Wave Life Sciences J.P. Morgan Healthcare Conference January 13, 2026 Forward-looking statements Translating genetic insights into potentially best-in-class medicines This document contains forward-looking statements. All statements other than statements of historical facts contained in this document, including statements regarding possible or assumed future results of operations, preclinical and clinical studies, business strategies, research and development plans, collaborations and partnerships, regulato ...

Metabolic Health - The company demonstrated improvements in body composition by reducing fat, including visceral fat, while preserving lean mass[14]. - Increased visceral adiposity is associated with maintaining metabolic rate, which is linked to various diseases including cardiometabolic disorders[14]. - Silencing INHBE mRNA has potential to treat obesity and associated metabolic diseases, indicating a strategic focus on metabolic health[17]. - Higher circulating Activin E levels correlate with higher BMI, abdominal fat, and fasting insulin in non-diabetic adults, supporting the company's weight loss approach[19]. - The company is exploring the use of GalNAc-siRNA injections for potential treatment of obesity and metabolic diseases, indicating ongoing research and development efforts[20]. - The company aims to reduce abdominal adiposity to lower the risk of cardiovascular disease (CVD) and type 2 diabetes (T2D)[17]. - The company reported favorable traits in heterozygous INHBE carriers, including lower risk of abdominal obesity and higher HDL-c levels[16]. - The company is focused on developing strategies to enhance insulin sensitivity and reduce inflammatory risks associated with T2D[20]. - The company is committed to addressing metabolic dysfunction through innovative therapies and research initiatives[19]. - The company is actively pursuing market expansion in the metabolic health sector, leveraging its research on INHBE and Activin E[17]. - WVE-007 is expected to drive fat reduction and improve key measures of cardiometabolic health[21]. - A single dose of INHBE GalNAc-siRNA resulted in a 23% reduction in epididymal fat weight and a 40% reduction in body weight in DIO mice[22]. - WVE-007 shows potential for synergistic use with GLP-1s, leading to approximately 2x greater weight loss compared to GLP-1 alone[23]. - The INLIGHT clinical trial for WVE-007 is set to initiate in 1H 2026, targeting individuals with a BMI of 28-35 kg/m²[24]. - Improvements in body composition were observed three months after a single WVE-007 dose, with a 4% reduction in total fat mass and a 2.3% preservation of lean mass[25]. - A single dose of WVE-007 led to improvements in body composition similar to GLP-1 without muscle loss[27]. - The study indicates that reductions in serum Activin E are highly durable, supporting dosing once or twice per year[25]. - Key measurements in the INLIGHT trial will include safety, tolerability, pharmacokinetics, and body composition[24]. - Data from preclinical studies indicate that a 10 mg/kg dose of INHBE GalNAc-siRNA is effective in reducing body weight and fat mass[22]. - The company aims to address over one billion individuals globally with obesity through its innovative treatments[29]. - WVE-007 is expected to initiate new trials in 2026, focusing on fat loss while preserving muscle mass, with follow-up data anticipated in 1H 2026[30]. - The treatment strategy includes leveraging an orthogonal mechanism to incretins for enhanced efficacy in obesity management[29]. - The anticipated updates for WVE-007 include data from multiple dosing cohorts, which will inform future treatment protocols and market strategies[30]. Alpha-1 Antitrypsin Deficiency (AATD) - The treatment goals for Alpha-1 antitrypsin deficiency (AATD) include minimizing episodic exacerbations and decreasing liver damage, with approximately 200,000 individuals in the US and Europe affected by the severe form of the disease[33]. - RNA editing technology is being developed to restore physiological AAT production during acute phase responses, aiming to shift Pi*ZZ individuals to a biomarker profile consistent with Pi*MZ genotype[36]. - WVE-006 is positioned as a potential first-in-class therapy for AATD, addressing both liver and lung manifestations of the disease[35]. - The company anticipates significant improvements in metabolic safety and tolerability with its combination treatments for obesity[29]. - The follow-up data from the 240 mg and 400 mg single-dose cohorts of WVE-007 will provide insights into its efficacy in individuals with higher BMI and comorbidities[30]. - WVE-006 achieved total AAT levels exceeding 11 µM, with production of wild-type M-AAT greater than 50% during acute phase response[43]. - The RestorAATion-2 clinical trial is ongoing, with 400 mg MAD data expected in Q1 2026 and 600 mg SAD and MAD data expected in 2026[44]. - Total AAT reached 20.6 µM during an acute phase response, indicating a significant increase in AAT production[40]. - Serum AAT levels increased to 2.8 µM with a single 400 mg dose and 11.9 µM with a 200 mg multi-dose regimen[42]. - WVE-006 also reduces levels of Z-AAT, aiming to restore dynamic AAT physiology[41]. - The clinical trial objectives include safety, tolerability, pharmacokinetics, and serum M-AAT levels[44]. - The augmentation therapy has no impact on liver disease, while WVE-006 enables endogenous AAT production[41]. - Published data on CRP levels and AAT levels across different genotypes showed significant increases in one patient during an acute phase response[40]. PNPLA3 I148M Liver Disease - The RNA editing program WVE-008 targets PNPLA3 I148M liver disease, with a strong foundation in human genetics and durable RNA editing[47]. - Plasma AAT levels of approximately 13 µM were achieved, with 64% of patients reaching levels greater than 20 µM during acute phase response[43]. - The company reported a significant decrease in liver fat with PNPLA3 editing in the human HEPATOPAC® model, indicating effective treatment potential[52]. - WVE-008 is expected to be a first-in-class, disease-modifying therapy for PNPLA3 I148M-driven liver disease, with a Clinical Trial Application (CTA) anticipated to be filed in 2026[53]. - RNA editing is projected to restore PNPLA3 function, addressing liver diseases across various stages, with a focus on correcting the I148M mutation[51]. - Heterozygous carriers of PNPLA3 I148M have an 80% lower risk of liver-related death compared to homozygous carriers, highlighting the genetic impact on liver disease outcomes[49]. - The company aims to utilize a bifunctional modality to simultaneously knockdown and edit RNA, potentially unlocking complex indications requiring multiple target engagements[56]. - The editing approach is expected to restore full PNPLA3 activity, countering liver disease progression by improving lipid mobilization and reducing fat accumulation[51]. - Significant editing efficiency was achieved with AIMers, leading to a marked reduction in liver fat levels[52]. - The company is focusing on developing therapies that address the underlying genetic causes of liver diseases, particularly those related to PNPLA3 mutations[51]. - The RNA editing strategy is designed to mitigate inflammation and fibrosis associated with liver diseases, aiming for comprehensive treatment solutions[51]. - The company is committed to advancing its research and development efforts in RNA medicines to address complex liver disease indications[56]. Duchenne Muscular Dystrophy (DMD) - WVE-N531 demonstrated an average dystrophin expression of 7.8% between 24 and 48 weeks, with 88% of boys achieving greater than 5% dystrophin[62]. - The therapy has shown a mean exon skipping of 54% (95% CI: 46-63%) and a mean dystrophin expression of 7.8% (95% CI: 5.4-10.3%) at 48 weeks[64]. - Significant reductions in creatine kinase (CK) levels were observed, with approximately 50% reduction from baseline at 48 weeks[69]. - Evidence of reversal of fibrosis was noted, with fibrotic muscle declining by 28.6% at 48 weeks[72]. - WVE-N531 has received Rare Pediatric Disease Designation and Orphan Drug Designation from the FDA, addressing a high unmet need in Duchenne muscular dystrophy (DMD) affecting ~1 in 5,000 newborn boys annually[61]. - The company plans to file for NDA with an accelerated approval strategy and monthly dosing planned for 2026[62]. - A significant decrease (~48%) in internalized nuclei was observed at 48 weeks, indicating a transition to healthier muscle[71]. - The therapy has shown statistically significant improvements in muscle health, including reduced inflammation and necrosis[65]. - WVE-N531 is the only DMD therapeutic to show uptake in myogenic stem cells, indicating its potential for muscle regeneration[70]. - The average tissue half-life of WVE-N531 supports a monthly dosing regimen, enhancing patient compliance[64]. - Wave DMD portfolio addresses a market opportunity of over $2.4 billion in the US, targeting 40-50% of the DMD population that remains untreated today[75]. - WVE-N531 shows significant improvements in treatment rates, with 8-10% for exon 51 and 11-13% for exon 45, compared to no available therapies for exon skipping[75]. Huntington's Disease - The company is advancing WVE-003, an allele-selective silencing treatment for Huntington's Disease, which affects over 200,000 patients across all disease states[79]. - Pre-symptomatic Huntington's Disease is estimated to affect around 160,000 individuals in the US and Europe, with symptomatic cases around 65,000[78]. - WVE-003 is characterized by its ability to penetrate the brain fully and address both loss-of-function and gain-of-function disruptions caused by mutant huntingtin protein[79]. - The company is focusing on expanding its market presence and product offerings, particularly in the exon skipping therapies segment[75]. - The minimal clinically important difference (MCID) for TTR is reported at 1.4 seconds, indicating significant clinical relevance in treatment outcomes[74]. - The company aims to leverage its unique portfolio to capture a significant share of the DMD and Huntington's Disease markets, enhancing patient outcomes[75]. - The potential for best-in-class exon skipping therapies is highlighted, with no current therapies available for certain exons[75]. - The company is committed to advancing its research and development efforts to address unmet medical needs in genetic diseases[79]. - WVE-003 achieved an industry-leading 46% reduction in mutant HTT protein levels in CSF with three doses, demonstrating significant efficacy[82]. - The treatment led to a 4.68% reduction in caudate atrophy compared to 5.10% in the placebo group, indicating a trend towards less atrophy[83]. - A 1% absolute reduction in the rate of caudate atrophy is associated with a delay of disability onset by at least 7.5 years, highlighting the clinical significance of the findings[84]. - The company anticipates delivering data from a 400 mg multi-dose cohort for WVE-006 in Q2 2026, indicating ongoing development efforts[89]. - Phase 2 trials for WVE-007 are set to initiate in H2 2026, focusing on obesity treatment, showcasing the company's expansion into new therapeutic areas[90]. - The company plans to submit an NDA for WVE-N531 to support accelerated approval with monthly dosing, reflecting strategic regulatory initiatives[89]. - WVE-003's efficacy in reducing mutant HTT levels correlates with functional benefits, suggesting potential for improved clinical outcomes[83]. - The company is poised for significant growth driven by RNAi and RNA editing technologies, indicating a strong pipeline of innovative products[88]. - The preservation of wild-type HTT levels throughout the study suggests a favorable safety profile for WVE-003[83]. - The company is evaluating new trials for WVE-007 as an add-on treatment for individuals with obesity, indicating a commitment to addressing comorbidities[90].

Core Insights - Wave Life Sciences is advancing its clinical programs, particularly focusing on WVE-007 for obesity and expanding its RNA editing portfolio, with significant milestones expected in 2026 [1][2][10]. Group 1: WVE-007 for Obesity - Wave plans to initiate a Phase 2a multidose portion of the INLIGHT clinical trial for WVE-007 in individuals with obesity and higher BMI in the first half of 2026 [1][10]. - Initial data from a 240 mg single-dose study of WVE-007 showed fat loss comparable to GLP-1 (semaglutide) at three months, with muscle preservation and potential for infrequent dosing [1][3]. - The INLIGHT trial demonstrated sustained suppression of serum Activin E, supporting the feasibility of once or twice yearly dosing [3]. Group 2: RNA Editing Initiatives - Wave has achieved the first successful clinical translation of RNA editing with WVE-006 for alpha-1 antitrypsin deficiency (AATD) and plans to provide updates from the RestorAATion-2 trial in 2026 [1][10]. - The company is advancing WVE-008, targeting nine million individuals with homozygous PNPLA3 I148M liver disease in the U.S. and Europe, with a Clinical Trial Application (CTA) expected in 2026 [1][10]. Group 3: Financial Position - As of December 31, 2025, Wave reported preliminary, unaudited cash and cash equivalents of approximately $602 million, providing a cash runway into the third quarter of 2028 [1][9]. Group 4: Upcoming Events - Wave will present at the 44th Annual J.P. Morgan Healthcare Conference on January 13, 2026, highlighting its strategic priorities and clinical advancements [1][12].

Industry Overview - Genomics is a comprehensive study of genomes, which has gained significant interest from pharmaceutical and biotechnology companies for understanding diseases and developing therapies [2] - The distinction between genetics and genomics is crucial, with genomics focusing on the complete set of genes and their interactions within an organism [3] - Insights from genomic research are increasingly utilized to evaluate patient responses to drugs and support the development of targeted therapies, advancing personalized medicine [4] - The growth of genomics has also bolstered synthetic biology, which applies engineering principles to biology for various applications, including drug discovery and gene editing [5] - The rapid advancements in genomics are driven by significant reductions in the cost and time required for genome sequencing [6] Market Projections - The genomics market is projected to reach $80.17 billion by 2032 [9] - The global synthetic biology market was valued at $18.94 billion in 2025 and is expected to grow at a CAGR of 17.7% from 2026 to 2033 [9] Key Companies - **Pacific Biosciences of California (PACB)**: Specializes in advanced long-read sequencing systems for various applications, including healthcare and agriculture. The company has a Zacks Rank 2 (Buy) [12][14] - **Wave Life Sciences (WVE)**: A clinical-stage biotechnology company focusing on RNA medicines. The company reported positive interim data for its obesity treatment candidate WVE-007, which showed improvements in body composition [15][17] - **Sana Biotechnology (SANA)**: Developing cell engineering platforms for diseases like type 1 diabetes and B-cell cancers. The company has suspended its CAR T programs to focus on more promising candidates and has a Zacks Rank 3 [19][21]

Core Insights - Wave Life Sciences Ltd. is a clinical-stage biotechnology company focused on RNA medicines to improve human health [1][3] - The company will present at the 44th Annual J.P. Morgan Healthcare Conference on January 13, 2026 [1] Company Overview - Wave Life Sciences utilizes its PRISM platform, which integrates various modalities and chemistry innovations to develop RNA medicines [3] - The company’s pipeline includes clinical programs targeting obesity, alpha-1 antitrypsin deficiency, Duchenne muscular dystrophy, and Huntington's disease, along with several preclinical programs [3] - Wave Life Sciences aims to transform human health by addressing both rare and common disorders through its RNA-targeting modalities [3]

Core Insights - Wave Life Sciences Ltd. (NASDAQ:WVE) is highlighted as one of the best stocks under $25 to buy, with Oppenheimer raising its price target from $24 to $32 while maintaining an Outperform rating [1] - The company reported promising interim results for its drug WVE-007, showing a clean risk profile at doses up to 600mg and effective translation from human genetics to clinical outcomes [1][3] Clinical Trial Results - The medication WVE-007 demonstrated a 4.5% total fat loss, a 9.4% reduction in visceral fat, and a 3.2% gain in lean mass after three months of treatment [2] - Wave Life Sciences plans to release results from the second round of clinical trials, which will include a six-month study for the 240 mg single-dose cohort and a three-month study for the 400 mg single-dose cohort [2] Broader Implications - Oppenheimer views WVE-007 as a potential core therapy not only for obesity but also for other cardiometabolic diseases, indicating its broader therapeutic potential [3] - Wave Life Sciences is a clinical-stage biotech company focused on developing RNA medicines using its proprietary PRISM discovery and drug development platform [3]

Core Insights - Wave Life Sciences Ltd. (NASDAQ:WVE) is recognized as one of the 12 best genomics stocks to invest in [1] - H.C. Wainwright upgraded the price target for WVE from $22 to $30, maintaining a Buy rating based on positive clinical data for WVE-007 [2] - The company’s shares experienced a significant increase of 147% following the presentation of preliminary clinical data for WVE-007, an RNA-based obesity therapy [3] Financial Projections - Visible Alpha forecasts that risk-adjusted revenue for WVE-007 will rise from $26 million in 2030 to approximately $68 million, and from $1 billion to $2.1 billion by 2040 [4] - By 2040, WVE-007 is expected to contribute 15% to the company's revenue, increasing to 47% by that year [4] - The total revenue for Wave Life Sciences is projected to reach $459 million in 2030 and $4.5 billion by 2040 [4] Company Overview - Wave Life Sciences Ltd. is a clinical-stage biotechnology firm focused on RNA therapies, specifically oligonucleotides, aimed at transforming human health [5]

Core Insights - Artificial intelligence (AI) is identified as the greatest investment opportunity of the current era, with a strong emphasis on the urgent need for energy to support its growth [1][2][3] Investment Opportunity - A specific company is highlighted as a potential investment opportunity, possessing critical energy infrastructure assets that are essential for meeting the increasing energy demands of AI data centers [3][7] - This company is not a chipmaker or cloud platform but is positioned to benefit significantly from the anticipated surge in electricity demand driven by AI technologies [3][6] Energy Demand and Infrastructure - AI technologies, particularly large language models like ChatGPT, are extremely energy-intensive, with data centers consuming as much energy as small cities [2] - The company in focus owns nuclear energy infrastructure, making it a key player in the future of clean and reliable power in the U.S. [7] Financial Position - The company is noted for being completely debt-free and holding a substantial cash reserve, which is nearly one-third of its market capitalization [8] - It is trading at less than 7 times earnings, indicating a potentially undervalued position in the market [10] Market Trends - The company is positioned to capitalize on the onshoring trend driven by tariffs, as well as the surge in U.S. LNG exports under the current administration's energy policies [5][14] - There is a growing recognition on Wall Street of this company's potential, as it quietly benefits from multiple market tailwinds without the high valuations typical of other energy and utility firms [8][9] Future Outlook - The influx of talent into the AI sector is expected to drive continuous innovation and advancements, reinforcing the importance of investing in AI-related infrastructure [12] - The company is seen as a critical player in the upcoming AI infrastructure supercycle, which is anticipated to yield significant returns for investors [14][15]

Core Insights - Wave Life Sciences experienced a remarkable 147% surge in stock price due to unexpectedly positive clinical data for its RNA-targeted obesity treatment, WVE-007, which indicated significant fat reduction and increased lean muscle mass among participants [4][5][9] - The obesity treatment market is substantial, and any company demonstrating effective fat-loss outcomes without muscle loss is likely to gain significant investor interest and valuation [7] - The positive results from WVE-007 have led investors to reassess the value of Wave's entire pipeline, which includes candidates for rare genetic disorders and neuromuscular diseases, suggesting a broader potential for the company's technology [8][9] Company Developments - Wave Life Sciences has been recognized for its proprietary RNA editing and silencing technologies, but the recent obesity data has significantly raised its profile in the biotech sector [6] - The company is now viewed as a potential competitor in the weight-loss treatment space, previously dominated by GLP-1 drugs, which often face challenges such as muscle loss and side effects [5][7] - Investors are now focused on the upcoming comprehensive data for WVE-007, particularly regarding higher doses and longer follow-ups, as well as the company's financial management and potential partnerships [12][13] Market Reactions - The market's rapid reassessment of Wave Life Sciences reflects a shift from viewing it as a struggling mid-cap biotech to a serious contender in RNA medicine [11] - The 147% stock price increase signifies a pivotal moment for the company, marking its transition from obscurity to prominence in the biotech landscape [13] - Despite the optimism, the market remains aware that the therapy is still in early-stage trials, and future data will be critical in determining the sustainability of this valuation [10][11]

Core Insights - Wave Life Sciences Ltd. (NASDAQ: WVE) experienced a significant surge in share price, nearly tripling week-on-week, driven by positive results from its obesity drug clinical trial [1][2]. Clinical Trial Results - The first phase of the clinical trial for WVE-007 showed promising results, with a 4.5% total fat loss, 9.4% visceral fat reduction, and a 3.2% increase in lean mass over three months [3]. - No serious adverse reactions were reported during the trial, which contributed to investor confidence in the drug's safety and tolerability [3]. Future Expectations - Wave Life Sciences plans to release results from the second round of the clinical trial, which will include six-month data for the 240 mg single-dose cohort and three-month follow-up data for the 400 mg single-dose cohort [4][5]. - The company aims to evaluate WVE-007 as both a monotherapy and an add-on therapy for patients with higher BMI and related co-morbidities in phase 2 of the trial [5].