the consortium that we mentioned, the Huntington's Disease Image Harmonization Consortium, that's run by ICSCO and CHDI, has made these scans available and harmonized them in a way that they would meet the standard required for a regulatory submission so that we can show FDA this predictive value between the CORD-H and the outcome. So that's the first part of it. The second part of it is that you have to show that your drug is able to have an impact on CORD-H.

Ann Marie Lee Quichung: So the consortium that we mentioned, the Huntington's Disease Image Harmonization Consortium, that's run by ICSCO and CHDI, has made these scans available and standardized them in a way that they would meet the standards required for a regulatory submission so that we can show FDA this predictive value between the caudate atrophy and the outcome. So that's the first part of it. The second part of it is that you have to show that your drug is able to have an impact on caudate atrophy.

Speaker Change: That's run by Exco, and CACI, but made these scans available and harmonize them in a way that they would meet the standard required for a regulatory submission. So that we can show FDA. This predictive value between the cuda atrophy and the outcome. So that's the first part of the second.

Anne-Marie Lee-Kwai Chung: Most of it is that you have to show that your drug is able to.

Anne-Marie Lee-Kwai Chung: And obviously, in our Select HD study, we've already seen the first signs of that. So I think, taken together, this is a strong package. We're excited to be engaging with regulators on this.

Ann Marie Lee Quichung: And obviously, in our select HD study, we've already seen the first signs of that. So I think, taken together, this is a strong package. We're excited to be engaging with regulators on this.

Anne-Marie Lee-Kwai Chung: Have an impact on quota atrophy and overseeing our select HD study, we've already seen the first signs of that so I think taken together. This is a strong package, we're excited to be engaging with regulators on this package.

Paul Bolno: I think, you know, just to follow up, I think the profile is extraordinarily important. You know, initially, as Anne-Marie said, showing a high impact on the target, addressing questions that have been involved with the agency around wild type sparing, so knocking down the target substantially, showing that we preserve wild type, and showing that the concentration and the knockdown of the mutant protein correlates with caudate atrophy. And then, as Anne-Marie said, now having the imaging tools available to assess that relative to clinical outcome measurements, I think really sets up a dynamic for the HD community with disease modification for the first time to engage in this conversation around a potential accelerated registration pathway.

Paul Bolno: I think, you know, just to follow up, I mean, I think the profile is extraordinarily important. You know, initially, as Anne-Marie said, showing a high impact on the target, addressing questions that have, you know, been involved with the agency around wild-type sparing, so knocking down the target substantially, showing that we preserve wild-type, showing that the concentration and the knockdown of mutant protein correlates with caudate atrophy, and then, as Anne-Marie said, now having the imaging tools available to assess that relative to clinical outcome measurements, I think really sets up a dynamic for the first time, I think, for the HD community with disease modification to engage in this conversation around a potential accelerated registration pathway.

Speaker Change: Just a follow up I mean, I think the profile is extraordinary important initially at Emory that showing a high impact on the target addressing questions that have.

Paul Bolno: Been involved with the agency around wildfire sparing, so knocking down the target substantially showing that we preserve wildfire showing that the concentration in the knockdown the mutant protein correlates with caudate atrophy, and then as <unk> said now having the imaging tools available to assess that relative to clinical outcome measurement I think really sets up a dynamic for the first time I think for the <unk>.

Paul Bolno: The community with disease modification to engage in this conversation around a potential accelerated registration pathway.

Operator: Thank you. Please take a moment for our next question.

Paul Bolno: Thank you. One moment for our next question, and that will come from the line of Tiago Fauth with Wells Fargo. Your line is open.

Speaker Change: Thank you one moment for our next question.

Thiago <unk>: And that will come from the line of Thiago <unk> with Wells Fargo. Your line is open.

Operator: Great, thank you so much for taking the question. I had one just on the ATG.

Tiago Fauth: Great, thank you so much for taking the question. I have one just on the ATG.

Operator: Great. Thank you so much for taking the question.

Speaker Change: One just on the atg.

Tiago Fauth: Just wondering if you can discuss more about your expectations about the translatability of adult finding studies in animal models into humans. There are some questions, mostly about the mutations of those animal models and the novelty of the approach. So what gives you confidence at the dose levels we are taking forward. I actually would like to be at a therapeutic range in humans. More details, and that would be appreciated.

Speaker Change: Just wondering if you can discuss more on your expectations about the translate ability if the dose finding studies in animal models into humans. There are some questions mostly from limitations of those animal models and the novelty of the approach. So what gives you confidence that the dose levels are taking forward I actually likely to be at a therapeutic relevant range.

Speaker Change: In humans.

Operator: More details on that would be appreciated.

Paul Bolno: No, it's a wonderful question, and we put a lot of time into the modeling work going from the Serpent A1 study to our non-human primate studies to our humans. And I think that's really where we're able to take advantage of, and I think benefit from, gal neck conjugation and the translative pharmacology that we've seen in liver surface area between mouse, non-human primates, and humans So as we think about exposures, as we think about concentrations in those species, and we look at PK modeling of where the drug is going, I think we're able to say that there is again a very well-established pathway in pharmacology.

Speaker Change: No. It's a wonderful question and we put a lot of time into the modeling work going into from the <unk>. One study to our nonhuman primate studies to arguments and I think that's really where we're able to take advantage of and I think benefit gallon that conjugation and the translator pharmacology that were seen in liver surface area between now nonhuman primate.

Speaker Change: In humans, so as we think about exposures as we think about concentrations in those pieces and we look at PK modeling of wears drug going I think we are able to say that there is again, a very well established pathway and pharmacology.

Paul Bolno: I think what's exciting as we think about the field of RNA editing and particularly restoration is that even in healthy volunteers, while you don't get TD assessment, that PK is translating very nicely. So I think that gives us a lot of confidence in the early modeling where we've got PD in the preclinical experiment but can translate that PK modeling across species, again, from mouse to non-human primates. I think the piece of why we say this proof of mechanism data is so critical is that it will give us and affirm for us as we relate back to that modeling, the PD prediction.

Speaker Change: I think what's exciting as we think about the field of RNA editing and particularly restoration one is even in the healthy volunteers. While you don't get PD assessment that Teekay is translating very nicely. So I think that gives us a lot of confidence on the early modeling where we've got PD in the preclinical experiment, but can translate that PK modeling across species again mounts to non.

Speaker Change: In the province.

Speaker Change: I think the piece of why we say it is proof of mechanism data is so critical as it will give us an affirm for us as we relate back to that modeling the PD prediction and then that's why we have set up multiple cohorts, which is not just about dose findings, but the ability to really now access also dose frequency and so we do think again the advantage of <unk>.

Paul Bolno: And then that's why we have set up multiple cohorts, which is not just about dose finding but the ability to really now assess also dose frequency. And so we do think, again, the advantage of having GalNec does give us that predictability that we are seeing in the translation.

Speaker Change: Going down that does give us that predictability that we are seeing in the translation.

Tiago Fauth: Got it. Perhaps just one quick follow-up there. Because again, there are mixed expectations from investors on what's the actual bar given the perceived to be competitive ATG landscape. So at your optimal dose, is crossing the 11 micromolar range enough? Do you need to get to an MN phenotype? Well, how are you guys thinking about the product profile? Thank you.

Operator: Got it perhaps just one quick follow up there.

Operator: There's mixed expectations from investors on what's the actual bar given the proceeds to be competitive atg landscapes. So.

Operator: At your optimal dose, is crossing the 11 micromolar range enough? Do you need to get to an MN phenotype?

Speaker Change: At your optimal dose is crossing the 11th micro molar range enough do you need to get to NMM phenotype.

Paul Bolno: Well, how are you guys thinking about the product profile? Thank you. Yeah, I mean it.

Speaker Change: How are you guys thinking about the product profile. Thank you.

Paul Bolno: Yeah, I mean, and a great question. And obviously, we spent a lot of time thinking about that as we entered the clinic and why we see an advantage across the entire profile of the therapeutic, meaning gal neck subcutaneous conjugation, durable, and frequent dosing. And to the last point, high potent editing. So really, these are three really important ingredients for chronic therapy. As you mentioned, 11 micromolar is a threshold as we think about the conversion of an ZZ patient to an MZ patient. And that's really one of the features of editing.

Paul Bolno: Yeah, I mean, and great question. And obviously, we spent a lot of time thinking about that as we entered the clinic and why we see an advantage across the entire profile of the therapeutic, meaning galnec subcutaneous conjugation, durable and frequent dosing, and, to the last point, high potent editing. So really, three really important ingredients for chronic therapy. As you mentioned, 11 micromolars is a threshold as we think about the conversion of an ZZ patient to an MZ patient, and that's really one of the features of editing.

Speaker Change: Great question, and obviously, we spent a lot of time thinking about that as we entered the clinic and why are we seeing advantage across the entire profile of the therapeutic meeting <unk> conjugation durable infrequent dosing and the last point high potent editing so really as three really important ingredient for a chronic therapy as you mentioned 11, Mike.

Paul Bolno: <unk> is a threshold as we think about the conversion of the patient to an entity patients and that's really one of the best features of editing that really reflects what we're talking there about micro molar about a fold improvement over baseline and we saw that as a seven fold improvement from where patient startup where Mike started to where we got them through that threshold took us.

Tiago Fauth: That really reflects what we're talking about here about micromolar, about a fold improvement over baseline. And we saw that as a sevenfold improvement from where patients started, where mice started, to where we got them to. That threshold took us surpassing that threshold of an MZ even into the MM healthy phenotype. So our preclinical data really demonstrated the fact that fold editing. And that's really one of the best ways to look at it going forward, because while you always see where that micromolar threshold is, it's that ability to turn on and push that threshold above where those patients are.

Paul Bolno: That really reflects what we're talking about here about micromolar, about a fold improvement over baseline. And we saw that as a sevenfold improvement from where patients started, where mice started, to where we got them to. That threshold took us beyond that threshold of an MZ even into the MM healthy phenotype. So our preclinical data really demonstrated the fact that fold editing, and that's really one of the best ways to look at it going forward.

Paul Bolno: Surpassing that threshold of an empty even into the MF publicly phenotype. So our preclinical data really demonstrated the fact that the bold editing and Thats really one of the best ways to look at it going forward, because while you always see where.

Paul Bolno: Because while you always see where that micromolar threshold is, it's that ability to turn on and push that threshold above where those patients are. So we're going to get a sense of that. Obviously, the proof of mechanism is the first step on that journey, but through the study, both single, multi, and multiple cohorts, that's where we're going to be able to continue to establish what that upper limit looks like. Again, as you pointed out, our preclinical data supports that we can surpass an 11 micromolar threshold, which gives us a lot of confidence, given the totality of the profile, that this really could be a best-in-class therapeutic and first in class for RNA editing for the treatment of alpha-1 antitrypsin deficiency.

Paul Bolno: We are aware that micro molar threshold.

Paul Bolno: <unk> ability to turn on a question that threshold above where those.

Tiago Fauth: So we're going to get a sense of that. Obviously, the proof of mechanism is the first step on that journey. But through the study, both single, multi, and multiple cohorts, that's where we're going to be able to continue to establish what that upper limit looks like. But again, as you pointed out, our preclinical data supports that we can surpass an 11 micromolar threshold, which gives us a lot of confidence, given the totality of the profile, that this really could be a best-in-class therapeutic and first in class for RNA editing for the treatment of alpha 1 anti-Trypsin division.

Paul Bolno: Patients are so we're going to get a sense of that obviously the proof of mechanism as the first step on that journey, but through the study both single both the multiple cohorts, that's where we're going to be able to continue to establish what that upper limit looks like but again as you pointed out our preclinical data supports that we can surpass a 11 micro molar threshold, which gives us a lot of.

Paul Bolno: understood. Thank you very much for taking the questions.

Operator: Thank you. One moment for our next question, and that will be a follow-up question from Joon Lee with Truist. Your line is open.

Paul Bolno: Confidence given the totality of the profile that this really could be a best in class therapeutic and bursting plots for RNA editing.

Paul Bolno: For the treatment of Alpha one antitrypsin deficiency.

Operator: understood. Thank you very much for taking the questions.

Speaker Change: Understood. Thank you very much for taking my questions.

Operator: Thank you. One moment for our next question, and that will be a follow-up question from Joon Lee with Truist. Your line is open.

Operator: Okay.

Joon Lee: Thank you.

Speaker Change: One moment for our next question.

Operator: And that will be a follow up question from Joon Lee with <unk>. Your line is open.

Joon Lee: Hey guys, thanks for taking our follow-up question. We recently conducted a cable call discussing the data that's being generated in the Huntington space between you, PTC, Unicure, and Rausch. And regarding the safety signal of hydrocephalus seen with Rubin-Erson and AMD-130, there are sort of two competing or maybe complementary theories. One is, you know, hydrocephalus due to defective cilia due to nonspecific knockdown of wild, Huntington, and leading to defective CSF flow.

Joon Lee: Hey guys, thanks for taking our follow-up question. We recently conducted a cable call discussing the data that's been generated in the Huntington space between you, PTC, Unicure, and Rausch, and regarding the safety signal of hydrocephalus seen with Rubin-Erson and AMD-130, there are sort of two competing or maybe complementary theories. One is, you know, hydrocephalus due to defective cilia due to nonspecific knockdown of wild Huntington leading to defective CSF flow. And the other is, you know, what she described as pseudo-atrophy due to reduced inflammation within the caudate and the ganglia, basal ganglia, driving that sort of pseudo-atrophy and having the appearance of hydrocephalus. We'd love to hear your thoughts on these theories and what your, you know, your evidence, what sort of evidence you have in your preclinical models and whatnot to support one versus the other.

Joon Lee: Hey, guys. Thanks for taking my follow up question.

Joon Lee: We recently conducted okay, well call discussing the data that's being generated in the Huntington space between us.

Speaker Change: PTC unit churn Roche.

Speaker Change: Regarding the safety signal hydrocephalus team with Rubin, our sone and <unk> hundred 30, there are sort of two competing or maybe complementary theories one is hydrocephalus due to defective sale yet.

Joon Lee: And the other is, you know, what she described as pseudo atrophy due to reduced inflammation within the caudate and the ganglia, basal ganglia, driving that sort of pseudo atrophy and having the appearance of hydrocephalus. We'd love to hear your thoughts on these theories and what the evidence is, what sort of evidence you have in your preclinical models and whatnot to support one versus the other.

Joon Lee: With knockdown of wild type.

Joon Lee: Huntington, leading to a decisive CSF flow and the other is what you described pseudo atrophy to reduce inflammation within the coty and the ganglia basal ganglia driving that.

Joon Lee: Sort of pseudo atrophy and having the insurance.

Speaker Change: I would love to hear your thoughts on the CRE and <unk>.

Joon Lee: But the evidence what sort of evidence you have in your preclinical models and whatnot.

Joon Lee: One versus the other.

Paul Bolno: Yeah, no, I mean, I think those are dueling theories that have been out there since the Thomannerson experience, and I think they speak to why we looked at imaging at the point where we did, and the key driver was to show we weren't seeing hydrocephalus. So I think it was really important to note that we didn't see hydrocephalus in the study. I think to the point of that theory, and I think it was one that was prevailing, was the cilia that are responsible for the movement of CSF flow are structurally comprised of healthy Huntington protein.

Paul Bolno: Yeah, no, I mean, I think those are dueling theories that have been out there since the Toma-Nursen experience. And I think they speak to why we looked at imaging at the point where we did, and the key driver was, "Too short; we weren't seeing hydrocephalus." So I think it was really important to note that we didn't see hydrocephalus in the study. I think to the point of that theory, and I think it was one that was prevailing, was the cilia that are responsible for the movement of CSF flow are structurally comprised of healthy Huntington protein.

Speaker Change: Yes, no I mean, I think those are dueling theories that have been out there since the <unk> experience and I think they spoke to why are we looked at imaging at the point, where we did and the key driver was.

Paul Bolno: So I'm sure if we werent seeing hydrocephalus. So I think it was really important to note that we didn't see hydrocephalus on the study I think to the point on that theory and I think it was one that was prevailing was the cilia that are responsible for the movement of CSF flow.

Paul Bolno: Our structurally comprised of healthy Huntington protein and so I think it was really a driver and this goes back to the early starting point of when we decided to go into the Huntington's disease space wasn't to make a.

Paul Bolno: And so I think it was really a driver. And this goes back to the early starting point of when we decided to go into the Huntington's disease phase. It wasn't to make a lower dose, more potent and durable version of pulmonersan; it was really to reflect on the underlying biology of suppression of the mutant protein while sparing wildlife. So the ability to demonstrate that, the ability then to be able to assess whether or not the absence of hydrocephalus and some of those other signals were there, you know, again, we didn't see that, is highly encouraging. So it was really a fundamental driver, both in what we saw in the existing study, and we moved forward. I don't know, Emery, if there's anything you want to add to that.

Paul Bolno: And so I think it was really a driver. And this goes back to the early starting point of when we decided to go into the Huntington's disease phase. It wasn't to make a lower dose, so a more potent and durable version of pulmonersan, it was really to reflect on the underlying biology of suppression of the mutant protein while sparing wildlife. So the ability to demonstrate that, the ability then to be able to assess whether or not the absence of hydrocephalus and some of those other signals were there, again, we didn't see that, which is highly encouraging. So it was really a fundamental driver, both in what we saw in the existing study and how we moved forward. I don't know, Emory, if there's anything you want to add to that.

Emory: Lower dose so more potent and durable version of <unk>. If there is really to reflect on the underlying biology.

Emory: Suppression of the mutant protein, while sparing wildlife so the ability to demonstrate that the ability then to be able to assess whether or not the absence of hydrocephalus in some of those other signals, but there again, we didnt see that I think are highly encouraging so it was really a fundamental driver.

Paul Bolno: Both in what we saw in the existing study and we go forward I don't know Emory if there's anything you want to add to that.

Ann Marie Lee Quichung: Tom and Ethan also reported that they are targeting younger patients because they think that they've got a better benefit risk in a younger age group with a lower disease burden. And it's also known that as people age, CSF flow becomes slower and less functional, so that might also point towards the theory around.

Anne-Marie Lee-Kwai Chung: Tom and Erson also reported that they are targeting younger patients because they think that they've got a better benefit risk in a younger age group with a lower disease burden. And it's also known that as people age, CSF flow becomes slower and less functional, so that might also point towards the theory around.

Speaker Change: <unk> reported.

Anne-Marie Lee-Kwai Chung: They are targeting younger patients and.

Anne-Marie Lee-Kwai Chung: Because I think that they've got a better benefit risk in a younger age group with another disease burden and its also known as people age.

Anne-Marie Lee-Kwai Chung: Flow becomes slower and less functional so that might also point towards the theory around Sylvia.

Anne-Marie Lee-Kwai Chung: Yes.

Operator: Thank you all for your participation.

Operator: Great

Speaker Change: Okay, great that makes sense.

Operator: Okay.

Chip: Thank you chip.

Paul Bolno: Thank you. I'm showing no further questions in the queue at this time. I would now like to turn the call back over to Dr. Paul Bolno for any closing remarks. Thank you for joining our call this morning. We hope you all...

Speaker Change: Thank you I'm showing no further questions in the queue. At this time I would now like to turn the call back over to Mr. Doctor I am sorry to Dr. Paul Ball now with any closing remarks.

Operator: This concludes today's program. Thank you all for participating. You may now disconnect.

Paul Bolno: wonderful. Thank you for joining our call this morning. We hope you all take some time to enjoy the remainder of your summer, and we look forward to keeping you updated on our progress. Have a great day.

Speaker Change: Thank you for joining our call. This morning, we hope you all take some time to enjoy the remainder of your summer and we look forward to keeping you updated on our progress have a great day.

Paul Bolno: Yeah.

Operator: This concludes today's program. Thank you all for participating. You may now disconnect.

Paul Bolno: This concludes today's program. Thank.

Paul Bolno: Thank you all for participating you may now disconnect.

Paul Bolno: Okay.

Paul Bolno: [music].

Paul Bolno: Okay.

Paul Bolno: [music].

Paul Bolno: Okay.

Paul Bolno: Yes.

Paul Bolno: Okay.

Paul Bolno: We are very excited about the broad potential of this program in obesity and look forward to sharing more data at our annual R&D meeting. Looking ahead, we believe we can demonstrate clinical proof of concept with just a single dose of our inhibin-E siRNA in a study of healthy overweight volunteers. We remain on track to file a CTA for 007 as early as the end of the year and initiate a clinical trial in the first quarter of next year.

Paul Bolno: But we will be assessing both MAT protein total, and we will be able to assess that for the first time in humans. And the key driver of that is your point to really be able to assess it for the first time in humans.

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