Wave Life Sciences (WVE) Earnings Transcript

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CALL PARTICIPANTS

• Chief Executive Officer — Paul Bolno
• Chief Financial Officer — Kyle Moran
• Chief Medical Officer — Erik Ingelsson
• Senior Vice President, Platform Research and CMC — Chandra Varghese
• Senior Vice President, Clinical Development — Chris (no last name specified in transcript)

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TAKEAWAYS

• Revenue — $7.6 million was recorded for 2025, attributed to timing of GSK collaboration revenue; this compares to negative $7.7 million in the prior year.
• Research and Development Expenses — $45.9 million, up from $41.2 million, primarily driven by advancement of inhibitory and RNA editing programs, plus increased compensation costs.
• General and Administrative Expenses — $18.1 million, versus $15 million previously, mainly due to higher share-based and external expenses.
• Net Loss — $53.9 million, reflecting an improvement from $61.8 million in the prior year quarter.
• Cash and Equivalents — $196.2 million at quarter-end, down from $302.1 million at December 31, 2024.
• Cash Runway — Extended into Q2 2027 following $72.1 million in ATM proceeds and committed GSK milestones after quarter-end; future potential GSK milestones are excluded from this projection.
• WVE-007 Clinical Update — Over 70 participants enrolled, with plans to report data from more than 100 across Europe and the US in 2026; dose cohorts of 75mg, 240mg, 400mg, and 600mg tested.
• WVE-007 Dose Response — Reported 56% reduction (75mg), 75% reduction (240mg), and 85% reduction (400mg) in activin E one month post-single dose compared to baseline, with sustained reductions at 6 months for the 75mg cohort.
• WVE-007 Safety — Product was generally safe and well tolerated; independent data monitoring committee authorized escalation to higher doses.
• WVE-006 RESTORATION 2 Data — Demonstrated AAT levels of nearly 13 micromolar, 64% wild-type mAAT, and a 60% reduction in mutant z AAT protein, including restoration of acute phase protein response with over 20 micromolar following a single dose.
• WVE-006 Dosing — Ongoing in 400mg multidose cohort; single-dose 600mg cohort initiated; single and multidose 600mg data expected in 2026.
• WVE-008 (PNPLA3 I148M) — New clinical candidate targeting up to 9 million US/EU homozygotes with liver disease; first-in-human study CTA submission planned for 2026.
• WVE-N531 (DMD Exon 53) — Statistically significant improvement of 3.8 seconds in time to rise at 48 weeks vs. natural history; NDA submission targeted for 2026 with monthly dosing regimen.
• WVE-003 (HD SNP3) — Preparing for global phase 2/3 registrational study using caudate volume as primary endpoint; IND submission planned for the second half of the year.
• Allele-Selective Approach (WVE-003) — Achieved up to 46% reduction in mutant huntingtin with preservation of wild-type, correlating with a slowing of caudate atrophy.
• Strategic Control — Management explicitly stated, “there’s no inhibition for us to do anything related to inhibit any with GSK,” confirming full clinical and commercial control over the program.
• Bifunctional Construct — Preclinical evidence shows simultaneous silencing and editing activity in single oligonucleotide without observed off-target edits or indels.

SUMMARY

Wave Life Sciences (WVE +0.51%) disclosed expanded clinical and financial progress, highlighting strong pipeline momentum across obesity, hepatic, neuromuscular, and CNS therapeutics. Management showcased clinical evidence of high and sustained activin E suppression with WVE‑007 and restoration of wild-type alpha-1 antitrypsin at both basal and acute phase levels in the WVE‑006 program, with pivotal data timelines established. The company separately advanced a new RNA editing candidate, WVE-008, for a genetically defined high-risk liver disease population and indicated an unencumbered strategic path for their proprietary obesity program.

• Kyle Moran noted, “Our revenue for 2025 was $7.6 million, compared to negative $7.7 million in the prior year quarter,” emphasizing a shift attributed to GSK collaboration timing.
• Clinical management confirmed durable therapeutic responses, as well as favorable safety profiles, for WVE-007 and WVE-006 across multiple dosing cohorts.
• Pipeline expansion momentum continued into preclinical and regulatory domains as WVE-008 development advanced toward clinical trial application submission, and WVE-003 prepared for an IND filing leveraging FDA alignment on imaging endpoints.
• Subsequent ATM proceeds and GSK milestone receipts have materially extended the operational cash runway, with future GSK milestones excluded from the base projection, according to Kyle Moran.

INDUSTRY GLOSSARY

• Activin E: A hepatokine regulated by the INHBE gene, implicated in energy metabolism and targeted for reduction in obesity therapeutics.
• GalNAc-conjugated oligonucleotide: An RNA therapeutic delivery technology that targets drugs specifically to hepatocytes via the asialoglycoprotein receptor.
• AATD: Genetic disorder (Alpha-1 Antitrypsin Deficiency) resulting in deficient alpha-1 antitrypsin protein, leading to liver and lung disease.
• RESTORATION 2: Wave’s phase 1/2 clinical trial evaluating WVE-006 for treatment of AATD.
• DIO mouse model: Diet-Induced Obese mouse, an animal model used to study obesity and related metabolic outcomes.
• Enlight trial: Clinical study evaluating WVE-007 for activity reduction and weight loss in participants with overweight or obesity.
• Caudate atrophy: Degeneration of the caudate nucleus detected via MRI; used as a biomarker and imaging endpoint in Huntington’s disease clinical trials.
• AIMER: Wave’s proprietary design for RNA editing oligonucleotides, optimized for enzyme specificity and editing efficiency.
• MZ phenotype: Heterozygous genotype in AATD (one normal M allele, one mutant Z allele) associated with intermediate alpha-1 antitrypsin levels and protected acute phase response capability.

Full Conference Call Transcript

Paul Bolno: Thanks, Kate. Good morning to everyone joining us on today’s call. I would like to first thank those of you who are able to join us for our 2025 Research Day on October 29, where we shared the first-ever demonstration of active and e reductions in a clinical trial. Notably, with a single dose of WVE-007, our inhibiting GalNAc siRNA, we were excited to show highly significant and durable human activity reductions that exceeded levels needed in preclinical models to drive meaningful weight loss and prevent rebound weight gain following cessation of a GLP-1.

In addition, we provided an in-depth overview of our recent in RNAi and RNA editing and how we are building on the successful clinical translation of our WVE-007 and WVE-006 programs to advance our pipeline, including our new RNA editing clinical candidate WVE-008 for the treatment of the up to 9 million homozygous individuals living with PNPLA3 I148M liver disease in the US and Europe. We also unveiled how we’re harnessing the power of both siRNA and RNA editing to advance an innovative new bifunctional single oligonucleotide construct that is designed to silence one target while simultaneously editing or upregulating another distinct target.

All of these clinical and preclinical advancements are made possible by our unique and proprietary chemistry and platform innovations. Just last week, we had the privilege of sharing data on 007 at Obesity Week, where we received significant attention from the patient community, key opinion leaders, and companies with deep understanding of, and strategic interest in, the obesity space. There was a clear recognition for the need for non-incretin treatment approaches and overwhelmingly positive engagement on 007’s potential to induce fat loss, preserve lean mass, and improve cardiometabolic health all without the negative GLP-1 class effects and with the convenience of once to twice a year dosing.

There is particular excitement in 007’s potential as a maintenance therapy, which would allow patients to transition off chronic incretin therapies while at the same time preventing rebound weight gain, preserving lean mass, and sustaining cardiometabolic health. Reflecting on the rapid progress we’ve made in advancing 007 in our Enlight clinical trial, we have now enrolled over 70 participants and are well-positioned to deliver data on over 100 participants from the clinical trial sites in Europe and the US in 2026. We began testing WVE-007 in Enlight at our lowest subtherapeutic dose cohort of 75 milligrams in each participant.

Then for the subsequent cohorts, 240 milligrams, 400 milligrams, and 600 milligrams, which are in the potential therapeutic range, we have expanded to 32 participants. WVE-007 was generally safe and well-tolerated, and our independent data monitoring committee has approved further escalation to a next higher dose in cohort five. At Research Day, we shared highly significant dose-dependent and durable activin e reductions one month post-single dose of the 007 in the first three cohorts of Enlight, including a 56% reduction for the 75 milligram cohort, 75% reduction for the 240 milligram cohort, and an 85% reduction for the 400 milligram cohort compared to baseline.

In addition, we had the opportunity to evaluate our lowest dose cohort out to six months, and throughout the six-month follow-up period, we continue to see sustained reduction, supporting 007’s potential for once or twice yearly dosing. The durability and potency we’ve observed thus far is particularly encouraging, as we expect consistent and robust activity reduction over time is necessary to achieve meaningful weight loss. As we shared at Research Day, Wave’s unique spina design and proprietary chemistry enabled the achievement of the potent and durable suppression needed for the inhibiting target.

In our DIO mouse model, we demonstrated that weight loss in the same range as semaglutide occurred when Activin E was durably reduced by greater than 70% from baseline. The knockdown we’ve observed in the 240 and 400 milligram cohorts already exceed these levels. In our preclinical studies, we have shown extensive data supporting 007’s unique mechanism of action to drive weight loss in monotherapy, as well as maintenance in combination settings. Specifically, we share data that support 007’s ability to double weight loss when added to semaglutide and prevent rebound weight gain following cessation of GLP-1 in DIO mice.

Furthermore, we’ve shown that inhibit e reduction led to adipocyte shrinkage, fewer pro-inflammatory macrophages, less fibrosis, and improved insulin sensitivity in adipose tissues, highlighting mechanisms that could explain the risk reduction for type 2 diabetes and coronary artery disease observed in human genetic data. With robust and durable target engagement in the clinic and comprehensive preclinical data that support both the mechanism of action and impact of our proprietary chemistry, we are incredibly excited to build on this positive momentum. We plan to deliver multiple near-term updates that assess blood-based biomarkers, metabolic health, body composition, and weight loss across multiple cohorts.

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