Philadelphia-based Medicus Oncology gains global development and commercialization rights to PF-08046031 (CD228V), a melanotransferrin-targeted antibody-drug conjugate (ADC) originating from Pfizer’s Seagen acquisition, as Pfizer retains a co-development role, milestone eligibility, and tiered royalties.
Medicus Pharma Ltd. (Nasdaq: MDCX), through its wholly owned subsidiary Medicus Oncology, has entered into a co-development and license agreement with Pfizer Inc. (NYSE: PFE) covering PF-08046031, also designated CD228V, an early clinical-stage antibody-drug conjugate (ADC) directed against melanotransferrin (CD228, also known as MELTF or MFI2). The agreement, disclosed in a filing with the U.S. Securities and Exchange Commission, grants Medicus an exclusive, sublicensable, worldwide license to develop, manufacture, and commercialize the asset across human diseases and disorders, subject to certain rights and oversight retained by Pfizer.
Deal Structure
Under the terms of the agreement, Medicus assumes responsibility for the clinical development, manufacturing, and commercialization of CD228V, while Pfizer retains ownership of the underlying patent estate and a continuing role in program oversight. Medicus is required to share development plans and budgets with Pfizer for review and comment, and Pfizer holds an option to fund all or part of future development activities once a pivotal trial has been initiated.
Financial terms reported in connection with the transaction include an upfront payment from Medicus to Pfizer, an additional payment due on the first anniversary of the agreement (September 2, 2027), and $2 million in development funding contributed by Pfizer to support early-stage advancement of the program.
Pfizer is eligible for development, regulatory, and sales milestone payments that could exceed $1 billion in aggregate across indications, in addition to tiered, low double-digit royalties on net sales during the applicable royalty term. Pfizer is also entitled to a share of specified proceeds should Medicus pursue sublicensing arrangements, strategic transactions, or a change of control. Absent early termination, the agreement remains in effect on a product-by-product and country-by-country basis until royalty obligations expire.
The asset originated from Pfizer’s 2023 acquisition of Seagen for approximately $43 billion, a transaction that brought several ADC programs, including this one, into Pfizer’s oncology pipeline. Pfizer discontinued its Phase I clinical evaluation of PF-08046031 earlier this year.
Rationale for the CD228 Target
Melanotransferrin was first characterized as a cell-surface protein in melanoma and has since been identified across a range of additional solid tumor types. Immunohistochemical and RNA-sequencing analyses cited in support of the program indicate that CD228 expression is limited in normal tissue but elevated across several malignancies associated with sensitivity to microtubule-disrupting payloads, including melanoma, squamous non-small cell lung cancer, triple-negative breast cancer, colorectal cancer, and pancreatic cancer.
The protein has also been proposed to play a role in tumor cell proliferation and migration, a characteristic that, combined with its restricted normal-tissue distribution, has supported its evaluation as an ADC target. To date, no CD228-directed therapy has received regulatory approval.
Molecular Composition and Preclinical Foundation
PF-08046031 is composed of hL49, a humanized IgG1 monoclonal antibody with specificity for CD228, conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable valine-citrulline linker of the vedotin class, at an average drug-to-antibody ratio of four.
The scientific rationale for targeting CD228 with an MMAE-based ADC draws on preclinical work published in Molecular Cancer Therapeutics describing SGN-CD228A, a related investigational construct built on the same hL49 antibody backbone. That study reported that the anti-CD228 antibody was efficiently internalized across multiple tumor cell types, with cytotoxic activity dependent on CD228 expression, internalization, and intrinsic sensitivity to MMAE.
The publication also evaluated a novel glucuronide linker, distinct from the valine-citrulline vedotin chemistry used in PF-08046031, and reported that this alternative linker improved intracellular MMAE retention and antitumor activity relative to a valine-citrulline comparator in melanoma models. Antitumor activity was further observed in melanoma, triple-negative breast cancer, and non-small cell lung cancer models with heterogeneous CD228 expression, and the authors noted that expression levels did not uniformly correlate with response across all tumor types, suggesting that other factors also contribute to ADC activity. The preclinical construct examined in that publication was evaluated in a Phase 1 trial (NCT04042480) in patients with advanced solid tumors.
Because the published preclinical data describe a construct with a different linker chemistry from the current clinical candidate, the two should be understood as related but distinct constructs, sharing a common antibody and payload class, rather than as interchangeable descriptions of a single molecule.
Clinical History
Pfizer’s Phase 1 trial of PF-08046031, previously known as SGN-CD228A (NCT06799533), began in May 2025 as a monotherapy study enrolling patients with advanced melanoma, with additional cohorts evaluating lung, head and neck, and esophageal tumors. Pfizer discontinued the trial earlier in 2026 as part of a broader reassessment of programs acquired through the Seagen transaction, prior to the licensing arrangement with Medicus.
Strategic Context
The agreement is one of several actions Pfizer has taken to reprioritize its post-Seagen ADC portfolio, which has also included discontinuing other early-stage programs and, separately, a Phase 3 trial failure in non-small cell lung cancer for a different Seagen-derived ADC.
Medicus has characterized the transaction as a foundational addition to its oncology pipeline and a step toward building a broader portfolio of differentiated ADC programs, noting the significance of advancing an asset originally developed within a major pharmaceutical company’s ADC platform and Pfizer’s continued involvement in development oversight.
What’s Next
Medicus has indicated that near-term priorities include advancing CD228V through further clinical development under its own sponsorship and incorporating the manufacturing, regulatory, and budgetary planning processes specified in the agreement with Pfizer.
As with any early-stage oncology asset transitioning between sponsors, the program’s forward path will depend on the design and outcome of subsequent clinical studies; PF-08046031/CD228V remains an investigational compound whose safety and efficacy have not been established.
Clinical trials
A Study to Learn About the Study Medicine Called PF-08046031 in Advanced Melanoma and Other Solid Tumors
ClinicalTrials.gov ID NCT06799533
A Study of SGN-CD228A in Advanced Solid Tumors – ClinicalTrials.gov ID NCT04042480
References
[1] Mazahreh R, Mason ML, Gosink JJ, et al. SGN-CD228A Is an Investigational CD228-Directed Antibody-Drug Conjugate with Potent Antitumor Activity across a Wide Spectrum of Preclinical Solid Tumor Models. Mol Cancer Ther. 2023;22(4):421-434. doi:10.1158/1535-7163.MCT-22-0401. PMID: 36800443; PMCID: PMC10068445.
[2] Giraddi R, Jin S, Olson DJ, Mikell I, Moskovitz E, Mazahreh R, Sandall SL. PF-08046031: A promising first-in-class antibody-drug conjugate for targeting novel tumor antigen in melanoma. Poster presented at: American Association for Cancer Research (AACR) Annual Meeting 2025; April 25-30, 2025; Chicago, IL. Abstract nr 2959
[3] Medicus Pharma Ltd. Form 8-K, filed with the U.S. Securities and Exchange Commission. [Link]
Featured Image: Business partners, partnership, handshake. Courtesy: © 2018 – 2026. Fotolia/Adobe. Used with permission.
DOI
