Immunome (NASDAQ:IMNM) CEO and Chairman Clay Siegall outlined the company’s approach to building an oncology-focused pipeline and discussed recent clinical and regulatory milestones during a conversation with Guggenheim Senior Biotech Analyst Michael Schmidt.
Pipeline strategy: targeted oncology focus
Siegall said Immunome is building a targeted therapy pipeline centered on two core modalities: cell-surface targeting agents and small molecules that act inside the cell. He emphasized that the company is not pursuing cell therapy approaches such as CAR-T, citing the different infrastructure required.
Varegacestat in desmoid tumors: Phase 3 success and planned FDA submission
In discussing the company’s gamma secretase inhibitor program (varegacestat) in desmoid tumors, Siegall said Immunome reported positive Phase 3 results and has so far only released topline data. He noted the study included roughly 10 endpoints across primary, secondary, and tertiary measures, and said the drug “won on all of them.”
On the commercial opportunity, Siegall characterized desmoid tumors as a painful disease and a subset of sarcoma. He cited approximately 1,600 new cases per year in the U.S. and said around 11,000 prevalent U.S. patients seek therapy each year, with an estimated prevalence pool of nearly 30,000. While Immunome has not provided formal guidance, he argued the patient population could support a “very substantial” product.
Siegall also highlighted the magnitude of the Phase 3 effect size, stating the hazard ratio was 0.16. He said Immunome expects to submit an NDA “within the next few months” and expressed hope that the FDA would move quickly based on the results. He added that, based on pricing set by SpringWorks’ marketed product in the category, he believed a roughly 3,000-patient treated population could represent a billion-dollar market opportunity, and said he viewed that level as attainable for a strong drug.
On timing, Siegall described an internal push to accelerate the initial NDA submission package, noting that first submissions often take about six months due to manufacturing and quality documentation requirements. He said the team is working to move faster while ensuring the submission remains clear and navigable for FDA reviewers. He pointed to leadership experience within Immunome’s development organization—describing several key functions as staffed by former Seagen personnel—as a strength supporting execution.
Positioning versus the existing therapy
Schmidt noted that Ogsiveo is already on the market in desmoid tumors with the same mechanism of action. Siegall argued that varegacestat could differentiate on multiple dimensions, including:
- Higher objective response rate and median tumor regression (relative comments were qualitative, without detailed figures in the discussion)
- Pain relief, which he said is especially important in this disease; he said additional pain-relief data will be presented at conferences
- Once-daily dosing compared with twice-daily dosing for the competitive product, which he said could improve compliance
Siegall said physician and patient interviews indicated dosing frequency and compliance are meaningful issues, and he suggested that doctors told Immunome they would favor once-daily dosing if efficacy is comparable. He also said Immunome’s view is that patients benefiting from the existing therapy should remain on it, but that new patients, patients not responding, and the broader prevalent pool represent the primary opportunity for switching and uptake after approval.
When asked about lessons from the competitor’s launch, Siegall said he could only draw inferences, but emphasized the importance of medical affairs engagement with physicians and conducting follow-on studies that answer practical questions doctors have about dosing and the timeline of pain relief. He contrasted “developing a drug” with “making a medicine,” describing work with clinicians on dose adjustments over time, including the possibility of lower maintenance dosing after initial tumor reduction.
ADC platform and IM-1021 (ROR1): early activity in Phase 1
Siegall also discussed Immunome’s antibody-drug conjugate (ADC) efforts and his long-standing involvement in the field, describing a goal of advancing what he called “ADC 3.0.” He said one of the limitations of earlier ADC approaches is vulnerability to resistance mechanisms such as efflux pumps, and he described designing payloads intended to avoid being pumped out. He also highlighted the importance of bystander activity—killing neighboring tumor cells in heterogeneous tumors—enabled by payload permeability after internalization.
Immunome’s first clinical ADC using this approach is IM-1021, which targets ROR1. Siegall said the program is in dose escalation and has shown objective responses at multiple dose levels, adding that early results have exceeded his expectations for the beginning of Phase 1. He emphasized that the key challenge now is optimizing dose and schedule, drawing on examples from prior Seagen programs where schedule changes improved the balance of efficacy and toxicity.
He said Immunome is expanding the trial footprint by adding U.S. and European sites, but did not provide a timeline for identifying a recommended Phase 2 dose or detailed plans for expansion cohorts, explaining that the company wants investigators to present results at an appropriate medical meeting.
Siegall also described ROR1 as primarily associated with liquid tumors and said Immunome is focused on diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma within the ongoing study. He suggested an initial path could target heavily pretreated patients (three or more prior therapies) and said he sees an accelerated approval opportunity, while noting the company is not yet ready to disclose full datasets.
Looking ahead, Siegall said Immunome plans to submit three additional INDs this year for solid tumor programs. He noted that a diagnostic tool may be important for identifying solid tumors with relevant ROR1 expression and said that tool exists but is still being qualified.
Finally, Siegall briefly noted that Immunome’s radioligand therapy program has been cleared by the FDA and is expected to start a clinical trial soon.
About Immunome (NASDAQ:IMNM)
Immunome, Inc is a clinical-stage biotechnology company focused on discovering and developing novel antibody-based therapeutics for oncology and infectious diseases. The company leverages a proprietary platform that mines the natural B-cell repertoire of patients with active disease to identify fully human monoclonal antibodies with unique mechanisms of action. Immunome’s approach is designed to uncover antibodies that engage the immune system in ways that traditional discovery methods may miss, enabling the development of therapies with potential for improved efficacy and safety profiles.
The company’s lead oncology program, IMM-BCP-01, is a multi-antibody cocktail currently in early-stage clinical trials targeting breast cancer antigens.
