Immunome (NASDAQ: IMNM) reports positive Phase 3 RINGSIDE desmoid tumor data
Rhea-AI Filing Summary
Immunome reported positive topline results from its global Phase 3 RINGSIDE trial of varegacestat, an oral, once-daily gamma secretase inhibitor, in patients with progressing desmoid tumors.
The study met its primary endpoint of progression-free survival, cutting the risk of disease progression or death by 84% vs placebo (hazard ratio 0.16; 95% CI 0.071–0.375; p<0.0001). Confirmed objective response rate was 56% with varegacestat versus 9% with placebo, and median best tumor volume change was -83% vs +11% with placebo. All key secondary endpoints, including landmark tumor volume reduction and worst pain intensity, showed statistically significant benefits. Varegacestat was generally well tolerated, though diarrhea, fatigue, rash, nausea and cough were common, and about 55.6% of premenopausal women experienced ovarian toxicity. Immunome plans to present additional RINGSIDE data and submit a New Drug Application to the U.S. Food and Drug Administration in Q2 2026. The company also highlighted preclinical data suggesting its HC74 TOP1 inhibitor ADC payload may offer advantages over existing TOP1 inhibitor payloads.
Positive
- Phase 3 RINGSIDE met its primary endpoint, with varegacestat reducing the risk of disease progression or death by 84% vs placebo (hazard ratio 0.16; 95% CI 0.071–0.375; p<0.0001).
- Strong secondary efficacy and NDA plan, including a confirmed objective response rate of 56% vs 9% for placebo and an intended New Drug Application submission in Q2 2026.
Negative
- High ovarian toxicity in premenopausal women, with approximately 55.6% experiencing ovarian toxicity, highlighting a significant safety consideration for varegacestat.
- Regulatory and data uncertainties remain, as the topline RINGSIDE results are based on preliminary analyses and the company cautions that regulatory approvals for varegacestat may be delayed, conditioned or not obtained.
Insights
Phase 3 varegacestat data in desmoid tumors are strong for NDA plans, but ovarian toxicity and regulatory review remain important uncertainties.
The global pivotal Phase 3 RINGSIDE trial in progressing desmoid tumors met its primary endpoint of progression-free survival, with varegacestat reducing the risk of progression or death by 84% vs placebo (hazard ratio 0.16; 95% CI 0.071–0.375; p<0.0001). Confirmed objective response rate reached 56% vs 9% on placebo, and median best tumor volume change was -83% versus +11%, while all key secondary endpoints, including landmark tumor volume reduction and worst pain intensity, were statistically significant.
The safety profile was described as generally well tolerated and consistent with the gamma secretase inhibitor class. Common adverse events included diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%), mostly grade 1 or 2. A notable finding was ovarian toxicity in approximately 55.6% of premenopausal women, which may become an important factor for future labelling and clinical use.
Immunome plans to submit a New Drug Application for varegacestat to the U.S. Food and Drug Administration in Q2 2026 and to share additional RINGSIDE data at a major medical conference. The company also emphasized preclinical results for its proprietary HC74 TOP1 inhibitor payload, where HC74 antibody–drug conjugates showed greater cytotoxicity, permeability and bystander activity than deruxtecan-based comparators in cell and tumor models. Management notes that topline RINGSIDE data are based on preliminary analyses, preclinical studies may not predict clinical outcomes, and regulatory approvals, including for varegacestat, may be delayed, subject to conditions or not obtained.
8-K Event Classification
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
| |
||
| (Address of principal executive offices) | (Zip Code) |
Registrant’s telephone number, including area code:
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:
| Title of each class |
Trading |
Name of each exchange on which registered | ||
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.
Item 7.01 Regulation FD Disclosure.
On December 15, 2025, Immunome, Inc. (the Company, we or our) issued a press release announcing topline data from its Phase 3 RINGSIDE clinical trial of varegacestat, the Company’s investigational, oral, once-daily gamma secretase inhibitor (GSI), in patients with progressing desmoid tumors. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
On December 15, 2025, the Company made available on its website an investor presentation to be shared with investors and others from time to time. A copy of this presentation is being furnished as Exhibit 99.2 to this Current Report on Form 8-K.
The information set forth in this Item 7.01 and in the press release and investor presentation attached hereto as Exhibits 99.1 and 99.2, respectively, is deemed to be “furnished” and shall not be deemed to be “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. The information set forth in this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed incorporated by reference into any filing under the Exchange Act or the Securities Act of 1933, as amended, except to the extent that the Company specifically incorporates it by reference.
| Item 8.01 | Other Events. |
Phase 3 RINGSIDE Trial Topline Data
On December 15, 2025, Immunome, Inc. (the Company, we or our) announced positive topline results from the global pivotal Phase 3 RINGSIDE trial of varegacestat, an investigational, oral, once-daily gamma secretase inhibitor (GSI), in patients with progressing desmoid tumors.
The trial met its primary endpoint of improving progression-free survival, demonstrating a statistically significant and clinically meaningful improvement vs. placebo, with an 84% reduction in the risk of disease progression or death (hazard ratio (HR) = 0.16, 95% CI: 0.071, 0.375; p<0.0001). The confirmed objective response rate (ORR) based on RECIST v1.1 was 56% with varegacestat vs. 9% with placebo (p<0.0001), as assessed by blinded independent central review. In an exploratory analysis, varegacestat demonstrated a median best change in tumor volume of -83% vs. +11% with placebo, as assessed by blinded independent central review. In addition, the trial met all key secondary endpoints, with varegacestat achieving statistically significant improvements vs. placebo in landmark tumor volume reduction and worst pain intensity.
Varegacestat was generally well tolerated, with a manageable safety profile consistent with the GSI class. The most common adverse events for participants in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%). Most events were grade 1 or 2. Additionally, approximately, 55.6% of premenopausal women experienced ovarian toxicity.
The Company plans to share additional data from the RINGSIDE trial at an upcoming major medical conference.
Based on these data, the Company plans to submit a New Drug Application to the U.S. Food and Drug Administration in Q2 2026.
HC74 Overview and Update
Our proprietary HC74 TOP1 inhibitor payload is designed to have potential best-in-class attributes
Existing TOP1 inhibitors, such as deruxtecan (DXd), have several limitations, including:.
| • | High efflux potential, which leads to primary and acquired payload resistance when cancer cells “pump” the payload out of the cell before it can trigger cell death. |
| • | Low permeability, which leads to poor bystander activity by preventing uptake of cytotoxic payloads by nearby target negative cells. |
Efflux transporters, such as P-gp and MRP1 actively remove ADC payloads from cells.
We intentionally designed HC74 to overcome these limitations and to incorporate the attributes of a potential best-in-class ADC payload. These attributes include:
| • | Overcoming payload resistance: HC74 is designed to have a lower efflux potential, which is intended to overcome payload resistance mediated by transporters such as P-glycoprotein (P-gp) and multidrug resistance associated protein 1 (MRP1). |
| • | Increased bystander activity: HC74 is designed to have higher permeability, which increases killing of nearby tumor cells that do not express the target of the ADC via bystander activity. |
| • | Superior cytotoxicity: HC74 has demonstrated superior cytotoxic activity across 89 cell lines compared with DXd. |
With this combination of attributes, we believe HC74 ADCs have the potential for greater frequency and duration of benefit compared with DXd and other TOP1 inhibitor payloads. Preclinical studies have demonstrated that our HC74 TOP inhibitor payload and HC74 ADCs showed superior properties when compared with DXd and DXd ADCs. The lower efflux potential of HC74 resulted in increased payload cytotoxicity in cells that overexpress efflux transporters, compared with DXd. HC74 also showed increased permeability compared with DXd, resulting in significantly greater cytotoxicity. We believe these results supports the potential for superior bystander activity with HC74 compared with DXd.
We believe the reduced efflux ratio observed with HC74 in preclinical studies has the potential to provide clinical benefit because sensitivity to efflux meaningfully limits the clinical efficacy of existing TOP1 inhibitor ADCs. High P-gp expression has been shown to correlate with significantly lower ORR and progression-free survival (PFS) in patients with HER2-positive colorectal cancer treated with T-DXd.
Preclinical data presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025 also support the potential for HC74 ADCs to provide clinical benefit in the treatment of tumors with primary or acquired resistance to other TOP1 inhibitor therapies. In these studies, a tumor model using a colorectal cancer cell line that expresses high levels of P-gp (HCT-15) was refractory to T-DXd or irinotecan but sensitive to HC74 ADCs.
We believe the superior bystander activity observed with HC74 ADCs compared with DXd ADCs supports the potential for greater HC74 activity in tumors with target heterogeneity. Within a tumor, the target of the ADC may not be expressed on all cancer cells. Cells lacking the target will not be killed directly by the ADC but may be killed through bystander activity that occurs when target expressing cells killed by the ADC release payload that enters and kills neighboring target negative cells. Such effects cannot be discerned in tumor models that use cell lines in which every cell expresses the ADC target. The NCI-H292 bystander model comprises cells that are positive for TROP2 (a validated ADC target) as well as cells that lack TROP2 expression. In this model, a TROP2-HC74 ADC significantly reduced tumor volume compared with a TROP2-DXd ADC.
Forward-Looking Statements
This Current Report on Form 8-K contains forward-looking statements about the Company and its industry that involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this report are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “vision,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “promising,” “projected,” “first step,” “ongoing,” or the negative of these terms, and similar words or expressions to identify these forward-looking statements. These forward-looking statements include, but are not limited to, statements about: the Company’s expected timing for submitting an NDA for varegacestat with the U.S. Food and Drug Administration; the Company’s plans to provide additional data from the RINGSIDE trial; the benefits of HC74’s design and its potential to be a best in class payload; and other statements regarding the management’s intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, the risk that the RINGSIDE topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data and such topline data may not accurately reflect the complete results of the trial; the risk that the Company’s NDA submission for varegacestat is delayed based on regulatory feedback or otherwise, and that regulatory approvals for the Company’s programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions, including the risk that the results of our trials for varegacestat may not be deemed sufficient by the FDA to serve as the basis for an NDA submission or regulatory approval of varegacestat; the risks associated with the potential safety and other complications from varegacestat; the labelling for varegacestat, if approved; the scope, progress and expansion of developing and commercializing varegacestat, if approved; the size and growth of the market for varegacestat and the rate and degree of its market acceptance; the risk that preclinical studies are not predictive of clinical data; the risk that Immunome will not be able to realize the benefits of its strategic transactions; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway; Immunome’s ability to grow and advance its pipeline and successfully execute on its business plan; and other risks and uncertainties indicated from time to time as described in the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, filed with the SEC on November 6, 2025, and in the Company’s other filings with the SEC.
In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although the Company believes that it has a reasonable basis for each forward-looking statement contained in this report, the Company cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur at all. Furthermore, if the Company’s forward-looking statements prove to be inaccurate, the inaccuracy may be material. Except as required by law, the Company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. |
Description | |
| 99.1 | Press Release, dated December 15, 2025. | |
| 99.2 | Investor Presentation, dated December 15, 2025. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) | |
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 thereunto duly authorized.
| IMMUNOME, INC. | ||||||
| Date: December 15, 2025 | By: | /s/ Max Rosett | ||||
| Max Rosett | ||||||
| Chief Financial Officer | ||||||
FAQ
What did Immunome (IMNM) report about the Phase 3 RINGSIDE trial?
Immunome reported positive topline results from its global pivotal Phase 3 RINGSIDE trial of varegacestat, showing significant improvements in progression-free survival, tumor responses and pain in patients with progressing desmoid tumors compared with placebo.
What were the key efficacy results for varegacestat in desmoid tumors?
Varegacestat reduced the risk of disease progression or death by 84% vs placebo (hazard ratio 0.16; 95% CI 0.071–0.375; p<0.0001), achieved a confirmed objective response rate of 56% vs 9% on placebo, and produced a median best tumor volume change of -83% vs +11% with placebo.
How was varegacestat tolerated in the Phase 3 RINGSIDE trial?
Varegacestat was generally well tolerated with a safety profile consistent with the gamma secretase inhibitor class. The most common adverse events in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%), mostly grade 1 or 2, and about 55.6% of premenopausal women experienced ovarian toxicity.
When does Immunome (IMNM) plan to submit an NDA for varegacestat?
Based on the Phase 3 RINGSIDE data, Immunome plans to submit a New Drug Application for varegacestat to the U.S. Food and Drug Administration in Q2 2026.
What is Immunomes HC74 TOP1 inhibitor payload and why is it important?
HC74 is Immunomes proprietary TOP1 inhibitor payload for antibodydrug conjugates, intentionally designed to address limitations of existing TOP1 inhibitors such as deruxtecan. Preclinical studies showed HC74 ADCs had lower efflux, higher permeability and greater cytotoxicity and bystander activity than deruxtecan-based ADCs in certain models.
What risks and uncertainties did Immunome highlight around varegacestat and HC74?
Immunome noted that RINGSIDE topline results are based on preliminary analyses and may change, regulatory approvals for varegacestat could be delayed or not obtained, safety and labelling outcomes remain uncertain, and preclinical findings for HC74 may not predict clinical results.