1. The Molecule1 / 12
The MoleculeMechanism of ActionPreclinical & Clinical EvidenceSafety ProfileIP LandscapeTeamFinancialsRegulatory PathwayMarketCompetitive LandscapeRisks & Open QuestionsOptionalityReferences

BigBio.ai Signal Report

Immunome, Inc.

NASDAQ: IMNM · **Investor question:** What is true about this molecule's history and novelty? · 2026-05-01T23:43:53.977264+00:00

The Phase 3 read holds: a hazard ratio of 0.16 that stands up against the published record, intact through ASCO 2026 and the NDA review window unless the CTNNB1 subgroup data breaks the ORR.

PFS hazard ratio
0.16 (95% CI 0.071-0.375)
Confirmed ORR (BICR)
56% varegacestat vs 9% placebo
Sample size
n=156
Cash position
$653.5M (FY2025; runway into 2028)
ASCO catalyst
Abstract #11506, May 30, 2026, 3-6 PM CDT
NDA filed
April 29, 2026 (10-month standard PDUFA clock)

1. The Molecule

Investor question: What is true about this molecule's history and novelty?

1.1 History & Prior Art

Immunome acquired varegacestat (formerly AL102) from Ayala Pharmaceuticals in March 2024, assuming a license that Ayala had obtained from Bristol-Myers Squibb in 2017. The asset purchase agreement closed on February 5, 2024 [T1, SEC 10-Q: “We acquired varegacestat from Ayala Pharmaceuticals, Inc., or Ayala, in March 2024.” 1; T1, SEC S-3 filing: “we acquired the License Agreement from Ayala pursuant to the Asset Purchase Agreement, dated as of February 5, 2024.” 2].

Immunome owns U.S. patent US12274754B2, “Immunoconjugates and methods,” which claims immunoconjugates that link a ROR1-binding antibody to a topoisomerase I inhibitor payload [T1, Google Patents: “Assignee: Immunome Inc”; claims 2-8 describe ROR1-binding antibodies with specified CDRs and VH/VL sequences 345678910111213141516171819202122232425].

Earlier, Immunome built its discovery engine on a proprietary hybridoma technology that immortalizes memory B cells from oncology patient samples. This platform now stands separate from the company's current ADC and radioligand focus [T1, SEC S-3 filing: “Our discovery platform provides us with a proprietary hybridoma technology to immortalize memory B cells isolated from oncology patient samples.” 26].

1.2 Novelty Assessment

Two elements distinguish Immunome's current pipeline: IM-1021, a ROR1-targeted ADC carrying the proprietary TOPi payload HC74, and IM-3050, a lutetium-177 radioligand therapy that targets fibroblast activation protein (FAP) on cancer-associated fibroblasts across many solid tumors [T1, SEC 10-Q: “IM-1021 is a ROR1 ADC that incorporates HC74, our proprietary TOP1i payload.” 27; T1, SEC 10-Q: “FAP is expressed in 75% of solid tumors.” 28]. Beyond these assets, the dossier contains no evidence for other claimed platform novelties--hybridoma count, novel target numbers--leaving those claims unverified.

2. Mechanism of Action

Investor question: How validated is this target biology?

2.1 Target Biology

Desmoid tumors arise from constitutive Wnt pathway activation driven by CTNNB1 mutations in sporadic cases and APC mutations in familial adenomatous polyposis-associated disease. Wnt dysregulation turns on Notch signaling, which requires γ-secretase to cleave the Notch intracellular domain for nuclear translocation and tumor progression. Varegacestat inhibits γ-secretase, directly blocking this cascade [T2, NPJ Precis Oncol: “Given the role γ-secretase plays in Notch signaling through cleavage of the Notch intracellular domain…”; “Both sporadic DT and familial adenomatous polyposis (FAP)-associated DT are linked to constitutive activation of the Wnt signaling pathway…”; “Cross-talk between the Notch and Wnt pathways… suggest a possible therapeutic target for DT.” 293031323334353637; T1, CT.gov: “AL102 is an inhibitor of gamma secretase-mediated Notch signaling.” 38].

For IM-3050, cancer-associated fibroblasts in roughly 75% of solid tumors express FAP, supporting the broad potential of a FAP-targeted radioligand.

2.2 Validation Layers

The FDA approved nirogacestat (OGSIVEO), another GSI, for progressing desmoid tumors in November 2023, establishing clinical proof of mechanism [T1, FDA label: “OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment.” 3940]. A review article places varegacestat alongside nirogacestat as a later-stage GSI [T2, NPJ Precis Oncol: “Two GSIs, nirogacestat (PF-03084014) and AL102 are in later-stage clinical development.” 41].

Varegacestat's pivotal Phase 3 RINGSIDE trial met its primary endpoint of progression-free survival, showing an 84% reduction in the risk of disease progression or death versus placebo (HR=0.16, p<0.0001). Key secondary endpoints were strongly positive: objective response rate 56% vs. 9% (p<0.0001), and median best change in tumor volume −83% vs. +11% [T1, SEC 8-K: “with a statistically significant and clinically meaningful 84% reduction…”; “achieving an objective response rate of 56% vs. 9% with placebo (p<0.0001)”; “median best change in tumor volume of −83% vs. +11% with placebo” 424344].

2.3 Target Validation Score

Human genetics (CTNNB1 mutations), a positive randomized Phase 3 readout, and an approved same-class drug validate the target. Formal scoring lacks computational validation metrics, so we omit it.

3. Preclinical & Clinical Evidence

Investor question: What does the data actually show?

3.1 Data Summary

Varegacestat (AL102). The Phase 3 RINGSIDE trial (NCT04871282) randomized 156 patients double-blind to varegacestat or placebo. Topline results, announced in December 2025, revealed an 84% reduction in risk of disease progression or death (HR=0.16, p<0.0001), an objective response rate of 56% versus 9% (p<0.0001), and a median tumor volume reduction of 83% versus an 11% increase on placebo. Safety descriptors matched the gamma secretase inhibitor class [T1, SEC 8-K 424543444647; CT.gov primary and secondary endpoints 48495051525354; enrollment 55].

IM-1021 (ROR1 ADC). A Phase 1 open-label, dose-escalation/expansion study in advanced B-cell lymphomas and solid tumors (NCT06823167) dosed its first patient in February 2025. Preclinical models demonstrated sustained tumor regression in triple-negative breast cancer and mantle cell lymphoma. Initial clinical data are expected in 2026 [T1, SEC 10-Q 5657; CT.gov 5859; T1, SEC 8-K 606162].

IM-3050 (FAP-targeted RLT). A Phase 1 trial (NCT07505771) plans to enroll 105 participants to assess safety, dosimetry, and preliminary activity, starting in April 2026 with primary completion in December 2029. Preclinical data presented at AACR 2024 showed potent antitumor activity in a xenograft model [T1, CT.gov 6364; T3, PR 6566].

3.2 Anti-Anchor Check

Varegacestat delivered positive primary and key secondary endpoints (p<0.0001). The data show no anti-anchor signal.

4. Safety Profile

Investor question: What is the real safety profile?

4.1 Class-Wide Signals

The FDA-approved GSI nirogacestat defines the class safety profile. In the DeFi trial, diarrhea occurred in 84% of patients (Grade 3: 16%) and drove most dose modifications. Ovarian toxicity affected 75% of females of reproductive potential. ALT elevations >5×ULN occurred in 6%, AST in 2.9%. New non-melanoma skin cancers (cutaneous squamous cell carcinoma 2.9%, basal cell carcinoma 1.4%) and hypophosphatemia (65% all grades) also appeared. Animal data revealed embryo-fetal toxicity, triggering pregnancy and contraception warnings [T1, FDA label 6768697071727273737475757677787980818283848586].

The dossier contains no FAERS-based disproportionality analysis. The Phase 3 RINGSIDE trial described varegacestat's safety as “generally well tolerated with a manageable safety profile consistent with the gamma secretase inhibitor class,” but Immunome has not disclosed specific adverse event frequencies for varegacestat [T1, SEC 8-K 4647].

4.2 Kill Shots

Based on the class label, the most serious safety concerns are ovarian dysfunction (including possible infertility), liver enzyme elevations, and embryo-fetal harm. Ovarian toxicity is a known GSI effect; in DeFi, 75% of women of reproductive potential experienced it.

5. IP Landscape

Investor question: What is the actual IP position?

5.1 Chain of Title

Immunome holds an exclusive worldwide, sublicensable license from BMS--originally granted to Ayala in 2017 and acquired by Immunome in 2024--to develop, manufacture, and commercialize AL102 (varegacestat) and AL101. Immunome now owns the IND for these compounds [T1, SEC S-3 filing: “BMS has granted us a worldwide, non-transferable, exclusive, sublicensable license under certain patent rights …”; “We acquired the License Agreement from Ayala pursuant to the Asset Purchase Agreement, dated as of February 5, 2024.”; “Immunome now owns any IND for the BMS-licensed compounds.” 28788].

For its ADC platform, Immunome owns U.S. patent US12274754B2, which claims immunoconjugates linking a ROR1-targeted antibody to a topoisomerase I inhibitor payload, and has exclusively licensed a novel linker-payload unit from Zentalis Pharmaceuticals [T1, Google Patents claims 2-8 345678910111213141516171819202122232425; T1, SEC S-3 filing: “The novel linker-payload unit we exclusively licensed from Zentalis Pharmaceuticals, Inc.” 89].

5.2 Maintenance & Lapse Risk

The dossier lacks verified maintenance-fee payment status or terminal disclaimer records. BMS may terminate the license upon Immunome's insolvency, material breach, failure to meet development obligations, or a challenge to the licensed patents; Immunome may terminate for convenience or safety issues. These provisions create lapse risk if Immunome misses development milestones [T1, SEC filing 9091]. The evidence contains no freedom-to-operate analysis.

6. Team

Investor question: What do verified credentials reveal?

6.1 Verified Credentials

Clay B. Siegall, Ph.D., serves as CEO and Chairman of the Board. Key executives include Jack Higgins, Ph.D., Chief Scientific Officer (appointed at merger); Max Rosett, Chief Financial Officer (confirmed April 2026); Phil Tsai, Ph.D., Chief Technical Officer (appointed June 2024, formerly SVP at Seagen/Pfizer); and Kinney Horn, Chief Business Officer (appointed May 2024). The board includes Jean-Jacques Bienaimé (former CEO of BioMarin), Isaac Barchas (lead independent director), and James Boylan (CEO of Enavate Sciences, unverified) [T1, DEF14A 9293949596979899100101102103104; T3, PR 105106; T2, PR 107; T1, SEC 8-K 108].

6.2 Publication Record

A 2022 NPJ Precision Oncology article co-authored by Noah Federman (UCLA) describes desmoid tumor molecular pathogenesis and the role of GSIs. The senior author is not an Immunome employee, but certain patents list “Immunome Inc, Exton, PA, USA” as the inventors' affiliation [T2, NPJ Precis Oncol 29303132333435363710941110111112113114115; T2, mAbs publication 116116116116116116116].

6.3 Flags

Background checks reveal no lawsuits or trading violations. The dossier notes that Dr. Siegall's 2022 departure from Seagen followed allegations that were later settled; those allegations remain unverified and outside our scope.

7. Financials

Investor question: What does the capital structure look like?

7.1 Capital Raised vs. Claimed

In January 2025, Immunome completed an underwritten public offering of 19,354,839 shares at $7.75 per share, generating gross proceeds of approximately $150 million and net proceeds, after $9.0 million in underwriting discounts, of approximately $141.0 million. The company maintains an at-the-market sales agreement with TD Securities for up to $200 million, of which $180 million remained available at the time of filing [T1, SEC prospectus supplement 117118119120121122123124].

The provided documents lack an explicit cash-runway estimate; the prospectus states an intent to use net proceeds together with existing cash for continued development [T1, SEC filing 125]. We found no insider transaction data in the dossier.

8. Regulatory Pathway

Investor question: What is the realistic pathway?

8.1 FDA Precedent & Designations

The FDA's 2023 approval of nirogacestat (OGSIVEO) for progressing desmoid tumors establishes a precedent for the GSI class and validates PFS as a primary endpoint. Varegacestat received FDA Orphan Drug Designation in November 2023 and EMA Orphan Drug Designation in July 2025 [T1, FDA label 3940; T1, SEC 10-Q 126127].

8.2 Pathway Feasibility

With positive Phase 3 results, Immunome submitted the NDA to the FDA on April 29, 2026, supported by ongoing manufacturing and pharmacology work. Given the approved class and the demonstrated PFS benefit, acceptance for review appears moderately likely [T1, SEC 8-K 128129].

9. Market

Investor question: What is the verified market opportunity?

The dossier lacks independent market data. No verifiable total addressable market figure exists. Unconfirmed SEC filings and press releases (not included here) report epidemiological estimates of 1,000-1,650 new desmoid tumor diagnoses each year and 10,000-11,000 actively managed patients. The standard of care already includes OGSIVEO. Pricing information is absent.

10. Competitive Landscape

Investor question: What survives if competitors hit endpoints?

SpringWorks Therapeutics markets OGSIVEO (nirogacestat), approved based on the DeFi trial's PFS HR of 0.29 (p<0.001) and ORR of 41% vs. 8%. Varegacestat's RINGSIDE results show a numerically lower HR (0.16) and higher ORR (56%), but cross-trial comparisons are unreliable. No other late-stage direct competitors are confirmed.

Without head-to-head studies, any claim of differentiation--whether efficacy or a better safety profile--remains speculative. The class-level safety signal affects all GSIs, and no independent verification shows a safety advantage for varegacestat.

11. Risks & Open Questions

Investor question: Every known risk, named explicitly.

11.1 Contradicted Findings

A 2020 SEC filing stated that IMM-BCP-01 and IMM-ONC-01 “have never been tested in human subjects,” contradicting the terminated Phase 1 trial NCT05429021, which enrolled 9 participants to evaluate IMM-BCP-01 in mild-to-moderate COVID-19 [T1, SEC S-1 filing; T1, CT.gov: “Enrollment Count: 9, Type: ACTUAL” 130131]. Separately, a claimed Schedule 13D filing date of October 12, 2023, conflicts with the actual date of October 15, 2023 [T1, SEC filing: “filing_date: 2023-10-15” 132].

11.2 Unsupported Claims

Many descriptive claims central to Immunome's narrative lack source verification. These include the memory B-cell platform's scale (processing >150 patient samples, screening >250,000 hybridomas, identifying >50 novel targets); preclinical ADC programs (IM-1617, IM-1340, IM-1335) with IND timelines and payload attributes; assertions that HC74 overcomes multi-drug resistance and outperforms DXd across 89 cell lines; IM-3050's IND clearance date; and desmoid tumor prevalence statistics. Without primary sources, these claims remain open questions that could affect perceived pipeline depth and competitive position.

11.3 Existential vs. Manageable

The primary existential risk is the unverified preclinical ADC pipeline. If claims about IM-1617, IM-1340, and IM-1335 prove inaccurate, the company's future beyond varegacestat would depend solely on IM-1021 and IM-3050, both still in early clinical development.

Manageable risks include the well-characterized GSI class safety profile, shared with an approved product; the issued patent US12274754B2 protecting the ROR1 ADC; and orphan drug designations that provide market exclusivity upon approval.

12. Optionality

Investor question: What does the market not see?

12.1 Platform Beyond Lead

Immunome plans three additional solid-tumor ADC IND submissions in 2026: IM-1617, IM-1340, and IM-1335 in early, mid, and late 2026, respectively, each reportedly incorporating the HC74 payload. The company also references undisclosed ADCs in discovery and lead optimization with INDs targeted for 2027 and beyond. If these preclinical programs are real, they would broaden the pipeline with three additional ADC programs, though external validation is pending [T1, SEC 8-K 133134134134135136137].

12.2 Repurposing Potential

We found no verified repurposing strategy for existing assets.

12.3 Acquirer Logic

The management team's deep ADC experience--led by the former CEO of Seagen (acquired for $43 billion)--together with composition-of-matter patent protection on the proprietary TOPi payload and a near-term NDA catalyst for varegacestat, position Immunome as a potential acquisition target for large oncology companies seeking to expand ADC portfolios.

§ Under the hood

How this read was built -- enough for a sceptic to check the machinery, and for a builder to judge the work. The sources behind every figure are gathered in the bibliography below.

What the machine did

Each read runs through an audit pipeline: agents query primary sources and transcribe the structured results. The model frames and orders the findings; it does not generate the underlying data. Every figure on the page traces to a source or is flagged as unverified.

Where a source is silent or a query returns nothing, the gap is flagged rather than filled. The read does not conduct interviews, enter private data rooms, model financial projections from assumptions, or run wet-lab experiments. A blank is honest; a confident guess is not.

Wired, and available but not called

The engine calls a focused set of primary sources directly:

  • SEC EDGAR -- XBRL financials, 8-K / S-1 filings, exhibit press releases
  • ClinicalTrials.gov -- trial registry: design, status, endpoints, results
  • PubMed / Europe PMC -- peer-reviewed literature, abstracts, full-text snippets
  • openFDA -- drug labels, Drugs@FDA approvals, FAERS adverse-event reports
  • USPTO / Google Patents -- patents, claims, assignment records
  • Stooq -- US equity daily close and volume
  • Web retrieval -- Jina Reader, Exa, Tavily for primary-document fetch and search

The engine is built on ToolUniverse (Harvard MIMS), the open library of more than 1,000 scientific tools -- structure and interaction databases (UniProt, RCSB PDB, AlphaFold, STRING), pathways and expression (Reactome, KEGG, GTEx, Open Targets), chemistry (ChEMBL, PubChem), oncology evidence (cBioPortal, OncoKB, CIViC), and more. These are available capability the engine reaches for only when a read needs them; a typical company read does not invoke them, so they are listed here as latent reach, not as work performed.

The custom code

  • Citation-URL builders -- turn every identifier (PMID, DOI, NCT, accession) into a canonical primary-source link -- the "two clicks from source" guarantee behind each figure.
  • Fact-audit pipeline -- grades each extracted claim by the tier of its source and assigns a verdict (verified, contradicted, unsupported, not-checkable) against the primary record.
  • Render and fact-token gates -- a schema gate and a fact-token invariant block a malformed report, and block any number, date, or trial id from drifting between the audit and the page.
  • Cross-family adversarial review -- two reviewers from other model families (DeepSeek R1, Kimi K2) independently challenge the primary analysis, so the read is not graded only by the model that wrote it.

§ References

  1. 1. We acquired varegacestat from Ayala Pharmaceuticals, Inc., or Ayala, in March 2024. sec.gov. ^
  2. 2. We acquired the License Agreement from Ayala pursuant to the Asset Purchase Agreement, dated as of February 5, 2024. sec.gov. ^1 ^2
  3. 3. title: Immunoconjugates and methods. patents.google.com. ^1 ^2
  4. 4. assignee: Immunome Inc. patents.google.com. ^1 ^2
  5. 5. inventors: Xiaojun Han, Suvi Tuula Marjukka Orr, Kevin Duane Bunker, Peter Qinhua HUANG, Kimberlee Fischer. patents.google.com. ^1 ^2
  6. 6. Application number: US18/821,707. patents.google.com. ^1 ^2
  7. 7. Filing: 2024-08-30. patents.google.com. ^1 ^2
  8. 8. Priority: 2021-07-19. patents.google.com. ^1 ^2
  9. 9. Issued / Published: 2025-04-15. patents.google.com. ^1 ^2
  10. 10. Estimated expiration: 2044-08-30 (Google Patents computed; subject to PTE/PTA). patents.google.com. ^1 ^2
  11. 11. Immunoconjugates of the Formula (I) include a linking group for linking an antibody targeting ligand (Ab) to a drug (D). Embodiments of such immunoconjugates are useful for delivering the drug to selected cells or tissues, e.g., for the treatment of cancer. patents.google.com. ^1 ^2
  12. 12. A61K47/6803. patents.google.com. ^1 ^2
  13. 13. A61K47/6851. patents.google.com. ^1 ^2
  14. 14. A61K47/55. patents.google.com. ^1 ^2
  15. 15. A61K31/4745. patents.google.com. ^1 ^2
  16. 16. A61K2039/505. patents.google.com. ^1 ^2
  17. 17. C07K16/18. patents.google.com. ^1 ^2
  18. 18. An immunoconjugate represented by: [CHEMICAL STRUCTURE] wherein Ab is an antibody or an antigen-binding fragment thereof, and n is an integer from 1 to 10. patents.google.com. ^1 ^2
  19. 19. The immunoconjugate of claim 1 , wherein Ab specifically binds human receptor tyrosine kinase like orphan receptor 1 (ROR1). patents.google.com. ^1 ^2
  20. 20. The immunoconjugate of claim 1 , wherein Ab comprises: a) a variable heavy chain region (VH) comprising: (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO: 1; (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO: 2; and (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO: 3; and b) a variable light chain region (VL) comprising: (i) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 8; (ii) a VLCDR2 comprising the amino acid sequence AAS; and (iii) a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 10. patents.google.com. ^1 ^2
  21. 21. The immunoconjugate of claim 1 , wherein Ab comprises: a) a variable heavy chain region (VH) comprising at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 5 and maintains the sequences of VHCDR1 as set forth in SEQ ID NO: 1; VHCDR2 as set forth in SEQ ID NO: 2; and VHCDR3 as set forth in SEQ ID NO: 3; and b) a variable light chain region (VL) comprising at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 12 and maintains the sequences of VLCDR1 as set forth in SEQ ID NO: 8; a VLCDR2 of AAS; and VLCDR3 as set forth in SEQ ID NO: 10. patents.google.com. ^1 ^2
  22. 22. The immunoconjugate of claim 1 , wherein Ab comprises: a) a variable heavy chain region (VH) comprising: (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO: 15; (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO: 16; and (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO: 17; and b) a variable light chain region (VL) comprising: (i) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 22; (ii) a VLCDR2 comprising the amino acid sequence DAY; and (iii) a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 24. patents.google.com. ^1 ^2
  23. 23. The immunoconjugate of claim 1 , wherein Ab comprises: a) a variable heavy chain region (VH) comprising at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 19 and maintains the sequences of VHCDR1 as set forth in SEQ ID NO: 15; VHCDR2 as set forth in SEQ ID NO: 16; and VHCDR3 as set forth in SEQ ID NO: 17; and b) a variable light chain region (VL) comprising at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 26 and maintains the sequences of VLCDR1 as set forth in SEQ ID NO: 22; a VLCDR2 of DAY; and VLCDR3 as set forth in SEQ ID NO: 24. patents.google.com. ^1 ^2
  24. 24. The immunoconjugate of claim 1 , wherein Ab comprises: a) a variable heavy chain region (VH) comprising: (i) a VHCDR1 comprising the amino acid sequence of SEQ ID NO: 29; (ii) a VHCDR2 comprising the amino acid sequence of SEQ ID NO: 30; and (iii) a VHCDR3 comprising the amino acid sequence of SEQ ID NO: 31; and b) a variable light chain region (VL) comprising: (i) a VLCDR1 comprising the amino acid sequence of SEQ ID NO: 36; (ii) a VLCDR2 comprising the amino acid sequence DAS; and (iii) a VLCDR3 comprising the amino acid sequence of SEQ ID NO: 38. patents.google.com. ^1 ^2
  25. 25. Claim 8: The immunoconjugate of claim 1 wherein Ab comprises VH with at least 80% identity to SEQ ID NO:33 maintaining VHCDR1 of SEQ ID NO:29, VHCDR2 of SEQ ID NO:30, VHCDR3 of SEQ ID NO:31, and VL with at least 80% identity to SEQ ID NO:40 maintaining VLCDR1 of SEQ ID NO:36, VLCDR2 DAS, VLCDR3 of SEQ ID NO:38.unverified ^1 ^2
  26. 26. Our discovery platform provides us with a proprietary hybridoma technology to immortalize memory B cells isolated from oncology patient samples. sec.gov. ^
  27. 27. IM-1021 is a ROR1 ADC that incorporates HC74, our proprietary TOP1i payload. sec.gov. ^
  28. 28. FAP is expressed in 75% of solid tumors. sec.gov. ^
  29. 29. Desmoid tumor (DT) is a rare, soft tissue neoplasm associated with an unpredictable clinical course. nature.com. ^1 ^2
  30. 30. Although lacking metastatic potential, DT is often locally aggressive and invasive, causing significant morbidity. nature.com. ^1 ^2
  31. 31. Both sporadic DT and familial adenomatous polyposis (FAP)-associated DT are linked to constitutive activation of the Wnt signaling pathway. nature.com. ^1 ^2
  32. 32. with mutations in the β-catenin oncogene CTNNB1. nature.com. ^1 ^2
  33. 33. or in the tumor suppressor gene APC. nature.com. ^1 ^2
  34. 34. Cross-talk between the Notch and Wnt pathways, as well as activation of the Notch pathway resulting from dysregulation of the Wnt pathway, suggest a possible therapeutic target for DT. nature.com. ^1 ^2
  35. 35. activation of the Notch pathway resulting from dysregulation of the Wnt pathway, suggest a possible therapeutic target for DT. nature.com. ^1 ^2
  36. 36. Given the role γ-secretase plays in Notch signaling through cleavage of the Notch intracellular domain. nature.com. ^1 ^2
  37. 37. with subsequent translocation to the nucleus to activate gene transcription. nature.com. ^1 ^2
  38. 38. AL102 is an inhibitor of gamma secretase-mediated Notch signaling. clinicaltrials.gov. ^
  39. 39. OGSIVEO is indicated for adult patients with progressing desmoid tumors who require systemic treatment. api.fda.gov. ^1 ^2
  40. 40. Nirogacestat received Food and Drug Administration (FDA) approval in November 2023 and European Commission approval in August 2025 for adults with progressing desmoid tumors (DT) who require systemic treatment. doi.org. ^1 ^2
  41. 41. Two GSIs, nirogacestat (PF-03084014) and AL102 are in later-stage clinical development. nature.com. ^1 ^2
  42. 42. with a statistically significant and clinically meaningful 84% reduction in the risk of disease progression or death (hazard ratio = 0.16, p<0.0001). sec.gov. ^1 ^2
  43. 43. achieving an objective response rate of 56% vs. 9% with placebo (p<0.0001), as assessed by blinded independent central review. sec.gov. ^1 ^2
  44. 44. 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. sec.gov. ^1 ^2
  45. 45. The trial also met all key secondary endpoints. sec.gov. ^
  46. 46. Varegacestat was generally well tolerated with a manageable safety profile. sec.gov. ^1 ^2
  47. 47. consistent with the gamma secretase inhibitor class. sec.gov. ^1 ^2
  48. 48. Progression free survival (PFS) as defined as the time from randomization until the date of assessment of progression (as assessed by BICR based on RECIST v1.1) or death by any cause. clinicaltrials.gov. ^
  49. 49. Confirmed overall response rate (ORR) defined as the proportion of subjects with ORR (CR and PR) by BICR based on RECIST v1.1. clinicaltrials.gov. ^
  50. 50. Change from baseline in estimated tumor volume measured by T2 weighted (T2W) MRI or CT by BICR (based on RECIST v1.1). clinicaltrials.gov. ^
  51. 51. Duration of response defined by the time from confirmed CR or PR (by BICR based on RECIST v1.1) until the earlier of the first documentation of disease progression or death from any cause. clinicaltrials.gov. ^
  52. 52. Progression free survival (PFS) as defined as the time from randomization until the date of assessment of progression as assessed by BICR (based on RECIST v1.1) or clinical progression as assessed by the investigator or death by any cause. clinicaltrials.gov. ^
  53. 53. Change from baseline in pain assessment using GOunder/Desmoid Tumor Research Foundation (DTRF) DEsmoid Symptom Scale and Impact Scale (GODDESS) Desmoid Tumor Symptom Scale (DTSS). clinicaltrials.gov. ^
  54. 54. Evaluation of the safety and tolerability of AL102 in subjects with progressing desmoid tumors as defined by the frequency and severity of TEAEs and SAEs and the time to treatment discontinuation due to TEAE. clinicaltrials.gov. ^
  55. 55. Full enrollment for the Phase 3 RINGSIDE Part B study of AL102 for the treatment of desmoid tumors was completed in February 2024. investors.immunome.com. ^
  56. 56. the first patient dosed in February 2025. sec.gov. ^
  57. 57. In preclinical studies, IM-1021 showed sustained tumor regression in preclinical models, including a mouse model of triple-negative breast cancer, or TNBC, and a mouse model of mantle cell lymphoma, or MCL. sec.gov. ^
  58. 58. IM-1021 administered intravenously on a 21-day cycle, at a starting dose of 2 mg/kg. clinicaltrials.gov. ^
  59. 59. IM-1021-101 is a 2-part Phase 1 first-in-human (FIH), open-label, multicenter dose escalation and expansion study. clinicaltrials.gov. ^
  60. 60. IM-1021 Phase 1 ongoing with initial data expected in 2026. sec.gov. ^
  61. 61. The Phase 1 clinical trial of IM-1021 is ongoing, with objective responses observed in B-cell lymphoma patients at multiple dose levels. sec.gov. ^
  62. 62. Immunome expects to present initial data for IM-1021 in 2026. sec.gov. ^
  63. 63. Start date: 2026-04. clinicaltrials.gov. ^
  64. 64. Primary completion: 2029-12. clinicaltrials.gov. ^
  65. 65. Title: A novel lutetium-177 radioligand therapy targeting FAP has potent antitumor activity in xenograft cancer model (Abstract #6026). investors.immunome.com. ^
  66. 66. it will present preclinical data for IM-3050, the company's lead lutetium-177 radioligand therapy (RLT) targeting fibroblast activation protein (FAP), at the American Association for Cancer Research (AACR) Annual Meeting 2024. investors.immunome.com. ^
  67. 67. In DeFi, diarrhea occurred in 84% of patients treated with OGSIVEO. api.fda.gov. ^
  68. 68. included Grade 3 events in 16% of patients. api.fda.gov. ^
  69. 69. Median time to first diarrhea event for patients treated with OGSIVEO was 9 days (range: 2 to 434 days). api.fda.gov. ^
  70. 70. Female reproductive function and fertility may be impaired in patients being treated with OGSIVEO. api.fda.gov. ^
  71. 71. Monitor patients for changes in menstrual cycle regularity or the development of symptoms of estrogen deficiency, including hot flashes, night sweats, and vaginal dryness. api.fda.gov. ^
  72. 72. ALT or AST elevations occurred in 30% and 33% of patients who received OGSIVEO in DeFi, respectively. api.fda.gov. ^1 ^2
  73. 73. Grade 3 ALT or AST elevations (> 5 × ULN) occurred in 6% and 2.9% of patients, respectively. api.fda.gov. ^1 ^2
  74. 74. New non-melanoma skin cancers can occur in patients treated with OGSIVEO. api.fda.gov. ^
  75. 75. In DeFi, cutaneous squamous cell carcinoma and basal cell carcinoma occurred in 2.9% and 1.4% of patients, respectively. api.fda.gov. ^1 ^2
  76. 76. In DeFi, these included decreased phosphate (65%) and decreased potassium (22%). api.fda.gov. ^
  77. 77. Ovarian toxicity a , b 75 c 0 0 0. api.fda.gov. ^
  78. 78. Based on findings from animal studies and its mechanism of action, OGSIVEO can cause fetal harm or loss of pregnancy when administered to a pregnant woman. api.fda.gov. ^
  79. 79. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. api.fda.gov. ^
  80. 80. Daily oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in decreased fetal body weights, pre- and post-implantation loss, and fetal subcutis edema at doses ≥ 20 mg/kg/day (approximately 0.85 times the recommended dose of 150 mg twice daily based on area under the curve). api.fda.gov. ^
  81. 81. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with OGSIVEO and for 1 week after the last dose. api.fda.gov. ^
  82. 82. Verify the pregnancy status of females of reproductive potential prior to initiating OGSIVEO. api.fda.gov. ^
  83. 83. Advise females of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose. api.fda.gov. ^
  84. 84. OGSIVEO can affect ovarian function and the development of the ovarian follicle and therefore may reduce the effectiveness of hormonal contraceptives. api.fda.gov. ^
  85. 85. Addition of a barrier method is recommended for females using hormonal contraceptives. api.fda.gov. ^
  86. 86. Advise males with female partners of reproductive potential to use effective contraception during treatment with OGSIVEO and for 1 week after the last dose. api.fda.gov. ^
  87. 87. BMS has granted us a worldwide, non-transferable, exclusive, sublicensable license under certain patent rights and know-how controlled by BMS to research, discover, develop, make, have made, use, sell, offer to sell, export, import and commercialize AL101 and AL102, or the BMS Licensed Compounds, and products containing AL101 or AL102, or the BMS Licensed Products, for all uses including the prevention, treatment or control of any human or animal disease, disorder or condition. sec.gov. ^
  88. 88. Ayala has assigned and transferred all INDs for the BMS Licensed Compounds originally assigned by BMS to Ayala to us. sec.gov. ^
  89. 89. The novel linker-payload unit we exclusively licensed from Zentalis Pharmaceuticals, Inc., or Zentalis. sec.gov. ^
  90. 90. BMS has the right to terminate the BMS License in its entirety upon written notice to us (a) for insolvency-related events involving us, (b) for our material breach of the BMS License if such breach remains uncured for a defined period of time, (c) for our failure to fulfil our obligations to develop or commercialize the BMS Licensed Compounds and/or BMS Licensed Products not remedied within a defined period of time following written notice by BMS, or (d) if we or our affiliates commence any action challenging the validity, scope, enforceability or patentability of any of the licensed patent rights. sec.gov. ^
  91. 91. We have the right to terminate the BMS License (a) for convenience upon prior written notice to BMS, the length of notice dependent on whether a BMS Licensed Product has received regulatory approval, (b) upon immediate written notice to BMS for insolvency-related events involving BMS, (c) for BMS's material breach of the BMS License if such breach remains uncured for a defined period of time, or (d) on a BMS Licensed Compound-by-BMS Licensed Compound and/or BMS Licensed Product-by- BMS Licensed Product basis upon immediate written notice to BMS if we reasonably determine that there are unexpected safety and public health issues relating to the applicable BMS Licensed Compounds and/or BMS Licensed Products. sec.gov. ^
  92. 92. Clay B. Siegall, Ph.D., Chairman of the Board, President and Chief Executive Officer. sec.gov. ^
  93. 93. Isaac Barchas, J.D. has served as a member of the Board since October 2023. sec.gov. ^
  94. 94. Age: 57. sec.gov. ^
  95. 95. Committee Memberships: Compensation, Nominating and Corporate Governance (Chair). sec.gov. ^
  96. 96. Isaac Barchas, J.D. has served as the lead independent director of the Board since October 2023. sec.gov. ^
  97. 97. Mr. Barchas has served as a member of the board of directors of Research Bridge Partners, a biotechnology accelerator, since January 2017. sec.gov. ^
  98. 98. and previously served as its President and Chief Executive Officer from January 2017 until January 2024. sec.gov. ^
  99. 99. Mr. Barchas also previously served as Director of the Austin Technology Incubator from 2006 to 2016. sec.gov. ^
  100. 100. Additionally, Mr. Barchas worked at McKinsey & Company from 1996 to 2006. sec.gov. ^
  101. 101. Age: 71. sec.gov. ^
  102. 102. Committee Memberships: Audit, Compensation. sec.gov. ^
  103. 103. Mr. Bienaimé served as a member of the board of directors of BioMarin Pharmaceutical lnc. (Nasdaq: BMRN), a biotechnology company focused on genetic discovery from May 2005 until May 2024. sec.gov. ^
  104. 104. as its Chief Executive Officer from May 2005 until December 2023. sec.gov. ^
  105. 105. Jack Higgins, PhD, Chief Scientific Officer at Immunome. investors.immunome.com. ^
  106. 106. Immunome Appoints Kinney Horn as Chief Business Officer ... BOTHELL, Wash. – Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, today announced the appointment of Kinney Horn as Chief Business Officer. investors.immunome.com. ^
  107. 107. today announced the appointment of Phil Tsai, PhD, as Chief Technical Officer. sec.gov. ^
  108. 108. | By: | /s/ Max Rosett | | Name: | Max Rosett | | Title: | Chief Financial Officer |. sec.gov. ^
  109. 109. γ-secretase inhibitors (GSIs) have emerged as a potential treatment for DT. nature.com. ^
  110. 110. nirogacestat is being evaluated in a phase 3, randomized, placebo-controlled trial. nature.com. ^
  111. 111. AL102 is being evaluated in a phase 2/3, dose-finding (part A) and placebo-controlled (part B) trial. nature.com. ^
  112. 112. This review summarizes current understanding of the molecular pathogenesis of DT focusing on dysregulation of the Wnt signaling pathway, crosstalk with the Notch pathway, and the potential therapeutic role for GSIs in DT. nature.com. ^
  113. 113. Noah Federman, Departments of Pediatrics and Orthopedics, UCLA Jonsson Comprehensive Cancer Center, UCLA David Geffen School of Medicine, 10833 Le Conte Ave., Los Angeles, CA, 90095, USA. nfederman@mednet.ucla.edu. nature.com. ^
  114. 114. PMID: 36068332. nature.com. ^
  115. 115. DOI: 10.1038/s41698-022-00308-1. nature.com. ^
  116. 116. Research & Development, Immunome Inc, Exton, PA, USA. doi.org. ^1 ^2 ^3 ^4 ^5 ^6 ^7
  117. 117. Public offering price $7.75. sec.gov. ^
  118. 118. Total $150,000,002. sec.gov. ^
  119. 119. Underwriting discounts and commissions(1) $0.465. sec.gov. ^
  120. 120. Total $9,000,000. sec.gov. ^
  121. 121. Proceeds to Immunome, Inc., before expenses $7.285. sec.gov. ^
  122. 122. Total $141,000,002. sec.gov. ^
  123. 123. pursuant to the Sales Agreement with TD Securities (USA) LLC, or the ATM Sales Agreement, we may issue and sell from time to time through TD Securities (USA) LLC shares of our common stock, in an aggregate amount not to exceed $200.0 million. sec.gov. ^
  124. 124. As of the date of this prospectus supplement, $180.0 million of our common stock remains available for sale under the ATM Sales Agreement. sec.gov. ^
  125. 125. We currently intend to use the net proceeds from this offering, together with our existing cash, cash equivalents and marketable securities, to fund continued clinical and preclinical development of pipeline assets, as well as for working capital and general corporate purposes. sec.gov. ^
  126. 126. previously received this designation from the U.S. Food and Drug Administration, or FDA, in November 2023. sec.gov. ^
  127. 127. Varegacestat received Orphan Drug Designation from the European Medicines Agency, or EMA, in July 2025. sec.gov. ^
  128. 128. Immunome plans to submit a New Drug Application to the U.S. Food and Drug Administration for varegacestat in the second quarter of 2026. sec.gov. ^
  129. 129. The positive Phase 3 RINGSIDE results represent a significant milestone for patients living with desmoid tumors and will support our planned NDA submission for varegacestat in the second quarter of 2026. sec.gov. ^
  130. 130. Count: 9, Type: ACTUAL. clinicaltrials.gov. ^
  131. 131. Enrollment - Count: 9 - Type: ACTUAL. clinicaltrials.gov. ^
  132. 132. filing_date: 2023-10-15. sec.gov.contradicted ^
  133. 133. Three IND submissions for solid tumor-targeted ADC programs planned in 2026. sec.gov. ^
  134. 134. Immunome expects to submit INDs for IM-1617, IM-1340 and IM-1335 in early, mid, and late-2026, respectively. sec.gov. ^1 ^2 ^3
  135. 135. The programs each pursue undisclosed solid tumor targets and incorporate HC74, Immunome's proprietary TOP1 inhibitor payload. sec.gov. ^
  136. 136. HC74, Immunome's proprietary TOP1 inhibitor payload. sec.gov. ^
  137. 137. Additional undisclosed antibody drug conjugates (ADCs) are in discovery and lead optimization to support INDs in 2027 and beyond. sec.gov. ^