Q2 2025 Wave Life Sciences Ltd Earnings Call

Operator: Thanks, Cole. We ask that you please hold all questions until the completion of the formal remarks, at which time you will be given instructions for the question and answer session. Also, as a reminder, this conference is being recorded today. I will now pass the call over to Kate Rausch, Vice President of Corporate Affairs and Investor Relations.

Questions until the completion of formal remarks at which time.

You will be given instructions for the question and answer session also as a reminder, this conference is being recorded today I will now pass the call over to Kate Walsh, Vice President of corporate Affairs and Investor Relations.

Thank you operator, and good morning to everyone on the call earlier. This morning, we issued a press release outlining our second quarter 2025 earnings update joining.

Kate Rausch: Thank you, operator. Good morning to everyone on the call. Earlier this morning, we issued a press release outlining our Q2 2025 earnings update. Joining me today with prepared remarks are Dr. Paul Bolno, President and Chief Executive Officer, Dr. Erik Ingelsson, Chief Scientific Officer, and Kyle Moran, Chief Financial Officer. Dr. Christopher Wright, Chief Medical Officer, is also in the room and will be available for questions. 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 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.

Joining me today with prepared remarks are Dr. Pagano, President and Chief Executive Officer, Dr. Eric Angleton, Chief Scientific Officer, and calm Moran Chief Financial Officer, Dr. Chris Wright Chief Medical Officer is also in the room and will be available for questions. The press release issued this morning is available on the investors section of our website Www dot.

Wave life Sciences dotcom.

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, we undertake no obligation to update or.

Kate Rausch: 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.

Or revise any forward looking statement for any reason I'd now like to turn the call over to Paul.

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

Paul Bolno: Thanks, Kate. Good morning, and thank you all for joining us on today's call. We enter the H2 2025 with strong momentum as we continue on our mission of unlocking the broad potential of RNA medicines using our proprietary and best-in-class oligonucleotide chemistry. Since the start of the year, we have made considerable progress. We continue to extend our leadership in RNA editing with our AATD clinical program. We initiated and rapidly advanced our INLIGHT clinical program for obesity, delivered positive data from our FORWARD-53 clinical trial of WVE-N531 for DMD, and continue to advance our Allele-Selective HD program in preparation for a potentially registrational study. In tandem with our recent progress, we welcome Dr. Christopher Wright as our Chief Medical Officer in May.

We enter the second half of 2025 with strong momentum as we continue on our mission of unlocking the broad potential of RNA medicines, using our proprietary and best in class Oligonucleotide chemistry.

Since the start of the year, we have made considerable progress we continue to extend our leadership in RNA editing with our <unk> clinical program, we initiated and rapidly advance our enlighten clinical program for obesity delivered positive data from our 453 clinical trial of in fact, three one for D. M D and continued to advance our allele.

<unk> HD program in preparation for potentially Registrational study.

In tandem with our recent progress we welcomed Dr. Chris Wright as our Chief Medical Officer Ms. Chris.

Chris brings considerable expertise in drug development that spans both rare and common diseases as well as an impressive track record of success working with U S and EU regulatory agencies to oversee the development of therapeutics from early stages to approval.

Paul Bolno: Christopher Wright brings considerable expertise in drug development that spans both rare and common diseases, as well as an impressive track record of success working with US and EU regulatory agencies to oversee the development of therapeutics from early stages to approval. His extensive experience in development and his background as a practicing physician will prove invaluable as we continue to advance our pipeline in the clinic and approach key data readouts and prepare for regulatory filings. Starting with WVE-006, our GalNAc-conjugated RNA editing oligonucleotide, or AIMer, for alpha-1 antitrypsin deficiency. WVE-006 is designed to be the first treatment for AATD that addresses the root cause of the disease with a convenient subcutaneously dosed therapeutic. WVE-006 does not require IV-administered LNPs or complex delivery vehicles like other treatments in development. This profile supports treating the AATD population, those with liver or lung manifestations of disease, or both.

His extensive experience in development and his background as a practicing physician will proven valuable as we continue to advance our pipeline in the clinic and approach key data readouts and prepare for regulatory filings.

Starting with WV zero-zero, six our galvanic RNA editing oligonucleotides or Amer for Alpha one antitrypsin deficiency.

<unk> is designed to be the first treatment for ACD that addresses the root cause of the disease with a convenient subcutaneously dosed therapeutic.

<unk> does not require IV administered lnp's or complex livery vehicles like other treatments in development. This profile supports treating the ATB population, those with liver or lung manifestations of disease or both.

We've heard powerful testimonies directly from patients that speak to the harsh impact of this disease, which begins early in life and is often misdiagnosed underscoring the immense need for effective therapies.

Paul Bolno: We've heard powerful testimonies directly from patients that speak to the harsh impact of this disease, which begins early in life and is often misdiagnosed, underscoring the immense need for effective therapies. Our initial proof of mechanism data from RestorAATion-2 last year delivered a breakthrough in the field of RNA medicines, representing the first-ever clinical demonstration of RNA editing in humans. In the first 2 patients after a single 200-milligram dose, we observed mean 6.9 micromolar of circulating M-AAT and 10.8 micromolar of total AAT. We also observed increases in AAT from baseline as early as day 3 and as late as day 57, which highlights 006's impressive durability of effect and support the potential for monthly or less frequent dosing. In both RestorAATion-2 and our RestorAATion-1 clinical trial of healthy volunteers, we reported that 006 was well-tolerated with a favorable safety profile.

Our initial proof of mechanism data from restoration to last year delivered a breakthrough in the field of RNA medicines, representing the first ever clinical demonstration of RNA editing in humans and.

In the first two patients after a single 200 milligram dose we observed mean six nine micro molar circulating <unk> and $10 eight micro molar total AG. We also observed increases in <unk> from baseline as early as day, three and his latest day 57, which highlights <unk> impressive durability of effect.

And support the potential for monthly or less frequent dose.

And both restoration too and our restoration one clinical trial of healthy volunteers, we reported that <unk> was well tolerated with a favorable safety profile.

As a reminder, by editing at the RNA level <unk> differs from DNA editing technologies, which rely on hyperactive exogenous fleet delivered artificial enzymes.

Paul Bolno: As a reminder, by editing at the RNA level, 006 differs from DNA editing technologies, which rely on hyperactive exogenously delivered artificial enzymes. Preclinical data has clearly demonstrated DNA-based editing results in irreversible collateral bystander edits and indels. These known bystander edits must be taken into consideration when interpreting clinical results. Following our proof of mechanism announcement, we saw a surge in community and clinician engagement in our program. We have completed multi-dosing in the first cohort, where 8 patients received 7 200-milligram doses of 006 administered every other week. We've completed dosing in our second single-dose cohort at 400 milligrams. We are on track to deliver data from the complete 200-milligram single and multi-dose cohorts in the Q3. Single-dose data from our 400-milligram cohort in the fall.

Preclinical data has clearly demonstrated DNA base editing results of irreversible collateral bystander edits in inbound and these don't buy standard edits must be taken into consideration when interpreting clinical results.

Following our proof of mechanism announcements, we saw a surge in community and clinician engagement in our program. We have completed multi dosing in the first cohort where patients received <unk> 200 milligram doses of <unk> administered every other week and we've completed dosing in our second single dose cohort at 400 milligrams, we are on track.

To deliver data from the complete 200 milligram single and multi dose cohort in the third quarter at a single dose data from our 400 milligram cohort in the fall.

As we look ahead to sharing complete data from the first cohort. This quarter. We are encouraged by the profile we observed thus far from just the first two patients at our lowest dose we are already at <unk> protein levels indicative of converting from Z to MSC phenotypes, and our preclinical data and clinical data with Pn.

Paul Bolno: As we look ahead to sharing complete data from the first cohort this quarter, we are encouraged by the profile we observed thus far. From just the first 2 patients at our lowest dose, we are already at AAT protein levels indicative of converting from ZZ to MZ phenotypes. Our preclinical data and clinical data with PN chemistry, as well as our novel N3-uridine modifications, indicate the potential for even greater production of protein with multi-dosing. We believe the multi-dose 200-milligram data, coupled with data from the higher 400-milligram single-dose cohort, will inform the therapeutic potential of 006 and how we strike the balance between driving higher protein levels and extending the dosing interval as our preclinical and clinical data support the potential for extended dosing intervals in subsequent cohorts.

Chemistry, as well as our novel <unk> modifications indicate the potential for even greater production of protein with multi dosing.

We believe the multi dose 200 milligram data coupled with data from the higher 400 milligram single dose cohort, we will inform the therapeutic potential of <unk> and how we strike the balance between driving higher protein levels and extending the dosing interval as our preclinical and clinical data support the potential for extended dosing intervals and subsequent.

Cohorts.

Turning to <unk> 007, our <unk> inhibitor candidate designed to deliver healthy sustainable weight loss for obesity.

Paul Bolno: Turning to WVE-007, our GalNAc-siRNA INHBE candidate designed to deliver healthy, sustainable weight loss for obesity. Since our last update, we have rapidly advanced our INLIGHT clinical study, which is currently evaluating single doses of 007 in adults living with overweight or obesity. Today, we are pleased to share that we have expanded our second cohort of INLIGHT, which evaluates a 240 mg dose from 8 to 32 participants. This expansion cohort has completed dosing. The decision to expand was triggered by favorable safety and tolerability as well as robust Activin E reduction observed in cohort 1, which is evaluating a single 75 mg dose of 007. The clinical Activin E reduction we saw in cohort 1 confirms the successful clinical translation of our siRNA platform and strengthens our conviction in our preclinical model.

Since our last update we have rapidly advanced our in light clinical study, which is currently evaluating single doses of 007 and adults living with overweight or obesity.

Today, we are pleased to share that we have expanded our second cohort of enlighten, which evaluate the 240 milligram dose from 8% to 32 participants and this expansion cohort has completed dosing.

The decision to expand was triggered by favorable safety and Tolerability as well as robust active and <unk> reduction observed in cohort, one which is evaluating a single 75 milligram dose of <unk> seven.

The clinical active an <unk> reduction we saw in cohort one confirms the successful clinical translation of our RNA platform and strengthens our conviction in our preclinical model.

Based on these models are preclinical Io weight loss data cohort, two which tested dose more than three times higher than cohort one is projected to be therapeutically active and enable the evaluation of healthy weight loss.

Paul Bolno: Based on these models, our preclinical DIO weight loss data, cohort 2, which tests a dose more than three times higher than cohort 1, is projected to be therapeutically active and enable the evaluation of healthy weight loss. The favorable safety and tolerability profile observed to date have also enabled us to dose escalate to a third 400 mg cohort, dosing is now underway in cohort 3. Our ability to rapidly recruit, enroll, expand, and dose participants has positioned us to deliver multiple impactful data sets. We expect to deliver data from the expanded 240 mg second dose cohort of INLIGHT, as well as data from the 75 mg cohort 1 in Q4 2025, including safety, tolerability, and measurements reflective of healthy weight loss, and data from the 400 mg third dose cohort of INLIGHT in Q1 2026.

The favorable safety and Tolerability profile observed to date have also enabled us to dose escalate to a third 400 milligram cohort and dosing is now underway in cohort three.

Our ability to rapidly recruit enroll expand and dose participants has positioned us to deliver multiple impactful datasets, we expect to deliver data from the expanded 240 milligram second dose cohort have been light as well as data from the 75 milligram cohort one in the fourth quarter of 2025.

Including safety Tolerability and measurements reflective of healthy weight loss and data from the 400 milligram third dose cohort of <unk> light in the first quarter of 2026.

Upcoming data from both restoration and in light serve as key inflection points to inform our growing wholly owned discovery pipeline addressing both hepatic and extra hepatic targets with our RNA editing <unk> and Rsi Rnase.

Paul Bolno: Upcoming data from both RestorAATion and INLIGHT serve as key inflection points to inform our growing wholly-owned discovery pipeline, addressing both hepatic and extrahepatic targets with our RNA editing AIMers and our siRNAs. We look forward to providing an update on these programs at our upcoming research day this fall and remain on track to initiate clinical development of new programs in 2026. Turning to our late-stage pipeline in DMD and HD. Over the quarter, we have been actively engaging with the DMD community around our exciting FORWARD-53 clinical results. These data have supported WVE-N531 as a best-in-class and important new therapeutic option for boys with exon 53 amenable DMD.

Look forward to providing an update on these programs at our upcoming research day. This fall and remain on track to initiate clinical development of new programs in 2026.

Turning to our late stage pipeline in DMD and HD over the quarter, we have been actively engaging with the DMD community around our exciting forward 53 clinical results. These data have supported <unk>. Three one is a best in class and important new therapeutic option for boys with exon 53 amenable DMD.

As a reminder, following 48 weeks of treatment with <unk> hundred one we observed a statistically significant and clinically meaningful improvement of three eight seconds and time to rise versus natural history, which is the largest effect observed relative to any approved district and restoration therapy at 48 weeks.

Paul Bolno: As a reminder, following 48 weeks of treatment with WVE-N531, we observed a statistically significant and clinically meaningful improvement of 3.8 seconds in time to rise versus natural history, which is the largest effect observed relative to any approved dystrophin restoration therapy at 48 weeks. There were also additional functional benefits observed in other outcome measures, including North Star Ambulatory Assessment. These data were also the first-ever demonstration of substantial improvements in muscle health with exon skipping, including a statistically significant reduction in fibrosis and decreases in creatine kinase and circulating inflammatory biomarkers. Notably, we observed clinical evidence of myogenic stem cell or satellite cell uptake of WVE-N531 earlier in our trial, which supports the improvement in muscle health and muscle fiber maturation we observed at 48 weeks.

There were also additional functional benefits observed in other outcome measures, including Northstar ambulatory assessment.

These data were also the first ever demonstration of substantial improvements in muscle health with exon skipping, including a statistically significant reduction in fibrosis and decreases in creatinine kinase and circulating inflammatory biomarkers.

Notably we observed clinical evidence of myogenic stem cell or satellite so uptake.

And in fact, we won earlier in our trial, which supports the improvement in muscle and muscle fiber maturation, we observed at 48 weeks.

Aware of any other clinical data for exon skippers or gene therapy, they have been able to demonstrate myogenic stem cell uptick.

Paul Bolno: 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. WVE-N531 is also differentiated by the supporting preclinical evidence, demonstrating even greater access to heart and diaphragm as compared to skeletal muscle. Following a positive and productive meeting with the FDA on our 24-week data, we aligned with the agency on next steps for N-531. We intend to submit an NDA in 2026 for accelerated approval of N-531 with a monthly dosing regimen. In the interim, we plan to continue to engage with the agency with our 48-week data and our planned global confirmatory trial design.

<unk> and 531 is also differentiated by the supporting preclinical evidence demonstrating even greater access to heartland diaphragm as compared to skeletal muscle.

Following a positive and productive meeting with the FDA on our 24 week data, we align with the agency on next steps are in fact, we won and we intend to submit an NDA in 2026 for accelerated approval of in fact, we won with a monthly dosing regimen.

In the interim we plan to continue to engage with the agency with our 48 week data at our planned global confirmatory trial design.

And HD, we are continuing to prepare for a global potentially registrational phase III study of WV easier zero three in adults with SNP, III and HD using cartage volume as a primary endpoint.

Paul Bolno: In HD, we are continuing to prepare for a global, potentially registrational phase II/III study of WVE-003 in adults with SNP3 and HD using caudate volume as a primary endpoint and are actively engaged in discussions with prospective strategic partners. Developed using our platform specificity of stereochemical control and best-in-class chemistry, we designed 003 to be the first allele-selective approach in HD. By reducing mutant huntingtin at the mRNA and protein level, 003 addresses the underlying drivers of neurodegeneration. By sparing wild-type protein, which is critical to the health of central nervous system, 003 is uniquely positioned to address the full spectrum of HD, from early asymptomatic stage through the onset of symptoms and beyond.

And are actively engaged in discussions with prospective strategic partners.

Developed using our platform specificity of stereo chemical control and best in class Chemistry, we designed zero-zero three to be the first allele selective approach in HD.

By reducing mutant Huntington at the mrna and protein levels.

Zero three addresses the underlying drivers of nerve degeneration.

And by sparing Wild type protein, which is critical to the health of the central nervous system Zero-zero three is uniquely positioned to address the full spectrum of HD from early asymptomatic stage through the onset of symptoms can be up.

And select HD, we demonstrated the impact of our novel chemistry, and OBL selective approach as we observed potent and durable Huntington reductions of up to an industry, leading 46% and preservation of wild type Huntington with just three doses importantly, we observed a statistically significant correlation between.

Paul Bolno: In SELECT-HD, we demonstrated the impact of our novel chemistry and allele-selective approach as we observed potent and durable mutant huntingtin reductions of up to an industry-leading 46% and preservation of wild-type huntingtin with just 3 doses. Importantly, we observed a statistically significant correlation between allele-selective mutant huntingtin reductions and slowing of caudate atrophy, marking the first time this correlation has been observed in HD. At the beginning of the year, we shared our own internal analysis, which investigated natural history datasets, including TRACK-HD and PREDICT-HD, and observed that an absolute reduction of just 1% in the rate of caudate atrophy is associated with a delay of onset of disability by more than 7 and a half years. This is a staggering number with meaningful implications for both health and economic outcomes and provides further evidence supporting rate of caudate atrophy as a primary endpoint for an efficient clinical trial.

No real selective mutant Huntington reductions and slowing of chordate atrophy, marking the first time. This correlation that's been observed in HD.

At the beginning of the year, we shared our own internal analysis, which investigated natural history dataset, including track and predict HD and observed that an absolute reduction of just 1% in the rate of call. It atrophy is associated with the delay of onset of disability by more than seven and a half years. This is a staggering number with meaningful implications.

Patients for both health and economic outcomes and provides further evidence supporting rate upon rate atrophy as a primary endpoint for an efficient clinical trial.

These data along with the full clinical results in select HD were both part of our engagement with FDA last year and led to supportive initial feedback we remain on track to submit clinical trial applications, including an IND application for this phase three study in the second half of this year.

Paul Bolno: These data, along with the full clinical results from SELECT-HD, were both part of our engagement with FDA last year and led to supportive initial feedback. We remain on track to submit clinical trial applications, including an IND application for this phase II/III study in the H2 of this year. With that, I'll now turn the call over to Erik to share more detail on our inhibin program and emerging oligo pipeline.

With that I'll now turn the call over to Eric to share more detail on our inhibitor program and emerging wholly owned pipeline.

Thank you Paul and thank you to everyone joining us on the call today.

Erik Ingelsson: Thank you, Paul, and thank you to everyone joining us on the call today. I'll begin by discussing our inhibin program for obesity, INLIGHT. INLIGHT is our first-in-human study of WVE-007, designed to assess safety, tolerability, pharmacokinetics, target engagement, body weight and composition, and other measures of cardiometabolic health. The first stage of INLIGHT is investigating single doses of WVE-007 in healthy adults living with overweight or obesity in up to five single ascending dose cohorts of eight participants each, with the option to expand specific cohorts. Our first cohort began with eight participants receiving a single 75mg dose of WVE-007. In this cohort 1, our goal was to demonstrate favorable safety and target engagement, which would enable us to advance INLIGHT to therapeutically relevant doses where we would expect to see healthy weight loss.

I'll begin by discussing our M&A program for obesity and lives in.

And lives is our first in human study of <unk> seven designed to assess safety Tolerability pharmacokinetics target engagement bodyweight and compensation and other measures of cardio metabolic health.

First stage in life is investigating single doses of <unk> in.

In healthy adults living with overweight or obesity in up to five single ascending dose cohorts of eight participants each.

<unk> expense specific cohorts are first court again with eight participants receiving a single 75 milligram dose. There is there are seven and this cohort one our goal was to demonstrate favorable safety and target engagement, which would enable us to advance in life at therapeutically relevant doses, where we would expect to see healthy weight loss at.

As Paul said earlier, there are seven was safe and well tolerated and delivered robust activity reduction, enabling us to expand our second dose cohort from eight to 32 patients at 240 milligrams, which is the dose level, we are modeled to be therapeutically relevant for achieving healthy weight loss and.

Erik Ingelsson: As Paul shared earlier, 007 was safe and well-tolerated and delivered robust active inhibin reduction, enabling us to expand our second dose cohort from 8 to 32 patients at 240 mg, which is a dose level we have modeled to be therapeutically relevant for achieving healthy weight loss. In addition, the favorable safety and tolerability that we've observed to date has enabled us to dose escalate to 400 mg in cohort 3, which is now underway. The favorable safety profile and target engagement we're seeing with 007 is very encouraging, as we have now checked the boxes on several key factors increasing probability of successful drug development. The first key factor is human genetics.

In addition, the favorable safety and Tolerability that we've observed to date has enabled us to dose escalate to 400 milligrams in cohort three which is now underway.

The favorable safety profile and target engagement, we're seeing with <unk> is very encouraging as we are now check the boxes on several key factors increasing probability of successful drug development.

The first key factor, assuming genetics targets supported by human genetics are on average.

Erik Ingelsson: Targets supported by human genetics are on average associated with a 2 to 4 times higher probability of success in drug development, with coding variants with known directionality in the upper part of that range, around 4 times more likely to reach market than those without human genetics. Several large human genetic studies have found that carriers of heterozygous loss-of-function variants in the INHBE gene have favorable metabolic profiles, including reduced abdominal obesity and visceral fat, serum triglycerides, ApoB, fasting glucose, HbA1c, and decreases in several measures of liver disease. These carriers also have reduced risks of type 2 diabetes and coronary heart disease. In a sense, the outcome studies have already been conducted with this target using nature's experiment. Secondly, drug development programs with biomarker evidence are also associated with higher probability of success.

Two to four times higher probability of success in drug development with coating binds with known directionality in the upper part of that range around four times more likely to reach market than those without.

Several large <unk> studies have found a carriers of heterozygous loss of function Barnes <unk> been aging have favorable metabolic profiles, including reduced abdominal obesity on Vishal Shah Chairman triglycerides, APB fasting glucose HB, one fee and decreases in several measures of liver disease. These carriers also have reduced stress.

<unk> of type two diabetes and coronary heart disease in a sense. The outcome studies have already been conducted with its target using matrix experiment.

Secondly, drug development programs with biomarker evidence or all of this is with higher probabilities of success. Therefore, the successful target engagement data with reduction in circulating activity levels is an important step towards clinical translation of our preclinical data.

Erik Ingelsson: Therefore, the successful target engagement data with reduction in circulating active inhibin E levels is an important step towards clinical translation of our preclinical data. In our recent presentation at the American Diabetes Association Conference, we presented data showing that circulating active inhibin E levels decreased by 80% following a single dose of inhibin E siRNA treatment in diet-induced obesity mouse models that showed weight loss on par with semaglutide, with a strong correlation of circulating active inhibin E with liver inhibin E mRNA. Now, with our first clinical cohort, we have demonstrated target engagement in the clinic, as treatment with 007, our inhibin E GalNAc-siRNA, is leading to robust reductions in active inhibin E, even at 75 mg, a dose modeled to be subtherapeutic. The third key factor for successful drug development is safety and tolerability.

In a recent presentation at the American diabetes.

Association Conference, we presented data showing that circulating activity levels decreased by 80%. Following a single dose of <unk> treatment in diet induced obese mouse models that showed wastewater on par with some of this type.

The strong correlation of circulating activity with limb ran a binney mrna.

And now with our first clinical cohort demonstrated target engagement in the clinic as treatment with <unk> seven are in and many gallon I guess RNA is leading to robust reductions in activity, even at 75 milligram dose malls to be sub therapeutic.

The third key factor for successful drug development, the safety and Tolerability.

Profile of their seven has the potential to be clearly differentiated from current standard of care approaches <unk>. One agonists have rapidly become the standard of care in obesity or use is often limited by core colorability, primarily due to Gi side effects, which contributes to a high discontinuation rates. In addition to the loss of muscle mass as well as frequent dose.

Erik Ingelsson: The profile of 007 has the potential to be clearly differentiated from current standard of care approaches. While GLP-1 agonists have rapidly become the standard of care in obesity, their use is often limited by poor tolerability, primarily due to GI side effects, which contributes to high discontinuation rates in addition to loss of muscle mass, as well as frequent dosing. In contrast, 007 is designed to leverage an entirely orthogonal mechanism of action focused on directly inducing fat loss by increasing lipolysis in adipocytes while preserving muscle mass, all with infrequent dosing of once or twice a year. Our data to date support that 007 has a favorable safety and tolerability profile. The last key factor for successful drug discovery is robust efficacy data from translationally relevant models.

In contrast, <unk> is designed to leverage an entirely or <unk> mechanism of action focused on directly and using fast pulse by increasing like policies in adipocyte, while preserving muscle mass all with infrequent dosing of once or twice a year.

Our data today support that <unk> has a favorable safety and tolerability profile.

And the last key back of our successful drug discovery is robust efficacy data from translation only relevant models.

Pre clinically we have shown extensive data supporting <unk> unique mechanism of action replicating the human genetic findings from heterozygous <unk> loss of function. Cherish. This includes weight loss on par with summit Glucide driven entirely by reductions in fact with muscle sparing on monotherapy doubled effects when combined with <unk> and <unk>.

Erik Ingelsson: Preclinically, we have shown extensive data supporting WVE-007's unique mechanism of action, replicating the human genetic findings from heterozygous inhibin E loss-of-function variant carriers. This includes weight loss on par with semaglutide, driven entirely by reductions in fat with muscle sparing on monotherapy, doubled effect when combined with semaglutide, and prevention of weight regain upon discontinuation of semaglutide. Additionally, as we showed in our recent American Diabetes Association conference presentation, treatment with inhibin E GalNAc-siRNA was linked to decreases of adipocyte size and shrinkage of visceral fat volume, as well as lower inflammation of adipose tissue with strong suppression of proinflammatory M1 macrophages, shifting the balance from a proinflammatory to an anti-inflammatory state in visceral fat in DIO mice. Taken together, these data highlight mechanistic insights potentially explaining the risk reduction for type 2 diabetes and coronary heart disease suggested by the human genetics data.

<unk> way three gains upon this combination of some of your.

Additionally, as we showed in our recent American Diabetes Association conference presentation treatment with <unk> like SMA was linked to decreases of adipose adipocyte size and shrinkage of visual flat volume as well as lower inflammation of adipose tissue with strong suppression of pro inflammatory am one macrophages shifting to battle.

From a pro inflammatory and anti inflammatory state and Vishal fast in Dio mice.

Together these data highlight mechanistic insights potentially explaining the risk reduction for type two diabetes and coronary heart disease suggested by the human data.

With upcoming data from cohort two at a dose level, we expect to be therapeutically active we'll look forward to demonstrate <unk> ability to deliver healthy weight loss and.

Erik Ingelsson: With upcoming data from cohort 2 at a dose level we expect to be therapeutically active, we'll look further to demonstrate 007's ability to deliver healthy weight loss. In addition to straight weight loss, we'll have the opportunity to assess key measurements reflective of healthy weight loss, such as body composition from DEXA scans and biomarkers reflecting cardiometabolic health. It is important to note that based on inhibin E mechanism of action and preclinical and human genetics data, it's expected that any weight loss observed would be entirely driven by fat loss.

In addition to straight weight loss will have the opportunity to assess key measurements reflective of healthy weight loss, such as multi competition from Baxter scans and biomarkers, reflecting part of metabolic count. It is important to note that based on the mechanism of action in preclinical and Jim genetics data is expected of any weight loss absurd would be entirely driven by <unk>.

Bob This is particularly notable difference from current standard of care approaches such as <unk>, which are associated with substantial muscle loss of can account for 30% to 50% of total weight loss.

Erik Ingelsson: This is particularly a notable difference from current standard care approaches, such as the GLP-1s, which are associated with substantial muscle loss that can account for 30% to 50% of total weight loss. With equivalent fat loss but without muscle loss, the insulin sensitivity is expected to be substantially higher given the importance of skeletal muscle for insulin sensitivity, further emphasizing the potential for 007 as a transformational approach to healthy weight loss. Our upcoming AATD and inhibin E data readouts will also provide us with valuable insights into our growing pipeline of RNA editing and mRNA programs. Behind 006 and 007, we're continuing to advance a wholly-owned discovery pipeline addressing both hepatic and extrahepatic targets. Our pipeline of preclinical candidates utilize our proprietary chemistry to achieve best-in-class RNA editing and mRNA silencing in both rare and common diseases.

With equivalent fat salt, but without muscle loss insulin sensitivity is expected to be substantially higher given the importance of skeletal muscle for insulin sensitivity further emphasizing the potential for <unk> seven as a transformational approach to healthy weight loss.

Our upcoming <unk> data Readouts will also provide us with valuable insights into our growing pipeline of RNA editing MF RNA programs.

<unk> seven we're continuing to advance our wholly owned discovery pipeline addressing both the <unk> and extra product targets, our pipeline of preclinical candidates utilize our proprietary chemistry to achieve best in class RNA editing MSR, a nice balancing in both rare and common diseases.

We unveiled several Holly owned programs at our research day last call, which is gallon conjugation, including <unk> III and RNA correction program, but it's on track for Cta filing in 2026. This approach is likely to be superior to <unk> RNA knockdown due to the important role of the wild type protein and lipid metabolism and has the potential to address the nine.

Erik Ingelsson: We unveiled several wholly-owned programs at our research day last fall, which use GalNAc conjugation, including PNPLA3, an RNA correction program that is on track for CTA filing in 2026. This approach is likely to be superior to mRNA knockdown due to the important role of the wild type protein in lipid metabolism and has the potential to address the 9 million homozygous I148M carriers in the US and Europe with liver disease. In addition, last year, we shared preclinical data highlighting our ability to direct silencing and editing to high-priority extrahepatic tissues, including CNS, skeletal muscle, adipose, heart, pancreas, and lung. We look forward to providing a further update from our emerging pipeline at our research day this fall. With that, I'd like to turn the call over to Kyle to provide an update on our financials. Kyle?

Homozygous <unk> hundred 48 am carriers in the U S and Europe with Liberty.

In addition last year, we've shared preclinical data highlighting our ability to direct financing and other things of high priority extra productivity, including CNS skeletal muscle adipose cart Congress.

We look forward to providing a further update from our emerging pipeline at our research day. This fall with that I'd like to turn the call over to Karl to provide an update on our financials.

Thanks, Eric.

Our revenue for the second quarter of 2025 was $8 7 million.

Kyle Moran: Thanks, Erik. Our revenue for Q2 2025 was $8.7 million, compared to $19.7 million in the prior year quarter. The year-over-year decrease was attributable to the timing of revenue recognized under our collaboration agreement with GSK. Research and development expenses were $43.5 million for Q2 2025 as compared to $40.4 million in the same period in 2024. This increase was primarily driven by spending in our inhibin E program and RNA editing programs, as well as compensation-related expenses, including share-based compensation. Our G&A expenses were $18 million for Q2 2025 as compared to $14.3 million in the prior year quarter, primarily related to share-based compensation and other external expenses. As a result, our net loss was $50.5 million for Q2 2025 as compared to a net loss of $32.9 million in the prior year quarter.

Compared to $19 7 million in the prior year quarter.

The year over year decrease was attributable to the timing of revenue recognized under our collaboration agreement with GSK.

Research and development expenses were $43 $5 million for the second quarter of 2025 as compared to $44 million in the same period in 2024.

This increase was primarily driven by spending in our inhibitor program and RNA editing programs as well as compensation related expenses, including share based compensation.

Our G&A expenses were $18 million for the second quarter of 2025.

<unk> to $14 3 million for the prior year quarter.

Primarily related to share based compensation and other external expenses.

As a result, our net loss was $50 5 million for the second quarter of 2025 as compared to a net loss of $32 $9 million in the prior year quarter.

We ended the second quarter of 2025 with $208 5 million in cash and cash equivalents compared to $302 1 million as of December 31, 2024.

Kyle Moran: We ended the Q2 2025 with $208.5 million in cash and cash equivalents, compared to $302.1 million as of 31 December 2024. We expect that our current cash and cash equivalents will be sufficient to fund operations into 2027. It's important to note that potential future milestones and other payments to Wave under our GSK collaboration are not included in our cash runway. I'll now turn the call back over to Paul for closing remarks.

We expect that our current cash and cash equivalents will be sufficient to fund operations into 2027.

It's important to note the potential future milestones and other payments to waive under our GSK collaboration are not included in our cash runway.

I'll now turn the call back over to Paul for closing remarks.

Thank you.

We're excited to see the continued translation of our novel chemistry in the clinic and look forward to building on our success in the second half with comprehensive data updates expected from a restoration too and in late trials. We look forward to keeping you updated on our progress throughout the year as we continue to re imagine what's possible for patients with that.

Paul Bolno: Thank you, Kyle. We are excited to see the continued translation of our novel chemistry in the clinic, and look forward to building on our success in the H2 with comprehensive data updates expected from our RestorAATion-2 and INLIGHT trials. We look forward to keeping you updated on our progress throughout the year as we continue to reimagine what's possible for patients. With that, I'll turn it to the operator for Q&A. Operator?

I'll turn it to the operator for Q&A operator.

Okay.

Thank you at this time, if you would like to ask a question. Please click on the right hand button, which can be found at the bottom of using screen you may remove yourself from the queue at any time by lowering your hand.

Operator: Thank you. At this time, if you would like to ask a question, please click on the raise hand button, which can be found at the bottom of your Zoom screen. You may remove yourself from the queue at any time by lowering your hand. When it is your turn, you will hear your name called. Once you've been called on, please unmute yourself and begin to ask your question. Please limit to one question and one follow-up before jumping back into the queue. We will now wait a moment to allow the queue to form. Great. Our first question comes from Joon Lee at Truist Securities. Please unmute yourself and ask your question.

And as you will hear union called once you've been called on mute yourself can begin to ask a question. Please limit to one question and one follow up before jumping back into the queue. We will now wait a moment to allow this uniform.

Yeah.

Okay.

Our first question comes from Joon Lee with Securities. Please on yourself and ask your question.

Hi.

Can you guys hear me yes.

Joon Lee: Hi. Can you guys hear me?

Okay. Thanks for the updates and for taking our questions.

Paul Bolno: Yes.

Joon Lee: Okay. Thanks for the updates and for taking our questions. For the inhibin E program, can you elaborate on your reasons for expanding cohort 2 over advancing to cohort 3 sooner? If the cohort 2 dose was well-tolerated, why not just advance to cohort 3 versus expanding cohort 2? Also, when you say cohort 2 dose is therapeutically relevant, is that in reference to semaglutide-like weight loss? Finally, is the goal of Activin E knockdown around 50% based on your human heterozygous/zygote having the protective phenotype, or is the goal something other than 50% knockdown? Thank you.

Inhibit E program can you elaborate on your reasons for expanding cohort two over advancing two cohort III sooner if the core two dose was well tolerated why not just advanced the cohort three versus.

<unk> two and also when you say core two doses therapeutically relevant is that in reference to <unk> type light weight loss and finally is.

Is the goal of active an E knocked down around 50% based on your human heterozygous <unk>.

I was having to protect the phenotype or is the goal something other than 50%. Thank you.

Thank you Julien did take those various pieces. The first question yes.

Paul Bolno: Thank you, Joon, and to take those into various pieces. The first question, yes, we didn't wait to start. As you noticed, we're already dosing the 400 mg cohort 3, so that's important to us. That was principally driven because safety tells us that we can continue to dose escalate to 400, and we'll continue to follow that. That's going well. To the point on cohort 2 and why the focus on cohort 2 is to your specific question on relationship between the DIO weight loss data, Activin E reduction, and cohort 2 modeling. That is the dose that we modeled in the clinic. If we think about where we started subtherapeutic to get to that dose, that was the target dose that would align with weight loss similar to semaglutide based on the DIO model.

Yes, we didn't wait to start as you noticed we're already dosing cohort of 400 milligram cohort three so that's important to us and that was principally driven because safety tells us that we can continue to dose escalate to 400, and we will continue to follow that.

So that's going well to the point on cohort two and why the focus on cohort two as to your specific question on relationship between the Dio weight loss data active any reduction and cohort two modeling that is the dose that we modeled in the clinic. So if we think about where we started sub therapeutic to get to that dose.

That was the target dose that would align with weight loss similar to <unk> <unk> based on the DIR model, we recognize that in humans remember if we were to ever see that that would be amazing that would mean, we're actually getting more fat loss than the <unk>, 60% of the <unk> weight loss being fat reduction would be impressive in that day.

Paul Bolno: We recognize that in humans, remember, if we were to ever see that would be amazing. That would mean we're actually getting more fat loss than the GLP-1s. 60% of the GLP-1 weight loss being fat reduction would be impressive in that data set. That's how we're thinking about it. In those models, we've seen in excess of 50% reduction of Activin E. Our confidence based on what we've demonstrated preclinically, highly encouraged by what we're seeing in the clinical translation and the ability. It's safe and well-tolerated to continue to explore doses, I think has us highly optimistic as we come into Q4 data readout on cohort 2, and continue to follow the program as it progresses.

But that's how we're thinking about it in those models, we've seen an excess of 50% reduction of back to the knee. So our confidence based on what we've demonstrated pre clinically highly encouraged by what we're seeing in the clinical translation and the ability to get the safe and well tolerated to continue to explore doses I think has us.

Really optimistic as we come into Q4 data readout on cohort two and continue to follow the program as it is.

Yes.

Just to clarify.

No.

Joon Lee: Just to clarify, should we be expecting a linear dose response, or does the preservation of lean mass offset or counteract the weight loss aspect that's coming from the fat loss as you go to cohort 3, et cetera?

Should we be expecting a linear dose response or does the fat.

Preservation of lean mass offset or counter act sort of the weight loss aspect of it is coming from the fat loss.

As you go to court.

Et cetera.

I mean, I think when we split what we see and I think this is always important when we look at the model and delineate that and the model, we see weight loss.

Paul Bolno: I think what we see, and I think this is always important when we look at the model and delineate that. In the model, we see weight loss that's comparable with GLP-1s, except it's fat, and as we evaluate it, is not impacting muscle. Again, in the animal model where we can look at that in isolation, we are seeing that as parity of weight loss being driven by fat without muscle. I think given the human experience, we'll have to see how linear that translation becomes.

It's comparable with DLP, one accepted fat and as we evaluated is not impacting muscle. So again any animal model, where we can look at that in isolation. We are seeing that as parity of weight loss being driven by fat without bumps I think given the human experience, we'll have to see how linear that translation becomes but ultimately were.

Going to have that opportunity and I say that in the form of weight loss by having multiple doses with which we can explore that and by increasing the size of cohort two and the confidence around expanding the 32 patient enrich that data set for what we believe is necessary to actually be able to assess weight loss in cohort two which remember is <unk>.

Paul Bolno: Ultimately, we're going to have that opportunity, and I say that in the form of weight loss, by having multiple doses with which we can explore that, and by increasing the size of cohort 2, hence the confidence around expanding to 32 patients, enrich that data set to what we believe is necessary to actually be able to assess weight loss in cohort 2, which remember, is over 3 times higher than what we've seen already in our first cohort. Again, everything's tracking as we would hope and expect, and I think reaffirms our modeling data now that we have human data.

Over three times higher than what we've seen already in our first cohort. So again everything is tracking as we would hope and expect and I think reaffirms our modeling data now that we have human data.

Thank you so much thank you.

Joon Lee: Thank you so much.

Thanks Candice.

Paul Bolno: Thank you.

Our next question comes from Roger song from Jefferies. You May now ask your question.

Operator: Thanks, Joon. Our next question comes from Roger Song from Jefferies. You may now ask your question.

Hey, guys.

Excuse me.

Roger Song: Excellent. Can you guys hear me?

Yes.

Awesome alright. Thanks.

Paul Bolno: Yes.

Roger Song: Awesome. All right. Thanks for taking the question and congrats for the progress. Two questions from us. First one is the 006 AATD data readout in the Q3 and then in the Q4. Just given this is a MAD data versus single dose and obviously different dose level, what is your guidance on the different expectations from those two data readout? Should we focus more on the absolute level of the M protein production versus the percentage of the total protein? That's number one. In terms of the 007 INHBE data readout, just curious about the follow-up period for the initial data readout in Q4. How much kinetic and the durability of the weight loss and the biomarker change we can observe from the initial data readout? Thank you.

Thanks for taking the question and congrats for a progress also two questions from us. So first one is the digital CX HED data readout in the <unk> and then in the.

For so just given this is a mad data versus single dose and that obviously different dose level. What is your guidance on the different expectation from those two data readout should we focus more on the absolute level of the M protein production versus the percentage of the total protein so.

That's number one.

And then in terms of the old seven hidden data readout, just curious about that.

Follow up period for the initial data readout.

For Q, how much kinetic and the durability of the.

We lost in the biomarker change we cannot.

We can observe from the initial data readout. Thank you.

Thank you starting with your first question on the <unk> readout Mad versus single, obviously, the exposures on the multi dose.

Paul Bolno: Thank you. Starting with your first question on the WVE-006 readout, MAD versus single. Obviously, the exposures on the multi-dose, we believe, if we think about the 400 single versus the 200 multi. The exposures with 200 multi will give us larger liver concentration, larger liver exposure. We're much more anchored on that 200 mg multi-dose data. As a comparison between the 200 single and the 200 multi-dose, obviously we're highly encouraged to achieve MZ levels of both M protein and total protein from the single dose data that we have to date. It's reasonable to expect to see more as we go to multi-dose. I think that's encouraging. As we think about what to follow M versus total, I think we've talked about this a lot. I think M protein is critical to follow because it's very standardized, right?

Believe so if we think about the 400 single versus.

200, multi the exposures with 200 multi will give us larger liver concentration larger liver exposure. So we are much more anchored on that 200 milligram multi dose data as a comparison between the 200 single and the 200 multi dose.

Obviously, we are highly encouraged to achieve MZ levels of both M protein and total protein from the single dose data that we have to date.

But it is reasonable to expect to see more as we go to multi dose. So I think thats encouraging as we think about what the follow EM versus total I think.

<unk> talked about this a lot I think M protein is critical to follow because it's very standardized way. The only way you make M protein and I would say M protein not N plus one or other by tenders, but pure edited corrected protein, which is the native protein.

Paul Bolno: The only way you make M protein, I say M protein, not M plus one or other bis-edits, but pure M edited corrected protein, which is the native protein. That assay, these patients have zero. It's a very good way to follow that protein level to be able to assess editing efficiency and therapeutic levels. That's not to say Z protein doesn't also have a benefit, and therefore, we'll still be looking at the total levels, too. I think that combination of M plus total will give us a good insight, just as it did on the early single-dose data, which again, was highly encouraging.

That assay patients have zero so its a very good way to follow that protein level to be able to assess editing efficiency and therapeutic levels. That's not to say Z protein doesn't also have a benefit and therefore, we will still be looking at the total level, two but I think that combination of <unk>.

Plus total will give us a good insight just as it did on the early single dose data, which again was highly encouraging.

To your question second on inhibiting you follow up timeline I mean, we would expect.

Paul Bolno: To your question, second, on INHBE follow-up timeline, we would expect to have at least 3 months of follow-up on cohorts 1 and 2 at the data readout, and then we'd have a subsequent readout, as we said, 400 mg in Q1 2026.

To have at least three months of follow up on cohorts, one and two at the data readout.

And then we'd have a subsequent readout as we said 400 milligrams in Q1 at 206.

Thank you.

Roger Song: Thank you.

Thanks, Roger and next question comes from Tien Huang from Wedbush Securities. Please.

Operator: Thanks, Roger. Our next question comes from Yun Zhong from Wedbush Securities. Please unmute your audio and ask your question.

Ask your question.

Okay.

Okay.

Hi, good morning, Thank you very much.

Yun Zhong: Hi, good morning. Thank you very much for taking my question. The first question is a kind of follow-up question to a previous one asked on the call. On the inhibin E knockdown, what would you see as desirable knockdown level that you want to see and related to the dose cohort 2 expansion versus dose cohort 3? Do you have a plan to continue dose escalation after dose cohort 3?

Taking my question. So the first question is.

Kind of a follow up question to a previous one asked on the call.

On the distributed knockdown.

Would you see.

<unk> knockdown levels that you see in there related to the dose cohort two expansion versus dose cohort three and.

Do you have a plan to continue dose escalation as it goes through.

St.

Yes, it's a wonderful question I mean, obviously the modeling is aligning between our preclinical data and clinical data to date.

Paul Bolno: Yeah. A wonderful question. Obviously, the modeling is aligning between our preclinical data and clinical data to date. We modeled at 240 to replicate what we've seen in our DIO mouse model. We'll continue to follow that to assure that translation. I think what's helpful about our GalNAc-siRNAs is that ability to translate preclinical data to clinical data for modeling. I think, again, our human data tells us that we're on that track, and we'll have that data to be able to assess in Q4 to look at how well we're tracking between, again, the human experience and the DIO mouse model, which has translated well for other weight loss programs. I think that's highly encouraging. We're not stopping at 240. As we've said, our dosing 400 mg cohort, we believe that we'll continue to be able to dose escalate if required.

We model the $2 40 to replicate what we've seen in our DIY mouse model. So we.

We will continue to follow that to assure that translation, but I think what's what's helpful. About our <unk> is that ability to translate preclinical data to clinical data for modeling I think again, our human data tells us that we're on that track and we'll see we'll have that data to be able to assess in the fourth quarter to look at how well we're.

<unk> between again, the human experience and the <unk> mouse model, which has translated well for other weight loss programs. So I think thats highly encouraging.

But we're not stopping at $2 40, I mean, as we've said we've.

Our dosing 400 milligram cohort.

We believe that will continue to be able to dose escalate if required. So I think really stepping back with these dose levels that we currently have knowing that.

Paul Bolno: I think really stepping back with these dose levels that we currently have, knowing that cohort 2 threads the model, and we still have a dose that's greater than what we've seen in the model. I think we straddle the model very well with the cohorts we have. As we've shown in the data, we're not capped by safety to continue to go higher.

Cohort two threads the model and we still have a dose that's greater than what we've seen in the model I think we straddle the model very well with the cohorts, we have but as we've shown in the data were not capped by safety to continue to go higher.

Okay.

Follow up question on the DMD program next week I believe there were some.

Yun Zhong: Okay. A follow-up question on the DMD program, actually. I believe there were some updates at the FDA level this morning, and I am curious, will that affect your approach or strategy that you are going to take with response to your DMD program, please? Thank you very much.

Based on the answers.

FTE levels this morning and.

Curious would that affect your approach or strategy that you are going to take with regard to your DMD program. Please thank you very much.

I mean, our program goes to Cedar, which now has a new division director. That's that continues to be there I think within <unk> that was the division that established the threshold for accelerated approvals for exon skipping therapies.

Paul Bolno: Yeah. Our program goes to CDER, which now has a new division director that continues to be there. I think within CDER, that was the division that established the threshold for accelerated approvals for exon-skipping therapies. I think we've all been following the news overnight, and we're all watching the agency and seeing how those discussions continue to evolve. I think there's nothing imminently based on any of the discussions that we're having that suggests anything's changing. Like everybody else, we'll continue to follow the space.

But I think we've all been following the news overnight and we're all watching the agency and seeing how those how those discussions continue to evolve, but I think theres nothing eminently based on any of the discussions that we're having that suggest anything's changing but like everybody else, we'll continue to follow the space.

Great. Thank you.

Yes.

Yun Zhong: Great. Thank you.

Thanks for your question. Our next question comes from Katherine Novak from Jones trading. Please on mute your line and ask a question.

Paul Bolno: Yeah.

Operator: Thanks for your question. Our next question comes from Catherine Novack from JonesTrading. Please unmute your line and ask your question.

Yeah.

Hi, good morning, Thanks for taking my question.

Catherine Novack: Hi. Good morning. Thanks for taking my question. At the last update in May, you reported that dosing was ongoing for the 200 mg multi-dose. Can you be specific about when dosing was completed? Did all patients receive all 7 doses? What's the minimum follow-up for reporting top-line data? Thanks.

So at the last update in May you reported that dosing was ongoing for the 200 milligram multi dose can you be specific about when dosing was completed.

Did all patients receive all seven doses and what's the minimum follow up sorry reporting top line data.

Yeah, what's important in this dataset is all patients have received seven doses with follow up so to the point that the study is designed and executed to that design and will deliver data. There is no changes to the guidance and it remains on track for the third quarter again with all patients receiving their seven doses of 200 milligrams.

Paul Bolno: Yeah. What's important in this data set is all patients have received 7 doses with follow-up. To the point that the study was designed and executed to that design and will deliver data, there's no changes to the guidance, and it remains on track for Q3, again, with all patients receiving their 7 doses at 200mg.

Okay, great and if I can just ask one more when you mentioned last earnings that doesn't less complete for the first two cohorts of enlighten is this before or after the extension of cohort two just checking thanks.

Catherine Novack: Okay, great. If I can just ask one more. When you mentioned last earnings that dosing was complete for the first 2 cohorts of INLIGHT, was this before or after the expansion of cohort 2 was triggered? Thanks.

So this is the update as the ongoing so before I think the new update today is that based on that data in the this quarter expanded the cohort from 8% to 32 and in addition to that the new update as those patients have completed their dosing so.

Paul Bolno: This was the update as the ongoing. I think the new update today is that based on that data, we've, in this quarter, expanded the cohort from 8 to 32. In addition to that, the new update is those patients have completed their dosing. That was the interim update that we triggered the threshold, expanded the cohort, and as well, it initiated the cohort 3 at 400. A lot of activity over the past quarter and continuing to dose escalate as well as expand the size of the study.

That was the interim update that we triggered the threshold expanded the cohort and now at the end as well it initiated the cohort three at 400, so a lot of activity over the past quarter and continuing to dose escalate as well as expand the size of the study.

Okay, great. Thanks for taking my question.

Catherine Novack: Okay, great. Thanks for taking my question.

Thanks, so much Catherine thank you <unk>.

Paul Bolno: Yeah.

Operator: Thanks so much, Catherine. Right, our next question comes from Tiago Fauth from Wells Fargo. Please unmute your line and ask your question.

Our next question comes from Thiago <unk> from Wells Fargo. Please on mute your line and ask a question.

Alright, thanks for taking the question.

Tiago Fauth: Hi. Thanks for taking the question. One quick one on AATD for me. Is there anything right now that you can say qualitatively about the consistency of effect for the dose patients in both cohorts, both single dose and multi-dose? I know GalNAc PK, well understood relatively. Just trying to gauge what other factors could influence circulating M-AAT protein plasma across patients. Thank you.

One quick one on a different like is there anything right now that you can say qualitatively about the consistency of effect for those patients in both cohorts both single dose and most of those because I know garnock became well understood relatively so just trying to gauge what other factors could influence circulating MAA.

Protein plasma across patients.

Thank you.

Yes. Thank you for the question and we agree I mean, one of the benefits that gallon that gives that.

Paul Bolno: Yeah. Thank you for the question. We agree, one of the benefits to GalNAc is that the qualitative distribution to cell, we saw pre-clinically across hepatocytes with consistent editing and substantial amounts of protein production. As we said on the data, even on the proof of mechanism, what we saw on editing was consistency. I think consistency is there. We now have the ability to evaluate the full single-dose and multi-dose cohort. Again, with 7 doses at 200 mg, this is a substantial amount of exposure. Again, we're highly encouraged based on our pre-clinical models, based on our early proof of clinical mechanism data in translation, and ultimately the B data coming, that it'll be a comprehensive ability to assess that.

Qualitative distribution to settle we saw I mean.

Pre clinically across pad sites with consistent editing and substantial amounts of protein production.

And as we said on the data even on the proof of mechanism. What we saw on editing was consistency. So I think consistency there. We now have the ability to evaluate the full single dose and multi dose cohort and again with seven doses of 200 milligrams with the substantial amount of it.

<unk>. So again, we're highly encouraged based on our preclinical models based on our early proof of clinical mechanism data and translation and ultimately that these data come back then it will be a comprehensive ability to assess that.

Perfect. Thank you very much.

<unk>.

Tiago Fauth: Perfect. Thank you very much.

Thanks for your question channel.

Paul Bolno: Thank you.

Operator: Thanks for your question, Tiago. Right. Our next question comes from Samantha Seemann-Kow from Citi. Please unmute your line and ask your question.

Our next question comes from Samantha <unk>.

<unk> from Citi. Please on mute your line and ask a question.

Hi, good morning, and thanks very much for taking the questions I have a couple of related questions on a way the seven I'm wondering if you're able to characterize the amount of acumen <unk> reduction you saw in cohort one in relation to your preclinical modeling was it in line.

Samantha Seemann-Kow: Hi. Good morning, and thanks very much for taking the questions. I have a couple related questions on WVE-007. I'm wondering if you're able to characterize the amount of Activin E reduction you saw in cohort one in relation to your preclinical modeling. Was it in line with your expectations, or was it greater? If it is greater, I'm wondering if you've seen any early Activin E data from cohort two and if that is tracking higher than your expectations. Just kind of pulling it all together, is there a dose response or a correlation that you see between the amount of Activin E reduction and the amount of weight loss you expect? I'm wondering if it's a linear relationship based on your understanding or some other curve on the correlation there. Thanks very much.

If your expectations or was it greater and if it is greater I'm wondering if you've seen any early accident E data from cohort two in a status tracking higher than your expectations and then just kind of pulling it all together their dose response or a correlation that you see between the amount of active and a reduction in the amount of weight loss.

Spectrum wondering if its not linear relationship based on your understanding or some other.

Curve.

Correlation there thanks very much. Thank you for the question I think it's important as we go back to our preclinical data that we have seen at dose response and engagement not just have been have been knocked out but we have to remember we were the first to show that correlation between inhibiting knockdown and activity reductions so again differentiated approach to <unk>.

Paul Bolno: No, thank you for the question. I think it's important as we go back to our preclinical data, that we have seen a dose response in engagement, not just of inhibin E knockdown. We have to remember, we were the first to show that correlation between inhibin E knockdown and Activin E reduction. Again, differentiated approach to our siRNAs with both potent and durable knockdown in the preclinical models. Actually there, we could assess a dose response, and ultimately tie that to productive weight loss. We shared that at our ADA presentation. We do see consistency in our clinical, cohort 1, we did see consistency on our PK/PD modeling.

S Irna's with both potent and durable knockdown in the preclinical models and actually there we could assess a.

Dose response, and ultimately tie that to productive weight loss and we shared that.

At our presentation. So we do see consistency in our click.

Clinical so cohort one we did see consistency on our PK PD modeling. So again there is good consistency between clinical data preclinical data, which ultimately again has us projecting two Y and this past quarter, we expanded the cohort to 32 patients and are going to evaluate we believe healthy weight loss at a modeled dose.

Paul Bolno: Again, there was good consistency between clinical data, pre-clinical data, which ultimately, again, has us projecting to why in this past quarter, we expanded the cohort to 32 patients and are going to evaluate, we believe, healthy weight loss at a model dose to what we do see in the pre-clinical models relative to that relationship between Activin E and weight loss. It's a good biomarker for us to continue to follow. We haven't looked at our cohort 2 yet, this is all based on the projection of that first dose cohort decision to expand.

What we do see in the preclinical models relative to that relationship between activity and weight loss. So it's a good biomarker for us to continue to follow.

We haven't looked at our cohort two yet. So this is all based on the projection of that first dose cohort decision to extend.

And again robust preclinical data, where again the first to show activity reduction within the <unk> RNA approach to inhibit preclinical and again with these day to day, a robust statistically significant activity reduction in cohort one the person demonstrating the humans that you can knockdown inhibit enc a correlation between preclinical and clinical data.

Paul Bolno: Robust pre-clinical data, where again, the first to show Activin E reduction with an siRNA approach to inhibin E pre-clinically, and again, with these data today of robust statistically significant Activin E reduction in cohort 1, the first to demonstrate in the humans that you can knock down inhibin E and see a correlation between pre-clinical and clinical data on Activin E reductions.

Any reactions.

Got it thanks very much for that one follow up for me on the <unk> program I'm wondering what you believe the target conversion rate from data and should be or are you looking.

Samantha Seemann-Kow: Got it. Thanks very much for that. One follow-up from me on the AATD program. I'm wondering what you believe the target conversion rate from Z to M should be. Are you looking for near complete conversion, so the vast majority being M, or is there an acceptable amount of residual Z protein in your view for the target dose that you select over time? Thank you.

For a complete conversion from vast majority being M or is there an acceptable amount of residual G protein in your view for the target dose that you selected over time. Thank you.

Yes. Thank you I mean, I think one we're at the beginning part of our dose titration curve. So I'd say, if we're going to get a look at again, our lowest astellas now going from lowest single the lowest multi but I think what we do see and we saw this preclinical he is a conversion of creating and that was the target goal and MZ phenotype, we cross that with the single dose, where we got well.

Paul Bolno: Thank you. I think, one, we're at the beginning part of our dose titration curve. I'd say we're going to get a look at, again, our lowest dose, now going from lowest single to lowest multi. I think what we do see, and we saw this pre-clinically, is a conversion of creating, and that was the target goal, an MZ phenotype. We crossed that with the single dose, where we got well over 60% edited M protein versus Z, so well above what's theoretical for a ZZ to an MZ, which is highly encouraging given that that was the therapeutic potential. I think what's interesting there is continuing to follow where we get to with multi-dosing, where, as we said, it's reasonably expected that we should see more protein. The goal has always been could you convert ZZ patients to MZ patients?

Over 60% edited and protein versus these so well above what's theoretical for these.

<unk>, two <unk>, which is highly encouraging given that that was the therapeutic potential I think what's interesting. There is continuing to follow where we get to with multi dosing where as we said it's reasonably expected that we should see more protein, but the goal has always been could you convert Z patients to MD patients because those.

<unk> patients have sufficient protection to be.

Paul Bolno: Those MZ patients have sufficient protection to avoid hepatic disease, lung disease. There's still room on that specter in terms of M protein production and total protein production within that range of MZ. If we think about MZ as the desired phenotype, that's a 50% correction.

To avoid hepatic disease lung disease.

There is still room on that sector in terms of M protein production.

Total protein production within that range.

But if we think about envy the desired phenotype at the 50% correction.

Great. Thanks for your questions. Our next question comes from Joe Schwartz from Leerink partners. Please on mute your line and ask your question.

Operator: Great. Thanks for your question, Samantha. Our next question comes from Joseph Schwartz from Leerink Partners. Please unmute your line and ask your question.

Hi.

Great. Thanks, Congrats on all the progress and the update today.

Joseph Schwartz: Great. Thanks. Congrats on all of the progress and the update today. I have a couple of questions on WVE-006 as well. First, following on the last question, I was just wondering conceptually how you're thinking about the amount of editing and M-AAT that's possible to see from the 200mg MAD and 400mg SAD regimens based on what's known about the kinetics of the enzyme and where you're expecting to be on the editing curve based on what you've seen across your pre-clinical healthy volunteer and early patient experience.

I have a couple of questions on <unk> as well.

First following on the last question I was just wondering conceptually how youre thinking about the amount of editing in M protein that's possible too.

You see from the 200 milligram Mad and 400 milligrams said regimens.

Based on what's known about the kinetics of the enzyme and where you expect it to be on the editing curve based on what you've seen across your preclinical healthy volunteer and early patient experience.

Yes, I mean, I think to the point of healthy volunteers theres not a lot. We can gathered is to take that one at the beginning because the healthy volunteers are not patients with correction, but actually their conviction is ample amplitude on dosing well above where we currently planned for even our third cohort. So again, that's very much of a safety driven exposure question.

Paul Bolno: I think to the point of healthy volunteers, there's not a lot we can gather just to take that one at the beginning, because the healthy volunteers are not patients with correction, but actually their conviction is ample amplitude on dosing well above where we currently plan for even our 3rd cohort. Again, that's very much of a safety-driven exposure question. As it relates to just where we can get to, I think it is an important question, Joseph Schwartz, because we definitely know from pre-clinical models that we haven't exhausted the ADAR enzyme. This is not where we are on this curve between our single and even how we model our multidose, that we've yet to kind of hit peak, both saturation of the GalNAc receptors based on our modeling, nor peak saturation of the enzyme at that stage.

As it relates to just where we can get to and I think it is.

Question, Joe because of it.

We definitely know from preclinical models that we haven't exhausted the ADR ensign. So this is not where we are on this curve between single and even how we model our multi dose that we've had a kind of hit peak.

Saturation of the gallon that receptors based on our modeling nor peak saturation of the environment at that stage. So we do believe that there is ample room to grow from our single dose see increases in protein from a multi dose and still have opportunity to be talking about a 400 and progress forward.

Paul Bolno: We do believe that there's ample room to go from our single dose, see increases in protein from multi-dose, and still have opportunity as we talk about the 400 in progress forward to still see continued opportunities for more protein. The trade-off ultimately being at some point, how much more protein do you need if theoretically you could get to normal levels of protein? Then you can make trade-offs. I think from an exposure piece, we have ample room to go, both on our dose escalation, again, where others have been versus where we are. We're at the very beginning of this dosing regimen versus where some of the DNA editors are. I think our opportunity to continue to explore and push that opportunity there.

Still see continued opportunities for more protein the tradeoff ultimately being at some point how much more protein do you need if theoretically you could get to normal levels of protein. Then you can make tradeoffs. So I think from an exposure piece, we have ample room to grow both on our dose escalation again, where others have been versus where we are we're at the very beginning of this.

Dose dosing regimen versus where some of the DNA editors are and so I think our opportunity to continue to explore and push that opportunities. There. The other thing we saw in our preclinical models.

Paul Bolno: The other thing we saw in our pre-clinical models, which again is highly encouraging, is as cells actually get more efficient because you clear out the Z protein you correct, they're also able to get healthy and actually start generating more protein. Therefore, being able to repeat dose and get access to those other cells over time is also, again, encouraging as we continue to follow these patients over time.

Which again is highly encouraging is as sell or actually get more efficient because you clear out the <unk> protein you're correct. They are also able to get healthy and actually start generating more protein and therefore BMO the repeat dose and get access to those other cells over time is also again encouraging as we continue to follow these patients over time.

Thank you for that helpful context.

Joseph Schwartz: Thank you for that helpful context. As a follow-up, other companies developing RNA editing therapeutics for AATD claim to have designed them to have best-in-class characteristics. We've heard you say best-in-class when referring to your platform overall, but I was wondering if you could discuss the extent to which you've focused on optimizing 006 so that it's competitive with others who are following in your footsteps.

And then as a follow up.

Companies developing RNA editing therapeutics for a T. D claimed to have designed to have best in class characteristics.

We've heard you say best in class when referring to your platform overall.

If you could discuss the extent to which you feel.

On optimizing low six that is competitive with others, who are following the footsteps.

Yes, I mean, one I think.

Paul Bolno: Yeah. One, I think we've developed it within the clinic to have substantial editing properties that translate from our pre-clinical data to clinical data. Done this beyond the alpha-1 antitrypsin, as we think about both other hepatic and extrahepatic editing data sets that we've shown. I think what really speaks to the fact of, there's best-in-class, as you point out, from editing. There's also what best-in-class looks like for hepatic editing. I think for hepatic editing, the utility of GalNAc as an efficient delivery tool, in addition to what we see as optimized chemistry, specifically for ADAR editing, give us two angles for the AATD program that we think distinguishes, right? There's the opportunity to get better delivery subcutaneously administered, high exposure in the cells, in addition to what happens once the medicine gets into the cell and is then able to edit.

We've developed within the clinic to have substantial editing properties that translate from a preclinical data to clinical data.

Beyond the Alpha one antitrypsin as we think about both other hepatic and extra hepatic editing data sets that we've shown I think would really speaks to the factory.

There is best in class as you point out from editing is also with best in class looks like for hepatic editing and I think for hepatic editing the utility of gallon neck as an efficient delivery tool. In addition to what we see as optimized chemistry, specifically for <unk> editing give us kind of two angles for an ATV program that we think is distinguished.

Right. There is the opportunity to get better delivery subcutaneously administered high exposure in the South in addition to what happened once the medicine gets into the cell and has been able to edit.

The beauty of them when we think about editing in general and how we're differentiated data you take down that cost. So you can think about <unk> and extra hepatic implications. There, we're really bringing novelty and chemistry, which is really at the heart of medicinal chemistry, if youre, making a medicine chemistries at the heart of designing that in between what we've seen in the improvements.

Paul Bolno: The beauty of when we think about editing in general and how we're differentiated is if you take GalNAc off, so you can think about both hepatic and extrahepatic implications. There, we're really bringing novelty in chemistry, which is really at the heart of medicinal chemistry. If you're making a medicine, chemistry is at the heart of designing that. Between what we've seen in the improvements with PN modifications on top of chirality, but importantly with N3-uridine specifically to our editing at a very specific site, we've seen the optimization of our AIMer editing platform separate from, again, if we think about AATD best-in-class, not having to use LNPs, and so creating the stability intrinsically.

With Pn modifications on top of chirality, but importantly, within three years and specifically.

Editing at a very specific site, we've seen the optimization of our aim or editing platform suffered from again, if we think about HED best in class not having to use LMT is not and so creating stability intrinsically youth.

Using <unk>. So we can do subcutaneously administration again high of how does that uptick into specific cells that you want delivery to I think I'll speak to that kind of bifurcation of best in class Alpha one Antitrypsin program and stepping back more broadly what we believe to be a leading RNA editing platform.

Paul Bolno: Using GalNAc so we can do subcutaneously administration and get high hepatocyte uptake at the specific cells that you want delivery to, I think all speak to that kind of bifurcation of best-in-class alpha-1 antitrypsin program and stepping back more broadly, what we believe to be a leading RNA editing platform.

Thank you.

Thank you.

Joseph Schwartz: Thank you.

Thanks for your question gentlemen, our next question comes from Salim Syed from Mizuho Securities. Please mute your line and ask your question.

Paul Bolno: Thank you.

Operator: Thanks for your question, Joe. Our next question comes from Salim Zaidi from Mizuho Securities. Please unmute your line and ask your question.

Okay.

Great. Thanks for the questions guys.

Salim Zaidi: Great. Thanks for the questions, guys. Paul, maybe just one from us on 007, then a quick one on 006. On 007, on this call, you guys mentioned that you saw robust Activin E reduction at cohort 1. You also initially structured this trial with 5 cohorts in the single dose, but you're already expanding at cohort 2. I'm just trying to understand a little bit more about your decision to expand at cohort 2. Is there any protocol requirement here that forced you to expand at cohort 2 before moving to multi-dose? Was there any variability you saw in the first 8 patients that led to this sort of expansion in the single dose? Is there something strategic about it that you can move this quicker to pivotal if you think cohort 2 is really your go forward dose?

Paul maybe just.

One from us on seven and a quick one on <unk>.

On <unk> on this call you guys mentioned.

Robust active and a reduction of cohort one you also initially structured this trial.

Five cohorts in the single dose that youre already expanding.

Cohort two so I'm, just trying to understand a little bit more about.

Your decision to expand.

Cohort.

Two is there any protocol requirement here.

That forced you to expand that cohort two before moving to multi dose was there any variability you saw in the first eight patients that led to the sort of expansion.

And a single dose or is there something strategic about it but you can move quicker to pivotal if you'd think cohorts who is really your go forward.

And then as my follow up.

Salim Zaidi: I'll ask my follow-up on 006.

No I think the insight there is important because we designed the study knowing that in a phase one healthy volunteer study starting with lowest dose is that something that you believe to be sub therapeutic but what you really wanted to do is also teach you something about translation of your pharmacology right like what can we learn about biomarker translation that gives us.

Paul Bolno: Yeah. No, I think the insight there is important because we designed the study knowing that in a phase I healthy volunteer study, you have to start at your lowest dose at something that would be believed to be subtherapeutic. What you really want it to do is also teach you something about translation of your pharmacology, right? What can we learn about biomarker translation that gives us confidence and conviction that as we plan dose 2 to be within the range of our DIO mouse model, that should be able to demonstrate weight loss, the dose escalation study continues to affirm that we could dose higher.

And conviction that as we planned dose.

Be within the range of our DIY mouse model that should be able to demonstrate weight loss and the dose escalation study continue to affirm that we can dose higher.

I think our internal metrics to say, how do you do that study efficiently, meaning how can we get to that stage in that where you believe to have your efficacy and activity. How do you get there as quickly as possible. So we were efficient with the number of patients in the early cohorts to give us robust signal as we saw and as we said the active in <unk>.

Paul Bolno: I think our internal metrics to say, how do you do that study efficiently, meaning how can you get to that stage and that where you believe to have your efficacy and activity, how do you get there as quickly as possible? We were efficient with the number of patients in the early cohorts to give us a robust signal, as we saw. As we said, the Activin E reduction was robust and statistically significant and translated well to our PK/PD modeling preclinically. When we hit that threshold at cohort 2, the decision was that's a cohort because it could be to that point of relevance as it relates to weight losses, expand that to an appropriate number of patients that we could assess that on. Hence the shift from 8 to 32.

<unk> was robust and statistically significant and translated well to our PK PD modeling pre clinically when.

When we hit that threshold at cohort two the decision was that the cohort because it could be to that point of relevant as it relates to waive often expand that to an appropriate number of patients that we could assess that aren't so hence the district from 8% to 32, but that's stopping realizing that and that's why we were already on to the 400 as we said in that dosing underway.

Paul Bolno: Not stopping, realizing that, and that's why we were already onto the 400, as we said, and that's dosing underway. We do ultimately want to explore the dose range of a novel therapy and understand the pharmacology and continued translation. I think the team's done a wonderful job designing a study that expeditiously gets us to an appropriate dose cohort to be able to evaluate weight loss and has it designed to adapt to be sufficient to provide that data. We're excited about what we've seen to date and how that translates to what's going to be important, I think, for all of us to really move from kind of generation 1.0 in the obesity space of incretins, really to generation 2.0, which is what does healthy, sustainable weight loss look like? How do you deliver that data? We're poised to deliver that in Q4.

Because we do ultimately want to explore the dose range of a novel therapy and understand the pharmacology and continued translation. So yes, I think the team's done a wonderful job designing a study that expeditiously gets us to an appropriate dose cohort to be able to evaluate weight loss and has it designed to adapt to be sufficient to provide that data. So we're excited.

About.

What we've seen to date and how that translates to what is going to be important I think for all of us to really move from kind of generation one point on the obesity space of increases really to generation two point out which is what does healthy sustainable weight loss look like how do you deliver that data and we're poised to deliver that in Q4.

Okay. Thanks, and then just quickly on <unk> are there any GSK milestones, we need to be aware of in this upcoming data set whether it's the 200 multi hundred single.

Salim Zaidi: Okay. Thanks. Just quickly on WVE-006, are there any GSK milestones we need to be aware of on this upcoming data set, whether it's a 200 multi or 400 single?

I can't obviously speak specifically to the milestones and deliverables, but we have said that there are milestone payments that we can reasonably expect in 'twenty five 'twenty six.

Paul Bolno: I can't, obviously, speak specifically to the milestones and deliverable, but we have said that there are milestone payments that we can reasonably expect in 2025, 2026 from GSK.

GSK.

From the data or from moving it.

Salim Zaidi: From the data or from moving it to something else?

Yes.

We can't speak to the how the App milestone payments are allocated into the course of the agreement with GSK other than to make a statement as to when we would anticipate central milestones from guest check.

Paul Bolno: Yeah, we can't speak to how the milestone payments are allocated over the course of the agreement with GSK other than to make the statement as to when we would anticipate potential milestones from GSK.

Okay, all right. Thanks, Paul.

Salim Zaidi: Okay. All right. Thanks, Paul.

Your question. Please our next question comes from Martin Auster from Raymond James Please UN mute your line and ask your question.

Paul Bolno: Yeah.

Operator: Thanks for your question, Salim. Our next question comes from Jeffrey Oster from Raymond James. Please unmute your line and ask your question.

Yes, thanks, guys.

Jeffrey Oster: Thanks, guys. Thanks for taking the call. Paul, wanted to follow up on some of the conversation you were having on the last question earlier with Samantha. As you're moving into cohort 3 dosing, it sounds like assessing Activin E reduction in cohort 2 might influence what the ultimate size, whether it's going to be expansion of that cohort 3 might be. Can you talk about when you'll be able to make that decision, how you'll communicate that, and whether that would potentially shift the timeline of planned disclosure for Q1 next year for that cohort 3 and those? Thanks.

As part of the call Paul wanted to follow up on some of the conversations you're having on the last question earlier was Memphis as you're moving into cohort three dose can sounds like assessing activity reduction core two might influence what the ultimate size models can be expansion of our cohort three might be can you talk about sort of when you'll be able to make that decision how yields really say about a month.

That would potentially shift the timeline.

Plenty to soldier for Q1 next year for the cohort three and both of them. Thanks.

Yes, I think what we've seen based on how we've designed cohort two it's reasonable to expect something similar around cohort. Three so is that study continues to move forward, we wouldn't expect anything to shift our timeline for delivering that data set for the 400 milligram in Q1 of 2026.

Paul Bolno: Yeah, I think what we've seen based on how we've designed Cohort 2 is it's reasonable to expect something similar around Cohort 3. As that study continues to move forward, we wouldn't expect anything to shift our timeline for delivering that data set for the 400 milligram in Q1 of 2026 based on the continued progress. I think with this shift on where we already have seen the shift in activity as it relates to Cohort 1, we're highly optimistic as we follow that into Cohort 2 and beyond in terms of levels of target engagement, how that models to our preclinical data, and how that shows up as they translate.

Based on the continued progress so I think with this shift where we already have seen.

Shift in activity as it relates to cohort one we're highly optimistic as we follow that into cohort two and beyond in terms of levels of target engagement, how that models of our preclinical data and how that should ultimately translate so I think the opportunity we're going to have us really assessing that dose response between $2 40 and 400.

Paul Bolno: I think the opportunity we're going to have is really assessing that dose response between 240 and 400, which is going to be interesting as we continue to look for what does, at the first ability to reduce inhibin E and translate to Activin E and ultimately translate that to healthy, sustainable weight loss, really define what those kinetics look like in the clinic across various doses and time points. I think the study was well-designed to be able to do that, and we're excited about delivering those data, and we've said we will.

Which is going to be interesting as we continue to look for what does what does at the first ability to reduce <unk> and translate the activity and ultimately translate that the healthy sustainable weight loss really define what those kinetics look like in the clinic across various doses and time.

I think the study was well designed to be able to do that and we're excited about delivering those data.

February.

Yeah I appreciate the prepared incredibly yes, we.

Jeffrey Oster: Yeah, appreciate the update.

Paul Bolno: Recruitment's been incredibly efficient. Yeah, I would say also, which is I think helpful because studies always go at different rates. Recruitment's been incredibly efficient. As you've seen in the question earlier of dosing, where we were in the expansion, being able to not only just recruit the expanded cohort and fully dose, but move into the subsequent. We're highly encouraged by where our sites are, what they're delivering, and how we can ultimately utilize that totality of data to deliver on our clinical data set on time.

We can say also which is I think helpful. Because it doesn't always go in different rate recruitment has been incredibly efficient I mean as you've seen in the question earlier dosing kind of where we were in the expansion being able to not only just recruit the expanded cohort fully dose of a move into the subsequent so we're highly encouraged by where our sites are what they are delivering and how we can ultimately utilize that.

That totality of data.

Ron articulated.

Thanks again I appreciate it thank you.

Jeffrey Oster: Thanks again. Appreciate it.

Paul Bolno: Thank you.

Thanks for your question Martin Our next question comes from Steve <unk> from Cantor Fitzgerald. Please UN mute your line and ask your question.

Operator: Thanks for your question, Jeffrey. Our next question comes from Steve Seedhouse from Cantor Fitzgerald. Please unmute your line and ask your question.

Hi, good morning, Thanks for taking the question.

Steve Seedhouse: Yes, hi. Good morning. Thanks for taking the question. Paul, I want to follow up on a comment you made earlier about the liver exposure at the 200 mg multi-dose, compared to the 400 mg single dose. It sounded like you're pretty confident that the multi-dose would give you higher liver exposure. It sounded like maybe even substantially higher, but I wanted to see if you could elaborate and expand on that comment. What gives you the conviction that the PK, the liver exposure, would be higher or so much higher at 200 mg? Sort of relatedly, you're accumulating quite a bit of data now with your own GalNAc-siRNAs as well as siRNA inhibin E in addition to the GalNAc mRNA and AATD. Is there anything different about just the clinical translation at the level of PK?

Paul I wanted to follow up on <unk>.

Comments made earlier about the liver exposure.

200, <unk> multi dose.

Third to this 400 gig single dose it sounded like you're pretty positive.

With the multi dose.

Would you be higher liver exposure.

One was maybe.

Substantially higher but I wanted to.

You see if you can elaborate and expand on that comment what do you get conviction.

P J the liver exposure.

Higher ore so much higher at 200 milligrams.

And then.

Sort of related.

Youre accumulated quite a bit of data.

Own galvanic because they are on it.

As well.

Yes.

In addition to the Dol that game right.

Is there anything different about just the clinical translation level.

Obviously, you don't have liver exposure data, there, but PK PD and got it.

Steve Seedhouse: Obviously, you don't have liver exposure data there, but PK/PD in general, are GalNAc mRNA behaving similar to GalNAc siRNAs? Thank you.

Got it.

Behaving similar to Delek us.

Thank you.

Yeah no. Thank you I think if we take the last question is actually informs going back to your earlier question, but I think what we're seeing consistently is <unk>.

Paul Bolno: Yeah, no, thank you. I think if we take the last question, it actually informs going back to your earlier question. I think what we're seeing consistently is GalNAc distribution, how that's distributing effectively to the cell type is behaving remarkably similar. From an exposure standpoint, GalNAc is doing what it should be doing relative to these different modalities. I should say our team's modeling is getting more and more efficient about predicting those exposures. I think what we're still going to learn from ADAR is, again, enzymatic efficiency. There we lean heavily on our preclinical data. To your early question about what gives us confidence and conviction as we've seen this is we are seeing with the early data good translation between preclinical models, exposure, and that translation to efficiency.

Distribution, either distributing effectively to the cell type is behaving remarkably similar so from an exposure standpoint.

<unk> is doing what it should be doing relative to these different modalities.

And I should say our team's modeling is getting more and more efficient about predicting those exposures I think what we're still going to learn from ADR is again enzymatic efficiency in there we lean heavily on our preclinical data. So to your early question about what gives us confidence and conviction as we've seen this as we are seeing.

The early data good translation between preclinical models exposure and that translation to efficiency and therefore have been able to look at what happens when you give single dose versus multi dose in preclinical models and retention of drug and increased exposure and thats translated well now as you pointed out across Calvin I think whats important is <unk> solves your drug.

Paul Bolno: Therefore, have been able to look at what happens when you give single dose versus multi-dose in preclinical models and retention of drug and increased exposure. That's translated well now, as you pointed out, across GalNAc. I think what's important is GalNAc solves your drug in. What keeps your drug in the cell and actually creates the stability to drive long-term durability and efficacy. Again, getting back to that earlier question of how do we define, because it is a term of what does best-in-class mean? I think when we step back and say, what does that really mean?

And what keeps your drug in the cell and actually create the stability to drive long term durability and efficacy.

Getting back to that earlier question.

How do we define.

And as it turns out what does that mean class me and I think when we step back and say what does that really mean it.

The chemistry design, let's say not only how do you get your drug in the solid efficiently to be able to work on that target, but how do you actually in crude and increase retention of that drug inside the cell and prevent it from degrading so that it can exert its effect on our catalytic enzymes.

Paul Bolno: It's the chemistry designs that say not only how do you get your drug in the cell efficiently to be able to work on that target, but how do you actually improve and increase retention of that drug inside the cell and prevent it from degrading so that it can exert its effect on a catalytic enzyme. I think the fact that ADAR is catalytic also highly demonstrates that if you can deliver efficiently a molecule, which we do with GalNAc, and it's highly retentive designed to engage with a catalytic enzyme, then you can optimize for that efficiency over time. If that drug's retained in your repeat dosing, then yes, you should increase exposure over time. Again, when we saw that in our preclinical models, we saw where we were on the curve of actual human clinical data with proof of mechanism.

The fact that <unk> catalytic also highly.

Demonstrates that if you can deliver efficiently a molecule, which we do with <unk>.

And it's highly retentive designed to engage with a catalytic enzymes and you can optimize for that efficiency over time and if that drug is retained in your repeat dosing then yes, you should increase exposure over time and again when we saw that in our preclinical models. We saw where we were on the curve of actual human clinical data with proof of mechanism all events.

Speaks very well to that clinical and preclinical translation, which is again highly encouraging as we're coming into our 200 milligram.

Paul Bolno: All of that speaks very well to that clinical and preclinical translation, which is again, highly encouraging as we're coming into our 200 mg dose data.

Okay and just on.

You hit the knee study.

Steve Seedhouse: All right, thanks. Just on the inhibin E study, did an analysis of blinded weight loss data or the distribution of weight loss play any role in the expansion of the cohort decision?

The analysis is blinded weight loss distribution of weight loss play any role in the expansion.

<unk> decision.

Six stations.

Paul Bolno: No. 6 treated patients, so 8 patients in the cohort, is insufficient to design that study to be triggered on body weight changes. Obviously, given statistically significant robust levels of Activin E changes, highly consistent in terms of Activin E reductions and being able to utilize biomarker-driven determination, as well as importantly safety to make that trigger to go to the expanded cohort. Which is insufficient in terms of number of patients to be able to evaluate.

<unk> treated patients with HAE patients in the cohort is insufficient to design that study to be triggered on body weight changes.

But obviously given statistically significant robust levels of activity changes highly consistent in terms of activity reductions in being able to utilize a biomarker driven determination as well as importantly safety to make that trigger to go to the expanded cohort which is in sufficient in terms of number of patients to be able to evaluate.

Okay. Thank you.

Thanks for your question Steve. Our next question comes from Ananda Walsh from H C. Wainwright. Please on mute your line and ask a question.

Operator: Thanks for your question, Steve. Our next question comes from Ananda Ghosh from H.C. Wainwright. Please unmute your line and ask your question.

Okay.

Hi, Thanks, guys.

Ananda Ghosh: Hey. Hi. Thanks, guys. Paul, I have a couple of questions. One, the first one on the inhibin program, and then two, three on the 006. Maybe, one of the things which we wanted to know is what are the takeaways from the bimagrumab phase II data at the ADA, which was discussed, especially with respect to the trial design, as well as some of the aspects of receptor activity, receptor blocking, and data with respect to the bimagrumab combination potentials and safety with respect to the LDL and TG levels that Lilly saw in the trial. How are you thinking about 007 as you plan to develop the program with respect to some of those datas which were discussed quite widely at the ADA?

Paul and I have couple of questions from lung the first one on the program then to <unk> on those.

Maybe you know.

One other thing.

What are they coming from the B micro app.

The EBITDA, which was disclosed, especially with respect to the trial design as well as numerous all of the aspects of.

Yeah.

Mike.

Okay.

Walking.

And Ddos.

These loss combination potential.

Indiana.

That really saw in the trial.

How does it.

How how are you thinking about seven as you plan to develop the program.

<unk>.

With respect to <unk>, which were which was difficult.

Quite widely at the AGM.

Yeah, No wonder it's always great. When people are starting to talk about muscle preservation and fat reduction in general and I think stepping out of how to have to think about it as combination therapies and how are we thinking about totality of a landscape, where youre stacking expensive drugs on top of expensive drugs, but ultimately how can you get single agent activity that actually delivers healthy.

Paul Bolno: No. One, it's always great when people are starting to talk about muscle preservation and fat reduction in general. I think stepping out of how to have to think about it as combination therapies and how are we thinking about totality of a landscape where you're stacking expensive drugs on top of expensive drugs. Ultimately, how can you get single agent activity that actually delivers healthy, sustainable weight loss? Fat reduction, as Erik pointed out, but importantly, muscle sparing to provide the insulin sensitivity. Remember, ultimately, when you're stepping back, what are we doing? Yes, we're talking about what weight loss is, but it's really about changing a metabolic profile, right? How do we reduce bad fat, and how do we preserve healthy muscle in order to ultimately impact health? I think when we look at those data sets, I think it's encouraging looking at mixed TGF-beta.

Sustainable weight loss at reduction as Eric pointed out, but importantly muscle sparing to provide the influence sensitivity remembering ultimately when youre stepping back what are we doing yes.

Yes, we're talking about what weight losses, but it's really about changing a metabolic profile, how do we reduce that and how do we preserve healthy muscle in order to ultimately impact I think when you look at those data sets I think it's encouraging looking at mix TGF.

When I look at inhibiting it gives us a clean pathway on activity that has a very clean pathway onto the receptor to fat cells to actually reduce that.

Paul Bolno: When I look at inhibin E, it gives us a clean pathway on Activin E that has a very clean pathway onto the receptor, the fat cells, to actually reduce that and encouraging safety tolerability profiles as we look now all the way through 400. I think looking at what we're seeing across some of these other weight loss programs targeting these other receptor pathways come with substantial safety risks that you're stacking on top of other medicine safety and tolerability complications. I think it's encouraging in that pathways can have this approach and demonstration of muscle sparing as being important. I think our ability and coming off of those data sets, again, remains highly encouraged that if we follow an Activin E pathway, reduce visceral abdominal fat, so reduce bad fat, get weight loss from that, which is important, so we're not discounting that.

Encouraging safety and Tolerability profile as we look now all the way through 400, I think looking at what we're seeing across some of these other weight loss programs targeting these other receptor pathways come with substantial safety risks that youre stacking on top of other medicine safety and Tolerability complications and so I think.

It's encouraging in that pathway. It can have this approach and demonstration of muscle sparing as being important.

Our ability and coming off of those datasets again remains highly encouraged that if we follow up and activation pathway reduce visceral abdominal fat so reduce fab.

Get weight loss from that which is important so we're not discounting that but again preserve muscle and do so with an infrequent sub Q administration like we expect with inhibitor.

Paul Bolno: Again, preserve muscle and do so with an infrequent sub-Q administration like we expect with inhibin E and expect safety tolerability that comes with GalNAc-siRNA sub-Q. I think it's highly encouraging given where the field is moving, and I think that was the real take-home coming out of ADA. I think in subsequent conversations that we've seen, this real shift from incretins and how do you solve the complications to that, to really is what does obesity treatment 2.0 look like that's really focused on a healthy weight loss?

And expect safety Tolerability comes a gallon that guests irna sub Q.

I think it's highly encouraging given where the field is moving and I think that was the real take home coming out of Adi.

In subsequent conversations that we have seen this real shift from <unk> and how do you solve the complications that really is what does obesity treatment to point out look like that's really focused on a healthy weight loss.

Alright. Thanks.

Ananda Ghosh: All right. Thanks. I will now shift to the questions on the AATD program. While speaking with some of our KOLs, there were a couple of things which are pointed out. The first one was that based on the KOL's feedback, their opinion was that an ability of a disease-modifying therapy to reach around, let's say, 22 micromolar of AAT or above, and the ability for the therapy to replicate acute phase response might be important. What's your thought as you are thinking about developing 007 with respect to some of these ideas?

When speaking with.

Im not sure.

My question is on the HBV program, what speaking with some of our Q.

There are a couple of things, which I pointed out.

The first one was.

Based on the feedback like that.

Opinion was then the beauty of a disease modifying therapy.

To reach our own let's say micro molar.

Okay.

And the beauty of the <unk>.

To replicate.

Response might be important so what's your thought as you.

Developing.

Respect to some of these ideas.

As evidenced asbury confirm predominate.

Paul Bolno: 007, I just want to confirm. We're talking about AATD?

Hey, guys.

Yes, the numerical.

Ananda Ghosh: Sorry, 007.

Paul Bolno: Okay.

Ananda Ghosh: Yeah.

Closely right now but to.

Paul Bolno: The numerical. We'll see how close they are. No, to your point, we don't discount that. That's why we're actually encouraged by RNA editing because when you do correct the transcript, right, and this ability to then have the transcript from promoter region effective so that when there is an insult, you're actually like, right, body gets an insult and needs to create a reactive protein. You haven't taken away the dynamic effect of that body to have that response rate. Now, this early study to demonstrate that is a challenge test to look to that, but all of the data suggests to date that that's one of the important pieces of fixing and repairing, so hence RNA editing, where you preserve endogenous expression, right? That acute phase response remains intact. I think that's a highly, again, we are very much aligned with where the KOLs are.

To your point, we don't discount that I mean, thats why we are actually encouraged by RNA editing because when you do correct. The transcripts right and this ability to then have the.

The transcript promoter reached attack.

Alright.

So that when there is an insult you actually like body gets in and solve the needs to create a reactive protein you haven't taken away the dynamic effective that body to have that response rate.

This early study to demonstrate that as a challenge tests to look to that but all of the data suggest today, but that's one of the important pieces of fixing and repairing so hence RNA editing.

You preserve endogenous expression.

Cute phase response remains intact. So I think that's a highly again vehicles are very much in line with where it kols are I mean, but that was the thesis around RNA editing for <unk> to begin with which is great that if you're creating that heterozygous phenotype, you create that background level of protective circulating proteins and preserve the ability to.

Paul Bolno: That was the thesis around RNA editing for AAT to begin with, which is create that. If you're creating that heterozygous phenotype, you create that background level of protective circulating protein and preserve the ability to continue to respond beyond that. I think stepping back, that is the difference between IV protein replacement therapy and the field of editing, right? RNA, if you do IV protein replacement therapy, that's as much as you're ever. It's kind of a race to the bottom. You're pouring water in a bucket with holes in it, and you're constantly having to add more protective protein, but you haven't repaired the body's endogenous ability to respond to that acute phase response. Editing is very different. You're creating that background level of a healthy normal protein, hence why we think M-AAT is important, the distinct total.

To respond beyond that.

Because I think stepping back.

Is the difference between IV protein replacement therapy in the field of editing right. Because if you do IV protein replacement therapy, that's as much as Europe, where it's kind of a race to the bottom pouring water in a bucket with alternate and you're constantly having to add more protective protein, but you havent repair the body's endogenous ability to respond to.

To that.

<unk> faced response editing is very different you are creating that background level of a healthy global protein and hence why we think M protein is important.

Total.

And you preserve the ability for the body to responded to make more of a need.

Paul Bolno: You preserve the ability for the body to respond and make more inhibin E.

Thank you for your question Amanda Our next question comes from Jamie from Oppenheimer. Please UN mute your line and ask your question.

Operator: Thanks for your question, Ananda. Our next question comes from Chang Lee from Oppenheimer. Please unmute your line and ask your question.

Hey, Thanks for taking the question and congrats on the quarter just for like a two quick questions from us.

Chang Lee: Hey, thanks for taking the question, and congrats on the quarter. Just like two quick questions from us on the inhibin E program. I'm wondering if you can talk about the baseline characteristics for the cohort 2 enrolled, and considering the weight loss is driven mostly by fat mass. I'm wondering any key metric you will point to that we should keep an eye on. I just have a quick follow-up on this one. Thanks.

<unk> E program.

I'm wondering if you can talk about the baseline characteristics for the cohorts fueling a road in Pennsylvania.

We're largely driven mostly by fat mass.

I'm wondering any key metrics point to that maybe that we should keep an eye on.

And a quick follow up.

I would just have a quick follow up for Scott. Thanks, Yes.

On the first one it is a healthy overweight.

Paul Bolno: Yeah. On the first one, it is a healthy overweight study. There are, as we've shared in the past, our enrollment criteria to be a healthy overweight individual. We'll obviously, with the data release of cohort 1 and 2, likely be normally on the full data set, be able to share all of the baseline characteristics, how that translates to Activin E shifts, and then ultimately, and importantly, how that translates to the potential for weight loss. That will definitely be there. Patients are meeting, obviously, we're screening and successfully translating patients over onto the study that meet the criteria for a healthy overweight study and obese study within the characteristics that are required to follow that. The BMI between 20 and 35.

Studies. So there are as we've shared in the past our enrollment criteria to be a healthy overweight individual.

Well, obviously with the data release of cohort, one and two type of a normal full dataset to be able to share all of the baseline characteristics how that translates to active in east shifts and then ultimately and importantly, how that translates to the potential for weight loss and so that will definitely be there but.

Patients are meeting obviously.

We're screening and successfully translating patients over onto the study that meet the criteria for a healthy overweight and obese.

There'll be study.

Within the characteristics that are required to follow the BMI of between 28, 35%.

Okay got it.

Follow up question from the.

Chang Lee: Okay. Got it. The follow-up question is on the data expected in Q4. I think you mentioned individual will have at least three months follow-up. I'm wondering by the time you release the data, whether you can have a clear idea of the dosing frequency, whether it'll be every three months or every six months or every 12 months, or you need more data or more follow-up. Thank you.

For Q I think you mentioned.

In addition, we will have at least three months follow up so I'm wondering.

By the time it would be today that whether you can have a clear idea.

And see whether it can be over three months were averaged six months whatever it is 12 months, where do you need more data or more a whole lot.

Yes, I think the benefit of that data set over time between two cohorts of data with Barrick and then again, that's why it's important to look at 75% to 40 is we'll have a sense of dosing kinetics on active in knee, we're still going forward right with the 400 and that will give us a sense using activity as a biomarker to look at that PK relationships.

Paul Bolno: Yeah, I think the benefit of that data set over time between two cohorts of data with varying, again, that's why it's important to look at 75 to 240, is we'll have a sense of dosing kinetics on Activin E. We're still going forward, right, with the 400, and that'll give us a sense using Activin E as a biomarker to look at that PK relationship as you're pointing out. We'll have sufficient time to continue to track that and continue to follow it and look at that association with weight loss.

As you're pointing out so we will have sufficient time to continue to track that and continue to follow it and look at that association with weight loss.

Okay got it thanks for taking my question.

Chang Lee: Okay. Got it. Thanks for taking the question.

Thanks, So much. Our next question is going to be from Nelson <unk> from <unk> Securities. Please on mute your line and ask your question.

Operator: Thanks so much. Our next question is going to be from Madison El-Saadi from B. Riley Securities. Please unmute your line and ask your question.

Okay.

Hi, good morning, Thanks for taking our question.

Madison El-Saadi: Hi. Good morning. Thanks for taking our question. A couple questions from us. Have you initiated dosing in the subsequent RNA editing cohorts? Presumably the 400 mg MAD dosing is ongoing. I guess, would you wait to complete that before moving on? Is there a trigger that could initiate that subsequent dosing or even expand the arm similar to what we've seen in cohort 2 in INLIGHT? Yeah, just what could these triggers be?

A couple of questions from us.

So have you.

<unk> initiated dosing in the subsequent <unk> cohorts.

Cohorts, presumably the 400 million Matt.

Ongoing.

I guess with new ways to complete that before moving on is there a trigger.

<unk> initiated a subsequent dosing.

Spend on arms similar too.

What we've seen in cohort two.

Right.

Yes.

The distributors.

And just to confirm you're talking about.

Paul Bolno: Just to confirm, you're talking about 006, so AATD for the subsequent cohorts? Is that what I heard?

Yes.

<unk>, so ATV for subsequent cohorts.

If I heard correct.

<unk>.

Madison El-Saadi: Correct. I was just using 007 as an example.

Your line.

Paul Bolno: Everybody listening online. As they started to crisscross around 400 and 200, I always think people kind of.

Criss cross around 400.

I always thought that people would kind of so I think.

Alright.

What's important as we think about the decisions on where we get to with US. So we still have as you mentioned the third cohort about that I think were approximate in the third quarter to looking at our 200 multi dose data that's going to be highly informative and translating our PK PD relationship to really thinking about what do we need relative to <unk>.

Madison El-Saadi: Oh.

Paul Bolno: Sorry. What's important is we think about the decisions on where we get to with dose. We still have, as you mentioned, the third cohort above it. I think we're proximate in Q3 to looking at our 200 multi-dose data. That's going to be highly informative in translating our PK/PD relationship to really thinking about what do we need relative to making more protein? Where are we on that kinetic curve, given the single-dose data we've already seen, which is therapeutically relevant. We'll have a good sense off the 200 multi. We'll have the 400 SAD in the fall. Those data are going to help us a lot as we think about the subsequent dosing intervals, and in particular to your question, how we utilize that third cohort, right?

Making more protein where are we on that kinetic curve given the single dose data we've already seen just therapeutically relevant. So we'll have a good sense of the 200 multi will have the 400 fad.

Paul those data are going to help us a lot as we think about the subsequent dosing intervals and in particular to your question, how we utilize that third cohort right.

Do we need to go higher as we look at the 400 and exposure is 200 exposures isn't really about pushing out the interval or do we benefit from a low or.

Paul Bolno: Do we need to go higher as we look at the 400 in exposures and the 200 exposures? Is it really about pushing out the interval, or do we benefit from a higher that can even go farther? I think we're going to let the clinical data from the 200 and 400 help us establish how we utilize that third cohort. I think stepping back, the most important feature from our healthy volunteer study is we have ample room to go from a safety perspective to utilize that cohort how we need to.

The higher that can even go are there. So I think we're going to let the clinical data from the 204 hundred help us establish how we utilize that third cohort I think stepping back the most important feature from our healthy volunteer study as we have ample room to go from a safety perspective to utilize that cohort.

Sure.

Yeah.

Got it understood and then.

Quickly going back to DMT I'm just given.

Madison El-Saadi: Got it. Understood, Paul. Quickly going back to DMD, just given the community is, I guess, newly sensitized to the AAV liability. Just wondering how enrollment's going in the open label monthly extension cohort. How long do you think these boys need to be on drug before you submit your NDA package? Thanks.

I guess newly sensitized the AAV liability just wondering how enrollment is going in the open label extension.

Extension cohort.

And how long.

<unk> needs to be.

On drug.

Before you.

So fixture in the package.

Yes. Thank you.

Paul Bolno: Yeah. Thank you. We have been engaged with this community now for over a decade, so we know the community very well. We engage with them on the other side of data. That's obviously how encouraging patients who are on the study remain on the study and getting their dosing. We're not providing more updates on the subsequent study other than to say they continue to keep us track and there's no change to our timeline of NDA filing in 2026. All that remains encouraging, but I think the community's been through a lot, and we continue to engage with them on a path forward.

We've been engaged with the community and that for over a decade. So we know the community very well.

Engage with them on the other side of data so.

Thats, obviously highly encouraging patients who are on the study remain on the study and getting their dosing, we're not providing more updates on the subsequent study other than to say they continue to keep us track and there's no change to our timeline.

NDA filing in 2026, so all of that meant to encourage it but I think the community has been through a lot and we continue to engage with them on.

On our path forward.

Understood.

Yeah.

Madison El-Saadi: Understood. Thanks.

Thank you for your question Medicine. Our last question comes from Luca <unk> from RBC capital markets, Amit Your line and ask a question.

Operator: Thanks for your question, Madison. Our last question comes from Luca Issi from RBC Capital Markets. Please unmute your line and ask your question. Hi, Luca, can you hear us? Okay. It looks like Luca’s having some audio issues, so we’re going to end the Q&A here. Thank you. There are no further questions at this time. I want to turn the call back to Paul Bolno for closing remarks.

And Luca can you guess.

Okay.

Okay and it looks like we're just having some audio issues.

The Q&A. Thank you there are no further questions at this time I will now turn the call back to Paul for closing remarks.

Thank you for joining our call. This morning. We appreciate your continued support have a great day.

Paul Bolno: Thank you for joining our call this morning. We appreciate your continued support. Have a great day.