Core Insights - TransCode Therapeutics, Inc. has announced a collaboration with Quantum Leap Healthcare Collaborative to evaluate its lead therapeutic candidate TTX-MC138 in the PRE-I-SPY clinical trial platform [1][2] Group 1: Clinical Trial Details - The PRE-I-SPY program will include TTX-MC138 in a Phase 2a dose-expansion clinical trial, enrolling up to 45 patients with colorectal cancer who are ctDNA positive after standard therapy [2][3] - The Phase 2a trial is set to begin in the first half of 2026 and will be led by Dr. Paula Pohlmann from MD Anderson Cancer Center [2] Group 2: Therapeutic Potential - The trial aims to assess the biological and clinical activity of TTX-MC138 in the Minimal Residual Disease (MRD) setting, targeting patients with a high risk of recurrence [3][4] - TTX-MC138 is designed to inhibit microRNA-10b, which is believed to play a critical role in the progression of metastatic cancers [5][6] Group 3: Company Background - TransCode Therapeutics is focused on developing immuno-oncology and RNA therapeutic treatments for high-risk and advanced cancers, with TTX-MC138 being its lead candidate [6] - The company has a portfolio of first-in-class therapeutic candidates aimed at mobilizing the immune system to combat cancer cells [6] Group 4: Collaborative Efforts - Quantum Leap Healthcare Collaborative sponsors the I-SPY Trials, which aim to rapidly screen promising treatments and identify effective therapies for specific patient subgroups [7][8] - The collaboration aims to accelerate the evaluation of TTX-MC138, with the goal of advancing effective and less toxic precision therapies into later trial phases [4][8]

Summary of Ionis Pharmaceuticals Conference Call Company Overview - **Company**: Ionis Pharmaceuticals - **Industry**: Biotechnology, specifically focusing on genetic medicines targeting RNA for therapeutics - **Recent Achievements**: Launched two FDA-approved medicines independently in the U.S. in 2025: Tryngolza for Familial Chylomicronemia Syndrome (FCS) and Donidalorsen for hereditary angioedema [2][3] Core Points and Arguments - **Successful Product Launches**: - Tryngolza, the first FDA-approved medicine for FCS, launched successfully in 2025 [2] - Donidalorsen launched as a prophylactic treatment for hereditary angioedema [2] - **Pipeline Progress**: - Announced positive phase three data for severe hypertriglyceridemia and a neurology drug for Alexander disease [3][4] - Anticipating five phase three readouts and two to three FDA approvals in the upcoming year [4] - **Market Opportunity**: - Severe hypertriglyceridemia affects millions in the U.S., with a focus on patients at high risk for acute pancreatitis [7][9] - Plans to target both severely at-risk patients and those with mildly elevated triglycerides [10][11] - **Combination Therapy Potential**: - Exploring combination therapies for managing triglycerides and other cardiovascular risk factors [12][13] - Collaboration with AstraZeneca to combine treatments for TTR cardiomyopathy [14][17] Additional Important Insights - **Self-Administration Preference**: - Patients prefer self-administered treatments, which could enhance market penetration, especially in community settings [20][21] - **Regulatory and Market Dynamics**: - Anticipated inclusion in treatment guidelines for severe hypertriglyceridemia, with a significant patient population of over 3 million in the U.S. [40] - **Spinraza Update**: - Ionis is developing a next-generation Spinraza with once-per-year dosing, expected to re-emerge as a leading treatment for spinal muscular atrophy (SMA) [32][33] - Economic terms for the next-gen product are more favorable, with royalties in the mid-20% range compared to mid-teens for the current compound [34] Conclusion - Ionis Pharmaceuticals is positioned for significant growth with its innovative therapies targeting severe hypertriglyceridemia and SMA. The company is leveraging its unique RNA-targeting platform to address unmet medical needs and expand its market presence through strategic partnerships and a focus on patient convenience.

Core Insights - CRISPR Therapeutics (CRSP) shares have increased by 41.4% over the past three months, driven by positive data from the CTX310 study and strong sales of Casgevy in Q2 2025 [1][9]. In Vivo Pipeline Programs - CRISPR Therapeutics is advancing its in-vivo candidates, CTX310 and CTX320, in separate phase I clinical studies targeting ANGPTL3 and lipoprotein(a) respectively [2]. - Updated data from the CTX310 study showed significant reductions in low-density lipoprotein (LDL) and triglyceride (TG) levels, with peak reductions of up to 86% in LDL and 82% in TG [2][9]. - Data for CTX320 is anticipated in the first half of 2026, raising hopes for its potential in treating heart disease [3]. Casgevy Sales Performance - Casgevy, a one-shot gene therapy developed in partnership with Vertex Pharmaceuticals, was approved for sickle cell disease and transfusion-dependent beta-thalassemia [4]. - After a slow start in 2024 with only $10 million in revenue, Casgevy's sales surged to $30.4 million in Q2 2025, marking a 114.1% sequential increase [5][6]. - Over 75 treatment centers have been activated for Casgevy, with expectations for significant growth in new patient starts throughout 2025 [6]. Other Pipeline Candidates and Collaborations - CRISPR Therapeutics is developing next-generation CAR-T therapy candidates, CTX112 and CTX131, in separate phase I/II studies, with data expected later in 2025 [7]. - The company plans to expand its in-vivo pipeline with two additional programs, CTX340 and CTX450, by the end of the year [8]. - A recent collaboration with Sirius Therapeutics aims to diversify CRSP's pipeline into RNA therapeutics, focusing on the development of SRSD107 for thromboembolic disorders [10][11]. Competitive Landscape - CRISPR Therapeutics faces competition from other companies in the gene-editing space, including Beam Therapeutics and Intellia Therapeutics, which are advancing their own therapies [12]. - Casgevy also competes with chronic therapies like Bristol Myers' Reblozyl and Novartis' Adakveo [13]. Stock Performance and Valuation - CRSP shares have risen 34.8% year-to-date, outperforming the industry and the S&P 500 [14]. - The stock is trading at a price-to-book (P/B) ratio of 2.68, lower than the industry average of 2.95, indicating a potential valuation opportunity [15]. Estimate Movements - Estimates for CRISPR's 2025 loss per share have widened from $5.58 to $6.26, while estimates for 2026 have narrowed from $4.30 to $3.98 [18]. Financial Position - CRISPR Therapeutics has a strong cash balance of approximately $1.7 billion as of June-end, which supports ongoing operations and potential late-stage studies [20].

Core Insights - CRISPR Therapeutics reported a second-quarter 2025 loss of $2.40 per share, wider than the previous year's loss of $1.49, primarily due to a $96.3 million expense related to a collaboration with Sirius Therapeutics [1][6] - Adjusted loss, excluding special items, was $1.29 per share, better than the Zacks Consensus Estimate of a loss of $1.47 [2] - Total revenues for the quarter were $0.89 million, significantly below the Zacks Consensus Estimate of $6.6 million, compared to $0.5 million in the same period last year [2] Financial Performance - CRISPR Therapeutics' stock fell over 8% in after-market trading following the wider-than-expected loss, continuing the downward trend in pre-market trading [3] - The stock has increased by 51% year-to-date, outperforming the industry growth of 2% [3] - Research and development expenses decreased by 13% year-over-year to $69.9 million, while general and administrative expenses fell by 3% to $18.9 million [8] Product Development and Sales - Casgevy, a CRISPR/Cas9 gene-edited therapy developed in partnership with Vertex Pharmaceuticals, saw sales of $30.4 million in Q2, up from $14.2 million in the previous quarter [5][6] - Over 75 treatment centers have been activated globally for Casgevy, with approximately 115 patients completing their first cell collection since its launch [6][7] - The company is advancing its CAR-T and in-vivo therapy pipelines, with updates expected later this year [10][11] Pipeline Expansion - CRISPR Therapeutics is developing two next-generation CAR-T therapy candidates, CTX112 and CTX131, currently in phase I/II studies [10] - The company is also studying in-vivo candidates CTX310 and CTX320, with promising early data showing significant reductions in LDL and triglyceride levels [11] - A collaboration with Sirius Therapeutics has diversified the pipeline into RNA therapeutics, with a focus on the investigational siRNA candidate SRSD107 [12][13] Financial Position - As of June 30, 2025, CRISPR Therapeutics had cash and marketable securities totaling $1.72 billion, down from $1.86 billion at the end of March 2025 [9]

Financial Data and Key Metrics Changes - Total operating loss from continuing operations increased from $6.6 million in 2023 to $6.9 million in 2024 [22] - Research and development expenses rose to $3.7 million in 2024 from $3.4 million in 2023 [22] - General and administrative expenses decreased from $3.5 million in 2023 to $3.2 million in 2024 [22] - Net loss for 2024 was $8.5 million compared to $4.3 million in the previous year [23] - Cash and cash equivalents at year-end 2024 increased to $1 million from $700,000 at the end of 2023 [25] Business Line Data and Key Metrics Changes - The RNA delivery business showed progress with new partnerships and improved manufacturing processes [6] - The company aims to advance at least one flagship program to an investigational new drug IND filing with the FDA in 2026 [14] - The legacy assets, including the nasal spray products, are expected to see significant commercial opportunities with ongoing discussions for partnerships [20] Market Data and Key Metrics Changes - The global radiopharmaceutical market reached $8.4 billion in size in 2024 and is expected to grow to $17.1 billion by 2033 [13] - The company received marketing approval for its nasal spray in Mainland China, indicating a major commercial opportunity [17] Company Strategy and Development Direction - The company plans to spin off a majority of its RNA delivery subsidiary, Altamira Therapeutics AG, to better capitalize on growth opportunities [8] - The strategy includes licensing the RNA delivery platform technology to partners in the biotech and pharma industry [12] - The company is transitioning to a holding company model, focusing on managing and monetizing its participations and assets [25] Management's Comments on Operating Environment and Future Outlook - Management acknowledged the challenges posed by the NASDAQ delisting but expressed optimism about the planned spin-off and private equity involvement [28] - The company is focused on building its RNA delivery business and addressing the potential for RNA therapeutics [28] Other Important Information - The financial statements for 2024 were presented in U.S. dollars for the first time, reflecting a shift in reporting [20] - The company has filed several patent applications to protect its proprietary programs [14] Q&A Session Summary Question: What are the expectations for the RNA delivery business? - Management highlighted the growing momentum in the RNA delivery business and the importance of appropriate funding to continue progress [27] Question: How does the company plan to address the NASDAQ delisting? - Management discussed the painful experience of the delisting but emphasized the planned spin-off and private equity involvement as beneficial alternatives [28]

TABLE OF CONTENTS As filed with the U.S. Securities and Exchange Commission on June 6, 2023. Registration No. 333-272082 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 2 to FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 TRANSCODE THERAPEUTICS, INC. (Exact name of Registrant as specified in its charter) 2834 (Primary Standard Industrial Classification Code Number) (I.R.S. Employer Delaware (State or other jurisdiction of incorporation or organization) ...

Washington, D.C. 20549 Amendment No. 1 to FORM S-1 TABLE OF CONTENTS As filed with the U.S. Securities and Exchange Commission on June 5, 2023. Registration No. 333-272082 UNITED STATES SECURITIES AND EXCHANGE COMMISSION REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 TRANSCODE THERAPEUTICS, INC. (Exact name of Registrant as specified in its charter) 2834 (I.R.S. Employer Delaware (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) ...

TABLE OF CONTENTS As filed with the U.S. Securities and Exchange Commission on May 19, 2023. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 UNDER THE SECURITIES ACT OF 1933 TRANSCODE THERAPEUTICS, INC. (Exact name of Registrant as specified in its charter) Delaware (State or other jurisdiction of incorporation or organization) 2834 (Primary Standard Industrial Classification Code Number) FORM S-1 REGISTRATION STATEMENT 81-1065054 (I.R.S. Employer Identification ...