Wave Life Sciences Ltd. Ordinary Shares Q2 2026 Earnings Call

Hello. And welcome to Wave Life Sciences second quarter 2020 earnings call. We ask that you please hold all questions until the completion of the formal remarks, at which time you'll be given instructions for the question and answer session Also, as a reminder, this conference is being recorded today. I will now turn the call over to Kate Rausch, 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 2020 earnings update. Joining me today with prepared remarks are doctor Paul Bolno President and Chief Executive Officer. Doctor Erik Ingelsson Chief Scientific Officer, Doctor Chris Wright, Chief Medical Officer and Kyle Moran, chief Financial financial Officer. The press release issued this morning is available on the investor section of our website, w w w dot Wave Life Sciences dot 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. 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.

Thanks, Keith, and good morning to everyone. Joining us on today's call At Wave, we are focused on harnessing the convergence of deep genetic insights with our proprietary chemistry to rapidly advance a pipeline of transformational RNA medicines. Over the past decade, we have built the most sophisticated and broadly enabled oligonucleotide platform in the industry Multiple clinical data sets now demonstrate our ability to rapidly advance programs from novel genetic target to proof of mechanism in the clinic. Our proprietary chemistry is what differentiates our pipeline and distinguishes our molecules from others in the field. In the first half of 2026, we delivered multiple positive data sets across our RNAi and RNA editing pipeline, led by WV007 for obesity and WVE006 for D, positioning us to advance both programs to their next stage of development. We also continue to progress our second RNA editing candidate, WVE008 for Pnpla3 liver disease, and remain on track for a CTA filing later this year. In March, we shared positive data from the single dose phase one portion of the Inlight trial of 007 in obesity. These data fortified our conviction in a best in class siRNA design with robust and extremely durable silencing demonstrated in the clinic, supporting potential dosing of once or twice a year Also, even in this otherwise healthy population, a single dose of 007 led to substantial reductions in visceral fat and subcutaneous fat without muscle loss or other adverse events associated with increased therapy.

We have three opportunities to explore in the next phase of development for this program. First, a. W 007 in a phase two, a population with higher BMI and comorbidities typical of other obesity trials. To demonstrate 007 potential in obesity as well as evaluate biomarkers to unlock other cardiometabolic indications, including Nash and type two diabetes. Second. Kate combination with Incretin, which has the potential to deepen weight loss and enhance metabolic benefits. Third, and perhaps one of the most exciting and unique opportunities. Evaluate maintenance therapy, which would represent an entirely new commercial frontier, enabling patients an off ramp for their GLP one. We often hear from patients about the fear of weight regain post cessation of incretins. Up to 70% of patients discontinued GLP one therapy within the first year of treatment, and for many, it's due to challenges that WE00 7th May address, including tolerability issues, treatment burden or anhedonia. Loss of joy, among others. In this maintenance setting, 007 would have the potential to enable individuals and payers to realize the sustained health benefits of fat loss and improve body composition for the long term. Over the past quarter, the FDA accepted the phase two a inlay trial amendment, and dosing is now underway.

The phase two A is enrolling individuals living with obesity with BMI between 35 and 50 and comorbidities with and without diabetes. These patients are expected to have higher total body fat and higher levels of visceral fat than the phase one. Otherwise healthy patients. With this multi-dose clinical trial. We are evaluating our target patient population and have the potential to deliver further improvements in body composition, meaning weight loss driven off of fat loss without muscle loss, as well as other improvements in cardiometabolic biomarkers, including liver fat and hba1. C. We are also working expeditiously to initiate the additional phase two trials of 007 in combination and maintenance settings this year Collectively, our development program has the potential to redefine the treatment landscape in obesity. In RNA editing. We delivered data supporting 006 potential to offer a new standard of care for individuals living with a. By treating both lung and liver manifestations of the disease and restoring the dynamic. A T protein response with convenient, infrequent subcutaneous dosing. We are planning to engage the FDA as the agency has granted our request for a meeting to discuss a potential accelerated approval pathway for WVE006. This meeting is expected at the end of summer and will help inform our Registrational plans and path toward bringing a much needed new treatment option to the 200 000 individuals in the US and Europe living with homozygous Z, a, D. As a.

Scalable. Infrequent. Subcutaneously dosed oligonucleotide therapy. 006 would offer a potentially differentiated value proposition for both healthcare providers and payers Current IV augmentation standard of care does not have any impact on liver manifestations of the disease. While investigational DNA editing. In addition to any safety concerns, would be associated with payer challenges for one time, costly therapy with uncertain durability and multi-year enrollee retention. Building. On our RNA editing success, we are advancing our second RNA editing candidate, WVE008, toward the clinic this year. For Pnpla3 liver Disease. 008 aims to address an area of high unmet need, with 9 million individuals living with homozygous Pnpla3 i148m liver disease. Human genetic data demonstrates these homozygous individuals have about a nine fold higher risk of dying from liver disease as compared with Non-carriers. The landscape of therapies and development for this target has been narrowed by recent clinical demonstration that silencing approaches do not address the disease, and may actually exacerbate it. And RNA editing approach is the only way to restore the functional protein and offers a potential for a novel, infrequently dosed therapy with strong support from human genetics. Beyond our lead RNA and RNA editing programs, we continue to push the boundaries of innovation with our proprietary chemistry.

We are planning to host our annual Investor Day in the fall to shed more light on our latest platform advancements and work on our bifunctional modality. At the start of the year, we outlined our pipeline priorities. WVE007006 and 008, demonstrating our core focus on RNA, I and RNA editing, as well as our intent to seek partnership opportunities for HD and DMD. Given the evolving regulatory and commercial landscape in DMD, we are exploring potential partnerships in advance of filing an NDA for n 531. We continue to believe in N 531 and 003 potential as best in class treatment options and look forward to continuing our partnering discussions with our continued success in the clinic and robust balance sheet. We are well positioned and well capitalized to bring our pipeline of potential first and best in class candidates to the next stage of development. As we reimagine what's possible for patients. Now, I'd like to turn the call over to Eric, who will discuss 007 and how we are leveraging our proprietary chemistry and human genetic insights to advance a transformative approach for obesity and other cardiometabolic diseases. Eric.

Thank you. Paul. I'll start today by discussing our eagle like shrna WV007 and how our program aims to fill a large unmet need with a differentiated approach grounded in human genetics to. Today, there are over 1 billion individuals living with obesity globally, including 175 million in the US and Europe alone. These individuals face markedly higher risks of a range of diseases such as type two diabetes and other cardiometabolic diseases. Excess body fat, in particular. Visceral fat is the key driver behind this elevated risk of disease. While there are several therapeutic options available for weight loss and countless more in clinical development, with similar modes of action to those already on the market, these therapies come with several limitations. Current standard of care therapies reduce body weight through both fat loss and muscle loss, and they carry high discontinuation rates due to the GI side effects. Limiting potential for long term health benefits. The loss of muscle associated with current weight loss therapies is substantial, with up to 40% of the total weight loss This has significant health implications as skeletal muscle in addition to muscle strength and function, also plays a key role in metabolism. By sustaining basal metabolic rate, glucose disposal, and insulin sensitivity.

Muscle also prevents weight regain, which occurs mostly from fat in a majority of individuals. That discontinuing treatment therapies. Remember as much as up to 70% of individuals discontinue Incretins within the first year of treatment and. Obesity therapy should instead selectively reduce excess fat, including harmful, visceral fat. The fat surrounding one's organs that is most strongly linked to Mash, type two diabetes and other cardiometabolic diseases, while also lowering subcutaneous fat and liver steatosis and critically preserve skeletal muscle. It is well established that a 5 to 10% reduction in visceral fat mass is associated with positive health outcomes. By reducing risk of multiple preventable metabolic diseases and preserving patient function and quality of life. All these benefits can be delivered by 007 mechanism of action. Rather than acting on appetite. 007 silences in Ebony and lowers serum activity. A liver derived hepatokine that signals adipocytes to put the brakes on lipolysis, removing those brakes drives fat loss without calorie restriction, and without the muscle loss seen with incretin based therapies. RNA. Approach is strongly grounded in human genetics, as carriers of heterozygous inhibin-a loss of function variants. Nature's own knockdown experiment exhibit a healthier overall metabolic profile as. Paul discussed earlier.

Sera sera. Seven unique ability to durably suppress any. Is driven by our proprietary chemistry and spina Shrna design. Our next generation spinner designs enhance interactions with two. Stabilize the loaded risk complex and improve liver exposure, all of which contribute to dramatically improved silence potency, and durability. When compared with industry leading Shrna designs. Something we have shown repeatedly for Inhibin, E and other targets. While. RNAi is a well established therapeutic modality and there are extensive human genetic data supporting inhibiting as a target, we believe our proprietary chemistry distinguishes us from others attempting a similar approach. Our interim phase one in life data sets from lower BMI, otherwise, healthy individuals confirm that this proprietary chemistry and underlying human genetics are already translating in the clinic. We have observed consistent, durable, and dose dependent serum activity reductions of up to 88%, which were sustained through at least seven and a half months, supporting 007 potential for once or twice yearly dosing. Notably, we observed the translation of target engagement to substantial improvements of cardiometabolic risk factors with preservation of lean mass and clinically meaningful reductions. In total fat, visceral fat, and waist circumference. After just a single dose.

To provide context for our results at this early development stage, we calculated the visceral fat and ratio, or vmr, which is a measure of body composition that integrates harmful, visceral fat and beneficial lean mass into a single index. Lower Vmr is associated with a decreased risk of type two diabetes and cardiometabolic disorders with a. Dose of 007 in our phase one population, we already observed a 16.5% improvement in Vmr, which was more than 12.2% achieved with weekly semaglutide in the phase two belief study and approached the 18.8% observed with the microbiome We believe Vmr has the potential to serve as a novel composite biomarker that captures body composition improvements, more holistically than BMI, and that may better predict long term clinical benefits. Together with the patient community and colleagues, we're working to engage with regulators on the importance of improving body composition, including decreasing excess fat and preserving muscle consistent with the recent guidance. What makes the. Listen with the belief study, particularly exciting is that our In-life participants had substantially lower baseline BMI, lower visceral fat, and lower total fat compared to phase two and phase three obesity studies, including the Believe study. Clinical experience also highlights the importance of baseline adiposity.

Early phase one studies in leaner individuals typically show more modest, modest reductions, while studies of individuals with higher baseline obesity demonstrate substantially larger decreases in total and visceral fat mass. Early follow up from our 400 milligram cohort, which included a substantially higher proportion of individuals with low levels of body fat, also confirmed that higher baseline visceral fat led to greater visceral fat reductions overall. As Chris will speak to shortly, we've been working expeditiously to advance 007 into participants with higher BMI and co-morbidities in the phase two, a portion in light, we're existing science predicts a larger effect actively binds Alk7 on all adipocytes and visceral fat being more metabolically active and better perfused mobilizes first exactly what we have observed in phase one, with more excess fat to lose, we expect both visceral and total fat loss, with 007 to be substantially more pronounced in higher BMI, participants in the two. A study for further detail on our 007 development plans and our RNA editing programs, I'd now like to turn the call over to Chris.

Thanks, Eric. As you recently announced, we're excited to have advanced 007 to a population well suited to its mechanism of action. We would expect even more pronounced effects on visceral and subcutaneous fat loss. Dosing is. Currently underway in the phase two, a multi-dose portion of Inlight. This. Placebo controlled trial will enroll individuals with higher BMIs in the range of 35 to 50 and comorbidities across two dose levels 240mg and 400mg, and two study populations with and without type two diabetes for a. Total of four cohorts of 40 patients each. Assessments in this multi-dose portion are like those in the single dose portion, with additional inclusion of body composition measured by MRI, liver fat content as measured by MRI. Pdff Hba1 c lipid levels and other measures. The design and study population enables enhanced evaluation not only of improved body composition and weight loss. But also informs additional opportunities for 007 in Nash type two diabetes and cardiometabolic diseases. Participants will be given two doses of 0071 at day one and one at day 85, and followed for 12 months with the first key assessments occurring at day 85. We believe that oh seven orthogonal mechanism, ability to drive fat reductions while preserving muscle and favorable safety profile are also aptly suited to combination and maintenance approaches.

Our preclinical data provides compelling support for both use cases. You've observed approximately two fold greater weight loss as an add on to incretin versus Incretin alone. In obese mice, and have demonstrated the ability to curtail weight, regain. Following cessation of incretin. Planning is well underway for clinical studies addressing Incretin combination and post maintenance, and remain on track to initiate this year. We also expect to share additional data from the phase one portion of Inlight this year, including data from our 600 milligram cohort, which will further inform the durability of 007. Turning to our. Ongoing restoration to clinical trial of WVE06 for a. Attd is a uniquely compelling disease for RNA editing. It is a monogenic disorder caused by a single well, genetic variant and the Serpina1 gene. This leads to misfolded protein and an absence of healthy circulating M, a protein which normally protects the lung. During inflammation or infectious events. Without dynamic production of functional a protein, individuals with alpha one are at risk for lung damage and ultimately developing emphysema and bronchiectasis, which is characterized by chronic cough. Recurrent infections, and shortness of breath. In parallel, misfolded Z t accumulates in hepatocytes and causes progressive liver injury and increased risk of liver disease.

Approximately 200,000 individuals in the US and Europe live with homozygous PIZZATD. Currently the only approved treatment for Aatd is weekly IV plasma derived augmentation therapy, which carries several limitations with a fixed schedule dose. There's no restoration of dynamic response, leaving individuals with alpha one at risk of a T protein levels fall too low. During an infectious or inflammatory event. IV therapy is time consuming and often requires inpatient visits and does nothing to lower ZAT to address the risk of liver disease. Investigational. Therapies and development also come with several limitations. DNA based editing approaches target both lung and liver, but they introduce permanent DNA modifications, carry by standard editing risk and rely on LNP delivery, which is associated with liver enzyme elevations. The risk of irreversible off target effects is particularly notable, as genomic DNA editing has been connected to editing and cancer associated genes. Also in development are a t c, RNA approaches, which reduce ZAT. However, they do not restore MAT, potentially exacerbating lung disease through chronic a T knockdown. Oh six. Has the potential to be the first treatment for aatd that enables an. Individuals with Alpha one to produce protective. A T protein when needed most.

And address the root cause of the disease with a convenient and infrequent subcutaneously dosed therapy. With zero six, our goal is to recapitulate an m z like phenotype as it's well established that heterozygous individuals have low risk of both lung and liver disease m z. A individuals compared to disease. Have reduced levels of ZAT, which protects the liver from damage and are able to protect the lung with basal a T levels above 11 Micromolar of which at least 50% is wild. Type M, a T, and most importantly, are able to mount a dynamic a T response during an acute infection. That. Nation ZAT reduction protective basal levels with a meaningful proportion of wild type M, a T and a preserved acute phase response is the bar we set for oh six. As we shared in May, this is exactly the profile we've consistently achieved. WV06 delivered a compelling therapeutic profile following only three months of treatment across both 200mg biweekly and 400 milligram monthly dosing. Importantly, oh six RNA editing. The. The oh six RNA editing approach produces only wild type canonical M, a t and does not include bystander edited isoforms as seen with DNA editing.

This specificity is crucial as bystander edits. Not only introduce functional activity risk, but may also render patients ineligible for future base editing or RNA editing therapies. Enrollment and dosing are now complete in the 200mg, 400 milligram, and 600 milligram cohorts of restoration, two, and we remain on track to share data from the 600 milligram monthly dosing cohort in the second half of this year, which will help inform an optimal dose regimen. With the compelling profile of oh six we've observed to date. We're continuing to engage with the community. Key opinion leaders and advance our discussions with regulators. We're excited to announce today that the FDA granted our request for a meeting, which is planned for the end of this summer. During this, we intend to discuss a potential accelerated approval pathway for 006 and a TV feedback. From this meeting will help inform our potential registration study design and our plans to efficiently advance. Oh six for individuals with Alpha one who are in urgent need of new treatment options. Building on our. Success with oh six, we are advancing our second RNA editing clinical candidate WVE08 for homozygous Pnpla3 I148m liver disease. Similar. To oh six and oh seven.

Our approach to oh eight is deeply grounded in genetics. The Pnpla3 variant is a well driver of Nash and liver disease is more generally. Yet there are no approved medicines that directly address this biology. There are an estimated 9 million homozygous pnpla3 i148m carriers across the US and Europe, who are at a nine fold higher risk of dying from their liver disease compared to Non-carriers. Currently, the only treatment options are non precision medicines aimed at reducing liver steatosis and early fibrosis, with limited efficacy for these i148m carriers, silencing Pnpla3 can only partially address disease biology. It's likely to leave residual pathology since it knocks down all pnpla3 protein without restoring healthy wild type protein, which has important physiologic functions in the liver. As a result, silencing partially addresses steatosis, but inflammation and fibrosis remain unaddressed or worse. Recent clinical trials of pnpla3 silencing support this notion as dose dependent increases in liver enzymes were observed. By contrast, with oh eight. We aim to correct the I148m variant using our leading RNA editing capability. Which is expected to restore Pnpla3 activity and lipid mobilization, reversing steatosis and fibrosis, and improving liver health. In May, we shared pre-clinical data supporting our approach at Easl, the European Association for the Study of the Liver Congress.

We demonstrated that our Pnpla3 Amers delivered substantial editing of the I148m transcript exceeding the 50% threshold expected to lower risk for liver disease. Achieved concentrations in the liver expected to support substantial editing and decreased lipid droplet density more than siRNA. In our upcoming first in human study of oh eight, we plan to leverage previously genotyped populations to efficiently identify homozygous i148m carriers and accelerate enrollment. We will evaluate target engagement with circulating biomarkers and assess early signs of efficacy using noninvasive imaging. We remain on track for a CTA submission in 2026. With that, I'll turn the call over to Kyle to provide an update on our financials. Kyle.

Thanks, Chris. Our revenue for the second quarter of 2026 was $2.3 million, compared to $8.7 million in the prior year quarter and relates to our ongoing collaboration agreement with GSK, which. Search and development expenses were $51.3 million in the second quarter of 2026, as compared to $43.5 million in the same period in 2025. The. Increased, particularly reflects primarily reflects continued investment in advancing our clinical programs, including preparation for the phase two. A portion of Enlight and continued progress on our RNA editing pipeline. Our Gena expenses were $24.8 million for the second quarter of 2026, as compared to $18 million for the prior year quarter. The increase primarily reflects costs associated with supporting our expanding pipeline and preparing for the next stages of development. As a result, our net loss for $69.4 million for the second quarter of 2026 as compared to a net loss of $50.5 million in the prior year quarter. We ended the second quarter with $490.6 million in cash, cash equivalents and marketable securities, which we expect to be sufficient to fund operations into 2028 while we. Expect to receive milestone payments from GSK in the second half of 2026, it's important to note that potential future milestones and other payments to us under our collaboration are not included in our cash runway.

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

Thank you Kyle, as we look to the second half of 2026, we believe we are well positioned to unlock value across our pipeline. With 007, our phase two, a trial in individuals with obesity is underway, and we are rapidly working to advance in Crete in combination and post treatment. Maintenance studies later this year, with 006, we are on track to meet with regulators on a pathway to accelerated approval, and we are also working to bring our second RNA editing candidate into clinical development for Pnpla3 liver disease. In the second half of this year, before turning to questions, I want to thank our team for the progress we've made and for their continued commitment to reimagining what's possible for patients. I'll now turn the call over to the to the operator. Operator.

We will now move into our Q&A session For those of you who are joining us via the Q&A webcast. If you would like to ask a question at this time, please raise your hand by clicking the raise your hand at the bottom of your window. We would like to ask all analysts to please limit yourself to one question per person. Once called upon, please unmute your audio to ask a question. We'll take our. First question from Yun Zhong with Wedbush. Please unmute your line and ask your question.

Hi. Good morning. Thank you very much for taking the questions. And so the question is on the 007 program for obesity. And I wanted to confirm that for the ongoing phase two, a portion, the goal is to confirm that you are able to achieve 5% weight loss as compared to placebo at 12 months to support the advancement for this program into the indication of obesity. And then,, on combination therapy,, I believe other programs have reported or will report data and given the same mechanism of action. What would be your expectation on data from your own program? Do you think you will potentially be able to show any differentiation? Thank you very much.

Thank you., I'll start with the second question. Then we'll work backwards to the first question, because I think the answer to the second question is. We do believe that, you know, I think it's valuable to see what others have been generating in that space, not just for the potential for increasing fat loss. And remember, these other data sets that people have seen in combination were in phase two, a high BMI, high, visceral fat, high, total fat, patient populations. And they were able to see, as you point out, substantial reductions in both fat, visceral fat, in particular., and. And liver fat, we should remind that the liver fat was, was pretty substantial, I think, given that in comparison, both on preclinical ed50, where we're about three fold more potent and