# EDGAR Filing Document

**Accession Number:** 0001472012
**File Stem:** 0001193125-25-318429
**Filing Date:** 2025-12
**Character Count:** 50457
**Document Hash:** f1e1219caa956d5b5f715417fc774e5e
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001193125-25-318429.hdr.sgml**: 20251215

**ACCESSION NUMBER**: 0001193125-25-318429

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 51

**CONFORMED PERIOD OF REPORT**: 20251215

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20251215

**DATE AS OF CHANGE**: 20251215

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Immunome Inc.
- **CENTRAL INDEX KEY:** 0001472012
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 770694340
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-39580
- **FILM NUMBER:** 251569984

**BUSINESS ADDRESS:**
- **STREET 1:** 18702 N. CREEK PARKWAY
- **STREET 2:** SUITE 100
- **CITY:** BOTHELL
- **STATE:** WA
- **ZIP:** 98011
- **BUSINESS PHONE:** 610-321-3700

**MAIL ADDRESS:**
- **STREET 1:** 18702 N. CREEK PARKWAY
- **STREET 2:** SUITE 100
- **CITY:** BOTHELL
- **STATE:** WA
- **ZIP:** 98011

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

### UNITED STATES

### SECURITIES AND EXCHANGE COMMISSION

#### Washington, D.C. 20549

### FORM 8-K

#### CURRENT REPORT

#### Pursuant to Section 13 or 15(d)

#### of the Securities Exchange Act of 1934

#### Date of Report (Date of earliest event reported): December 15, 2025

## Immunome, Inc.

#### (Exact name of registrant as specified in its charter)

---

| | | |
|:---|:---|:---|
| **Delaware** | **001-39580** | **77-0694340** |
| **(State or other jurisdiction**<br> **of incorporation)** | **(Commission**<br> **File Number)** | **(IRS Employer**<br> **Identification No.)** |

---

---

| | |
|:---|:---|
| **18702 N. Creek Parkway, Suite 100**<br> **Bothell, WA** | **98011** |
| **(Address of principal executive offices)** | **(Zip Code)** |

---

#### Registrant's telephone number, including area code: (425) 939-7410
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** | **Name of each exchange**<br> **on which registered** |
| Common Stock, $0.0001 par value per share IMNM | The Nasdaq Capital Market |

---

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.

![LOGO](g793961g01g01.jpg)

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.

------

![LOGO](g793961g02g02.jpg)

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.

![LOGO](g793961g03g03.jpg)

------

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.

![LOGO](g793961g04g04.jpg)

#### 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**<br> **No.** | **Description** |
| 99.1 | [Press Release, dated December 15, 2025.](d793961dex991.htm) |
| 99.2 | [Investor Presentation, dated December 15, 2025.](d793961dex992.htm) |
| 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.** | **IMMUNOME, INC.** |
| Date: December 15, 2025 | By: | /s/ Max Rosett |
|  |  | Max Rosett |
|  |  | Chief Financial Officer |

---

## Exhibit 99.1

**Exhibit 99.1**![LOGO](g793961g1214052110982.jpg)

**Immunome Announces Positive Topline Results from Phase 3 RINGSIDE Trial** 

**of Varegacestat in Patients with Desmoid Tumors** 

Registrational trial met primary endpoint, with varegacestat significantly improving

progression-free survival vs. placebo (hazard ratio = 0.16, p<0.0001)

Trial also met all key secondary endpoints, with varegacestat delivering an objective response rate of 56%

Varegacestat was generally well tolerated with a manageable safety profile

New Drug Application submission to U.S. FDA planned for Q2 2026

Company to host conference call today at 8:30 a.m. ET

BOTHELL, Wash., December 15, 2025 – Immunome, Inc. (Nasdaq: IMNM), a biotechnology company committed to developing first-in-class and best-in-class targeted cancer therapies, today 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.

------

Based on these data, Immunome plans to submit a New Drug Application to the U.S. Food and Drug Administration in Q2 2026.

"RINGSIDE is the largest and most comprehensive clinical trial conducted to date in patients with desmoid tumors, and the topline results represent the highest objective response rate observed in a randomized clinical trial in this patient population," said Immunome's CEO Clay Siegall, Ph.D. "These findings demonstrate the potential of varegacestat to offer best-in-class results in a convenient, once-daily, oral medicine that may help patients reclaim their lives."

"Desmoid tumors can have a devastating physical and emotional impact on patients given their unpredictable nature and the limitations of current treatment options," said Mrinal M. Gounder, M.D., sarcoma medical oncologist and drug development specialist at Memorial Sloan Kettering Cancer Center, and RINGSIDE primary investigator. "The progression-free survival benefit, high response rate and reduction in tumor volume with varegacestat in the RINGSIDE trial are striking. These findings elevate the role of GSIs and confirm varegacestat could become standard of care in the treatment of desmoid tumors."

Dr. Siegall added, "The RINGSIDE results represent a major milestone for Immunome as we advance our emerging pipeline of targeted oncology therapies that have exceptional potential to meaningfully improve the lives of patients."

Immunome plans to share additional data from the RINGSIDE trial at an upcoming major medical conference.

**Webcast, Presentation Slides and Conference Call Information** 

Immunome will host a webcast and conference call on Monday, December 15, 2025, at 8:30 a.m. ET / 5:30 a.m. PT to discuss the Phase 3 RINGSIDE trial topline results. A live webcast, which will include presentation slides, can be accessed using this <u>link</u> or by visiting the Events and Presentations section of the Immunome website at <u>https://investors.immunome.com/events</u>. The conference call can be accessed by clicking on the call link and completing the online registration form, which will enable the selection of a dial-in number or callback from the system. A live question-and-answer session will follow the prepared remarks. Participants wishing to ask a question must do so via the conference call; the webcast will be listen-only. After the live webcast, the event will remain archived on the Immunome website for 90 days.

------

**About the RINGSIDE Trial** 

The global, randomized, double-blind, placebo-controlled Phase 3 RINGSIDE trial (<u>NCT04871282</u>) evaluated the efficacy and safety of varegacestat in patients with progressing desmoid tumors. A total of 156 patients were randomized to receive varegacestat 1.2 mg daily or placebo until disease progression or death. The primary endpoint of the trial was progression-free survival as assessed by blinded independent central review. Statistically controlled secondary endpoints were ORR using RECIST v1.1 and change in tumor volume at week 24, both determined by blinded independent central review, as well as change in pain intensity as determined using a patient reported outcome instrument. Additional secondary endpoints included duration of response, best reduction in tumor volume, patient-reported outcomes, and safety and tolerability. RINGSIDE includes an open-label extension phase, which is ongoing.

**About Desmoid Tumors** 

Desmoid tumors (also known as aggressive fibromatosis or desmoid-type fibromatosis) are aggressive non-metastatic soft tissue tumors that are prone to recurrence. Approximately 1,000-1,650 people are diagnosed with desmoid tumors each year in the United States, and there are approximately 10,000-11,000 actively managed patients. Those affected face debilitating pain, deformity and, in some cases, life-threatening organ damage. The chronic pain and physical limitations associated with desmoid tumors lead to a high clinical burden and impaired quality of life. Although desmoid tumors are not considered cancerous, they often require systemic treatment to prevent permanent disability and alleviate disease burden.

**About Varegacestat** 

Varegacestat (formerly AL102) is an investigational, oral, once-daily gamma secretase inhibitor. In December 2025, Immunome reported positive topline results for the Phase 3 RINGSIDE trial of varegacestat in adults with progressing desmoid tumors. Immunome plans to submit a New Drug Application for varegacestat to the U.S. Food and Drug Administration in Q2 2026.

**About Immunome, Inc.** 

Immunome is a clinical-stage targeted oncology company committed to developing first-in-class and best-in-class targeted cancer therapies. We are advancing an innovative portfolio of therapeutics, drawing on leadership that previously played key roles in the design, development, and commercialization of cutting-edge therapies, including antibody-drug conjugate therapies. Our pipeline includes varegacestat, a late-clinical stage GSI; IM-1021, a clinical-stage ROR1 ADC; and IM-3050, a FAP-targeted radiotherapy that recently received IND clearance. We are also advancing a broad portfolio of early stage ADCs pursuing undisclosed solid tumor targets. For more information, visit <u>www.immunome.com</u>.

------

**Financial Disclosure** 

Dr. Gounder has financial interests related to Immunome.

**Cautionary Statement Regarding Forward-Looking Statements** 

Statements in this press release that are not purely historical in nature are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. We use words such as "focused," "advance," "anticipate," "if warranted," "potential," "plan," "expect," and similar expressions to identify these forward-looking statements. These forward-looking statements include statements regarding: the best in class potential of varegacestat and its potential to help patients reclaim their lives; Immunome's expected timing for submitting an NDA for varegacestat with the U.S. Food and Drug Administration; the potential for varegacestat to become the new standard of care; Immunome's plans to provide additional data from the RINGSIDE trial; the potential of Immunome's targeted oncology therapies to be first-in-class or best-in-class status and deliver therapeutic breakthroughs to patients; and other statements regarding management's intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on Immunome'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 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 our NDA submission for varegacestat is delayed based on regulatory feedback or otherwise, and that regulatory approvals for Immunome'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 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 included under the caption "Risk Factors" in Immunome's Quarterly Report on Form 10-Q for the quarter ended September 30, 2025, filed with the Securities and Exchange Commission on November 6, 2025. These documents can also be accessed on Immunome's website at <u>www.immunome.com</u> by clicking on the link "Financials" under the "Investors" tab. The forward-looking statements included in this press release are made only as of the date hereof. Except as required by law, Immunome assumes no obligation and does not intend to update any forward-looking statements included in this press release.

\# \# \#

**Investor Contact:** 

Max Rosett

Chief Financial Officer, Immunome

<u>investors@immunome.com</u> 

**Media Contact:** 

Nicole Foderaro

Real Chemistry

media@immunome.com

## Exhibit 99.2

![Slide 1](g793961ex99_2s1g1.jpg)

Corporate Presentation Transformative Targeted Therapeutics December 2025 Exhibit 99.2

------

![Slide 2](g793961ex99_2s2g1.jpg)

Disclosures For purposes of this notice, the "presentation" that follows shall mean and include the slides that follow, any oral presentation of the slides by members of management of Immunome, Inc. ("Immunome") or any person on its behalf, any question-and-answer session that follows that oral presentation, hard copies of this document and any materials distributed at, or in connection with, that presentation. References to "we," "our," and "us" refers to Immunome and its subsidiaries. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy or sell Immunome securities. Forward-Looking Statements Statements in this presentation that are not purely historical in nature are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. We use words 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 expansion and advancement of Immunome's platform and pipeline and Immunome's approach; the expected benefits of Immunome's proprietary payload, HC74, and strategy related to Immunome's platform and pipeline; assessments of the clinical efficacy, best-in-class potential, and potential commercial success of Immunome's product candidates, including IM-1021 and varegacestat; the potential of Immunome's current and future pipeline to produce first-in-class and/or best-in-class drugs; Immunome's expectations with respect to future performance, anticipated financial impacts, ability to complete and success of Immunome's strategic transactions; Immunome's timeline for filing an NDA, INDs and other regulatory filings, commencing clinical trials, receiving and reporting data from such clinical trials, and seeking regulatory approval, for Immunome's current and future programs and product candidates and other anticipated milestones; the best-in-class potential of varegacestat and its ability to become the new standard of care for treating desmoid tumors; Immunome's launch strategy and the expected results therefrom; Immunome's ability to expand its platform, establish a broad pipeline and advance it through efficient clinical development decisions; and other statements regarding management's intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on Immunome'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: 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 Immunome's NDA submission for varegacestat is delayed based on regulatory feedback or otherwise, and that regulatory approvals for Immunome's programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions, including the risk that the results of Immunome's 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 market acceptance thereof; the risk that Immunome will not be able to realize the benefits of its strategic transactions; the risk that regulatory approvals for Immunome's programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions; the risk that preclinical or early clinical data may not be predictive of future results; the risk that Immunome's product candidates and development candidates fail to achieve their intended endpoints; the reliance on Immunome's management; the prior experience and successes of Immunome's management team not being indicative of any future success; the risk of reliance on vendors; uncertainties related to Immunome's capital requirements and Immunome's expected cash runway; Immunome's ability to grow and successfully execute on Immunome's business plan, including the development and commercialization of its pipeline and integration of newly acquired assets; and other risks and uncertainties indicated from time to time described in Immunome's Annual Report on Form 10-K for the year ended December 31, 2024, filed with the SEC on March 19, 2025, and in Immunome's other filings with the SEC. Except as required by law, Immunome assumes no obligation and does not intend to update any forward-looking statements included in this presentation. Product Candidates In this presentation, we may discuss current and potential future product candidates that have not yet undergone clinical trials or been approved for marketing by the U.S. Food and Drug Administration or other governmental authority. No representation is made as to the safety or effectiveness of these current or potential future product candidates for the use for which such product candidates are being studied. Industry and Market Data In this presentation, we rely on and refer to publicly available information and statistics regarding market participants in the sectors in which we compete and other industry data. Any comparison of us to the industry or to any of our competitors is based on this publicly available information and statistics and such comparisons assume the reliability of the information available to us. We obtained this information and statistics from third-party sources, including reports by market research firms and company filings. While we believe such third-party information is reliable, there can be no assurance as to the accuracy or completeness of the indicated information. We have not independently verified the information provided by the third-party sources. Trademarks This presentation may contain trademarks, service marks, trade names and copyrights of other companies, which are the property of their respective owners. Solely for convenience, some of the trademarks, service marks, trade names and copyrights referred to in this presentation may be listed without the TM, SM© or® symbols, but we will assert, to the fullest extent under applicable law, the rights of the applicable owners, if any, to these trademarks, service marks, trade names and copyrights. Disclaimer and Forward-Looking Statements

------

![Slide 3](g793961ex99_2s3g1.jpg)

Establishing a Premier Targeted Oncology Company i Varegacestat, an oral, once-daily gamma secretase inhibitor for the treatment of desmoid tumors, with positive Phase 3 topline data NDA submission planned for 2Q 2026 Positioned to be a best-in-class option Deep expertise in ADCs driving differentiated early-stage pipeline leveraging proprietary HC74 TOP1i payload ROR1 ADC in dose escalation with activity observed at multiple dose levels Pairing first-in-class targets with exceptional technology Positioned to deliver multiple INDs per year driven by a team that combines deep expertise and decisive execution Complementary radioligand therapy entering Phase 1 Experienced, successful leadership team Delivering Breakthroughs In Oncology

------

![Slide 4](g793961ex99_2s4g1.jpg)

Broad Portfolio of Targeted Oncology Therapeutics Program Target / Modality Preclinical Phase 1 Phase 2 Phase 3 Commercial Next Anticipated Milestone Varegacestat Gamma Secretase Inhibitor NDA Submission \| 2Q 2026 IM-1021 ROR1 ADC Initial Lymphoma Data \| 2026 IM-3050 FAP Radiotherapy First Patient In \| Early 2026 IM-1617 First-in-Class Solid Tumor ADC IND \| Early 2026 IM-1340 First-in-Class Solid Tumor ADC IND \| Mid 2026 IM-1335 First-in-Class Solid Tumor ADC IND \| Late 2026

------

![Slide 5](g793961ex99_2s5g1.jpg)

Varegacestat Phase 3 Oral, Once-Daily Gamma Secretase Inhibitor

------

![Slide 6](g793961ex99_2s6g1.jpg)

Generally well-tolerated with manageable safety profile Confirmed Objective Response Rate2: 56% Progression-Free Survival1: Hazard Ratio 0.16 (p<0.0001) Median Best Tumor Volume Reduction3: 83% (1) Primary endpoint (2) Key secondary endpoint (3) Exploratory endpoint 2Q26 NDA Submission Planned Varegacestat Demonstrated Exceptional Results For Patients Study Met Primary and All Key Secondary Endpoints

------

![Slide 7](g793961ex99_2s7g1.jpg)

Desmoid tumors often strike in young adulthood, with 1,000-1,650 patients diagnosed each year and 10-11,000 actively managed patients in the US1 Can lead to debilitating pain, deformity, and life-threatening organ damage depending on location1 Quality of life is a major challenge with a majority of patients experiencing chronic pain that can significantly limit physical functioning1 Up to ~60-80% of patients experience recurrence, which can be exacerbated by surgery1 Following progression during initial active surveillance, systemic therapy is recommended for ~75% of tumors based on location2,3 Approved systemic therapy options remain limited with only one approved therapy Desmoid Tumors are Locally Aggressive & Debilitating Sources: (1) Bektas et al., Advances in Therapy, 2023; (2) The Desmoid Tumor Working Group, European Journal of Cancer, 2020; (3) The Desmoid Tumor Working Group, JAMA Oncology, 2024

------

![Slide 8](g793961ex99_2s8g1.jpg)

Varegacestat is a Gamma Secretase Inhibitor with a Differentiated Pharmacokinetic Profile Desmoid tumors are driven by nuclear accumulation of β-CATENIN resulting from cross-talk between WNT and NOTCH pathways2 Kasper et al. Sources: (1) Figure adapted from Kasper et al., ESMO 2022. Abstr LBA2, based on Andersson et al., Development, 2011 and Bui and Kummar, Oncotarget, 2017; (2) Federman, NPJ Precision Oncology, 2022; (3) Immunome data on file; (4) Aung et al., Investigational New Drugs. 2018; (5) Varegacestat Investigator's Brochure Version 8.0 78% Longer Half-Life than Nirogacestat3 Sustained Exposure Above Target Threshold4,5 1.2 mg Once Daily

------

![Slide 9](g793961ex99_2s9g1.jpg)

Key Inclusion Criteria Progressed within last 12 months1 Treatment naïve or recurrent/refractory disease appropriate for systemic treatment RINGSIDE is the Largest Phase 3 Study in Desmoid Tumors Design consistent with prior registrational trials Key Endpoints Primary: Progression-free survival2 (PFS) Alpha-controlled key secondary Objective Response Rate Tumor Volume3 at Week 24 Worst Pain Intensity at Week 124 Safety and tolerability Additional efficacy assessments, including median best percent change in Tumor Volume3 (1) Progression was defined as ≥20% increase per RECIST v1.1 (2) PFS was defined as time from randomization until the date of assessment of radiographic progression as assessed Blinded Independent Central Review (BICR) based on RECIST v1.1 (3) Measured by T2 weighted MRI or CT per BICR (4) Measured using Desmoid Tumor Symptom Scale Item 1 from the GOunder/Desmoid Tumor Research Foundation Desmoid Tumor Symptom/Impact Scale (GODDESS) Global Phase 3 Double-Blind Placebo-Controlled R Varegacestat 1.2mg QD, n=79 Placebo, n=77 Varegacestat 1.2mg QD Open Label Extension Cross over to OLE if progressive disease Cross over to OLE if active at primary analysis 1:1

------

![Slide 10](g793961ex99_2s10g1.jpg)

Varegacestat Achieved Primary Endpoint 84% Reduction in the Risk of Progression or Death vs Placebo Progression-Free Survival: HR 0.16; 95% CI: 0.071, 0.375; p < 0.0001

------

![Slide 11](g793961ex99_2s11g1.jpg)

Par 56% ORR With Varegacestat vs 9% With Placebo (p<0.0001) -83% Median Best Percent Change in Tumor Volume With Varegacestat vs +11% With Placebo -83% Best Percent Change in Tumor Size with Varegacestat PR Varegacestat Demonstrates Robust Antitumor Activity PD

------

![Slide 12](g793961ex99_2s12g1.jpg)

Varegacestat was generally well-tolerated, with a manageable safety profile consistent with the GSI class of medicines 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 55.6% of premenopausal women experienced ovarian toxicity There were no deaths on study Varegacestat Was Generally Well-tolerated With a Manageable Safety Profile

------

![Slide 13](g793961ex99_2s13g1.jpg)

Elevating an Established Class and Solidifying the Role of GSIs in Desmoid Tumor Treatment ORR (%) 2018 2023 2025 Sorafenib 400mg Once Daily Oral NCT02066181; N=87 Nirogacestat 150 mg Twice-Daily Oral DeFi; n=142 Varegacestat 1.2mg Once-Daily Oral RINGSIDE; N=156 TKI Era GSI Era Phase 3 Studies in Desmoid Tumors Reliance on limited P1/2 and observational studies and local therapy FOR ILLUSTRATIVE PURPOSES ONLY: no head-to-head clinical trial has been conducted evaluating varegacestat against nirogacestat or other candidates or products. Differences exist between trial designs and subject characteristics, and strong caution should be exercised when comparing data across unrelated studies. Placebo ORR: 9% Pre-2018

------

![Slide 14](g793961ex99_2s14g1.jpg)

Launch Strategy Become Standard of Care treatment of Desmoid Tumors START Drive patient initiation on varegacestat SUPPORT Sustained benefit and adherence with a once-daily treatment SCALE Efficiently expand reach across the community through treatment center growth GSI Non-GSI Treatment 10-11k Actively Managed Patients (US) 1 ~85 Sarcoma Centers-of-Excellence4 ~50% of patients have desmoid tumors for more than 5 years 2 A Long, Chronic, Treatment Journey 1) Immunome Analysis 2) K Mercier et al. ESMO Sarcoma 2024 Poster 3) Immunome Primary Market Research 4) Immunome Analysis Dx. Rx Rx Patients may receive ~1.5–2 years of treatment, pause, and return for treatment3

------

![Slide 15](g793961ex99_2s15g1.jpg)

IM 1021 ROR1 ADC

------

![Slide 16](g793961ex99_2s16g1.jpg)

HC74 is a TOP1i Payload Designed to Overcome Fundamental Limitations of Existing Technology Unstable linker Natural payloads High toxicity Stable peptide linker Synthetic payloads Narrow therapeutic window Improved therapeutic index Susceptible to resistance Limited bystander effect Improved therapeutic index Overcomes resistance Bystander effect 25 Years of ADC Technological Advancement HC74 ADCs 2000 2011 2019 2025 First Approved ADC VcMMAE Linker-Payload TOP1i Payloads

------

![Slide 17](g793961ex99_2s17g1.jpg)

IM-1021: Potential Best-in-Class ROR1 ADC Starting dose is 2 mg/kg of adjusted ideal bodyweight (AIBW) 2. Data sources: TCGA data (solid tumors and DLBCL) from UCSC Xena, version 2016-09-03. Blueprint data (MCL and CLL) from the Blueprint consortium, version 20160816. ROR1 Receptor with oncofetal expression pattern, including little or no normal tissue expression1 Expression on solid and liquid tumors IM-1021 Development Status Optimized ROR1 ADC with HC74 TOP1i payload Dose escalation ongoing with B-cell lymphoma and solid tumor patients Clinical starting dose of 2 mg/kg1 similar to MK-2140 recommended phase 2 dose Objective responses observed in B-cell lymphoma patients at multiple dose levels ROR1 Expression by RNA2 DLBCL TNBC NSCLC, Adeno Ovarian Sarcoma Mesothelioma MCL CLL ROR1 Expression by RNA2

------

![Slide 18](g793961ex99_2s18g1.jpg)

IM-1021 Preclinical Activity Supports Development in Lymphoma and Solid Tumors IM-1021 Achieves Tumor Regressions in Jeko-1 MCL Model IM-1021 Achieves 8/8 CRs at 2.5 mg/kg in NSCLC PDX Model

------

![Slide 19](g793961ex99_2s19g1.jpg)

Clinical Development Plan: Rapid Establishment of PoC to Enable Pivotal Studies Across Multiple Indications DL1: 2 mg/kg AIBW DL2 DL3 DL4 DL5 Part A: Dose Escalation Part B: Indication-Specific Dose Expansion DL-Y DL-X Indication Cohort B1 DL-Y DL-X DL-Y DL-X Indication Cohort B2 Indication Cohort B3 AIBW: Adjusted Ideal Body Weight DL6 DL7 B-cell Lymphomas DLBCL Mantle Cell Follicular SLL Solid Tumors NSCLC (non-squam) TNBC Ovarian Mesothelioma Liposarcoma Pancreatic Dose escalation design: mTPI-2 adaptive design Expand 2 or more doses Required minimum representation of lymphoma and solid tumor in Part A before expansion Optional cohorts to test split dosing Population includes: R/R B-cell lymphoma R/R solid tumors Population includes: Up to 3 indication-specific expansion cohorts (B1, B2, B3) Potential indications include those listed in Inclusion 4.a Dose expansion design: Per cohort, randomize 1:1 to 2 regimens (DL-X, DL-Y) Per indication-specific cohort

------

![Slide 20](g793961ex99_2s20g1.jpg)

HC74 Platform

------

![Slide 21](g793961ex99_2s21g1.jpg)

HC74's Low Efflux Potential and High Permeability Lead to Improved Properties Superior HC74 cytotoxic activity across 89 cell lines High HC74 permeability2 drives superior bystander effect Low HC74 efflux potential1 overcomes payload resistance ADC Bystander Cytotoxicity4 Payload Cytotoxicity3 N = 89 Payload Cytotoxicity5 ADC IC50 (ng/mL) 7 290 1. Bidirectional Caco-2 permeability assay. The efflux ratio was 10 for HC74 versus 79 for DXd; 2. Bidirectional MDCK II permeability assay in the presence of Pgp inhibitor (GF120918). MDCK II permeability (Papp), was 9.01 x 10-6 cm/s for HC74 versus 1.96 x 10-6 cm/s for DXd; 3. IC50 values of HC74 and DXd, in parental or engineered NCI-N87 cells overexpressing ABCB1 (P-gp) or ABCC1 (MRP1) 4. In vitro bystander activity of HC74 and DXd ADCs in a co-culture model using NCI-H446 cells engineered to express either TROP2 (Positive) or luciferase (Negative). 5. IC50 values determined by 72hr CellTiter-Glo assay. Median IC50 (nM) 5 20 Low HC74 efflux potential1 overcomes payload resistance High HC74 permeability2 drives Superior bystander effect Superior HC74 cytotoxic activity across 89 cell lines

------

![Slide 22](g793961ex99_2s22g1.jpg)

Sensitivity to Efflux Meaningfully Limits the Clinical Efficacy of Existing TOP1i ADCs High P-gp Expression Correlates With Lower ORR and PFS in HER2+ CRC Patients Treated With T-DXd2 Schematic created with BioRender.com Sienna et al. Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) treatment for HER2-positive (HER2+) metastatic colorectal cancer (mCRC) in DESTINY-CRC02. AACR, 2025. Baseline P-gp Expression ORR, % P value PFS, months P value < Median 47.1 0.003 8.1 < 0.001 ≥ Median 17.6 4.2 Progression free survival based on P-gp expression status Efflux Transporters Like P-gp and MDR1 Actively Remove ADC Payload From Cells1 Free payload Efflux transporter High P-gp Expression Correlates With Lower ORR and PFS in HER2+ CRC Patients Treated With T-DXd2

------

![Slide 23](g793961ex99_2s23g1.jpg)

HCT-15 is a P-gp High Colorectal Model HCT-15 is Refractory to T-DXd but Sensitive to T-HC74 HCT-15 is Refractory to Irinotecan but Sensitive to T-HC74 HC74 ADC Shows Activity in a CRC Model Refractory to Other TOP1i Agents Source: Zhang et al., AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025_A111. "Colorectal cancer (CRC) mRNA values for ABCB1 are from UCSC Xena TCGA-TARGET-GTEx re-analysis, version 2016-09-03 (Vivian et al. Nat Biotech, 2017). HCT-15 mRNA data were generated internally and represent the median of 3 replicates." HCT-15 HCT-15 is Refractory to T-DXd But Sensitive to T-HC74 HCT-15 is Refractory to Irinotecan But Sensitive to T-HC74

------

![Slide 24](g793961ex99_2s24g1.jpg)

HC74 ADC Demonstrates Superior Bystander Activity vs. DXd ADC Potential for Greater HC74 Efficacy in Target Heterogenous Tumors NCI-H292 Bystander Model (75% TROP2+; 25% TROP2 KO) Clonal Preclinical Models Do Not Capture Expression Heterogeneity Source: Zhang et al., AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics 2025_A111 Antigen-positive cells Antigen-negative cells ADC HC74 ADC Demonstrates Durable Response in NSCLC Model of Tumor Heterogeneity

------

![Slide 25](g793961ex99_2s25g1.jpg)

Expanding the Universe of ADC Targets Targets: Prioritize targets with compelling tumor biology and no approved ADCs. Focus on dynamic receptors that drive efficient ADC payload delivery Antibodies: Optimize and evaluate as ADCs Technology: Proprietary HC74 TOP1i payload designed to achieve wide therapeutic index while escaping chemo resistance and generating robust bystander effect Capabilities: High-throughput conjugation and screening supports empirical evaluation of hundreds of ADCs 10 Targets Account for 50% of Active Clinical ADC Programs1 Immunome ADC Strategy Pairs Novel Targets with Differentiated Technology 1. Immunome analysis of Hanson Wade Beacon ADC data as of November 2025 Majority of ADC Activity is Concentrated in a Small Number of Targets

------

![Slide 26](g793961ex99_2s26g1.jpg)

IM-1617: Potential First-in-Class ADC for Multiple Solid Tumor Indications IM-1617 efficacy IM-1617 Target mRNA Expression (Log2 TPM+1) No IM-1617 efficacy Target Expression In Major Indications Corresponds to CDX Models Where IM-1617 Showed Activity IM-1617 Showed Activity In PDX Models That Are Resistant to Dato-DXd

------

![Slide 27](g793961ex99_2s27g1.jpg)

Robust Pipeline of Preclinical Candidates Pursuing Undisclosed Solid Tumor Targets Solid tumor model Anticipated 2026 IND Submissions Additional Candidates IM-1617 ADC-U10 IM-1340 IM-1335 ADC-U11 ADC-U12

------

![Slide 28](g793961ex99_2s28g1.jpg)

IM-3050 FAP-Targeted Radioligand Therapy

------

![Slide 29](g793961ex99_2s29g1.jpg)

IM-3050 is a 177Lu-FAP Candidate with Best-in-Class Potential Tumor Regression in U87MG Model No Weight Loss Observed Potential Best-in-Class Characteristics Sub-nanomolar affinity High specificity Radiostability Superior tumor retention and tumor absorbed dose in vivo Preclinical activity and tolerability DEVELOPMENT STATUS: Phase 1 initiation expected in early 2026 In Vivo Radiotherapy Studies GLP/GMP Manufacturing IND cleared in 2Q25 ✓ Clinical Formulation Development ✓ In vivo data show single dose antitumor activity and tolerability ✓ ✓ ------

![Slide 30](g793961ex99_2s30g1.jpg)

Company Overview

------

![Slide 31](g793961ex99_2s31g1.jpg)

Management Team with a Demonstrated Track Record of Success Chief Executive Officer and Founder, Seagen (1998-2022) Grew company to $2B+ revenue (2022) leading to $43B acquisition Led development of 4 FDA-approved therapeutics Raised over $1B in public and private capital Oversaw acquisition and integration of Cascadian Therapeutics Generated >$3B in partnership and licensing revenue Clay Siegall, Ph.D. PRESIDENT & CHIEF EXECUTIVE OFFICER Sandra Stoneman CHIEF LEGAL OFFICER Jack Higgins, Ph.D. CHIEF SCIENTIFIC OFFICER Max Rosett CHIEF FINANCIAL OFFICER Bob Lechleider, M.D. CHIEF MEDICAL OFFICER Kinney Horn CHIEF BUSINESS OFFICER Phil Tsai CHIEF TECHNICAL OFFICER Roee Shahar EVP, COMMERCIAL

------

![Slide 32](g793961ex99_2s32g1.jpg)

Varegacestat NDA Submission Planned 2Q26 IM-1021 Ph1 Data 2026 Novel solid-tumor targeted ADCs ROR1 ADC Gamma Secretase Inhibitor Positive RINGSIDE Phase 3 topline data IM-1617 IND 2026 IM-1340 IND 2026 IM-1335 IND 2026 ADC portfolio including the HC74 platform represents substantial value Varegacestat provides strong first product opportunity Proven, successful leadership Multiple programs expected to enter clinic in 2026 IM-3050 Ph1 Initiation Early 2026 FAP RLT Accelerating the Pursuit of Breakthrough Oncology Therapies Anticipated Milestones