Summary of Wave Life Sciences Conference Call Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Focus**: Building a fully integrated RNA medicines company capable of unlocking the potential of genetic medicines, particularly in RNA editing and siRNA technologies [3][4][39] Key Programs and Developments 1. Inhibin E (WVE-007) - **Target**: Obesity, focusing on fat loss without impacting lean mass - **Mechanism**: Utilizes siRNA to knock down inhibin E, leading to significant fat loss while preserving muscle mass - **Preclinical Results**: Demonstrated a 70% reduction in activin E levels in DIO mice, translating to fat loss equivalent to GLP-1s without affecting lean mass [10][12][13] - **Clinical Data**: - 75 mg cohort showed a 55% reduction in activin E sustained over six months - 240 mg cohort achieved a 75% reduction at day 29, with ongoing decline [13][14] - **Future Outlook**: Q4 will provide three-month data on the 240 mg cohort, with further insights expected in Q1 2026 [14][20] 2. Alpha-1 Antitrypsin Deficiency (AATD) - **Mechanism**: RNA editing to convert Z protein to M protein, enhancing protein levels in patients - **Clinical Results**: At the lowest dose, patients showed a return to near-normal levels of total protein, with significant increases in M protein [32][34] - **Upcoming Data**: Focus on the 400 mg dose cohort to assess durability and editing efficiency [32][37] 3. PNPLA3 Program (WVE-008) - **Target**: Liver disease associated with homozygous mutations - **Potential Impact**: Could address a large patient population (approximately 9 million) at risk of liver diseases, with a unique mechanism that siRNAs cannot treat [39][40] Industry Context and Market Opportunity - **Obesity Treatment Landscape**: The company aims to shift the paradigm in obesity treatment from frequent dosing (weekly/monthly) to potentially once or twice a year with their siRNA therapies, addressing a significant global health issue [27][28] - **Market Size**: The global obesity market presents a substantial opportunity, with the potential to treat a billion patients worldwide [27] Important Considerations - **Kinetics of Fat Loss**: The company emphasizes the importance of understanding the kinetics of fat loss versus total weight loss, particularly in the context of preserving muscle mass [18][19][21] - **Regulatory Perspective**: The FDA's framing of healthy weight loss has influenced the company's approach to defining success in their clinical trials [17][18] Conclusion - Wave Life Sciences is positioned to make significant advancements in genetic medicine, particularly in obesity and liver disease, with promising data expected in the near future. The focus on innovative RNA technologies and the potential for long-term treatment regimens could disrupt current treatment paradigms in these areas [39][40]

Core Insights - Korro Bio, Inc. has provided updates on its Phase 1/2a REWRITE clinical trial for KRRO-110, reported third-quarter financial results, and outlined strategic business decisions [1][5]. Clinical Trial Update - KRRO-110 successfully generated functional M-AAT protein in patients with Alpha-1 Antitrypsin Deficiency (AATD), although the protein levels were below preclinical projections [2][5]. - The REWRITE trial has completed all six planned single ascending dose cohorts in healthy volunteers, with no dose-limiting toxicities observed [4][7]. - The trial is currently evaluating KRRO-110 in two AATD patient cohorts at doses of 0.6 mg/kg and 0.8 mg/kg [4][7]. Development Candidates - Korro has nominated KRRO-121, a GalNAc-conjugated construct aimed at treating hyperammonemia, marking an expansion of its RNA editing platform [3][5]. - The company plans to advance KRRO-121 and a GalNAc version for AATD patients into clinical trials in the second half of 2026 and 2027, respectively [3][5]. Financial Results - As of September 30, 2025, Korro reported cash, cash equivalents, and marketable securities totaling $102.5 million, down from $163.1 million at the end of 2024 [12][26]. - Collaboration revenue for the third quarter of 2025 was $1.1 million, compared to no revenue in the same period of 2024 [13]. - Research and development expenses decreased to $13.8 million from $16.0 million year-over-year, while general and administrative expenses also saw a decline [14][15]. Strategic Restructuring - The company is implementing a strategic restructuring that will reduce its workforce by approximately one-third to focus on generating clinical data and advancing GalNAc-conjugated programs [3][18]. - This restructuring is expected to extend Korro's cash runway into the second half of 2027, with one-time restructuring charges estimated at $2.4 million [18]. Regulatory Milestones - KRRO-110 has received Investigational New Drug clearance from the FDA, along with Fast Track and Orphan Drug Designations [7][19]. - The company is prioritizing high-potential GalNAc-conjugated programs targeting the liver, including KRRO-121 [7][8].

Summary of Wave Life Sciences FY Conference Call Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Industry**: RNA medicines, focusing on oligonucleotides, RNA editing, and genetic targets [3][4] Core Points and Arguments RNA Medicines and Pipeline - Wave Life Sciences is positioned at the forefront of RNA medicines, utilizing a proprietary chemistry engine to accelerate the development of oligonucleotides, including siRNA and RNA editing [3] - The company has successfully progressed from identifying genetic targets to generating meaningful human therapeutic data within 24 months, exemplified by their INHBE program for obesity [3] Alpha-1 Antitrypsin Program (WVE-006) - WVE-006 is the first RNA editing program to enter clinical trials, targeting alpha-1 antitrypsin deficiency [5] - The program achieved approximately 65% editing on protein levels, with a notable increase in protein response during acute exacerbations, demonstrating the potential for effective treatment [6][10] - The treatment paradigm is shifting from traditional IV protein replacement therapy to a more sustainable editing approach that can generate protein during acute events [9][10] - The FDA has not set a specific threshold for treatment efficacy, but the original approval for protein replacement therapy was based on an 11-micromolar threshold [19][20] Competitive Landscape - Wave Life Sciences is the only non-LNP derived therapy in the RNA editing space, differentiating itself through safety and durability by avoiding LNPs, which can cause liver injury [21][22] - The company emphasizes the specificity of its RNA editing approach, avoiding off-target effects and aberrant proteins, which are common in DNA editing [22][23] Obesity Program (INHBE - Program 007) - The INHBE program targets inhibin E, leveraging human clinical genetics to address obesity without inducing starvation or lean mass loss [28][29] - Wave has demonstrated significant reductions in activin E protein, correlating with weight loss similar to semaglutide, while maintaining lean muscle mass [30][31] - The potential for a once or twice yearly maintenance therapy is highlighted, with ongoing studies to assess fat loss and metabolic health [36][38] Future Studies and Market Strategy - Wave plans to conduct phase two studies on obese patients to evaluate fat reduction and sustainability of weight loss, with a focus on reducing reliance on GLP-1 therapies [42][43] - The company is exploring strategic collaborations while maintaining a wholly owned asset approach, aiming for clear registrational paths in the obesity landscape [42][43] Other Important Content - The company is optimistic about the potential for its therapies to transform patient outcomes in both alpha-1 antitrypsin deficiency and obesity [23][30] - Wave Life Sciences is focused on delivering data that demonstrates the efficacy and safety of its treatments, with upcoming data releases expected to provide further insights into their therapeutic potential [44][45]

Financial Data and Key Metrics Changes - Revenue for Q3 2025 was $7.6 million compared to a net loss of $7.7 million in the prior year quarter, attributed to the timing of revenue recognized under the collaboration agreement with GSK [22] - Research and development expenses increased to $45.9 million from $41.2 million year-over-year, driven by advancements in the inhibin E and RNA editing programs [22] - General and administrative expenses rose to $18.1 million from $15 million in the prior year quarter, primarily due to share-based compensation [22] - Net loss for Q3 2025 was $53.9 million, an improvement from a net loss of $61.8 million in the prior year quarter [23] - Cash and cash equivalents at the end of Q3 2025 were $196.2 million, down from $302.1 million as of December 31, 2024, but extended cash runway into Q2 2027 with additional proceeds [24] Business Line Data and Key Metrics Changes - The company highlighted significant advancements in the WVE-007 program, showing dose-dependent reductions in activin E levels, with reductions of 56%, 75%, and 85% for different dosing cohorts [8][9] - WVE-006 demonstrated the potential to restore physiological AAT production, achieving AAT levels of up to 13 micromolar and a 60% decrease in mutant ZAAT protein [13] - The DMD program, WVEN531, showed a statistically significant improvement in time to rise, with a 3.8 seconds improvement compared to natural history [18] Market Data and Key Metrics Changes - The company is addressing a significant market need with an estimated 9 million homozygous individuals living with PNPLA3I148M liver disease in the US and Europe, who are at a nine-fold higher risk of dying from their liver disease compared to non-carriers [16] - The obesity market is highlighted as having over 1 billion individuals living with obesity, many of whom lack access to current GLP-1 therapies, presenting a unique opportunity for the company's treatments [55] Company Strategy and Development Direction - The company is focused on advancing its pipeline, particularly in RNAi and RNA editing, with a strategy to leverage proprietary chemistry and platform innovations [5] - There is a strong emphasis on developing non-incretin treatment approaches for obesity, with WVE-007 positioned as a potential maintenance therapy to prevent rebound weight gain [6][11] - The company aims to build on its momentum in the obesity space, with plans for further studies and potential partnerships to enhance development [43] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress made in clinical trials, particularly with WVE-007 and WVE-006, and the potential for these therapies to transform treatment paradigms [25] - The management team acknowledged the competitive landscape in the obesity market and the need for innovative solutions that provide durable results without the side effects associated with current therapies [55] - There is confidence in the ability to meet regulatory requirements and achieve clinical milestones, with ongoing discussions with the FDA regarding imaging endpoints for Huntington's disease [29][30] Other Important Information - The company is preparing for a global potentially registrational phase 2-3 study of WVE-003 in adults with Huntington's disease, using caudate volume as a primary endpoint [19] - The company has received positive feedback from key opinion leaders regarding the potential of its RNA editing programs to address unmet medical needs [14] Q&A Session Summary Question: Inquiry about cholesterol fat mobilization post-inhibin knockdown - Management confirmed no observed changes in increased lipids and deposits in the liver from preclinical studies, indicating positive findings regarding fat mobilization [26][27] Question: Pre-IND meeting with FDA regarding Huntington's imaging endpoints - Management confirmed alignment with the FDA on using MRI as an imaging endpoint, emphasizing the importance of well-designed clinical trials [29] Question: Changes in gene expression timing in obesity studies - Management noted that while gene expression changes occur over time, early engagement of targets and sustained suppression of proteins are observed [34] Question: Insights on acute phase response in AATD patient - Management indicated that the patient responded as expected, with no new insights beyond the initial findings [48] Question: Future studies beyond NYTE for obesity program - Management expressed interest in exploring further studies and potential strategic partnerships, while noting that the GSK collaboration would not hinder these opportunities [62]

Received CTA authorization for Phase 1 trial of lead program AX-0810, targeting NTCP for cholestatic diseasesInitiating Phase 1 study of AX-0810 in healthy volunteers, with initial safety, tolerability, and PK data from Cohort 1 expected by year-end, and target engagement data from all cohorts in H1 2026€ 106.9 million cash and cash equivalents as of end Q3 – providing runway into mid-2027 LEIDEN, Netherlands & CAMBRIDGE, Mass., Nov. 06, 2025 (GLOBE NEWSWIRE) -- ProQR Therapeutics N.V. (Nasdaq: PRQR) (ProQR ...

Agenda Agenda | | | Corporate Outlook Dennis Hom Q&A ENTERING THE CLINIC WITH AX-0810 Establishing safety, PK, and the biomarker roadmap for proof of target engagement November 3, 2025 Strategic Overview Daniel A. de Boer AX-0810 Lead Pipeline Program in Liver Cristina Lopez Lopez Henkjan Verkade Daniel A. de Boer Cristina Lopez Lopez Gerard Platenburg Dennis Hom Cristina Lopez Lopez, MD, PhD Chief Medical Officer Dennis Hom Chief Financial Officer Gerard Platenburg Chief Scientific Officer Speakers Invited ...

Core Insights - Wave Life Sciences is hosting its 2025 Research Day, focusing on RNA editing and RNA interference (RNAi) technologies [2]. Group 1: Event Overview - The event is being recorded and is accessible for future reference [1]. - The presentation materials will be available on the company's website in the Investors section after the call [2]. Group 2: Management Statements - Management may provide forward-looking statements during the presentation, which are subject to various risks and uncertainties [3].

Summary of Wave Life Sciences FY Conference Call Company and Industry Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Industry**: RNA editing and gene therapy, specifically targeting alpha-1 antitrypsin deficiency (AATD) and other related conditions Key Points and Arguments 1. Targeting Alpha-1 Antitrypsin Deficiency - Wave Life Sciences is focusing on alpha-1 antitrypsin deficiency as an initial target due to its validation from a single point mutation and measurable biomarkers [2][4][6] - The company is the first to enter the clinic with data on this target, indicating significant progress in the field of RNA editing [2][3] 2. Mechanism of Action - The approach involves correcting mutations on the transcript level, transitioning patients from a ZZ phenotype (high risk of lung and liver disease) to an MZ phenotype (low risk) [5][6] - The editing process aims to increase the production of M protein, which is crucial for patient health during acute phase responses [8][9] 3. Clinical Data and Results - Initial clinical data showed a shift from 0% M protein to 44% after a single dose, with expectations of reaching 65% M protein with multi-dose administration [7][8] - The total protein levels increased to 12 micromolar, with ongoing studies indicating potential for further increases [6][9] - The 400 mg cohort is anticipated to provide insights into the durability and efficiency of the editing process [9][10] 4. Future Steps and FDA Approval - The next steps for the WVE-006 program include further trials with the 200 mg and 400 mg cohorts, focusing on the drug's ability to respond to acute phase events [11][13] - Discussions around FDA approval thresholds suggest that the focus should be on achieving clinically relevant protein levels, particularly the MZ phenotype [16][17] 5. Broader Implications for RNA Editing - The panel discussed the potential of RNA editing technologies to address a variety of genetic conditions beyond AATD, emphasizing the importance of selecting appropriate targets [44][45] - The ability to achieve high levels of editing and the precision of the ADAR enzyme were highlighted as significant advantages over traditional gene editing methods [62][63] 6. Competitive Landscape - Other companies in the RNA editing space, such as ProQR and Arana, are also targeting AATD, indicating a competitive environment [18][26] - ProQR's AX-810 program aims to modulate protein function for cholestatic diseases, while Arana is focusing on optimizing ADAR engagement for therapeutic applications [26][21] 7. Investor Sentiment and Market Expectations - There is a growing interest from investors in the RNA editing space, with discussions shifting from the technology itself to the selection of indications for proof of concept [71][73] - The panel expressed confidence that RNA editing could reach a level of acceptance similar to siRNA therapies, potentially in a shorter timeframe [65][66] 8. Challenges and Considerations - The need for clear biomarkers and therapeutic benefits associated with editing levels was emphasized as critical for advancing the field [59][60] - The panel acknowledged misconceptions about RNA editing capabilities compared to DNA editing, particularly regarding expected editing efficiencies [73][74] Additional Important Content - The discussion highlighted the importance of understanding the pharmacology of RNA editing and its translation from animal models to human clinical data [60][61] - The potential for RNA editing to provide temporary, reversible modifications without long-term consequences was noted as a significant advantage [62][63] This summary encapsulates the key discussions and insights from the Wave Life Sciences FY Conference Call, focusing on the advancements in RNA editing technology and its implications for treating genetic disorders.

Summary of Wave Life Sciences (WVE) Update / Briefing September 03, 2025 Company Overview - **Company**: Wave Life Sciences (WVE) - **Focus**: Development of therapies for Alpha-1 Antitrypsin Deficiency (AATD) and RNA editing technologies Key Industry Insights - **AATD Overview**: AATD is caused by the aggregation of mutant ZAAT protein in the liver and a lack of functional AAT in the lungs, leading to severe lung and liver diseases, particularly in homozygous PIZZ individuals [1][2] - **Current Treatments**: Existing treatments are limited to weekly IV augmentation therapy, which does not adequately address the acute phase response during exacerbations [1][2] Core Points and Arguments - **WVE-006 Development**: WVE-006 aims to correct the Z mutation, increasing circulating levels of wild type MAAT protein and reducing mutant ZAAT protein aggregation in the liver [4][5] - **Clinical Trials**: The Restoration 2 clinical trial is evaluating the safety, tolerability, and pharmacokinetics of WVE-006 in individuals with AATD [6][8] - **Safety Profile**: WVE-006 has shown a favorable safety profile with no serious adverse events reported across all doses tested [9][10] - **Biomarker Results**: In the single and multiple dose cohorts, mean max total AAT levels reached 12.9 and 11.9 micromolar, respectively, with MAAT protein levels increasing significantly [10][11] - **Dynamic Response**: WVE-006 demonstrated the ability to restore dynamic physiological AAT production during acute phase responses, a first for AATD therapies [15][17] Additional Important Insights - **RNA Editing Technology**: The proprietary RNA editing technology used in WVE-006 allows for efficient and durable editing, which is crucial for achieving therapeutic effects [19][20] - **Partnership with GSK**: GSK's involvement is expected to enhance the development and commercialization of WVE-006, leveraging their expertise in respiratory medicine [18][19] - **Future Programs**: Wave Life Sciences is advancing additional RNA editing programs, including PNPLA3 for liver disease, with a CTA filing expected in 2026 [19][20] - **Long-term Studies**: There are plans for long-term extension cohorts to gather additional data on repeat dosing and acute phase responses [87][88] Conclusion - **Transformative Potential**: WVE-006 has the potential to transform the treatment landscape for AATD by enabling patients to produce protective AAT protein when needed, addressing both lung and liver manifestations of the disease [17][18] - **Next Steps**: The company anticipates sharing further data from ongoing trials in early 2026, which will provide more insights into the efficacy and safety of WVE-006 [22]

WVE-006 Clinical Trial & Results - WVE-006 achieved durable production of serum AAT at levels associated with lower risk of AATD liver and lung disease following repeat 200 mg doses[5] - In the 200 mg cohort, circulating M-AAT reached 64.4% of total AAT protein[6, 31] - The 200 mg MAD cohort showed a 60.3% decrease in Z-AAT protein[6, 35] - A single 400 mg dose of WVE-006 resulted in total AAT reaching 20.6 µM during an acute phase response[7] - In the 400 mg SAD cohort, circulating M-AAT reached 47.2% of total AAT, with a 49.0% decrease in Z-AAT[41] Safety & Tolerability - WVE-006 was safe and well-tolerated in the RestorAATion-1 healthy volunteer study[26] - WVE-006 continues to be safe and well-tolerated in the RestorAATion-2 clinical trial[29] Ongoing Studies & Future Milestones - A 400 mg monthly multidose cohort is ongoing, with data expected in 1Q 2026[7, 43] - The company anticipates milestone payments in 2025 and beyond[49]