Core Insights - Korro Bio, Inc. is hosting a virtual Analyst Day on January 27, 2026, to discuss KRRO-121, a potential treatment for hyperammonemia, featuring insights from management and personal experiences from caregivers [1][2][3] Company Overview - Korro is focused on developing genetic medicines through RNA editing, targeting both rare and prevalent diseases, with a proprietary platform designed for precise and transient single base edits [7] - The company is based in Cambridge, Massachusetts, and aims to leverage established regulatory pathways for oligonucleotide drugs [7] Product Development - KRRO-121 is being developed for the treatment of hyperammonemia in patients with urea cycle disorders (UCDs) and hepatic encephalopathy (HE), utilizing a GalNAc-conjugated construct to activate a biological pathway [2][9] - The company plans to file for regulatory approval for the first-in-human trial of KRRO-121 in the second half of 2026, supported by preclinical data [2][3] Pipeline Updates - At the J.P. Morgan Healthcare Conference, Korro highlighted its momentum across multiple programs, including a GalNAc-conjugated antisense oligonucleotide for Alpha-1 Antitrypsin Deficiency (AATD), which has achieved over 90% in vivo RNA editing [4] - Korro is also expanding its RNA editing platform, OPERA, with promising preclinical data for additional targets, including AMPKγ1 for longevity and TDP-43 for amyotrophic lateral sclerosis (ALS) [4]

Summary of Korro Bio Conference Call Company Overview - **Company**: Korro Bio - **Industry**: Biotechnology, specifically focusing on RNA editing technologies for therapeutic applications Core Points and Arguments 1. **Vision and Technology**: Korro Bio aims to develop transformative medicines for both rare and prevalent conditions by activating biological pathways through RNA editing, which allows for precise modifications without altering DNA [2][4] 2. **RNA Editing Modality**: The company utilizes chemically modified oligonucleotides to edit RNA, enabling single base changes that can impact protein structure and function, offering a transient solution rather than permanent genetic modifications [3][10] 3. **Pipeline Focus**: The lead program, Korro 121, is set to enter clinical trials in the latter half of the year, targeting ammonia reduction in patients with liver conditions [4][11] 4. **Clinical Development**: Korro Bio plans to provide insights into their clinical approach and patient needs during an upcoming educational session on January 27 [5] 5. **Korro 110 Termination**: The company has decided to terminate the Korro 110 program due to unsatisfactory clinical data and structural integrity issues observed in patient trials [12][20] 6. **Market Potential**: Korro Bio identifies significant unmet medical needs in conditions associated with elevated ammonia levels, with a patient population of approximately 4,500 in the U.S. and a similar number in Europe [16][17] 7. **Regulatory Filing**: Anticipation of a regulatory filing for Korro 121 in the second half of the year, with expectations for rapid clinical data generation [11][18] 8. **Safety Profile**: RNA editing is posited to have a high specificity and low likelihood of off-target effects compared to DNA editing, enhancing the safety profile of Korro's therapies [30][31] Additional Important Content 1. **Biological Pathways**: The technology allows for modulation of proteins to activate biological pathways, which has not been achievable with traditional gene therapies [10][28] 2. **Next-Generation Programs**: Korro Bio is advancing towards a next-generation Alpha-1 product that shows promise for achieving over 90% editing in vivo, significantly improving upon previous attempts [22][23] 3. **Unique Therapeutic Approach**: The company emphasizes the transient nature of their therapies, which is particularly beneficial for chronic conditions where permanent changes could lead to complications [36] 4. **Dosing Frequency**: Korro Bio's therapies are designed for infrequent dosing, potentially once a month, which contrasts with the more frequent dosing required by traditional therapies [15][36] 5. **Research and Development**: The company is leveraging machine learning to enhance target identification and therapy design, indicating a forward-thinking approach to drug development [8][30] This summary encapsulates the key points discussed during the conference call, highlighting Korro Bio's innovative approach to RNA editing and its implications for future therapeutic developments.

Pipeline and Milestones - Korro Bio anticipates a regulatory filing for KRRO-121 in the second half of 2026 [26, 55] - The company expects to nominate a development candidate (DC) for its GalNAc-conjugated AATD program in the first half of 2026 [26, 55] - A development candidate is also expected for a third GalNAc-conjugated liver asset in the second half of 2026 [26, 55] KRRO-121 for Hyperammonemia - KRRO-121 targets hyperammonemia by stabilizing an intracellular protein in the liver to enhance ammonia clearance capacity [36, 39] - The addressable patient population for KRRO-121 includes 4,200 U S patients with Urea Cycle Disorders (UCD) and 80,000 U S patients with Hepatic Encephalopathy (HE) [37] - The market opportunity for KRRO-121 is estimated at $1 5 billion for UCD and $2 billion+ for HE [37] AATD Program - Korro Bio terminated the REWRITE clinical trial for KRRO-110 in AATD [27, 42] - The company achieved >90% editing of the SERPINA1 transcript using GalNAc delivery in vivo [43] AMPK Activation for Liver Function - In obese mice, approximately 20% editing was sufficient to normalize liver function and reduce body weight [47] Financial Runway - Korro Bio's cash runway extends into the second half of 2027 [14, 55]

Wave Life Sciences FY Conference Summary Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Industry**: RNA Medicines and Biotechnology Key Points and Arguments RNA Medicines Potential - Wave Life Sciences aims to unlock the potential of RNA medicines to transform human health, emphasizing the foundational role of their proprietary RNA chemistry [2][3] Clinical Portfolio and Innovations - The company has developed a proprietary chemistry engine that allows rapid translation of genetic insights into medicines, exemplified by their obesity therapy, which progressed from mouse data to human clinical data in 18 months [3] - The dominant program discussed is the GalNAc-conjugated INHBE siRNA program, which shows promise in treating obesity by improving body composition through fat reduction while preserving muscle mass [4][11] Manufacturing and Financial Position - Wave Life Sciences has in-house GMP manufacturing capabilities, enabling rapid advancement of their clinical programs [4] - The company entered 2026 with $602 million in cash, sufficient to fund operations into Q3 2028 [5] Clinical Data and Efficacy - The INHBE program has shown a reduction in fat mass and preservation of lean mass, with a focus on visceral fat reduction, which is critical for cardiovascular health [12][27] - Preclinical data indicated a potent and durable reduction in Activin E levels, leading to significant fat loss and muscle preservation [18][27] Treatment Paradigm Shift - Current obesity treatments, particularly GLP-1s, are limited by muscle mass loss. Wave's approach aims to provide a treatment paradigm shift by preserving muscle while reducing fat, potentially allowing for less frequent dosing (once or twice a year) [11][12][20] Future Clinical Studies - The company plans to accelerate the development of WVE-007 in obesity and initiate new clinical studies, including combination and maintenance studies [10][32] - The Phase 2A portion of the INLIGHT study will explore the effects of INHBE in patients with higher BMI and comorbidities [10][32] RNA Editing Programs - Wave Life Sciences is advancing its RNA editing programs, particularly for Alpha-1 Antitrypsin Deficiency (AATD) and PNPLA3-related liver disease, with a focus on correcting genetic mutations to restore protein function [35][41] - The AATD program targets a rare disease affecting approximately 200,000 patients in the US and Europe, with no approved therapies for liver manifestations [35] Bifunctional Constructs - The company is exploring bifunctional conjugates that combine the benefits of RNA editing and siRNA, potentially allowing for a single therapeutic construct that can both silence and upregulate targets [44] Regulatory Pathway and Milestones - Wave Life Sciences is focused on a regulatory pathway that emphasizes body composition changes in obesity studies, with a goal of demonstrating significant fat loss while preserving muscle mass [29][60] - Anticipated milestones include multiple data sets on obesity and updates on RNA editing programs throughout 2026 [44][60] Additional Important Insights - The company emphasizes the importance of body composition in obesity treatment, highlighting the need for therapies that not only reduce weight but also improve metabolic health by targeting visceral fat [12][30] - Wave Life Sciences is positioning itself to address the challenges of long-term adherence to current obesity therapies by offering a more tolerable and effective treatment option [55][58]

Core Insights - ProQR Therapeutics announced initial safety and pharmacokinetic (PK) data from its Phase 1 trial of AX-0810, indicating a positive early milestone for the company [2][5] - The company is advancing its pipeline with new development candidates for AX-2402 and AX-2911, targeting Rett syndrome and metabolic-associated steatohepatitis (MASH) respectively [7][12] AX-0810 Phase 1 Study - AX-0810 is a lead investigational RNA editing oligonucleotide targeting NTCP for cholestatic diseases [3][16] - The Phase 1 study is a randomized, double-blind, placebo-controlled trial with up to 33 participants, assessing safety, tolerability, and pharmacokinetics [4] - Initial data from the first cohort (3 mg/kg) showed no serious adverse events and PK observations aligned with non-clinical data, supporting continued dosing [5][9] Pipeline Progress - ProQR has selected development candidates for AX-2402 targeting MECP2 for Rett syndrome and AX-2911 targeting PNPLA3 for MASH [10][12] - AX-2402 demonstrated significant functional improvements in a mouse model, supported by funding from the Rett Syndrome Research Trust [11] - AX-2911 showed over 80% reduction in hepatic fat content in a humanized mouse model, outperforming a clinical-stage therapy [13] Strategic Collaboration - The collaboration with Eli Lilly achieved $4.5 million in milestones in 2025, validating ProQR's Axiomer platform and providing non-dilutive capital [14] Corporate Outlook - ProQR plans to report target engagement data for AX-0810 in the first half of 2026 and initiate a patient cohort in the trial [6][18] - The company aims to advance AX-2402 to a first-in-human trial in the first half of 2027 and continue to strengthen its financial position [18]

Core Viewpoint - Korro Bio, Inc. is set to present at the 44th Annual J.P. Morgan Healthcare Conference, highlighting its focus on developing innovative genetic medicines through RNA editing [1]. Company Overview - Korro Bio is a biopharmaceutical company dedicated to creating a new class of genetic medicines aimed at treating both rare and common diseases [3]. - The company is developing a portfolio of programs that utilize the body's natural RNA editing process, allowing for precise and transient single base edits [3]. - By focusing on RNA editing rather than DNA, Korro aims to enhance the precision and tunability of genetic medicines, potentially leading to improved specificity and long-term tolerability [3]. - Korro plans to leverage its proprietary platform, established regulatory pathways, and manufacturing expertise to bring its oligonucleotide-based medicines to patients [3]. Investor Relations - Korro intends to use its Investor Relations website, LinkedIn, and X (Twitter) for disclosing material nonpublic information and fulfilling its disclosure obligations under Regulation FD [4]. - Investors are encouraged to monitor Korro's Investor Relations website and follow its social media channels for updates and information [4].

ProQR Therapeutics Conference Call Summary Company Overview - ProQR Therapeutics is a biopharmaceutical company based in the Netherlands, focused on developing RNA editing medicines to treat genetic and common diseases by modifying human messenger RNA [1][2]. Core Technology and Partnerships - The company has developed a proprietary RNA editing technology over the past 10 years and controls all foundational intellectual property [2]. - In 2021, ProQR entered a $4 billion collaboration with Eli Lilly, receiving $125 million upfront and the potential for $250 million in milestone payments for each of the 15 targets [2]. Pipeline and Clinical Programs - ProQR is pursuing a wholly owned pipeline focusing on liver and CNS indications, with the lead program AX-0810 targeting cholestatic diseases [3]. - The company has initiated a clinical study for AX-0810, expecting first human clinical data in the first half of next year [3][11]. Trial Design and Expectations - The AX-0810 trial will enroll 33 healthy volunteers across three cohorts, with a randomized, placebo-controlled, and double-blinded design [10]. - Initial safety and pharmacokinetic data are expected by the end of this year, while pharmacodynamic data will be available in the first half of next year [11]. Unmet Medical Needs - The target diseases, Primary Sclerosing Cholangitis (PSC) and Biliary Atresia (BA), have no approved therapies and represent a significant unmet medical need [7][14]. - The company aims to develop a medicine that addresses this need while generating a robust dataset to validate its technology [8]. Safety and Efficacy Considerations - ProQR believes that pruritus (itching) associated with high bile acid levels is driven by inflammation rather than bile acids themselves, supported by data from healthy individuals with high bile acid levels who do not experience pruritus [17][22]. - The company aims for a twofold increase in bile acid levels in serum to halt disease progression, with a linear correlation between editing percentage and bile acid concentration [23][25]. Future Development Plans - Following the healthy volunteer study, ProQR plans to conduct a Phase 1B study in PSC patients, with results expected before the end of next year [13]. - The company is exploring accelerated development plans for potential approval based on efficacy data [31]. Rett Syndrome Program - ProQR is also developing a program for Rett syndrome, a neurodevelopmental disease caused by the absence of the MECP2 protein, with the potential to restore normal function through RNA editing [34]. - The program is co-financed by the Rett Syndrome Research Trust, and a clinical candidate is expected to be selected soon [35]. Differentiation from Gene Therapy - The RNA editing approach allows for precise restoration of the MECP2 protein without the risk of overexpression, which is a concern in gene therapy [37]. - ProQR plans to target specific mutations, particularly stop codon mutations, which affect approximately 5,000 patients each [38]. Conclusion - ProQR Therapeutics is positioned to address significant unmet medical needs in liver diseases and Rett syndrome through innovative RNA editing technologies, with ongoing clinical trials and strategic partnerships enhancing its development pipeline [1][2][34].

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]