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NASDAQ:GUTS September 1, 2026 The Potential Path to Commercializing Revita ® A Procedural Therapy for Post-GLP-1 Weight Maintenance Revita is for investigational use only in the United States. Revita has a CE mark in the EU/UK.
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Legal disclaimer . ©2026 Fractyl Health, Inc. All Rights Reserved. Market Data, Estimates and Industry Information The market size, addressable market, industry, business and related figures presented herein are estimates and projections provided for illustrative purposes only. This information is based in part on the Company's own internal estimates, research, analyses, assumptions and projections, and in part on third-party sources, including industry reports, research, surveys and studies prepared by market research firms and other third parties, industry, medical and general publications, government data, publicly available data and similar sources. Neither the Company's internal estimates nor the third-party information referenced have been independently verified, and while the Company is not aware of any misstatements regarding any third-party information presented herein, no representation or warranty, express or implied, is made as to the accuracy, completeness or reasonableness of any such information. This information, particularly estimates, forecasts and projections relating to market definition, growth rates, adoption trends and the Company's addressable market share, involves significant assumptions and judgments and is inherently subject to uncertainties and risks. Actual events, circumstances, market size and the Company's addressable share thereof may differ materially from those assumed or presented herein, based on various factors. Recipients should not place undue reliance on this information and should conduct their own independent investigation and analysis of the market opportunity described. Trademarks This presentation may contain trademarks, service marks, trade names and copyrights of the Company and other companies, which are the property of their respective owners. The use herein does not imply an affiliation with, or endorsement by, the owners of these trademarks, service marks, trade names and copyrights. Third-party logos herein may be provided simply for illustrative purposes only. Inclusion of such logos does not necessarily imply affiliation with or endorsement by such firms or businesses. There is no guarantee that the Company will work, or continue to work, with any of the firms or businesses whose logos are included herein in the future. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Forward-looking statements The study database has not been locked as this is an ongoing study, and the data are subject to further cleaning and validati on. This presentation contains forward-looking statements about Fractyl Health, Inc. (“Fractyl” or “the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact are forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this presentation include, without limitation, statements regarding: the expected initiation, timing, design, endpoints, site activation, and conduct of the REMAIN-1 clinical trial program; Fractyl’s regulatory strategy, including submissions to and communications with regulators; the promise, potential impact, and mechanism of action of the Revita DMR system and Fractyl’s Revita platform; Fractyl’s anticipated financial performance, including cash and cash equivalents, for any period of time; Fractyl’s expected cash runway; the promise and potential impact of Fractyl’s preclinical or clinical trial data and product candidates, including Revita’s potential for maintaining weight loss after glucagon-like peptide (GLP-1) based therapy discontinuation; the design, initiation, timing and results of clinical enrollment and any clinical studies or readouts, including readouts from the REVEAL-1 Cohort, the REMAIN-1 Midpoint Cohort and the REMAIN-1 Pivotal Cohort; the content, information used for, timing or results of any Investigational New Drug (IND)-enabling studies, IND applications, or CTAs; communications with regulators regarding the REVEAL-1 Cohort, the potential launch or commercialization of any of Fractyl’s product candidates or products, the REMAIN-1 Midpoint Cohort and the REMAIN-1 Pivotal Cohort; the potential treatment population or benefits for any of Fractyl’s product candidates or products; Fractyl’s regulatory strategy, including potential use and benefits of the De Novo pathway (U.S. Food and Drug Administration (FDA) pre-submission feedback is advisory and non-binding, and there is no assurance that FDA will accept a De Novo marketing application submission or that the Revita DMR System will receive marketing authorization); Fractyl’s commercial readiness activities and the development of commercial infrastructure; Fractyl’s strategic and product development objectives and goals; the potential sales and estimated total addressable markets, currently and in the future, for Fractyl's product candidates; the potential timeline for profitability following the launch of Revita;’ and the timing of any of the foregoing. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause Fractyl’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the fact that Fractyl’s product candidates may cause serious adverse events or undesirable side effects or have other properties that may cause it to suspend or discontinue clinical studies, delay or prevent regulatory development, prevent their regulatory approval, limit the commercial profile, or result in significant negative consequences; additional time may be required to develop and obtain regulatory approval or certification for Fractyl’s Revita candidates; Fractyl’s reliance on third parties to conduct certain aspects of Fractyl’s preclinical studies and clinical studies; Fractyl’s reliance on third parties for the manufacture of the materials for its Rejuva gene therapy platform for preclinical studies and its ongoing clinical studies; the regulatory approval process of the FDA, comparable foreign regulatory authorities and lengthy, time-consuming and inherently unpredictable, and even if Fractyl completes the necessary clinical studies, Fractyl cannot predict when, or if, it will obtain regulatory approval or certification for any of its product candidates, and any such regulatory approval or certification may be for a more narrow indication than we seek; and the potential launch or commercialization of any of Fractyl’s product candidates or products and Fractyl’s strategic and product development objectives and goals. These and other risks are discussed more fully in Fractyl’s filings with the Securities and Exchange Commission (the SEC), including the “Risk Factors” section of Fractyl’s Annual Report on Form 10-K for the year ended December 31, 2025, filed with the SEC on March 24, 2026, and other documents Fractyl subsequently files with or furnishes to the SEC, including Fractyl’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2026, filed with the SEC on August 10, 2026. These forward-looking statements are based on management’s current estimates and expectations. While Fractyl may elect to update such forward-looking statements at some point in the future, Fractyl disclaims any obligation to do so, even if subsequent events cause Fractyl’s views to change. 2
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Today’s speakers and agenda ©2026 Fractyl Health, Inc. All Rights Reserved. Harith Rajagopalan, MD, PhD Co-Founder & CEO Lara Smith Weber CFO Mike Zumdahl Sr VP of Market Access & Commercial Strategy Revita: the problem, the opportunity, and the evidence Center of Excellence strategy and Market Access Folahan Ayoola, MD, FACS, FASMBS Medical Director, Bariatric Surgery Texas Health in Flower Mound Metabolic interventionalist’s view on the unmet need in post-GLP-1 patients Commercial model and path to profitability 3
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©2026 Fractyl Health, Inc. All Rights Reserved. Revita: the problem, the opportunity, and the evidence Harith Rajagopalan, MD, PhD Co-Founder & CEO 4
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Revita highlights A one-time outpatient procedure targeting the biggest unmet need in obesity ©2026 Fractyl Health, Inc. All Rights Reserved. The problem is maintenance, not weight loss. Most patients discontinue GLP-1s within a year; there is no approved off-ramp. Existing randomized and open-label data show a durable signal. Encouraging results from REVEAL-1 and Midpoint 12 month data. Pivotal 6 mo topline is early Q4. The pivotal is built to support a De Novo filing beginning in late Q4 2026. Class II path, one registrational study, FDA Breakthrough Device. The commercial build is activation, not market creation. Patients, physicians, rooms, and obesity-procedure payment already exist in a finite set of Centers of Excellence (COEs.) Payment work is already in motion. Coding, coverage, Transitional Pass-Through (TPT) with favorable tailwinds in payer landscape supporting reimbursement strategy. We believe a focused COE launch can reach profitability 5–8 quarters after launch. Potentially high gross margin disposable sale without a large field force. 5
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GLP-1s unlocked weight loss, but durability remains unsolved 1KFF Health Tracking Poll, Nov 2025: ~1 in 8 adults currently on a GLP-1 2Rodriguez, Patricia J., et al. JAMA Network Open 8.1 (2025): e2457349-e2457349. 3Aronne et al. JAMA. 2023 Dec 11;331(1):38–48. 4Revita is currently being studied under an open Investigational Device Exemption (IDE) in the U.S. and holds FDA Breakthrough Device designation for weight maintenance in patients discontinuing GLP-1 therapy. Abbreviations: GLP-1, glucagon-like peptide-1; wk, week. ©2026 Fractyl Health, Inc. All Rights Reserved. Estimated U.S. patients on GLP-1s1 Patients regain lost weight after GLP-1 discontinuation3 ~29M 85% Percent change in body weight (week 0-88) from the SURMOUNT-4 Study3 Overall mean baseline body weight = 107.3 kg Tirzepatide PlaceboTirzepatide lead-in Change in Body Weight, % Time After Start of Lead-in Period, wk -9.9 -25.3 -9.5 -25.8 The next phase of obesity care will be defined by weight maintenance, not weight loss No FDA-approved therapies for post-GLP-1 weight maintenance 6
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Discontinuation is the rule Real-world persistence data reveals a systemic pattern, not individual failure Abbreviations: RA, receptor agonist; TBWL, total body weight loss; T2D, type 2 diabetes. 1. Rodriguez et al., JAMA Netw Open 2025;8(1):e2457349 ~65% of patients without T2D discontinue GLP-1 RA within 1 year1 Real-world persistence for GLP-1RAs in non-T2D1 1 Initiation 2 Weight loss 3 Discontinuation 4 Rapid regain ©2026 Fractyl Health, Inc. All Rights Reserved. 7
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Patient journey post-GLP-1 Patients and physicians are looking for a durable non-drug off-ramp that does not yet exist ©2026 Fractyl Health, Inc. All Rights Reserved. 220 lbs Starting weight 176 lbs Post-GLP-1 - 44 lbs GLP-1 Run-in on GLP-1 Do I have to be on this forever? ‹ I don't want a shot for life. ‹ Why is this lifelong therapy? Will the weight come back? ‹ Will I gain all of it back? ‹ How fast? weeks or months? Can I get off it more gently? ‹ Can I taper or microdose? ‹ Is it safe to just stop? What are my non-drug options ‹ Anything besides another drug? “What’s next for me?” 8
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A one-time, outpatient procedure to ablate duodenal mucosa for durable weight maintenance Revita is for investigational use only in the United States. Revita has a CE mark in the EU/UK. ← CONSOLE A single outpatient endoscopic procedure Designed to complement pharmacology FDA Breakthrough Device designation Robust IP portfolio protecting first-mover leadership Revita ® Revita: a potential new backbone therapy in obesity ©2026 Fractyl Health, Inc. All Rights Reserved. 9
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Revita Duodenal Mucosal Resurfacing (DMR) procedure Entire length of the post-papillar duodenum is treated through two primary actions: (A) Circumferential saline lift • Balloon engages tissue • Vacuum pulls mucosa into ports • Needle injects saline into submucosa (B) Hydrothermal ablation • Controlled hot water creates precise ablation at each lift site • Steps repeated along full duodenal length (>14cm) Revita is for Investigational Use Only under US Law Utilizes familiar skills, does not alter patient’s anatomy, complements other approaches Utilizes familiar skills. No implant or anatomy alteration. Does not preclude any other therapeutic option. Catheter engages tissue Vacuum pulls mucosa into catheter ports Saline injection to submucosa Hydrothermal ablation ©2026 Fractyl Health, Inc. All Rights Reserved. 10
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Sham-controlled pilot REMAIN-1 Midpoint Cohort (n ≈ 45) Randomized, double-blind, sham controlled • Tirzepatide run-in phase • Revita vs sham (2:1) With obesity (BMI 30-45 kg/m2) without T2D and GLP-1 drug naïve • 3-mo data: Sept '25 6-mo data: Jan '26 • 1-yr data: Q3 ‘26 REMAIN-1 weight maintenance program Stepwise validation through potential De Novo marketing application submission in late Q4 261 1These forward-looking statements are based on management’s current estimates and expectations. Refer to the latest disclosures filed with the SEC for a discussion regarding Risk Factors to these and other estimates and expectations. Abbreviations: BMI, body mass index; GLP-1, glucagon-like peptide-1; T2D, type 2 diabetes; TBWL, total body weight loss. ©2026 Fractyl Health, Inc. All Rights Reserved. Open-label exposure REVEAL-1 Cohort (n ≈ 20) Rationale Post-GLP-1 weight maintenance in a real-world setting Design • Open-label Participants With obesity (BMI > 30 kg/m2) prior to GLP-1 and >15% TBWL with GLP-1 drug Anticipated milestones1 • 3-mo data: June '25 • 6-mo data: Dec '25 1-yr data: Q2 ’26 Sham-controlled pivotal REMAIN-1 Pivotal Cohort (n ≈ 315) Randomized, double-blind, sham- controlled • Tirzepatide run-in phase • Revita vs sham (2:1) With obesity (BMI 30-45 kg/m2) without T2D and GLP-1 drug naïve • Enrollment: Q2 '25 Randomization: Feb ‘26 • Topline 6-mo data: early Q4 ‘26 • Potential De Novo marketing application submission: late Q4 ‘26 • Topline 1-yr data: 1Q ‘27 11
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Sham-controlled pilot REMAIN-1 Midpoint Cohort (n ≈ 45) REMAIN-1 Weight maintenance clinical trial program Stepwise validation through three ongoing clinical cohorts under investigation1 1. https://ir.fractyl.com/news-releases/news-release-details/fractyl-health-reports-positive-one-year-reveal-1-open-label 2. https://ir.fractyl.com/news-releases/news-release-details/fractyl-health-reports-positive-randomized-data-remain-1 ©2026 Fractyl Health, Inc. All Rights Reserved. Open-label exposure REVEAL-1 Cohort (n ≈ 20) Sham-controlled pivotal REMAIN-1 Pivotal Cohort (n ≈ 315) Revita is for Investigational Use Only under US Law Up to 84% of GLP-1 induced weight loss retained with Revita® versus 46% with sham at one year in patients receiving complete duodenal ablations 2 Participants retained ~78% of GLP-1 induced total body weight loss one year after discontinuation and a single Revita procedure1 Topline 6-mo data: early Q4 ’26 Topline 1-yr data: 1Q ‘27 12
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REMAIN-1 midpoint cohort at 1 year Clinically meaningful effect size 1Complete ablation population in REMAIN-1 Midpoint Cohort. ©2026 Fractyl Health, Inc. All Rights Reserved. Revita DMR Weight after 1 year with no GLP-1 Revita is for Investigational Use Only under US Law 220 lbs Starting weight - 44 lbs GLP-1 5-month run-in on GLP-1 Mean results as illustrative example1 81% Weight loss maintained 184 lbs 8 lbs 48% Weight loss maintained 199 lbs 23 lbs 176 lbs Post-GLP-1 Sham 13
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Midpoint cohort: favorable safety through 12 months No device-related serious AEs: a mild, periprocedural profile that supports outpatient use Exploratory REMAIN-1 Midpoint Cohort analysis; not powered for formal inference. *1 SAE: blocked bile duct (Grade IIIb, day 65); unrelated to device or procedure. **2 Grade 2 AEs: Revita worsening hypertension (day 258); Sham urinary tract infection (day 239); both unrelated. Related TEAEs = probably related to device/procedure; all Grade 1, onset day 0. Two Sham AEs previously ungraded in EDC: nausea (day 0), Type 2 diabetes (day 363) are now classified Grade 1.REMAIN-1 Stage 2a, through 52 weeks (12 months). Abbreviations: AE, adverse event; TEAE, treatment-emergent adverse event; SAE, serious adverse event. ©2026 Fractyl Health, Inc. All Rights Reserved. • No new device-related TEAEs between 6 and 12 months • No device-related SAEs: one SAE (blocked bile duct) adjudicated as unrelated to the device or procedure • No excess AEs with Revita: any-TEAE rates matched sham (24% vs 25%) • Mild and periprocedural: all 4 related events were Grade 1, on procedure day, and transient • 1 new diagnosis of Type 2 Diabetes in sham arm vs zero in Revita arm Treatment-Emergent Adverse Events Revita (n = 29) Sham (n = 16) Total (N = 45) Patients experiencing any TEAE n, (%) 7 (24) 4 (25) 11 (24) TEAEs by grade, n (%) 12 5 17 Grade ≥3 TEAEs 1 (8) 0 1* Grade 2 TEAEs 1 (8) 1 (20) 2** Grade 1 TEAEs 10 (83) 4 (80) 14 (82) Related TEAEs**, n 4 0 4 Abdominal discomfort 1 0 1 Nausea 1 0 1 Dry mouth 1 0 1 Sore throat 1 0 1 14
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REMAIN-1 randomized pivotal study in weight maintenance *Tirzepatide run-in modeled from SURMOUNT-4 trial. 1These forward-looking statements are based on management’s current estimates and expectations. Refer to the latest disclosures filed with the SEC for a discussion regarding Risk Factors to these and other estimates and expectations. Abbreviations: BMI, body mass index; GLP-1, glucagon-like peptide 1; R, randomization; TBW, total body weight; TBWL, total body weight loss; TZP, tirzepatide; T2D, type 2 diabetes. ©2026 Fractyl Health, Inc. All Rights Reserved. Top line results expected early Q4 2026 – de novo marketing submission to follow Patient population • Adults with obesity (BMI 30-45 kg/m2) • GLP-1 naïve; no T2D • n≈315 Co-primary endpoints • % TBW regain: Revita vs sham at 6 months and • Responder rate: % participants who maintain weight loss at 12 months Study design • Randomized (2:1 Revita vs Sham), double-blind, sham- controlled • TZP administration to achieve ≥ 15% TBWL, then discontinued • Diet and lifestyle counseling throughout Anticipated milestones1 Complete randomizations: Feb ‘26 • Topline 6-month pivotal data: Early Q4 '26 • Potential De Novo marketing application submission: Late Q4 '26 Tirzepatide initiation and titration* to achieve ≥15% TBWL Revita treatment Weight at 6 months Sham procedure Weight at 6 months Study design Discontinue TZP 2:1 R Weight at 12 months Revita is for Investigational Use Only under US Law | 15
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Co-primary endpoints well powered for pivotal trial success 1Values shown are model-based estimates (mITT MMRM at the 20% run-in weight-loss reference). REMAIN-1 Midpoint Cohort, exploratory. 2Maximum Revita weight regain at which the pivotal reaches statistical significance vs the sham scenario shown (~ 2.5-point gap at pivotal N=315). 35.1% = LS-mean percent total body-weight regain from post-run-in baseline at 6 months (Week 26); mITT MMRM at 20% run-in weight-loss reference; n=29 Revita. REMAIN-1 Midpoint Cohort, exploratory. 4Two-sided; Revita vs sham, pivotal N=315, randomized 2:1 (Revita:sham). Sham values illustrative. Abbreviations: LS-mean, least-squares mean; mITT, modified intention-to-treat; MMRM, mixed-model repeated measures; TBW, total body weight; TBWL, total body weight loss; . ©2026 Fractyl Health, Inc. All Rights Reserved. Illustrative sham 6-mo regain in mITT1 Revita regain needed to win1,2 Observed in midpoint cohort1,3 Projected pivotal p-value4 10% ≤ 7.4% 5.1% p<0.05 11.6% (base case, current) ≤ 9.0% 5.1% p<0.05 12.5% ≤ 9.9% 5.1% p<0.05 First co-primary: % TBW regain: Revita vs sham at 6 months Second co-primary: Responder rate: % of Revita patients maintain > 5% TBWL at 12 months 50% = FDA-mandated pre-specified performance goal (single-arm) 73% in midpoint cohort in mITT population1 (~91% in the Complete Ablation Cohort) 16
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Advancing toward a more efficient US regulatory path FDA pre-submission feedback received; de novo submission planned late Q4 2026 1These forward-looking statements are based on management’s current estimates and expectations. Refer to the latest disclosures filed with the SEC for a discussion regarding Risk Factors to these and other estimates and expectations 2FDA pre-submission feedback is advisory and non-binding, and there is no assurance that FDA will accept a De Novo marketing application submission or that the Revita DMR System will receive marketing authorization Source: FDA device classification regulations (21 CFR); FDA device classification regulations (21 CFR). Both De Novo and PMA pathways require demonstration of reasonable assurance of safety and effectiveness. Abbreviations: FDA, Food and Drug Administration; PMA, premarket approval. ©2026 Fractyl Health, Inc. All Rights Reserved. • Received favorable pre-submission feedback from the FDA in March 2026 • Safety profile of the Revita DMR System is consistent with a Class II (de novo) device classification • One pivotal study is the registrational package • A successful de novo would make Revita the reference device for the category • Company intends to submit de novo marketing application in late Q4 20261,2 De novo classification PMA (premarket approval) Intended device risk Class I or II (low to mid risk) Class III (high risk) Clinical evidence required “Reasonable assurance of safety and effectiveness” “Valid scientific evidence” Statutory FDA review timeline 150 FDA days 180 FDA days Downstream optionality Creates predicate for future 510(k)s No predicate created Capital efficiency Potentially more capital-efficient Potentially capital-intensive FDA regulatory pathways: De novo vs. PMA 17
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Potential pathway from de novo filing to commercial launch Illustrative review path Illustrative only; durations are assumptions, not FDA commitments. FDA days are calendar days between receipt and decision, excluding time on hold for an Additional Information request; the acceptance review falls within that count. Under MDUFA V the goal is a decision within 150 FDA days for 70% of De Novo requests. A refusal to a ccept would restart the clock. Timing of TPT, coverage and launch is not assured. 15 days Acceptance review Completeness check 75 days Substantive review Review runs until FDA issues an Additional Information request CLOCK STOPPED Pause for additional information Clock stops; up to 180 days allowed 75 days Review to decision Clock restarts on our response, through to FDA decision ~4 months Launch preparation TPT effective, hospital contracts signed, consoles placed Potential De Novo clearance ©2026 Fractyl Health, Inc. All Rights Reserved. 18
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One metabolic reset, three potential use cases in obesity Illustrative, forward-looking expansion framework contingent on pivotal success and future studies; not FDA-assessed. Timelines are management estimates. Subject to the risks described in the Company's SEC filings. ©2026 Fractyl Health, Inc. All Rights Reserved. Illustrative and hypothetical; schematic, not clinical data; contingent on pivotal results Step 1 · Prove it Step 2 · Combine Step 3 · Front line Maintenance after GLP-1 Adjunct to orals, injectables, procedures Front-line, drug-free Off-ramp: preserve weight and metabolic benefit after discontinuation Add-on: Pair with drugs to deepen and sustain response, enabling lower doses, drug holidays, and durable step- down Kick-start : An earlier one-time option for patients who can't tolerate, afford, or stay on chronic drugs. untreated Revita stop GLP-1 GLP-1 discontinuation Revita Weight Revita + GLP-1 GLP-1 alone Revita added 19
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©2026 Fractyl Health, Inc. All Rights Reserved. A metabolic interventionalist’s perspective on the unmet need in post-GLP-1 patients Folahan Ayoola, MD, FACS, FASMBS Medical Director, Bariatric Surgery Texas Health in Flower Mound 20
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©2026 Fractyl Health, Inc. All Rights Reserved. Commercial Strategy and Market Access Mike Zumdahl Sr VP of Market Access & Commercial Strategy 21
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The potential commercial build is an activation exercise in centers that are already prepared ©2026 Fractyl Health, Inc. All Rights Reserved. Open high-quality centers High-volume metabolic centers already exist today and are built for Revita Select appropriate patients Motivated GLP-1 discontinuers are already in the interventionalists’ clinic Perform great procedures Leverage interventionalists’ skillset and validated Revita training program Secure payment Align patient, provider, payer, and Fractyl economics 22
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U.S. adults on a GLP-1 for weight loss1 ~29M Discontinue within ~12 months2 ~18.8M × 65% Achieved ≥15% TBWL before stopping3 ~5.7M × 30% Eligible (BMI 30–45)4 ~4.0M × 70% Bars: ⚫ share of prior step retained (point estimate) ~4M eligible patients for Revita translates to $40-120B opportunity* US GLP-1 users → patients clinically eligible for Revita (post-GLP-1 weight maintenance) * TAM is an internal figure developed by management based on certain assumptions that management believes to be reasonable as of the date hereof. Please refer to the disclaimer titled "Market Data, Estimates and Industry Information" set forth on Slide 2 of this presentation.1Gallup 2026 — ~11% of ~262M US adults currently on a GLP-1 for weight loss. 2 65% discontinuation rate is for individuals without T2D - Rodriguez et al., JAMA Netw Open 2025;8(1):e2457349. 330% base · Monte Carlo median 29.3% based on Fractyl market estimates. 4On-label BMI 30–45 (~70%; RWE / Fractyl est.) Abbreviations: TAM, total addressable market ~4M eligible patients ~$40–120B TAM @ estimated cost of 10K – $30k / procedure ©2026 Fractyl Health, Inc. All Rights Reserved. 23
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Ready centers already have necessary infrastructure ─ only missing the GLP-1 off-ramp ©2026 Fractyl Health, Inc. All Rights Reserved. Already in place • Comprehensive metabolic program • Metabolic interventionalists who already manage GLP-1 patients • Nutrition and lifestyle counseling • Prior-authorization machinery • Endoscopy and fluoroscopy suite time • The interventional skillset • Registry participation Still missing An approved, reimbursed, durable off-ramp procedure 24
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Targeted and efficient COE launch strategy Focused on top 10-20% high volume comprehensive metabolic centers across the U.S. Locations approximated from the ASMBS center locator. Illustrative. 1 https://www.facs.org/quality-programs/accreditation-and-verification/metabolic-and-bariatric-surgery-accreditation-and-quality-improvement-program/ ~1,000 Accredited centers, U.S. and Canada1 100–200 Early launch starts with top 10–20% of potential COEs First wave includes Revita clinical centers and established ASMBS COEs ©2026 Fractyl Health, Inc. All Rights Reserved. 25
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Precision launch: depth before breadth High-touch activation of ready sites Phase 1 centers include REMAIN-1 trial sites, Everself (Bariendo) centers, and ASMBS Centers of Excellence [overlapping set of criteria] ©2026 Fractyl Health, Inc. All Rights Reserved. Phase 1 Phase 2 Phase 3 Year 1 30–50 highest-readiness centers of excellence: trial sites and centers already in dialogue Year 2 60-90 centers: early sites become regional training and referral hubs Year 3 onward 100-200 centers: at scale, representing 10- 20% of potential COE distribution Broader rollout as the procedure becomes routine and coverage solidifies Training, pathway integration, economic proof Replication of a proven pathway Scale on established policy 26
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Revita is delivered by metabolic interventionalists Proceduralists who already treat obesity with procedures and manage patients in clinic 1Physician counts are company estimates of the addressable operator pool. 300–400 GI endoscopists with bariatric practices1 2–3K Bariatric surgeons1 Physicians who already have these patients in their own obesity clinics Motivated proceduralists Expected revenue per physician is high and recurring A finite, nameable target list A field force of tens, not hundreds ©2026 Fractyl Health, Inc. All Rights Reserved. 27
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Initial target centers GLP-1 patients/center/year Potential procedures /center/year Site-level volume potential is material and credible 1. Company estimates 100–200 High-volume systems >2000 Patients at ready COEs1 250–500 Procedures during ramp1 ©2026 Fractyl Health, Inc. All Rights Reserved. 28
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Training is short and built on existing endoscopic skills REMAIN-1 protocol training requirements REMAIN-1 trial: • Half-day didactic + ~4 cases with Fractyl clinical specialist for physician & staff proficiency • Protocol-defined technical success = complete ablation of entire duodenum (>14 cm ablation covering the post-papillary duodenum) ©2026 Fractyl Health, Inc. All Rights Reserved. 29
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Three reimbursement tracks all underway * CPT, APC, and TPT outcomes are subject to AMA and CMS review cycles and are not assured. Abbreviations: APC, ambulatory payment classification; MAC, Medicare administrative contractor; NCD, national coverage determination; OPPS, outpatient prospective payment system. ©2026 Fractyl Health, Inc. All Rights Reserved. 1. Coding 2. Coverage 3. Payment • Filed: CPT Category III application submitted Jun'26 • Category III CPT code: Anticipate going into effect in 2027 • Medicare: Leverage FDA Breakthrough Designation and TCET/RAPID pathways to aim for early national coverage aligned with timing of FDA approval/clearance • Commercial: Medical policy informed by value dossier & HEOR. 3rd party prior auth/appeal support planned to facilitate early coverage with commercial payers • Facility: Potential Transitional Pass-Through (TPT)* to make hospitals whole on day one • Physician: professional payment established through CPT valuation over time 30
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Major payers already cover obesity procedures Bariatric surgery + GLP-1 coverage provide tailwinds for potential Revita coverage 1Total U.S. medical enrollment, all lines — Mark Farrah Associates / Peterson–KFF, 2025; CMS row is Medicare Part D enrollment, not commercial. 2Obesity indication; PA + employer election typically required (CVS Caremark 7/25; Evernorth 5/25). 3Payer commercial medical policies; typical criteria BMI ≥40 or ≥35 + comorbidity (UnitedHealthcare policy, 2026). 4Medicare GLP-1 Bridge: CMS §402 demonstration, Jul 1 2026–Dec 31 2027, outside Part D payment flow; $50/mo copay, central processor for PA (CMS, 2026). BALANCE Model indefinitely delayed. Bariatric surgery per NCD 100-1.1. ©2026 Fractyl Health, Inc. All Rights Reserved. Payer 2025 commercial lives¹ GLP-1s for obesity² Bariatric surgery³ ~35M Prior Auth + opt-in Covered ~30M Prior Auth + opt-in Covered ~20M Prior Auth + opt-in Covered ~14M Prior Auth + opt-in Covered ~18M Prior Auth + opt-in Covered ~190M lives sit with the six payers already reimbursing bariatric surgery CMS (Medicare) ~68M4 GLP-1 Bridge Covered 31
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Medicare alone is a multi-billion dollar opportunity GLP-1 Bridge program may create a massive discontinuation pool Revita is designed to help 1https://www.kff.org/medicare/nearly-four-million-medicare-beneficiaries-met-the-eligibility-criteria-in-2023-for-the-medicare-glp-1-bridge . 2CBO estimates 65% discontinuation - Publication 60441. 3Company estimates 510K – 830K CMS beneficiaries eligible for Revita & TPT3 ~4M Medicare beneficiaries expected to access GLP-1s through the Bridge1 2–3M expected to discontinue within a year | Bridge expires 12/31/20272 600–970K an estimated will achieve a deep response before stopping3 ©2026 Fractyl Health, Inc. All Rights Reserved. 32
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Highly cost-effective Payer’s willingness to pay (good-value range) Poor value Dominant ICER due to ~$10K ASPESG vs semaglutide (5 yr) * Revita can be highly cost-effective even at higher end of modeling REVITA (modeled at $10–30K ASP) $21kBariatric surgery (lifetime) $28kLAAC/Watchman (5–10 yr) $50kTAVR (vs med Rx/SAVR) $56kTEER/MitraClip (COAPT) $135kGLP-1s for obesity (net price) $171kPCI, stable angina (vs meds) $0k $25k $50k $75k $100k $125k $150k $175kCost- saving Incremental cost-effectiveness ratio ($ per QALY gained) We believe Revita's modeled cost-effectiveness is highly favorable: Better cost per QALY than widely covered CV procedures, bariatric surgery, and comparable to ESG-vs-GLP-1 at lower ASP Based on published cost to payers and cost-effectiveness benchmarks for obesity therapies and other device-based interventions A one-time procedure that maintains post-GLP-1 weight loss can be highly cost-effective Sources: JAMA Netw Open 2024 (ESG vs semaglutide, dominant at ~$10K ASP); ACS Clinical Congress 2024 & lifetime CE literature (bariatric surgery $10k–$25k/QALY); Stroke 2018 / PROTECT AF (LAAC); PARTNER economic substudies (TAVR); COAPT (TEER); ICER 2025 net-price review (GLP-1s); COURAGE (PCI). Revita value is internal model, not peer -reviewed. IVL omitted — no published ICER. Cross-study comparisons are directional: populations, comparators, & horizons differ. ©2026 Fractyl Health, Inc. All Rights Reserved. 33
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The commercial field team is potentially tens of people, not hundreds ©2026 Fractyl Health, Inc. All Rights Reserved. Open high-quality centers Business development managers focused on site selection and activation Select appropriate patients Account managers focused on site execution and procedure growth Perform great procedures Clinical specialists focused on clinical excellence and outcomes Secure payment HEMA experts focused on payer engagement, prior authorization, and billing support 34
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©2026 Fractyl Health, Inc. All Rights Reserved. The model and path to profitability Lara Smith Weber CFO 35
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Company Focus Key quantitative signals Investor outcome Inari (VTE) Specialized interventional centers; LimFlow → ~2002 high-vol COEs Rapid account growth then deeper penetration; >50 of ~200 target COEs accessed in year 1 for LimFlow2 Stryker, $4.9B – ~8x sales3,10 $277M1 → $603M2 (30% CAGR) Shockwav e (IVL) High-volume PCI centers (>750 PCIs/yr) 5 1–1.5 new accounts/ territory/month; reorder rates 83–92% quickly; majority of targets in ~2 yrs5 J&J, $13.1B – ~14x sales6,10 $237M4 → ~ $920M4 (~ 57% CAGR) Watchman (LAAC) Structural/EP centers Median hospital vols ~40– 70/yr (high-vol quartile >100) 7,8; programs scale to hundreds; >700 programs, >500k pts9 Boston Scientific, Revenue quickly scaled past $1B a year9 Precedent: Focused high-volume CoE launches work Sources : 1. Inari FY2021 results, 23 Feb 2022. 2. Inari Q3 2024 earnings call, 29 Oct 2024. 3. Stryker press release “Stryker completes acquisition of Inari Medical, Inc.“ 19 Feb. 2025. 4. Shockwave FY2021 results, 17 Feb 2022; FY2023 results and FY2024 guidance. 5. Shockwave quarterly earnings calls, 2021–2022. 6. J&J press release, 5 Apr 2024. 7. Freeman et al., JACC 2020;75:1503 (NCDR LAAO Registry). 8. Friedman et al., Circ Cardiovasc Interv 2024;17:e013466. 9. Boston Scientific 2024 Annual Report; BSX quarterly earnings calls. 10. Revenue multiples calculated on forward revenue — Inari FY2024 (~$603M), Shockwave FY2024 guidance midpoint ($920M). What drives value for shareholders • Finite list of high- volume centers • Deep utilization per site • Strong growth ©2026 Fractyl Health, Inc. All Rights Reserved. 36
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Revita pricing corridor Bracketed by the endoscopic and surgical benchmarks that payers already pay ¹ ESG Lower bound is the CY2026 Medicare national average in the hospital outpatient setting: $10,860 facility (OPPS APC 5362, a Comprehensive APC — device cost is bundled, not separately paid; CMS-1834-FC) plus $720 physician (PFS at a $33.40 conversion factor; CMS-1832-F), before the 2% sequestration reduction. Upper bound is the published US self-pay range for ESG, typically $8,000–$15,000 as a bundled package. ² Bariatric surgery Lower bound is CY2026 Medicare for an uncomplicated laparoscopic sleeve gastrectomy: MS-DRG 621 at $10,976 (IPPS) plus $1,000 physician (CPT 43775); MS-DRG 619 with a major complication or comorbidity pays $21,011. Upper bound is self-pay and uninsured list pricing from published market surveys — a charge, not a payer-allowed amount. Published commercial episode payments sit materially below it. Endoscopic sleeve gastroplasty ~$11,600¹+ CPT 43889 – APC 5362 Category I code effective Jan 1, 2026 Medicare, hospital outpatient $10,860 facility + $720 physician Self-pay market $8,000 – $15,000, bundled Revita DMR Pricing to be determined Outpatient endoscopic Under one hour, same-day discharge No resection or anatomic change Repeatable; no permanent implant Duodenal target Distinct mechanism from restriction Bariatric surgery Up to $33,0002 Sleeve gastrectomy, CPT 43775 Inpatient only under Medicare Commercial/uninsured $20,000 – $33,000 ©2026 Fractyl Health, Inc. All Rights Reserved. 37
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Potentially attractive unit economics at the center and at the company Unit economics potentially favorable for hospital and Fractyl Hospital economics assume pass-through plus facility payment. ©2026 Fractyl Health, Inc. All Rights Reserved. Recurring, high-margin procedure revenue concentrated in high-throughput centers The hospital's view Fractyl’s view • Endoscopy and bariatrics are major drivers of hospital contribution margin • TPT enables positive contribution margin by passing disposable costs through to CMS • No new capital footprint to justify • High gross margin of ~80% • Capital-light: no high cost, long lead-time sales cycle per site • Commercial cost scales with sites, not linearly with volume 38
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Potential launch expected early 2028: Center-led ramp with ~1,600– 3,000 procedures by EOY 2028 and 5,000–10,000 procedures in 2029 1. Figures presented are management estimates contingent on pivotal results and on FDA marketing authorization, neither of which is assured, and they are not guidance 18 30 45 60 25 50 70 90 2028 H1 2028 H2 2029 H1 2029 H2 Centers live (cumulative)1 Low–high range 500 1,100 2,000 3,000 900 2,100 4,000 6,000 2028 H1 2028 H2 2029 H1 2029 H2 Procedures (per half-year)1 Low–high range Centers of excellence1 30-50 live at the end of 2028 60-90 live at the end of 2029 Procedure volume1 1,600 to 3,000 procedures in 2028 5,000 to 10,000 procedures in 2029 ©2026 Fractyl Health, Inc. All Rights Reserved. 39
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Potential Revita unit economics and breakeven Potential 80% gross margin leads to cash break even 5-8 quarters after launch Price benchmarks: CY2026 Medicare national averages (OPPS APC 5362; IPPS MS-DRG 621) and a derived private-payer estimate. Gross margin, operating cash run-rate and center productivity are Fractyl assumptions. Break even quarters are contingent on De Novo authorization, coverage and financing, and are not guidance. Price per procedure $11–33K Published benchmark range ESG: $11,600 Medicare Bariatric: $20,000 private payer Bariatric: $33,000 self-pay list × Gross margin at scale ~80% Held constant across scenarios Margin held flat across scenarios rather than modeled; higher-ASP cases would carry higher margin and earlier break- even than shown Procedures to breakeven 80% gross margin, $22M quarterly operating cash burn ASP GP/proc Procedures/qtr Break-even $10,000 $8,000 2,750 2H 2029 $20,000 $16,000 1,375 1H 2029 $30,000 $24,000 920 Q1 2029 Every date assumes De novo approval in late 2027 ─ CMS coverage and transitional pass-through early 2028 ©2026 Fractyl Health, Inc. All Rights Reserved. 40
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Clear commercial strategy to potential cash profitability within 5–8 quarters of launch Timelines are management estimates and forward-looking; actual events may differ. Revita is investigational — commercialization is subject to REMAIN-1 results and FDA marketing authorization, neither of which is assured. 41 Commercial strategy day Pivotal topline: 315-patient, 6-month randomized trial Potential FDA de novo submission Potential FDA clearance and launch prep Anticipated U.S. commercial launch with TPT in place ©2026 Fractyl Health, Inc. All Rights Reserved. Cash profitability expected Late 2027 Early 2028 2029Today Early Q4 2026 Late Q4 2026
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Revita highlights A one-time outpatient procedure targeting the biggest unmet need in obesity ©2026 Fractyl Health, Inc. All Rights Reserved. The problem is maintenance, not weight loss. Most patients discontinue GLP-1s within a year; there is no approved off-ramp. Existing randomized and open-label data show a durable signal. Encouraging results from REVEAL-1 and Midpoint 12 month data. Pivotal 6 mo topline is early Q4. The pivotal is built to support a De Novo filing beginning in late Q4 2026. Class II path, one registrational study, FDA Breakthrough Device. The commercial build is activation, not market creation. Patients, physicians, rooms, and obesity-procedure payment already exist in a finite set of Centers of Excellence (COEs.) Payment work is already in motion. Coding, coverage, Transitional Pass-Through (TPT) with favorable tailwinds in payer landscape supporting reimbursement strategy. We believe a focused COE launch can reach profitability 5–8 quarters after launch. Potentially high gross margin disposable sale without a large field force. 42
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NASDAQ:GUTS Q&A ©2026 Fractyl Health, Inc. All Rights Reserved.