Executive Summary & Recent Corporate Highlights [Second Quarter 2025 Business Updates](index=1&type=section&id=Second%20Quarter%202025%20Business%20Updates) Entrada Therapeutics advanced its DMD clinical pipeline, initiated new studies, progressed preclinical programs, and strengthened leadership [Clinical-Stage Development Pipeline](index=1&type=section&id=Clinical-Stage%20Development%20Pipeline) Entrada advanced multiple clinical programs for DMD, including ELEVATE-44-201 and ELEVATE-45-201, and progressed regulatory submissions and partnered DM1 and inherited retinal disease programs - First patient dosed in ELEVATE-44-201 (ENTR-601-44), a global Phase 1/2 multiple ascending dose (MAD) clinical study for ambulatory DMD patients amenable to exon 44 skipping, with data from Cohort 1 (6 mg/kg patient dose) anticipated in the **first half of 2026**[1](index=1&type=chunk)[2](index=2&type=chunk)[3](index=3&type=chunk) - Initiated ELEVATE-45-201 (ENTR-601-45), a global Phase 1/2 MAD clinical study for ambulatory DMD patients amenable to exon 45 skipping, on track to dose the first patient in **Q3 2025**, with data from Cohort 1 (5 mg/kg) expected in **mid-2026**[1](index=1&type=chunk)[2](index=2&type=chunk)[6](index=6&type=chunk) - Planned Phase 1b MAD clinical study of ENTR-601-44 (ELEVATE-44-102) in ambulatory and non-ambulatory adults living with DMD in the U.S. is on track to initiate in the **first half of 2026**[6](index=6&type=chunk) - Global regulatory applications for ENTR-601-50 are expected in **Q4 2025** and for ENTR-601-51 in **2026**[3](index=3&type=chunk)[6](index=6&type=chunk) - Vertex continues to enroll and dose the MAD portion of the global Phase 1/2 clinical trial of VX-670 for myotonic dystrophy type 1 (DM1), with enrollment and dosing expected to complete in **H1 2026**[6](index=6&type=chunk) - Advanced two inherited retinal disease programs into lead optimization, with the first clinical candidate nomination expected by **year-end 2025**[6](index=6&type=chunk) [Preclinical Pipeline](index=2&type=section&id=Preclinical%20Pipeline) The company generated positive preclinical data from programs outside its neuromuscular franchise, indicating a broader scope of therapeutic development - Generated positive preclinical data from programs outside its neuromuscular franchise, including new moieties[4](index=4&type=chunk) [Organizational Evolution](index=2&type=section&id=Organizational%20Evolution) Entrada strengthened its leadership team with strategic appointments to support accelerated clinical growth and other strategic priorities - Appointed Navid Khan, PhD, as Senior Vice President of Medical Affairs in **August 2025**[1](index=1&type=chunk)[6](index=6&type=chunk) - Appointed Kiran Patki, MD, MSc, FFPM, as Senior Vice President of Clinical Development in **July 2025**[1](index=1&type=chunk)[6](index=6&type=chunk) - Appointed Maha Radhakrishnan, MD, to the Company's Board of Directors in **June 2025**[6](index=6&type=chunk) [Cash Position](index=2&type=section&id=Cash%20Position) Entrada's cash, cash equivalents, and marketable securities decreased to $354.0 million as of June 30, 2025, but are projected to fund operations into Q2 2027 Cash, Cash Equivalents, and Marketable Securities | Metric | As of June 30, 2025 | As of Dec 31, 2024 | | :-------------------------------- | :------------------ | :----------------- | | Cash, cash equivalents and marketable securities | $354.0 million | $420.0 million | - Cash runway expected into **Q2 2027** based on current operating plans[1](index=1&type=chunk)[5](index=5&type=chunk) Detailed Second Quarter 2025 Financial Results [Collaboration Revenue](index=3&type=section&id=Collaboration%20Revenue) Collaboration revenue significantly decreased in Q2 2025 to $2.0 million from $94.7 million in Q2 2024, primarily due to the substantial completion of research activities for the VX-670 collaboration Collaboration Revenue Overview | Period | 2025 (Q2) | 2024 (Q2) | Change | | :------- | :---------- | :---------- | :----- | | Revenue | $2.0 million | $94.7 million | -$92.7 million | - The decrease was primarily attributable to the substantial completion of the collaboration research plan activities associated with VX-670[7](index=7&type=chunk) [Operating Expenses](index=3&type=section&id=Operating%20Expenses) Total operating expenses increased to $48.8 million in Q2 2025 from $41.3 million in Q2 2024, driven by higher R&D costs for DMD programs and increased personnel costs Total Operating Expenses | Period | 2025 (Q2) | 2024 (Q2) | Change | | :------- | :---------- | :---------- | :----- | | Total operating expenses | $48.8 million | $41.3 million | +$7.5 million | [Research & Development (R&D) Expenses](index=3&type=section&id=Research%20%26%20Development%20(R%26D)%20Expenses) R&D expenses increased to $37.9 million in Q2 2025 from $32.0 million in Q2 2024, primarily due to additional costs for DMD programs and higher personnel costs Research & Development Expenses | Period | 2025 (Q2) | 2024 (Q2) | Change | | :------- | :---------- | :---------- | :----- | | R&D Expenses | $37.9 million | $32.0 million | +$5.9 million | - The increase was primarily driven by additional costs incurred related to the Company's DMD programs, as well as higher personnel costs (including non-cash, stock-based compensation)[8](index=8&type=chunk) [General & Administrative (G&A) Expenses](index=3&type=section&id=General%20%26%20Administrative%20(G%26A)%20Expenses) G&A expenses rose to $10.9 million in Q2 2025 from $9.2 million in Q2 2024, mainly due to increased personnel costs, including non-cash stock-based compensation General & Administrative Expenses | Period | 2025 (Q2) | 2024 (Q2) | Change | | :------- | :---------- | :---------- | :----- | | G&A Expenses | $10.9 million | $9.2 million | +$1.7 million | - The increase was primarily due to higher personnel costs (including non-cash, stock-based compensation)[9](index=9&type=chunk) [Net Income (Loss)](index=3&type=section&id=Net%20Income%20(Loss)) Entrada reported a net loss of $(43.1) million for Q2 2025, a significant decline from a net income of $55.0 million in Q2 2024, resulting in a basic net loss per share of $(1.04) Net Income (Loss) Summary | Period | 2025 (Q2) | 2024 (Q2) | Change | | :------- | :---------- | :---------- | :----- | | Net Income (Loss) | $(43.1) million | $55.0 million | -$98.1 million | | Net (Loss) Income per share, basic | $(1.04) | $1.61 | -$2.65 | [Condensed Consolidated Financial Statements (Unaudited)](index=5&type=section&id=Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) [Condensed Consolidated Statements of Operations](index=5&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The unaudited statements of operations show a significant decrease in collaboration revenue and an increase in operating expenses, leading to a net loss for both the three and six months ended June 30, 2025, compared to net income in the prior year periods Condensed Consolidated Statements of Operations (in millions of dollars, except per share data) | | Three Months Ended June 30, | | Six Months Ended June 30, | | :-------------------------------- | :---------- | :---------- | :---------- | :---------- | | | **2025** | **2024** | **2025** | **2024** | | Collaboration revenue | $1.95 | $94.69 | $22.51 | $153.81 | | Operating expenses: | | | | | | Research and development | 37.88 | 32.04 | 69.95 | 60.64 | | General and administrative | 10.92 | 9.24 | 21.20 | 18.64 | | Total operating expenses | 48.80 | 41.27 | 91.15 | 79.28 | | (Loss) income from operations | (46.85) | 53.42 | (68.64) | 74.54 | | Other income: | | | | | | Interest and other income | 3.92 | 4.37 | 8.37 | 8.58 | | Total other income | 3.92 | 4.37 | 8.37 | 8.58 | | (Loss) income before provision for income taxes | (42.93) | 57.79 | (60.27) | 83.12 | | Provision for income taxes | 0.18 | 2.76 | 0.18 | 4.59 | | Net (loss) income | $(43.10) | $55.03 | $(60.45)

Clinical Programs & Pipeline - Entrada Therapeutics expects to have four active clinical-stage programs by the end of 2025[7, 17] - ENTR-601-44 is currently dosing patients in the UK and EU and is authorized in the US[7] Data from Cohort 1 of the ELEVATE-44-201 study is expected in the first half of 2026[3, 38] - ENTR-601-45 patient study is currently enrolling in the UK and EU, with first patient dosing expected in Q3 2025 and initial data from the first patient cohort expected in mid-2026[3, 7, 41] - Global regulatory filings for ENTR-601-50 are on track for submission in Q4 2025, and for ENTR-601-51 in 2026[3, 7, 42] - Vertex's DM1 program, VX-670, has an ongoing MAD portion of its global Phase 1/2 study to evaluate safety and efficacy, with completion of enrollment and dosing expected in H1 2026[7, 18] Financial Position - The company reports a cash balance of approximately $354 million as of June 30, 2025[8] - This cash balance is expected to provide a runway into Q2 2027[3, 8, 60] EEV Platform & Technology - The company's Endosomal Escape Vehicle (EEV) technology achieves approximately 50% endosomal escape, compared to a standard of approximately 2%[12] - EEV therapies demonstrate approximately 90% cellular uptake[13] ENTR-601-44 Phase 1 Data - The ENTR-601-44-101 study showed strong clinical safety up to 6 mg/kg, with no treatment-related adverse events reported[21, 22] - Favorable target exposure and engagement were observed at 6 mg/kg, with statistically significant exon skipping versus placebo[30, 33]

Company Overview - Entrada Therapeutics, Inc. (TRDA) shares increased by 5.6% to $6.64 in the last trading session, following a period of 11.5% loss over the past four weeks [1][2] - The rise in stock price is linked to growing investor optimism regarding the company's lead oligonucleotide programs aimed at treating Duchenne muscular dystrophy for specific exon skipping [2] Financial Performance - The company is projected to report a quarterly loss of $0.86 per share, reflecting a year-over-year decline of 155.5% [2] - Expected revenues for the upcoming quarter are $8.87 million, which is a significant decrease of 90.6% compared to the same quarter last year [2] Earnings Estimates and Stock Trends - The consensus EPS estimate for Entrada Therapeutics has remained unchanged over the last 30 days, indicating a lack of upward revisions that typically support stock price increases [4] - Historical data suggests that trends in earnings estimate revisions are closely correlated with short-term stock price movements, highlighting the importance of monitoring these estimates [3] Industry Context - Entrada Therapeutics is part of the Zacks Medical - Biomedical and Genetics industry, where another company, Bicycle Therapeutics PLC (BCYC), experienced a slight decline of 0.1% to $8.51, but has seen a 21.2% return over the past month [5] - Bicycle Therapeutics has a consensus EPS estimate of -$0.95 for its upcoming report, which is a 23.4% decrease from the previous year [6]

Company Overview and Pipeline - Entrada Therapeutics expects to have four active clinical programs by the end of 2025[4, 15] - The company has a strong financial position with approximately $383 million in cash, providing a cash runway into Q2 2027[5] - The company's pipeline includes programs for Duchenne Muscular Dystrophy (DMD) and Myotonic Dystrophy Type 1 (DM1), with partnered product VX-670 for DM1[14] - Entrada's Endosomal Escape Vehicle (EEV) technology aims for approximately 50% endosomal escape, compared to the standard approximately 2%[11] DMD Program Updates - ENTR-601-44: Clinical studies are authorized in the UK, EU, and US, with Phase 1/2 MAD study initiation expected in Q2 2025[4, 36, 46] - ENTR-601-45: Clinical study is authorized in the UK and EU, with Phase 1/2 MAD study initiation expected in Q3 2025[4, 38, 53] - ENTR-601-50: The company is on track to submit global regulatory filings in H2 2025, with Phase 1/2 MAD initiation expected in Q4 2025[4, 42, 65] - ENTR-601-44 Phase 1 data showed strong clinical safety up to 6 mg/kg, with potential for best-in-class pharmacokinetics and pharmacodynamics[19, 20] ENTR-601-44 Phase 1 Data Highlights - No treatment-related adverse events were reported in the ENTR-601-44-101 study up to the highest dose of 6 mg/kg[20] - At a dose of 6 mg/kg of ENTR-601-44, robust target engagement with statistically significant exon skipping was observed versus placebo[31]

Summary of Conference Call on Entrada Therapeutics Company Overview - **Company Name**: Entrada Therapeutics - **Founded**: 2016 - **Focus**: Development of therapies for Duchenne muscular dystrophy (DMD) using a platform based on small cyclic peptides [4][3] Key Points and Arguments Technology and Platform - Entrada's platform utilizes a library of small cyclic peptides (8-10 kD) that facilitate drug delivery through endocytosis, significantly improving the therapeutic index by increasing the amount of drug that reaches intracellular targets [5][6] - The platform has demonstrated a 50% escape rate from endosomes compared to the industry average of 1-2%, allowing for more effective drug delivery [6][7] DMD Programs - Entrada is advancing multiple DMD programs, including ENTR 601-44 and ENTR 601-45, which have received regulatory clearance for clinical trials in the EU, UK, and the US [7][11] - The company has shown promising results in preclinical models, including significant exon skipping and dystrophin production in knockout mouse models [7][9] - A healthy volunteer trial demonstrated safety at the highest dose with no clinically relevant adverse events, indicating a strong pharmacokinetic profile [10][20] Competitive Landscape - Entrada positions itself as a leader in the DMD space by focusing on producing higher levels of functional dystrophin compared to existing therapies, including exon skippers and gene therapies [12][14] - The company emphasizes the importance of both the quantity and quality of dystrophin produced, which correlates with better functional outcomes for patients [33][34] Clinical Development Strategy - Entrada is targeting underserved adult DMD patients, who represent 40-50% of the market but are often overlooked in clinical trials [24][27] - The company plans to conduct adaptive trials, adjusting doses based on patient responses and safety data [24][26] Market Evolution - The DMD market is expected to evolve towards a polypharmacy approach, where multiple therapies are used in combination to optimize patient outcomes [32][37] - Entrada anticipates that as gene therapies and other modalities become available, there will be a need for complementary treatments that enhance dystrophin production and muscle regeneration [34][35] Future Outlook - Entrada is optimistic about the upcoming years, with significant milestones expected as clinical trials progress and data from various programs become available [38][41] - The company is also exploring partnerships to expand its capabilities and accelerate program development, similar to its collaboration with Vertex Pharmaceuticals [45][46] Additional Important Content - The company has not observed liver toxicity issues with its PMO-based chemistry, which is a concern for other therapeutic modalities [20][21] - Entrada's approach to DMD treatment is centered on improving quality of life for patients, focusing on both dystrophin production and functional metrics related to daily living [28][29] This summary encapsulates the key insights from the conference call regarding Entrada Therapeutics, its innovative platform, ongoing clinical programs, competitive positioning, and future strategies in the biotechnology sector focused on DMD.

Summary of Entrada Therapeutics (TRDA) 2025 Conference Call Company Overview - **Company**: Entrada Therapeutics (TRDA) - **Focus**: Development of intracellular therapeutics targeting neuromuscular diseases, specifically Duchenne muscular dystrophy (DMD) and myotonic dystrophy type one (DM1) [2][7] Key Clinical Programs - **Active Clinical Programs**: By the end of 2025, the company expects to have four active clinical programs [2] - **Duchenne Muscular Dystrophy (DMD) Franchise**: - **ENTR-601-44**: Clinical studies authorized in the UK, US, and EU; currently enrolling [3] - **ENTR-601-45**: Regulatory clearance obtained; clinical trial enrollment to begin [3] - **ENTR-601-50**: Regulatory submission expected in the second half of 2025 [4] - **Myotonic Dystrophy Type One (DM1)**: Collaboration with Vertex on VX-670; ongoing global study with 26 clinical sites [5] Financial Position - **Cash Position**: Approximately $383 million on the balance sheet, providing a cash runway into Q2 2027 [6][37] - **Importance of Cash**: Financial stability allows the company to navigate critical clinical data points and potential inflection points [6][37] Therapeutic Approach - **Intracellular Targets**: 75% of disease-causing targets are intracellular, which presents significant opportunities for the company [8][11] - **Endosomal Escape Vehicles (EEVs)**: Utilization of cyclic cell-penetrating peptides to enhance cellular uptake and improve therapeutic delivery [8][9] Clinical Data and Safety - **Phase 1 Study for ENTR-601-44**: - Conducted with 32 subjects (24 active, 8 placebo); demonstrated strong clinical safety with no treatment-related adverse effects [17][19] - Dose-dependent increase in plasma concentration observed, indicating a broad therapeutic window [21] - **Future Studies**: Plans to run a global two-part study for ENTR-601-44 and ENTR-601-45, focusing on safety, tolerability, and efficacy [28][30] Market Opportunity - **Duchenne Muscular Dystrophy**: Over 40,000 individuals affected in the US and Europe, highlighting a significant unmet clinical need [27] - **Pipeline Expansion**: Potential to explore ocular programs and other diseases beyond neuromuscular conditions [34][37] Conclusion - **Outlook**: The company is positioned for a busy 2025 and beyond with multiple clinical studies and a strong financial foundation, aiming to address significant unmet needs in neuromuscular diseases and potentially expand into other therapeutic areas [35][37]

Company Overview - Entrada Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing a new class of medicines that target intracellular mechanisms previously deemed inaccessible [4] - The company utilizes its proprietary Endosomal Escape Vehicle (EEV™) technology to enhance the intracellular delivery of therapeutics, aiming to improve therapeutic indices across various diseases [4] Recent Developments - The company announced the appointment of Dr. Maha Radhakrishnan to its Board of Directors, which is expected to bolster its clinical momentum, particularly in the Duchenne muscular dystrophy franchise [1][2] - Dr. Radhakrishnan brings extensive experience in global drug development, having previously held senior roles at Biogen and Sanofi, which will be instrumental as Entrada advances its clinical-stage portfolio [3] Clinical Focus - Entrada is advancing multiple patient-focused clinical trials for its Duchenne muscular dystrophy programs throughout the year, with promising Phase 1 safety and target engagement data [2][3] - The company is developing lead oligonucleotide programs targeting exon 44, 45, 50, and 51 skipping for the treatment of Duchenne muscular dystrophy [4]

Company Overview - Entrada Therapeutics is a clinical-stage biopharmaceutical company focused on developing a new class of medicines that target intracellular mechanisms previously deemed inaccessible [3] - The company utilizes its proprietary Endosomal Escape Vehicle (EEV™) technology to enhance the intracellular delivery of therapeutics, aiming to improve therapeutic indices across various organs and tissues [3] - Entrada is advancing a diverse portfolio of RNA- and protein-based programs, particularly targeting neuromuscular and ocular diseases, with lead programs aimed at treating Duchenne muscular dystrophy [3] Recent Developments - On June 1, 2025, Entrada Therapeutics granted a total of 23,820 restricted stock units (RSUs) to six newly-hired non-executive employees as part of its 2025 Inducement Equity Plan [1] - The RSUs will vest incrementally, with one-fourth vesting on the one-year anniversary of the vesting commencement date, followed by quarterly vesting of 6.25% thereafter [2] - The inducement grants were approved by the Compensation Committee of the Board of Directors to incentivize new employees in accordance with Nasdaq Listing Rule 5635(c)(4) [1][2]

Core Insights - Entrada Therapeutics is set to initiate the ELEVATE-45-201 clinical study in Q3 2025, following authorization from health authorities in multiple countries under the EU Clinical Trial Regulation [1][2] - ELEVATE-45-201 is a Phase 1/2 study focusing on ENTR-601-45, targeting patients with Duchenne muscular dystrophy (DMD) who are amenable to exon 45 skipping, addressing a significant unmet medical need [2][4] Company Overview - Entrada Therapeutics is a clinical-stage biopharmaceutical company developing a new class of medicines aimed at intracellular targets, utilizing its proprietary Endosomal Escape Vehicle (EEV™) technology [5] - The company is advancing a robust pipeline of RNA- and protein-based programs for neuromuscular and ocular diseases, with a focus on DMD therapies targeting exon 44, 45, 50, and 51 skipping [5] Clinical Study Details - ELEVATE-45-201 is a global, two-part, randomized, double-blind placebo-controlled study evaluating the safety, tolerability, and effectiveness of ENTR-601-45 in ambulatory DMD patients [2] - Part A of the study will involve approximately 24 patients, with dosing every six weeks across three cohorts, ranging from 5 mg/kg to 15 mg/kg [2] - Part B will further assess the optimal dose for safety and efficacy, including functional outcomes and quality of life measures [2] Product Information - ENTR-601-45 is a proprietary EEV™-conjugated phosphorodiamidate morpholino oligomer (PMO) designed to address the underlying cause of DMD by restoring the mRNA reading frame for dystrophin protein production [3] - The therapy targets a specific subpopulation of DMD patients who are amenable to exon 45 skipping, with the potential to produce a functional but slightly shortened dystrophin protein [3] Disease Context - Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by mutations in the DMD gene, leading to inadequate dystrophin production and progressive muscle weakness [4] - An estimated 41,000 individuals in the U.S. and Europe are affected by DMD, with approximately 9% being amenable to exon 45 skipping [4]

Financial Data and Key Metrics Changes - The company has generated significant safety data in human trials, which has allowed for the identification of a starting dose for their first patient trial in Duchenne muscular dystrophy (DMD) [8] - The company has cash runway extending into Q2 2027, which is considered unusual compared to peers [36] Business Line Data and Key Metrics Changes - The Endosomal Escape Vehicle (EEV) platform has shown a remarkable target exposure of 50%, significantly higher than the historical benchmark of 1% for biological material delivery [7] - The company is advancing multiple programs in DMD, including exon skipping candidates 44, 45, 50, and 51, with 44 and 45 being prioritized due to larger patient populations and proven efficacy [17][18] Market Data and Key Metrics Changes - The current treatment landscape for DMD has evolved, with the company expecting to be a center of care for patients due to the high-quality dystrophin produced by their therapies [22] - There are emerging safety concerns with gene therapies from competitors, which may open up market opportunities for exon skipping modalities [22] Company Strategy and Development Direction - The company is focused on DMD and myotonic dystrophy type one (DM1) as primary therapeutic areas, leveraging the flexibility of the EEV platform for various indications [10][12] - The company aims to maintain optionality in commercialization strategies, considering both self-commercialization and partnerships [31] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the accelerated approval pathway for DMD treatments, citing a clear correlation between dystrophin levels and functional outcomes [28][29] - The company is excited about the potential of their ocular programs, which target genetically defined retinal diseases with significant unmet needs [40] Other Important Information - The company has made strategic decisions to focus investments on timely execution of clinical trials while maintaining a robust research framework [37] - The partnership with Vertex for the DM1 program is seen as a significant opportunity, with high-quality preclinical data supporting the collaboration [33] Q&A Session Summary Question: How did ENTRATA select indications for DMD and DM1? - The selection was based on a combination of serendipity and strategic assessments, with DMD being a well-understood biology and a clear regulatory pathway [10][11] Question: What is the current state of the DMD treatment landscape? - The future looks promising for DMD patients, with the company expecting to provide significant therapeutic options and high-quality dystrophin production [22] Question: How does ENTRATA view commercialization strategies for DMD? - The company sees a straightforward path to commercialization in DMD, with a focus on maintaining optionality in their approach [31] Question: What are the upcoming value inflection points for the VX-670 program? - The program is in Phase 1/2 trials, and the company is optimistic about the data being generated, which could lead to significant advancements [33] Question: What is the focus of the ocular programs? - The ocular programs are aimed at genetically defined retinal diseases, targeting areas with significant unmet needs [40]