Core Insights - Fractyl Health, Inc. announced significant results from the REMAIN-1 Midpoint Cohort, indicating that Revita may be the first therapy to maintain weight loss after discontinuation of GLP-1 drugs, with Revita-treated patients losing an additional 2.5% total body weight compared to a 10% regain in sham-treated patients, achieving statistical significance (p=0.014) [2][3][8] Study Design and Results - The REMAIN-1 Midpoint Cohort involved 45 participants who had lost at least 15% of their body weight with tirzepatide, randomized to receive either Revita or a sham procedure after stopping the drug [4] - The study met its primary efficacy endpoint at 3 months, showing Revita's effectiveness in promoting further weight loss while ensuring excellent safety and tolerability, with no serious adverse events reported [8][10] Future Milestones - The ongoing REMAIN-1 Midpoint Cohort is expected to provide 6-month data in Q1 2026, while the Pivotal Cohort aims to complete randomization in early 2026, with topline primary endpoint data and potential PMA filing anticipated in H2 2026 [11]

Core Insights - Fractyl Health, Inc. announced significant results from the REMAIN-1 Midpoint Cohort, indicating that the Revita procedure may be the first therapy to maintain weight loss after discontinuation of GLP-1 drugs, with Revita-treated patients losing an additional 2.5% total body weight compared to a 10% regain in sham-treated patients [2][3][10] Study Results - The REMAIN-1 Midpoint Cohort study involved 45 participants who had achieved at least 15% total body weight loss with tirzepatide, randomized to receive either Revita or a sham procedure [4][5] - At the 3-month mark, the study met its primary efficacy endpoint with a statistically significant p-value of 0.014, demonstrating the effectiveness of Revita in promoting further weight loss [8][10] - Safety and tolerability were excellent, with no serious adverse events related to Revita observed, and side effects were mild and transient [8] Future Outlook - The ongoing REMAIN-1 Midpoint Cohort is expected to provide 6-month data in Q1 2026, while the Pivotal Cohort aims to complete randomization in early 2026, with topline primary endpoint data and potential PMA filing anticipated in H2 2026 [11] - These milestones are crucial for establishing Revita as a potential first-in-class treatment for post-GLP-1 weight maintenance, opening a new therapeutic category in obesity care [11] Company Background - Fractyl Health focuses on innovative metabolic therapeutics targeting the root causes of obesity and type 2 diabetes, aiming to transform treatment from chronic management to durable disease-modifying therapies [13][15] - The company holds a robust intellectual property portfolio, including 33 granted U.S. patents and approximately 40 pending applications, positioning it well in the metabolic disease treatment landscape [13]

Revita Program - The durable weight maintenance market represents an untapped opportunity of approximately $175 billion[7] - 85% of patients regain weight after stopping GLP-1 drugs, highlighting a significant unmet clinical and economic need[10] - The REMAIN-1 Pivotal Cohort is on track to complete randomization in early 2026, with potential PMA filing in H2 2026[10] - In the REMAIN-1 Midpoint Cohort study, Revita patients experienced a further 2.5% weight loss after stopping GLP-1s, compared to a 10% weight regain in sham-treated patients (p=0.014) at 3 months[54] Rejuva Program - The company submitted the first CTA module in the EU for RJVA-001, with anticipated preliminary data in 2026[10] - Rejuva aims for a cost of goods (COGs) of less than $10,000 per patient, targeting a price benchmark of approximately $10,000 per year based on ICER pricing[92] - Preclinical data showed that Rejuva's RJVA-001 demonstrated glucose-lowering activity and improved weight compared to daily semaglutide in a db/db murine model[101] - In a DIO mouse model, RJVA-001 prototype showed sustained weight loss while preserving lean mass, outperforming semaglutide[104] Intellectual Property - The company has a robust intellectual property estate with 100+ patents issued globally, including 33 U S patents, and 70+ pending patent applications as of June 2025[135]

Core Insights - Fractyl Health, Inc. has appointed Christopher Thompson, M.D. and Ian Sheffield as Independent Directors to strengthen its Board of Directors as it advances its product candidates Revita and Rejuva [1][2][5] Company Overview - Fractyl Health is a metabolic therapeutics company focused on innovative treatments for obesity and type 2 diabetes (T2D), aiming to transform disease management from symptomatic to disease-modifying therapies [6] - The company has a robust intellectual property portfolio with 33 granted U.S. patents and approximately 40 pending U.S. applications [6] Product Development - Revita is designed to remodel the duodenal lining to reverse damage caused by high-fat and high-sugar diets, and it has received U.S. FDA Breakthrough Device designation for weight maintenance in patients who discontinue GLP-1 based drugs [7] - The pivotal study REMAIN-1 for Revita has been initiated and completed enrollment [7] - The Rejuva platform focuses on developing AAV-based gene therapies for obesity and T2D, with the first Clinical Trial Application submitted for RJVA-001 [8] Leadership Appointments - Christopher Thompson, M.D. brings extensive experience in bariatric endoscopy and has co-founded several start-ups in endoscopic technology, which aligns with Fractyl's upcoming clinical milestones [2][3] - Ian Sheffield has a 20-year track record in healthcare investing and operations, which will aid Fractyl in navigating late-stage development and strategic partnerships [3][5] Strategic Importance - The appointments of Thompson and Sheffield are seen as timely as the company prepares for key milestones and aims to capture significant clinical and economic opportunities in metabolic care [5]

Summary of Fractyl Health (GUTS) FY Conference Call - August 13, 2025 Company Overview - Fractyl Health is focused on developing therapies for obesity and metabolic diseases, aiming for durable, long-lasting effects after a single therapeutic intervention [1][3] - The company is addressing the urgent need for post-GLP-1 weight maintenance solutions, as many patients experience weight regain after stopping GLP-1 medications [2][8] Core Strategies 1. **Revita**: A medical device-enabled therapeutic procedure targeting the duodenum to address obesity and diabetes by correcting the body's weight set point [2][4] - The procedure is designed to have long-lasting effects, potentially allowing patients to maintain weight loss after discontinuing GLP-1s [2][8] - Revita is currently in late clinical stages, with over 400 patients treated in clinical studies [6][7] 2. **Rejuva**: A gene therapy platform aimed at providing a one-time treatment for type 2 diabetes and obesity, with a focus on durability and safety [39][40] - REJUVA001 targets type 2 diabetes, while REJUVA002 is aimed at the obesity market [41] Market Dynamics - An estimated 10 million people are expected to receive GLP-1 prescriptions this year, with over half likely to stop within a year, and 85% of those regaining most or all of the weight lost [2][30] - The market is in need of solutions for the 5 million Americans expected to stop GLP-1 treatments annually, as they face hunger and weight regain without effective alternatives [8][16] Revita Mechanism and Efficacy - Revita targets the mucosa of the small intestine, specifically the duodenum, to reset the body's weight thermostat, allowing for sustained weight loss and improved blood sugar levels [5][12] - The procedure is minimally invasive, performed in under an hour, with immediate effects observed within four weeks and sustained results for two years or more [6][7] - Initial open-label data showed patients maintaining weight after stopping GLP-1s, contrary to expected weight regain [28][29] Clinical Trials and Future Expectations - The pivotal study, REMAIN one, involves patients losing 15% body weight on tirzepatide before randomization to either Revita or a sham treatment [18][19] - Interim updates from the study are expected, with the first randomized data set to be released in September [22][30] - The company anticipates filing for approval by the end of next year if clinical data supports efficacy [23] Economic Considerations - Revita is positioned to align the interests of patients, healthcare providers, and payers, with a pricing model that offers a cost offset to GLP-1s [30][32] - The procedure is expected to be priced between $5,000 to $8,000, with over 80% gross margins [32][33] Competitive Landscape - The company believes that small molecules, such as those being developed by competitors, will not adequately address the long-term needs of patients who wish to avoid lifelong medication dependency [34][35] Conclusion - Fractyl Health is poised to address significant gaps in the obesity and metabolic disease treatment landscape with its innovative Revita and Rejuva platforms, focusing on durable solutions that reduce dependency on ongoing medications [39][40]

Financial Data and Key Metrics Changes - The net loss for Q2 2025 was $27.9 million, compared to $17.2 million in Q2 2024, primarily due to changes in non-cash fair value of notes and warrants and increased operating expenses [20] - R&D expenses for the quarter were $21.2 million, up from $16.8 million in the same quarter last year, reflecting continued advancement in clinical studies [19] - SG&A expenses decreased to $4.9 million from $6.2 million in the same quarter last year, mainly due to lower stock-based compensation [19] Business Line Data and Key Metrics Changes - The Revita program is emerging as a foundational therapy for resetting the body's metabolic set point in obesity and type 2 diabetes, with new data showing up to two years of benefit in weight maintenance and blood sugar control following a single treatment [7][8] - The Rejuva program has completed preclinical efficacy, toxicity, and biodistribution studies, with plans for a phase one/two clinical study to evaluate safety and preliminary efficacy in adults with inadequately controlled type 2 diabetes [16][17] Market Data and Key Metrics Changes - The company is addressing the significant unmet need for weight regain after GLP-1 discontinuation, with a focus on patients who have lost weight through GLP-1 therapy but struggle to maintain it after stopping [4][5] - Insights from key stakeholders indicate a shift in patient and prescriber attitudes, with a growing desire for alternatives to long-term GLP-1 therapy [36] Company Strategy and Development Direction - The company has strengthened its financial position through a $23 million public offering, which could provide up to $69 million in total proceeds, positioning it to capture the value of clinical and strategic progress [6] - A nonbinding letter of intent with Bariendo aims to prepare for potential adoption of Revita pending FDA approval, focusing on pre-commercial preparation and distribution channels [13] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about upcoming data readouts and the potential for Revita to serve as a long-term solution for weight maintenance after GLP-1 therapy [10][22] - The company anticipates a transformational second half of the year, with multiple clinical milestones ahead, including randomized data from the REMAIN one midpoint cohort [21][22] Other Important Information - The company has been granted two new US patents, reinforcing its position as an innovation leader in gut-targeted metabolic therapy, with over 100 granted patents worldwide [14] - The company aims to redefine the risk-benefit profile of long-term GLP-1 therapy with Rejuva, potentially offering a durable solution for chronic metabolic disease [17] Q&A Session Summary Question: What additional data points will be shared in the midpoint update? - Management indicated that the update will focus on safety, tolerability, and effectiveness of weight loss maintenance, with visibility into the overall population's behavior [27][28] Question: What is the status of Rejuva IND clearance? - Management reported significant progress and expects to see the lot release of the GMP product soon, with preliminary data anticipated in 2026 [30] Question: What trends are observed in the GLP-1 market? - There is a growing desire among patients to stop long-term GLP-1 therapy, highlighting the need for better real-world outcomes, which bodes well for Revita and Rejuva [36] Question: How does GLP-1 therapy impact observed outcomes? - Management believes that the contribution from GLP-1 to weight loss in patients is minimal, as consistent signals of weight loss have been observed across various studies [42] Question: Will patients in the REMAIN one cohort be tracked longer for durability? - Management confirmed that patients will be followed for a year, with incremental data updates expected over time [48][49] Question: What are the expectations for DEXA scans in the REVEAL trial? - DEXA scans will not be included in the open-label REVEAL study, and historical comparators for body composition upon tirzepatide discontinuation are lacking [70]

[PART I FINANCIAL INFORMATION](index=10&type=section&id=PART%20I%20FINANCIAL%20INFORMATION) [Item 1. Financial Statements](index=10&type=section&id=Item%201.%20Financial%20Statements) The unaudited financial statements show a significant net loss, a decrease in cash, and substantial doubt about the company's ability to continue as a going concern Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $22,291 | $67,464 | | Total assets | $62,006 | $108,077 | | Total liabilities | $80,218 | $79,653 | | Accumulated deficit | $(466,934) | $(415,310) | | Total stockholders' equity (deficit) | $(18,212) | $28,424 | Condensed Consolidated Statements of Operations Highlights (in thousands, except per share data) | Metric | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Revenue | $0 | $76 | | Research and development | $40,586 | $31,186 | | Selling, general and administrative | $10,252 | $13,374 | | Loss from operations | $(50,838) | $(44,527) | | Net loss | $(51,624) | $(20,551) | | Net loss per share, basic and diluted | $(1.05) | $(0.57) | - The Company has a history of operating losses, with an accumulated deficit of **$466.9 million** as of June 30, 2025[48](index=48&type=chunk) - Management has concluded that there is **substantial doubt about the Company's ability to continue as a going concern** within twelve months from the report's issuance date[48](index=48&type=chunk) - In August 2025, the Company completed an offering of common stock and warrants, receiving net proceeds of approximately **$20.7 million**[44](index=44&type=chunk)[98](index=98&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=27&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses its focus on metabolic disease therapies, recent clinical progress, and a critical liquidity position that raises going concern doubts [Business Overview and Recent Developments](index=27&type=section&id=Business%20Overview%20and%20Recent%20Developments) The company is prioritizing its Revita program for post-GLP-1 weight maintenance and advancing its Rejuva gene therapy platform with a European regulatory submission - The company is prioritizing the **REMAIN-1 pivotal study** for Revita, which evaluates its potential to maintain weight loss after patients discontinue GLP-1 medication[105](index=105&type=chunk)[108](index=108&type=chunk) - Positive 3-month data from the REVEAL-1 Cohort of the REMAIN-1 study showed that **12 of 13 participants maintained or lost weight** after stopping GLP-1 therapy[116](index=116&type=chunk) - For the Rejuva platform, the company submitted the first module of a **Clinical Trial Application (CTA) in Europe** for its lead candidate RJVA-001[109](index=109&type=chunk)[122](index=122&type=chunk) - The company entered into a non-binding **Letter of Intent (LOI) with Bariendo Inc.** to evaluate a potential collaboration for using Revita as a post-GLP-1 weight maintenance intervention[124](index=124&type=chunk) [Results of Operations](index=33&type=section&id=Results%20of%20Operations) The company generated no revenue in H1 2025, while a significant increase in R&D expenses drove a wider net loss compared to the prior year Comparison of Results for the Six Months Ended June 30 (in thousands) | Line Item | 2025 | 2024 | Change ($) | Change (%) | | :--- | :--- | :--- | :--- | :--- | | Revenue | $0 | $76 | $(76) | (100.0%) | | Research and development | $40,586 | $31,186 | $9,400 | 30.1% | | Selling, general and administrative | $10,252 | $13,374 | $(3,122) | (23.3%) | | Loss from operations | $(50,838) | $(44,527) | $(6,311) | 14.2% | | Net loss | $(51,624) | $(20,551) | $(31,073) | 151.2% | - The **$9.4 million increase in R&D expenses** for the six-month period was primarily driven by a $4.4 million increase in Revita-related clinical expenses and a $5.7 million increase in Rejuva-related development[147](index=147&type=chunk)[148](index=148&type=chunk) - The **$3.1 million decrease in SG&A expenses** for the six-month period was mainly due to a $3.7 million decrease in stock-based compensation[150](index=150&type=chunk) [Liquidity and Capital Resources](index=35&type=section&id=Liquidity%20and%20Capital%20Resources) The company's liquidity is critically low, with existing cash insufficient to fund operations for the next twelve months despite recent financing efforts - As of June 30, 2025, the company had **$22.3 million in cash and cash equivalents**, which is not sufficient to fund the operating plan for at least twelve months[170](index=170&type=chunk) - The company raised approximately **$20.7 million in net proceeds** from its August 2025 Offering of common stock and warrants[166](index=166&type=chunk) - The company is subject to a **minimum liquidity covenant of $10.0 million** under its 2023 Notes agreement and will not be able to comply without additional financing[157](index=157&type=chunk)[170](index=170&type=chunk) Cash Flow Summary for the Six Months Ended June 30 (in thousands) | Cash Flow Activity | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(46,278) | $(30,448) | | Net cash used in investing activities | $(546) | $(1,319) | | Net cash provided by financing activities | $1,651 | $100,997 | [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=42&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company is exposed to various market risks, with no material changes reported since the end of the 2024 fiscal year - The company is exposed to interest rate, credit, foreign currency, and inflation risk, with **no material changes to these risks reported** during the quarter[192](index=192&type=chunk) [Item 4. Controls and Procedures](index=42&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that disclosure controls and procedures were effective as of the quarter's end, with no material changes to internal controls - Management concluded that as of June 30, 2025, the company's disclosure controls and procedures were **effective at the reasonable assurance level**[194](index=194&type=chunk) - There were **no changes in internal control over financial reporting** during the quarter that have materially affected, or are reasonably likely to materially affect, internal controls[195](index=195&type=chunk) [PART II OTHER INFORMATION](index=43&type=section&id=PART%20II%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=43&type=section&id=Item%201.%20Legal%20Proceedings) The company reports that it is not currently a party to any material legal proceedings - The company is **not subject to any material legal proceedings**[198](index=198&type=chunk) [Item 1A. Risk Factors](index=43&type=section&id=Item%201A.%20Risk%20Factors) The company faces numerous significant risks, including its financial condition, regulatory hurdles, third-party reliance, competition, and intellectual property protection [Risks Related to Financial Condition and Capital Requirements](index=43&type=section&id=Risks%20Related%20to%20Our%20Financial%20Condition%20and%20Capital%20Requirements) The company has a history of significant losses and an urgent need for capital, creating substantial doubt about its ability to continue as a going concern - The company has a **limited operating history**, has not completed any pivotal clinical studies, and has no products approved for commercial sale in the United States[200](index=200&type=chunk) - The company has incurred significant net losses since inception, with an accumulated deficit of approximately **$466.9 million** as of June 30, 2025[203](index=203&type=chunk) - **Substantial doubt exists about the company's ability to continue as a going concern**, as existing cash is not sufficient to fund operations for at least twelve months[210](index=210&type=chunk) [Risks Related to Development, Regulatory Approval and Commercialization](index=51&type=section&id=Risks%20Related%20to%20Development,%20Regulatory%20Approval%20and%20Commercialization) The company faces a lengthy and unpredictable regulatory approval process for its product candidates, with uncertain clinical outcomes and reimbursement challenges - The **regulatory approval process** for medical devices and biopharmaceutical products is lengthy, time-consuming, and inherently unpredictable[230](index=230&type=chunk) - Clinical studies are expensive, difficult to design, and have **uncertain outcomes**, with the potential for substantial delays[243](index=243&type=chunk) - The company's Rejuva gene therapy candidates are expected to be regulated as a **combination product**, which may add complexity to regulatory approval[274](index=274&type=chunk) - Commercial success depends on obtaining **adequate coverage and reimbursement** from third-party payors, which is uncertain[269](index=269&type=chunk) [Risks Related to Business and Strategy](index=69&type=section&id=Risks%20Related%20to%20Our%20Business%20and%20Strategy) The business is substantially dependent on its two lead candidates and faces significant challenges in gaining market acceptance and competing with established firms - The company is **substantially dependent on the success of its lead product candidates**, Revita and Rejuva[299](index=299&type=chunk) - The medical device and biopharmaceutical markets are highly competitive, and the company faces **significant competition from larger companies** with greater resources[323](index=323&type=chunk) - **Market acceptance of the company's products is not guaranteed** and depends on convincing physicians, hospitals, and payors of their benefits[313](index=313&type=chunk) [Risks Related to Manufacturing](index=82&type=section&id=Risks%20Related%20to%20Manufacturing) The company relies on third-party and sole-source suppliers for manufacturing, creating supply chain risks, and concentrates its operations in a single facility - The company **relies on third-party manufacturers** for components and materials, increasing the risk of supply shortages and cost issues[355](index=355&type=chunk) - The company **depends on third-party sole-source suppliers** for certain Revita components, and an interruption could materially harm the business[364](index=364&type=chunk) - The company's research, development, and manufacturing operations are conducted in a **single facility**, making it vulnerable to disasters or other interruptions[369](index=369&type=chunk) [Risks Related to Intellectual Property](index=95&type=section&id=Risks%20Related%20to%20Intellectual%20Property) The company's success depends on its ability to obtain and defend its intellectual property amid an uncertain patent process and litigation risks - The company's ability to commercialize its products depends on its ability to **obtain and maintain patent protection**, which is uncertain[409](index=409&type=chunk) - The company may face **intellectual property litigation**, which is expensive and time-consuming, and could require obtaining licenses on unfavorable terms[424](index=424&type=chunk)[431](index=431&type=chunk) - If the company is unable to **protect the confidentiality of its trade secrets**, its business and competitive position may be harmed[445](index=445&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=122&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports no unregistered sales of equity securities and confirms no material change in the intended use of its IPO proceeds - There were **no unregistered sales of equity securities** in the reporting period[511](index=511&type=chunk) - There has been **no material change in the planned use of proceeds** from the company's IPO[513](index=513&type=chunk) [Item 5. Other Information](index=122&type=section&id=Item%205.%20Other%20Information) An executive officer adopted a Rule 10b5-1 trading plan during the quarter for the potential sale of company stock - On May 28, 2025, Jay Caplan, President and Chief Product Officer, adopted a **Rule 10b5-1 trading arrangement** for the sale of up to 169,173 shares of common stock[520](index=520&type=chunk)

[Business Highlights and Clinical Pipeline Update](index=1&type=section&id=Business%20Highlights%20and%20Clinical%20Pipeline%20Update) The company reports positive clinical progress for its Revita® program and advancements in the preclinical Rejuva® gene therapy platform [Revita® Program](index=1&type=section&id=Revita%C2%AE%20Program) The Revita® procedure is advancing through the REMAIN-1 pivotal study to evaluate its efficacy post-GLP-1 drug discontinuation [REVEAL-1 Cohort](index=1&type=section&id=REVEAL-1%20Cohort) - Positive 3-month data showed that **12 of 13 participants maintained or further reduced their weight** after discontinuing GLP-1 medication and receiving a single Revita procedure[5](index=5&type=chunk)[6](index=6&type=chunk) - Median weight remained stable through 3 months (**0.46% change**), compared to a typical **5-6% weight rebound** seen in other clinical studies after GLP-1 withdrawal[6](index=6&type=chunk) - Upcoming data releases for the REVEAL-1 Cohort are expected for the 6-month follow-up in Q4 2025 and the 1-year follow-up in Q2 2026[6](index=6&type=chunk) [REMAIN-1 Midpoint Cohort](index=2&type=section&id=REMAIN-1%20Midpoint%20Cohort) - Enrollment is complete for the 45-participant randomized, double-blind REMAIN-1 Midpoint Cohort, designed to provide an early readout on Revita's potential for weight maintenance post-GLP-1[7](index=7&type=chunk)[10](index=10&type=chunk) - Key data readouts are anticipated in September 2025 (3-month data) and Q1 2026 (6-month data)[1](index=1&type=chunk)[10](index=10&type=chunk) [REMAIN-1 Pivotal Cohort](index=2&type=section&id=REMAIN-1%20Pivotal%20Cohort) - Enrollment is complete for the 315-participant randomized, double-blind REMAIN-1 Pivotal Cohort, which will evaluate the safety and efficacy of Revita for weight maintenance[8](index=8&type=chunk)[11](index=11&type=chunk) - The company expects to report 6-month primary endpoint data and submit a Premarket Approval (PMA) application to the FDA in the second half of 2026[1](index=1&type=chunk)[11](index=11&type=chunk) [Germany Real-World Registry Study](index=2&type=section&id=Germany%20Real-World%20Registry%20Study) - Data from the first 9 patients with 2 years of follow-up showed that a single Revita procedure led to a median **9.6% weight loss** and a **1.6% reduction in HbA1c** in participants with obesity and advanced T2D[9](index=9&type=chunk) - These effects were sustained through two years with **no device- or procedure-related serious adverse events** reported, supporting Revita's potential for durable, long-term metabolic control[9](index=9&type=chunk) [Rejuva® Gene Therapy Platform](index=3&type=section&id=Rejuva%C2%AE%20Gene%20Therapy%20Platform) The Rejuva® gene therapy platform is advancing its lead candidate, RJVA-001, toward first-in-human studies for T2D and obesity - Preclinical data presented at ADA and ASGCT showed a single dose of Rejuva prevented weight gain and hyperglycemia in animals, demonstrating durable metabolic improvements and supporting readiness for clinical trials[14](index=14&type=chunk) - The company submitted the first module of its CTA in Europe for RJVA-001 in May 2025 for a Phase 1/2 study in adults with inadequately controlled T2D[14](index=14&type=chunk) - Pending regulatory authorization, Fractyl expects to dose the first patients with RJVA-001 and report preliminary data in 2026[14](index=14&type=chunk) [Corporate Developments](index=3&type=section&id=Corporate%20Developments) The company strengthened its financial position, expanded its IP portfolio, and explored a potential commercial collaboration for Revita - Completed a **$23 million** underwritten public offering in August 2025, which is expected to extend the cash runway through key upcoming clinical data readouts from the REMAIN-1 Midpoint Cohort[2](index=2&type=chunk)[14](index=14&type=chunk) - Was issued **two new U.S. patents**, expanding protection for its duodenal mucosal resurfacing platform and bringing its portfolio to 32 granted U.S. patents[14](index=14&type=chunk) - Entered into a non-binding Letter of Intent with Bariendo Inc to evaluate a potential collaboration for Revita as a post-GLP-1 weight maintenance intervention, pending FDA approval[14](index=14&type=chunk) [Second Quarter 2025 Financial Results](index=4&type=section&id=Second%20Quarter%202025%20Financial%20Results) The company reported a wider net loss driven by increased R&D expenses, while maintaining a cash runway into 2026 Q2 2025 Financial Highlights (vs Q2 2024) | Metric | Q2 2025 | Q2 2024 | Change Driver | | :--- | :--- | :--- | :--- | | **R&D Expenses** | $21.2M | $16.8M | Advancement of REMAIN-1 study and Rejuva program | | **SG&A Expenses** | $4.9M | $6.2M | Lower stock-based compensation expenses | | **Net Loss** | ($27.9M) | ($17.2M) | Fluctuation in fair value of notes/warrants & higher operating expenses | | **Cash & Equivalents** | $22.3M | N/A | As of June 30, 2025 | - The company believes its cash position, including proceeds from the August 2025 offering, is sufficient to fund operations into 2026[17](index=17&type=chunk) [Financial Statements](index=6&type=section&id=Financial%20Statements) This section presents selected consolidated balance sheet and statement of operations data for the period ending June 30, 2025 [Selected Consolidated Balance Sheet Data](index=6&type=section&id=Selected%20Consolidated%20Balance%20Sheet%20Data) The balance sheet shows a significant decrease in cash and total assets, resulting in a stockholders' deficit as of June 30, 2025 Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $22,291 | $67,464 | | Total assets | $62,006 | $108,077 | | Total liabilities | $80,218 | $79,653 | | Total stockholders' equity (deficit) | ($18,212) | $28,424 | [Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) The statement of operations reveals a wider net loss for Q2 2025 compared to Q2 2024, driven by higher R&D spending Statement of Operations Highlights (in thousands) | Account | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | | :--- | :--- | :--- | | Research and development | $21,151 | $16,762 | | Selling, general and administrative | $4,928 | $6,242 | | Loss from operations | ($26,079) | ($22,985) | | Net loss and comprehensive loss | ($27,889) | ($17,229) | [About the Company and Products](index=4&type=section&id=About%20the%20Company%20and%20Products) This section provides an overview of Fractyl Health's mission and its key investigational product platforms, Revita® and Rejuva® [About Fractyl Health](index=4&type=section&id=About%20Fractyl%20Health) Fractyl Health is a metabolic therapeutics company developing disease-modifying therapies for obesity and Type 2 Diabetes - The company's goal is to transform metabolic disease treatment from chronic symptomatic management to durable therapies that target the root causes of disease[19](index=19&type=chunk) [About Revita®](index=4&type=section&id=About%20Revita%C2%AE) Revita® is an investigational duodenal remodeling procedure designed to maintain weight loss after GLP-1 drug discontinuation - Revita is designed to reverse damage to intestinal nutrient sensing and signaling mechanisms caused by chronic high-fat and high-sugar diets[20](index=20&type=chunk) [About Rejuva®](index=4&type=section&id=About%20Rejuva%C2%AE) The Rejuva® platform is a preclinical gene therapy program targeting the pancreas to provide durable treatment for T2D and obesity - Rejuva aims to offer novel, disease-modifying therapies by developing locally delivered gene therapies that address the underlying root causes of metabolic diseases[21](index=21&type=chunk)

Core Insights - Fractyl Health, Inc. is advancing its Revita and Rejuva platforms aimed at treating obesity and type 2 diabetes (T2D) through innovative approaches [2][3][18] - The company recently completed a $23 million underwritten public offering to extend its cash runway for upcoming clinical milestones [2][18] - Positive early data from the REVEAL-1 Cohort indicates that Revita can help maintain weight loss after discontinuation of GLP-1 drugs [7][20] Financial Performance - For Q2 2025, Fractyl reported a net loss of $27.9 million, compared to a net loss of $17.2 million in Q2 2024, largely due to increased operating expenses [16][27] - Research and development expenses were $21.2 million for the quarter, up from $16.8 million in the same period last year, reflecting ongoing clinical study advancements [16][27] - As of June 30, 2025, the company had approximately $22.3 million in cash and cash equivalents, which is expected to fund operations into 2026 [16][27] Clinical Developments - The REMAIN-1 pivotal study includes three cohorts: REVEAL-1, REMAIN-1 Midpoint, and REMAIN-1 Pivotal, with the latter expected to report 6-month data in H2 2026 [4][9][13] - The REVEAL-1 Cohort showed that 12 out of 13 participants maintained or reduced weight after a single Revita procedure following GLP-1 discontinuation [7][8] - The REMAIN-1 Midpoint Cohort is designed to assess Revita's efficacy in maintaining weight loss after GLP-1 discontinuation, with initial data expected in September 2025 [8][12] Strategic Initiatives - Fractyl has entered a non-binding Letter of Intent with Bariendo Inc. to explore collaboration for Revita as a post-GLP-1 weight maintenance intervention [18] - The company has been issued two new U.S. patents that enhance its duodenal mucosal resurfacing platform, strengthening its intellectual property portfolio [18] - The Rejuva platform is progressing towards clinical trials, with the first-in-human study expected to begin in 2026 [11][14]

Company Overview - Fractyl Health, Inc. is a metabolic therapeutics company focused on innovative approaches to treat obesity and type 2 diabetes (T2D) [3] - The company aims to shift the treatment of metabolic diseases from chronic symptomatic management to durable disease-modifying therapies targeting organ-level root causes [3] - Fractyl has a strong intellectual property portfolio with 32 granted U.S. patents and approximately 40 pending U.S. applications, along with numerous foreign patents [3] Upcoming Events - The company will report its financial results for the second quarter of 2025 and provide business updates on August 12, 2025, at 4:30 p.m. ET [1] - Harith Rajagopalan, M.D., Ph.D., Co-Founder and CEO, will present at the Canaccord Genuity 45th Annual Growth Conference on August 13, 2025, at 11:30 a.m. ET [2] - A live webcast of the conference call and presentation will be available on Fractyl Health's website, with an archived version for later access [2]