Fractyl Health, Inc. Common Stock (GUTS) Earnings

Management highlights

### Core Clinical Progress for RUVIDA (Post-GLP-1 Weight Maintenance Therapy) - The 6-month data from the Remain One midpoint cohort was selected for the PRESS program at Digestive Disease Week (DDW), one of only four featured studies out of over 6,000 accepted abstracts, providing independent external validation of the company's clinical signal. - A clinical advisory board with leading gastroenterologists and metabolic physicians confirmed alignment on RUVIDA's mechanism, procedural rationale, and pivotal trial design. The company is expanding its network of clinical champions to support a future center of excellence launch model pending FDA approval. - The Remain One pivotal trial completed randomization of over 300 participants across 30 U.S. sites in February 2026, making it the largest sham-controlled GI endoscopy pivotal trial ever conducted. Participant retention exceeds 90%, medication resumption rates are below modeled assumptions, and the blinded adverse event profile remains reassuring. The trial is on track to deliver top-line 6-month primary endpoint data in early Q4 2026, with FDA de novo submission planned for late Q4 2026. - The company previously received favorable FDA feedback confirming a moderate-risk device classification for RUVIDA, rather than high-risk. ### Commercial and Reimbursement Preparation - The underlying commercial opportunity for RUVIDA has accelerated: 1 million U.S. patients discontinue GLP-1 therapies monthly, and the recent approval of the first oral daily GLP-1 and expanded public payer coverage for GLP-1s are growing the pool of patients who will eventually face post-discontinuation weight rebound. - Fractal believes RUVIDA is well-positioned to benefit from the new CMS/FDA Rapid Coverage Pathway, which aligns Medicare national coverage determination with FDA authorization for breakthrough devices, potentially accelerating reimbursement access. RUVIDA holds FDA breakthrough device designation for post-GLP-1 weight maintenance, and the company plans to file a Category 3 CPT code application in summer 2027. ### Rejuva Gene Therapy Platform Progress - Rejuva 001, the platform's first clinical candidate (a one-time beta-cell targeted AAV gene therapy for type 2 diabetes), received regulatory authorization from Dutch authorities to initiate a Phase 1/2 first-in-human study, advancing Fractal's gene therapy platform to clinical stage. - A clinical trial application has been submitted in Australia, with regulatory feedback expected in Q3 2026. Pending site activation, the first patient is expected to be dosed and preliminary data reported in H2 2026. Clinical development of Rejuva is fully funded within the company's existing cash runway. ### Capital Position - The company reaffirms it has sufficient cash to fund operations into early 2027, beyond the pivotal RUVIDA data readout and planned de novo FDA submission. The ATM facility remains closed, and no capital raise is planned before pivotal data readout.

Guidance

- Three key clinical catalysts are expected between Q2 2026 and year-end 2026: 12-month open-label data from the REVEAL-1 cohort in Q2 2026; 12-month randomized sham-controlled data from the Remain One midpoint cohort in Q3 2026; top-line 6-month data from the Remain One pivotal cohort in early Q4 2026. The full clinical profile for RUVIDA is expected to be substantially clarified by Q4 2026. - A de novo marketing application submission for RUVIDA for post-GLP-1 weight maintenance is planned for late Q4 2026, maintaining the previously guided timeline. - A CPT code application for RUVIDA is on track to be submitted in summer 2027, maintaining prior guidance. - Rejuva 001 first patient dosing and preliminary data release are expected in H2 2026, with Australian regulatory feedback expected in Q3 2026. - No capital raise is planned prior to RUVIDA pivotal data readout, and the existing cash position is expected to fund operations into early 2027, maintaining the prior capital outlook.

Segment performance

Fractal Health is a clinical-stage biotech company with two core development segments: RUVIDA (post-GLP-1 weight maintenance procedural therapy) and Rejuva (GLP-1 gene therapy platform). No commercial revenue was generated in Q1 2026, as both segments remain in clinical development. Financial performance for the quarter: Research and development expenses were $15.6 million (representing 75% of total operating expenses), SG&A expenses were $5.2 million (25% of total operating expenses). The company reported net income of $9.2 million, driven by a $30.1 million non-cash fair value adjustment to warrant liabilities that does not reflect underlying operating performance. Adjusted EBITDA was negative $18 million for Q1 2026, an improvement from negative $23 million in Q1 2025. As of March 31, 2026, total cash and cash equivalents were $63.2 million.

Risks & headwinds

- All forward-looking statements related to trial success, regulatory approval, and commercial launch are subject to inherent risks and uncertainties, which may cause actual results to differ materially from expectations. Key risks are detailed in the company's SEC filings, including the Risk Factors section of the 2025 Form 10-K and recent Form 10-Q. - Clinical trial success is not guaranteed: even if midpoint and open-label data are positive, the pivotal trial may fail to meet its primary endpoints, or regulatory authorities may not approve RUVIDA for marketing. - Reimbursement pathway implementation is still early, and it is unclear whether RUVIDA will ultimately qualify for full and timely coverage under the new Rapid Coverage Pathway. - First-in-human gene therapy trials carry inherent safety and feasibility risks; adverse events could delay or halt development of Rejuva 001.

Analyst Q&A

• Q: Can you explain Rejuva 001's enrollment timeline, target profile, and what preliminary data will be available in H2 2026? /

  A: Rejuva 001 uses a 3x3 dose-escalation study design: after the initial 3 patients are dosed at the starting dose, safety, feasibility, and PK/PD will be evaluated before escalating to higher doses. Initial delivery feasibility and safety can be assessed 1-2 weeks after first dosing, but meaningful PK/PD and efficacy signals are not expected until roughly 8 weeks post-dose, when GLP-1 expression reaches target levels. An initial update on safety and feasibility after first patient enrollment will be provided, followed by further efficacy-related updates.

• Q: Is an all-comer pivotal success required for the RUVIDA de novo submission, or can dose/subgroup data support the regulatory package? Any updates on the German commercial use program? /

  A: The de novo pathway evaluates the totality of clinical evidence rather than requiring a single all-comer statistically significant outcome, so there is regulatory flexibility for subgroup data. While management is highly confident the full pivotal trial will meet endpoints, the flexibility will not need to be used. For the German commercial use program, the company continues to follow patients out to 5 years, and plans to provide an update once a meaningful number of patients reach the 3-year follow-up mark, which is expected in the coming quarters.

• Q: Will you include 1-year data from the Reveal 1 and Remain One midpoint cohorts in the de novo submission, and how will this data support the application? /

  A: All available data will be submitted to the FDA, per the 'totality of evidence' standard for de novo review. The company has over a decade of clinical data from hundreds of treated patients across multiple cohorts, and the 1-year data from non-pivotal cohorts will add to the full evidence base supporting benefit and safety, which the FDA will consider alongside the pivotal trial data for the marketing authorization decision.

• Q: Is the first Rejuva 001 dose cohort a lower safety checkpoint dose or an active therapeutic dose? /

  A: Per regulatory requirements, the first dose is an active dose intended to produce a therapeutic effect, and that is the company's explicit intent. The study will proceed with a cautious approach prioritizing patient safety, as this is the first time this route of administration has been used for this indication, but management is optimistic that active signals will be observed after sufficient follow-up.