# EDGAR Filing Document

**Accession Number:** 0001572616
**File Stem:** 0000950170-25-088710
**Filing Date:** 2025-6
**Character Count:** 37626
**Document Hash:** 4bfb3f7b2b8c2a2f6c42d4ca8fc2f556
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0000950170-25-088710.hdr.sgml**: 20250623

**ACCESSION NUMBER**: 0000950170-25-088710

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 12

**CONFORMED PERIOD OF REPORT**: 20250623

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20250623

**DATE AS OF CHANGE**: 20250623

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** FRACTYL HEALTH, INC.
- **CENTRAL INDEX KEY:** 0001572616
- **STANDARD INDUSTRIAL CLASSIFICATION:** SURGICAL & MEDICAL INSTRUMENTS & APPARATUS [3841]
- **ORGANIZATION NAME:** 08 Industrial Applications and Services
- **EIN:** 273553477
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-41942
- **FILM NUMBER:** 251062978

**BUSINESS ADDRESS:**
- **STREET 1:** 3 VAN DE GRAAFF DRIVE
- **STREET 2:** SUITE 200
- **CITY:** BURLINGTON
- **STATE:** MA
- **ZIP:** 01803
- **BUSINESS PHONE:** 781-902-8800

**MAIL ADDRESS:**
- **STREET 1:** 3 VAN DE GRAAFF DRIVE
- **STREET 2:** SUITE 200
- **CITY:** BURLINGTON
- **STATE:** MA
- **ZIP:** 01803

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Fractyl Health, Inc.
- **DATE OF NAME CHANGE:** 20210617

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** Fractyl Laboratories Inc.
- **DATE OF NAME CHANGE:** 20130320

?xml version='1.0' encoding='ASCII'? 8-K

**UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549**

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## **FORM** 8-K

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**CURRENT REPORT**

**Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934**

**Date of Report (Date of earliest event reported):** June 23, 2025<br>

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Fractyl Health, Inc.

**(Exact name of Registrant as Specified in Its Charter)**

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| | | |
|:---|:---|:---|
| Delaware | 001-41942 | 27-3553477 |
| **(State or Other Jurisdiction<br>of Incorporation)** | **(Commission File Number)** | **(IRS Employer<br>Identification No.)** |
| 3 Van de Graaff Drive<br>Suite 200 |  |  |
| Burlington**,** Massachusetts |  | 01803 |
| **(Address of Principal Executive Offices)** |  | **(Zip Code)** |

---

**Registrant's Telephone Number, Including Area Code:** (781) 902-8800<br>

**(Former Name or Former Address, if Changed Since Last Report)**

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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

**Securities registered pursuant to Section 12(b) of the Act:**

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| | | |
|:---|:---|:---|
| **<br>Title of each class** | **Trading<br>Symbol(s)** | **<br>Name of each exchange on which registered** |
| Common Stock, $0.00001 par value per share | GUTS | The Nasdaq Global Market |

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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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## **Item 7.01 Regulation FD Disclosure.** 
On June 23, 2025, Fractyl Health, Inc. (the "Company") issued the press releases furnished as Exhibits 99.1 and 99.2 to this Current Report on Form 8-K and incorporated herein by reference.

The information contained in Item 7.01 of this Current Report (including Exhibits 99.1 and 99.2 attached hereto) shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly provided by specific reference in such a filing.

## **Item 8.01 Other Events.** 
On June 23, 2025, the Company issued a press release announcing positive 3-month data from the open-label REVEAL-1 cohort of its ongoing REMAIN-1 pivotal study. To date, 22 participants have been treated in the REVEAL-1 Cohort, with 3-month follow-up data available for 13 individuals. At 3 months, 12 of 13 participants either lost or maintained their weight after GLP-1 discontinuation and a single Revita procedure. Notably, 6 of 13 experienced further weight loss. Median weight remained stable through 3 months, compared to the typical 5-6% rebound seen in clinical studies such as SURMOUNT-4. Only one participant experienced weight regain similar to that seen after tirzepatide withdrawal. Early signs also point to excellent weight stability following Revita procedure, with essentially no weight change between 1 and 3 months. Consistent with prior studies of Revita, the procedure was well tolerated, with no unanticipated or serious adverse effects. No new safety concerns were observed. The Company also announced that REMAIN-1 Midpoint Cohort data expected in the third quarter of 2025 and 6-month primary endpoint data from the REMAIN-1 Pivotal Cohort expected in the second half of 2026.

On June 23, 2025, the Company also issued a press release announcing new preclinical data from its Rejuva® Smart GLP-1™ pancreatic gene therapy platform, presented at the American Diabetes Association's 85th Scientific Sessions. The data demonstrated that a single dose of Rejuva was well tolerated in healthy animals and prevented obesity and hyperglycemia in animals exposed to a high-fat diet. The Company also announced that these findings support continued advancement of RJVA-001, Rejuva's first clinical candidate, toward first-in-human studies. Preliminary clinical data from RJVA-001 are anticipated in 2026.

**Forward-Looking Statements**

This Current Report on Form 8-K contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this Current Report on Form 8-K that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the promise and potential impact of our preclinical or clinical trial data, the design, initiation, timing, primary and secondary endpoints, and results of clinical enrollment and any clinical studies or readouts, the content, information used for, timing or results of any investigational new drug (IND)-enabling studies, IND applications or Clinical Trial Applications, communications with regulators, the potential launch or commercialization of any of our product candidates or products, the potential treatment population or benefits for any of our product candidates or products, and our strategic and product development objectives and goals, including with respect to enabling long-term control over obesity and type 2 diabetes without the burden of chronic therapies, redefining the future of metabolic disease treatment, positioning our Company at the forefront of the global opportunity for metabolic care, 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 the Company'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 following: the scope of protection we and/or any future licensors are able to establish and maintain for intellectual property rights covering our innovations or our product candidates; the Company's limited operating history; the incurrence of significant net losses and the fact that the Company expects to continue to incur significant net losses for the foreseeable future; the Company's need for substantial additional financing; the Company's ability to continue as a going concern; the lengthy and unpredictable regulatory approval process for the Company's product candidates; uncertainty regarding its clinical studies; the regulatory approval process of the FDA, comparable foreign regulatory authorities and lengthy, time-consuming and inherently unpredictable, and even if we complete the necessary clinical studies, we cannot predict when, or if, we will obtain regulatory approval or certification for any of our 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 Company's product candidates or products and our strategic and product development objectives and goals, and the other factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the "SEC") on May 13, 2025 and in our other filings with the SEC. These forward-looking statements are based on management's current estimates and expectations. While the Company may elect to update such forward-looking statements at some point in the future, the Company disclaims any obligation to do so, even if subsequent events cause its views to change.

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## **Item 9.01 Financial Statements and Exhibits.** 
The following exhibit relates to Item 7.01 and shall be deemed to be furnished, and not filed:

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| | |
|:---|:---|
| Exhibit<br>No. | Description |
| 99.1 | [<u>Fractyl Health, Inc. Press Release dated June 23, 2025</u>](guts-ex99_1.htm) |
| 99.2 | [<u>Fractyl Health, Inc. Press Release dated June 23, 2025</u>](guts-ex99_2.htm) |
| 104 | Cover Page Interactive Data File (embedded within the inline XBRL document) |

---

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**SIGNATURES**

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

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| | | | |
|:---|:---|:---|:---|
|  |  |  | **Fractyl Health, Inc.** |
| Date: | June 23, 2025 | By:  | /s/ Harith Rajagopalan |
|  |  |  | **Harith Rajagopalan, M.D., Ph.D.**<br>Co-Founder, Chief Executive Officer and Director<br>(Principal Executive Officer) |

---

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## Exhibit 99.1

Exhibit 99.1

**Fractyl Health Reports Positive 3-Month REVEAL-1 Cohort Data Showing Revita**<sup>®</sup> **Sustained Weight Loss After GLP-1 Discontinuation, Supporting its Potential as a First-in-Class Weight Maintenance Therapy**

*12 of 13 participants maintained or lost weight at 3 months, with 6 of 13 losing additional weight after stopping GLP-1 therapy and undergoing Revita procedure* 

*Median weight remained stable through 3 months (0.46% / ~ 1 pound weight change within the margin of error for daily weight measurement), compared to expected 5–6% weight regain (10–15 pounds) after stopping GLP-1 therapy*

*Revita continued to demonstrate excellent tolerability profile compared to GLP-1 drugs; treatment-emergent adverse effects were infrequent, mild, and transient*

*Randomized Midpoint Cohort data expected in Q3 2025; Pivotal Cohort data anticipated in H2 2026*

**BURLINGTON, Mass., June 23, 2025 (GLOBE NEWSWIRE)** – Fractyl Health, Inc. (Nasdaq: GUTS) (the Company or Fractyl), a metabolic therapeutics company focused on pattern-breaking approaches that treat root causes of obesity and type 2 diabetes (T2D), today announced positive 3-month data from the REVEAL-1 Cohort of its ongoing REMAIN-1 pivotal study. These findings suggest Revita may help people stay at their target weight or lose additional weight, even after discontinuing GLP-1 drugs, offering a potential path to durable, drug-free weight maintenance.

**<u>3-Month Outcomes in REVEAL-1 Show Strong Early Signal for Durable Weight Maintenance</u>**<br> REVEAL-1 is the open-label cohort within the ongoing REMAIN-1 pivotal study, designed to evaluate the safety, tolerability, and early efficacy signals of Revita in individuals with obesity who have lost at least 15% of their total body weight on a recently discontinued GLP-1 therapy. This cohort serves as an early clinical window into Revita's potential to support durable weight maintenance following GLP-1 discontinuation, a period of time when patients are typically vulnerable to rapid weight regain. Participants undergo a single Revita procedure in an open-label setting and receive structured diet and lifestyle support consistent with the ongoing randomized, controlled, REMAIN-1 clinical study. The insights from REVEAL-1 are intended to inform and complement data from the randomized Midpoint and Pivotal Cohorts in REMAIN-1.

To date, 22 participants have been treated in the REVEAL-1 Cohort, with 3-month follow-up data available for 13 individuals. The profile of the REVEAL-1 Cohort closely mirrors that of the REMAIN-1 Midpoint and Pivotal Cohorts, with an average age of 49 and a gender distribution of 11 women and 2 men. All participants had previously been treated with a GLP-1 therapy for durations ranging from approximately 5 months to 3 years, with a median total body weight (TBW) loss of 20.9% while on therapy. Fifteen percent of participants had pre-diabetes at baseline.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•At 3 months, 12 of 13 participants either lost or maintained their weight after GLP-1 discontinuation and a single Revita procedure. Notably, 6 of 13 experienced further weight loss.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Median weight remained stable through 3 months (TBW change of 0.46% / ~ 1 pound was within the margin of error for daily weight measurement), compared to the typical 5-6% (10–15 pounds) rebound seen in clinical studies such as SURMOUNT-4<sup>1 2</sup>. Only one participant experienced weight regain similar to that seen after tirzepatide withdrawal.

<sup>1</sup> Aronne et al. JAMA. 2024;331(1):38–48. doi:10.1001/jama.2023.24945

<sup>2</sup> Wilding et al. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Early signs also point to excellent weight stability following Revita procedure, with essentially no weight change between 1 and 3 months (median weight gain at 1 month: 0.43% and 3 months: 0.46%).

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Consistent with prior studies of Revita, the procedure was well tolerated, with no unanticipated or serious adverse effects. No new safety concerns were observed.

"There is an extraordinary unmet need in obesity treatment, which is the ability for patients to stop GLP-1 drugs without regaining weight. Currently, if patients achieve successful weight loss, but stop these medications, they regain lost weight and typically report a significant return of hunger, cravings, and food noise even when switching to another agent in the same class," said Shelby Sullivan, M.D., Professor of Medicine at the Geisel School of Medicine at Dartmouth University. "These early Revita data are better than I expected and suggest the potential to prevent the weight regain we see in practice. If these findings are sustained beyond 3 months and validated in the randomized cohort, this could become a viable solution for the many patients who would like to stop GLP-1 medications but currently can't."

**Post-Revita TBW maintenance data at 3 months were as follows:**

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| | | | | |
|:---|:---|:---|:---|:---|
| &nbsp;&nbsp;**n=13** | **Pre-GLP-1Rx**<br> **Weight (kg)**  | **Post-GLP-1Rx**<br> **TBW Change (%)** | **TBW Change** <br>**1-month Post-Procedure (%)** | **TBW Change** <br>**3 months Post-Procedure (%)** |
| **Mean** | **104.6** | **-23.0** | **0.66** | **0.84** |
| **Median** | **100.2** | **20.9** | **0.43** | **0.46** |
| **IQR** | **11.8** | **12.1** | **3.1** | **3.7** |

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"These REVEAL-1 Cohort data represent a powerful early signal of Revita's ability to sustain weight loss after GLP-1 therapy ends, which is a significant challenge in the obesity treatment landscape," said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl Health. "With over 90 percent of patients maintaining or continuing to lose weight after a single Revita procedure, we believe Revita may be uniquely positioned to define a new therapeutic area in metabolic care: post-GLP-1 weight maintenance. We are encouraged by the consistent and robust signal of weight maintenance observed in this study, and these results strengthen our confidence in Revita's potential and raise anticipation for the randomized data from the REMAIN-1 Midpoint Cohort expected in the third quarter. Alongside our Smart GLP-1<sup>TM</sup> Rejuva program, these advances underscore the depth of Fractyl's innovation strategy focused on durable, disease modifying therapies for metabolic disease."

**Available safety data at the 3-month cutoff were as follows:**

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| | | |
|:---|:---|:---|
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**n=13** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; **Patients, n (%)** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**Duration (days)** |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**Grade ≥III TEAEs**  | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**0 (0)** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**N/A** |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**Grade II TEAEs** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**0 (0)** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**N/A** |
| &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**Grade I TEAEs** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**3 (23)** | &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;**2-5** |

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Fractyl is advancing toward two key upcoming data readouts from its ongoing pivotal study of Revita: REMAIN-1 Midpoint Cohort data expected in the third quarter of 2025 and 6-month primary endpoint data from the REMAIN-1 Pivotal Cohort expected in the second half of 2026. Together, these clinical milestones are designed to demonstrate Revita's potential to help maintain weight loss after GLP-1 discontinuation and inform its possible role in supporting durable metabolic outcomes. Revita is being studied in an ongoing IDE-approved pivotal trial to evaluate its potential safety and efficacy in post-GLP-1 weight maintenance.

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**About Fractyl Health**

Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and T2D. Despite advances in treatment over the last 50 years, obesity and T2D continue to be rapidly growing drivers of morbidity and mortality in the 21st century. Fractyl's goal is to transform metabolic disease treatment from chronic symptomatic management to durable disease-modifying therapies that target the organ-level root causes of disease. The Company has a robust and growing IP portfolio, with 31 granted U.S. patents and approximately 40 pending U.S. applications, along with numerous foreign issued patents and pending applications. Fractyl is based in Burlington, MA. For more information, visit www.fractyl.com.

**About Revita**<sup>®</sup>

Fractyl Health's lead product candidate, Revita, is based on the company's insights surrounding the potential role of the gut in obesity. Revita is designed to remodel the duodenal lining via hydrothermal ablation (i.e. duodenal mucosal resurfacing) to reverse damage to intestinal nutrient sensing and signaling mechanisms caused by chronic high-fat and high-sugar diets that are a root cause of metabolic disease. In the U.S., Revita is for investigational use only under U.S. law. Revita has U.S. FDA Breakthrough Device designation in weight maintenance for people with obesity who discontinue GLP-1 based drugs. A pivotal study of Revita in patients with obesity after discontinuation of GLP-1 based drugs, called REMAIN-1, was initiated in the third quarter of 2024 and enrollment is now complete.

**About Rejuva**<sup>®</sup>

Fractyl Health's Rejuva platform focuses on developing next-generation adeno-associated virus (AAV)-based, locally delivered gene therapies for the treatment of obesity and T2D. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory agencies for investigational or commercial use. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeting the pancreas. The program aims to transform the management of metabolic diseases by offering novel, disease-modifying therapies that address the underlying root causes of disease. The Company has submitted the first Clinical Trial Application (CTA) module for RJVA-001 in T2D to regulators, and if the CTA is authorized, the Company expects to dose the first patients with RJVA-001 and report preliminary data in 2026.

**<br>Forward-Looking Statements**<br> This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding our anticipated financial performance, including cash and cash equivalents, for any period of time, the promise and potential impact of our preclinical or clinical trial data, the design, initiation, timing and results of clinical enrollment and any clinical studies or readouts, the content, information used for, timing or results of any Investigational New Drug (IND)-enabling studies, IND applications or Clinical Trial Applications, communications with regulators, the potential launch or commercialization of any of our product candidates or products, the potential treatment population or benefits for any of our product candidates or products, and our strategic and product development objectives and goals, including with respect to enabling long-term control over obesity and type 2 diabetes without the burden of chronic therapies, redefining the future of metabolic disease treatment, positioning our Company at the forefront of the global opportunity for metabolic care, 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 the Company'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 following: the Company's limited operating history; the incurrence of significant net losses and the fact that the Company expects to continue to incur significant net losses for the foreseeable future; the Company's need for substantial additional financing; the Company's ability to continue as a going concern; the restrictive and financial covenants in the Company's credit agreement; the lengthy and unpredictable regulatory approval process for the Company's product candidates; uncertainty regarding its clinical studies; the fact that the Company'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 the Company's Rejuva gene therapy candidates; the Company's reliance on third parties to conduct certain aspects of the Company's preclinical studies and clinical studies; the Company's reliance on third parties for the manufacture of sub-assembly components for Revita and for 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 we complete the necessary clinical studies, we cannot predict when, or if, we will obtain regulatory approval or certification for any of our 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 Company's product candidates or products and our strategic and product development objectives and goals, and the other factors discussed under the caption "Risk Factors"

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in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the "SEC") on May 13, 2025 and in our other filings with the SEC. These forward-looking statements are based on management's current estimates and expectations. While the Company may elect to update such forward-looking statements at some point in the future, the Company disclaims any obligation to do so, even if subsequent events cause its views to change.

**Contacts** 

Media Contact

Jessica Cotrone, Head of Corporate Communications

jcotrone@fractyl.com, 978.760.5622

Investor Contact

Brian Luque, Head of Investor Relations and Corporate Development

IR@fractyl.com, 951.206.1200

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## Exhibit 99.2

Exhibit 99.2

**Fractyl Health Presents New Data at the American Diabetes Association's 85**<sup>th</sup>**Scientific Sessions Demonstrating its Rejuva**<sup>®</sup> **Smart GLP-1**<sup>TM</sup>**Pancreatic Gene Therapy Platform Prevents Obesity and Type 2 Diabetes in Preclinical Models** 

 *New findings demonstrated that a single dose of Rejuva was well tolerated in healthy animals, with no evidence of toxicity*

*Rejuva-treated healthy animals exposed to a high fat diet were protected from weight gain and hyperglycemia* 

*Data reinforce advancement of RJVA-001 toward first-in-human studies; preliminary clinical data expected in 2026*

BURLINGTON, Mass., June 23, 2025 (GLOBE NEWSWIRE) – Fractyl Health, Inc. (Nasdaq: GUTS) (the Company), a metabolic therapeutics company focused on pattern-breaking approaches to treat the root causes of obesity and type 2 diabetes (T2D), today announced new preclinical data from its Rejuva Smart GLP-1 pancreatic gene therapy platform at the American Diabetes Association's (ADA) 85<sup>th</sup>Scientific Sessions. The abstract, titled "Single-Dose GLP-1-Based Pancreatic Gene Therapy Prevents Obesity and Diabetes in High-Fat Fed Mice," demonstrated that a single dose of Rejuva was well-tolerated in healthy mice, and prevented weight gain and hyperglycemia following a switch to a high-fat diet.

These findings further validate Rejuva's potential as a one-time, durable therapy with strong activity in obesity and diabetes and a favorable toxicity profile across multiple preclinical models. Importantly, these data highlight Rejuva's distinct mechanism of action, setting it apart from systemic GLP-1 receptor agonists. The Smart GLP-1 design of Rejuva enables nutrient-responsive secretion, exerting no physiologic effect under healthy metabolic conditions and only activating in the presence of metabolic stress. This targeted activity, which mimics the body's endogenous GLP-1 physiology, highlights the potential for Rejuva to offer superior potency and tolerability.

"These results underscore the transformative potential of Rejuva to offer protection from obesity and diabetes in the setting of modern environmental exposure to unhealthy diets," said Harith Rajagopalan, M.D., Ph.D., Co-Founder and Chief Executive Officer of Fractyl Health. "Unlike chronic systemic GLP-1 therapy, our approach localizes treatment to the pancreas and enables nutrient-stimulated GLP-1 secretion from beta cells, mimicking natural hormone regulation. These data support our belief that Rejuva could offer a fundamentally different risk-benefit profile in our effort to defend humanity from the inevitable metabolic diseases of modernity."

**<u>Key Findings</u>**

The study evaluated Rejuva treatment using an AAV vector designed for beta-cell-specific expression of a GLP-1 analog in four groups of mice (n=8/group). Key results include:

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•In a diet-induced obesity (DIO) model, Rejuva treatment resulted in a 20% reduction in body weight and a 38% decrease in blood glucose by day 21. These effects were maintained through the end of the study on day 37 despite continued exposure to a high-fat diet.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•In lean animals treated with Rejuva and then exposed to a high-fat diet, weight gain and hyperglycemia were fully prevented. By the end of the study, Rejuva treated animals maintained baseline body weight and showed an 8% reduction of blood glucose relative to baseline.

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;•Rejuva was well-tolerated across all treatment groups, with no signs of toxicity, excessive weight loss, or hypoglycemia in healthy animals. These findings reinforce the nutrient-responsive, self-limiting nature of Rejuva's mechanism of action, which activates only under metabolic stress and remains inactive under healthy conditions.<br>

These new preclinical results complement previously reported data showing the durable impact of Rejuva in diabetes and obesity models and further establish the platform's potential as both a therapeutic and preventative approach to metabolic disease.

**<u>Momentum Toward the Clinic</u>**

Fractyl has completed key in vivo studies for RJVA-001, its first clinical candidate from the Rejuva platform targeting T2D. Pending regulatory authorization, Fractyl expects to dose the first patients with RJVA-001 and report preliminary data in 2026, which the Company believes could lead to a potentially first-in-class, smart, durable gene therapy designed to reprogram the pancreas to deliver natural metabolic control.

**<u>Scientific Validation Backed by Leading Experts</u>**

The new study was led by an accomplished team of researchers from Fractyl Health and the University of Michigan, including renowned metabolic experts Dr. Timothy Kieffer (University of British Columbia) and Dr. Randy Seeley (University of Michigan), who bring deep expertise in gut-brain-pancreas biology and obesity pharmacology. Their involvement underscores the growing scientific momentum behind Rejuva's differentiated approach, which aims to restore physiologic GLP-1 regulation by targeting the pancreas at the source.

"Systemic GLP-1 drugs have set a high bar, but their limitations are becoming increasingly evident," said Dr. Kieffer, Scientific Advisor to Fractyl Health. "There is a need to deliver the therapeutic benefit of GLP-1 in a more physiologic, durable manner. Rejuva has the potential to meet this need by enabling sustained metabolic benefit from a single treatment."

The poster is available via the Presentations & Publications section of the Fractyl website.

**About Fractyl Health**

Fractyl Health is a metabolic therapeutics company focused on pioneering new approaches to the treatment of metabolic diseases, including obesity and T2D. Despite advances in treatment over the last 50 years, obesity and T2D continue to be rapidly growing drivers of morbidity and mortality in the 21st century. Fractyl's goal is to transform metabolic disease treatment from chronic symptomatic management to durable disease-modifying therapies that target the organ-level root causes of disease. The Company has a robust and growing IP portfolio, with 31 granted U.S. patents and approximately 40 pending U.S. applications, along with numerous foreign issued patents and pending applications. Fractyl is based in Burlington, MA. For more information, visit www.fractyl.com.

**About Rejuva**<sup>®</sup>

Fractyl Health's Rejuva platform focuses on developing next-generation adeno-associated virus (AAV)-based, locally delivered gene therapies for the treatment of obesity and T2D. The Rejuva platform is in preclinical development and has not yet been evaluated by regulatory agencies for investigational or commercial use. Rejuva leverages advanced delivery systems and proprietary screening methods to identify and develop metabolically active gene therapy candidates targeting the pancreas. The program aims to transform the management of metabolic diseases by offering novel, disease-modifying therapies that address the underlying root causes of disease. The Company has submitted the first Clinical Trial Application (CTA) module for RJVA-001 in T2D to regulators, and if the CTA is authorized, the Company expects to dose the first patients with RJVA-001 and report preliminary data in 2026.

**Forward-Looking Statements**

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements regarding the promise and potential impact of our preclinical or clinical trial data, the design, initiation, timing, primary and secondary endpoints, and results of clinical enrollment and any clinical studies or readouts, the content, information used for, timing or results of any investigational new drug (IND)-enabling studies, IND applications or Clinical Trial Applications, communications with regulators, the potential launch or commercialization of any of our product candidates or products, the potential treatment population or benefits for any of our product candidates or products, and our strategic and product development objectives and goals, including with respect to enabling long-term control over obesity and type 2 diabetes without the burden of chronic therapies, redefining the future of metabolic disease treatment, positioning our Company at the forefront of the global opportunity for metabolic care, 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 the

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Company'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 following: the Company's limited operating history; the incurrence of significant net losses and the fact that the Company expects to continue to incur significant net losses for the foreseeable future; the Company's need for substantial additional financing; the Company's ability to continue as a going concern; the restrictive and financial covenants in the Company's credit agreement; the lengthy and unpredictable regulatory approval process for the Company's product candidates; uncertainty regarding its clinical studies; the fact that the Company'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 the Company's Rejuva gene therapy candidates; the Company's reliance on third parties to conduct certain aspects of the Company's preclinical studies and clinical studies; the Company'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 we complete the necessary clinical studies, we cannot predict when, or if, we will obtain regulatory approval or certification for any of our 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 Company's product candidates or products and our strategic and product development objectives and goals, and the other factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the SEC) on May 13, 2025 and in our other filings with the SEC. These forward-looking statements are based on management's current estimates and expectations. While the Company may elect to update such forward-looking statements at some point in the future, the Company disclaims any obligation to do so, even if subsequent events cause its views to change.

**Contacts** 

Media Contact

Jessica Cotrone, Corporate Communications

jcotrone@fractyl.com, 978.760.5622

Investor Contact

Brian Luque, Head of Investor Relations and Corporate Development

IR@fractyl.com, 951.206.1200

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