Antibody-cytokine fusions
Fully human antibody-cytokine fusion proteins designed to localise cytokines at the disease site.
View programsPhilogen's Pipeline
A pipeline built on targeted delivery
Clinical and preclinical programs across antibody-cytokine fusions and small-molecule therapeutics.
Pipeline orientation
- 21
- Clinical trials
Two product classes.
Small-molecule therapeutics
Small organic ligands coupled to cytotoxic drugs, radionuclides, immunomodulators or universal CAR-T adaptors.
View programsAntibody-cytokine fusions
PreIIIIII
+PreclinicalPhase IPhase IIPhase III
A combination of the immunocytokines L19IL2 and L19TNF developed as an intralesional treatment for advanced locoregional melanoma and non-melanoma skin cancers.
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Nidlegy is a combination of the immunocytokines L19IL2 and L19TNF, developed as an intralesional treatment for advanced locoregional melanoma and non-melanoma skin cancers. In preclinical melanoma models, the combination produced anti-cancer responses with cures in the treated animals.
In a Phase II study in stage III/IVM1a melanoma, complete responses were observed in injected lesions and in the majority of non-injected lesions, consistent with a systemic immune response following intralesional treatment. A Phase III study in locally advanced melanoma showed a statistically significant and clinically meaningful progression-free-survival benefit for Nidlegy followed by surgery compared with surgery alone. A Marketing Authorization Application has been submitted to EMA, and EMA has approved a combination-pack request.
A second Phase III study is running in the United States and Europe. Additional Phase II development includes combination with systemic anti-PD-1 therapy after checkpoint-inhibitor progression and studies in basal cell carcinoma and other non-melanoma skin cancers. The skin-cancer program is partnered with Sun Pharma in Europe, Australia and New Zealand.
Selected references
- Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma.Kähler et al., Ann Oncol. 2025 Jul 7:S0923-7534(25)00829-4 · PubMed
- Intratumoral administration of daromun in non-melanoma skin cancer: Preliminary results from a phase 2 non-randomized controlled trial.Flatz et al., J Eur Acad Dermatol Venereol. 2025 Feb;39(2):e147-e149 · PubMed
- Intralesional administration of L19-IL2/L19-TNF in stage III or stage IVM1a melanoma patients: results of a phase II study.Danielli et al., Cancer Immunol Immunother. 2015 Aug;64(8):999-1009 · PubMed
- Indication
- Melanoma and Non Melanoma Skin Cancers
- Payload
- IL-2 + TNF
- Composition
- Combination of immunocytokines L19IL2 + L19TNF
- Route
- Intralesional
- Partner
- Sun Pharma (partnered in Europe, Australia and New Zealand)
Indications
- Stage III B,C,D Melanoma (EU)Phase IIINCT02938299
- Stage III B,C,D Melanoma (US)Phase IIINCT03567889
- + Pembrolizumab - Stage IV Melanoma (US)Phase IINCT06284590
- Non-Melanoma skin cancer basket trial (EU)Phase IINCT04362722
- Non-Melanoma skin cancer basket trial (EU)Phase IINCT05329792
- 1st line locally advanced basal cell carcinoma (efficacy characterization study) (EU + US)Phase IINCT07227350
- 3rd line locally advanced basal cell carcinoma (EU + US)Phase IINCT07227870
- 2nd line locally advanced cutaneous squamous cell carcinoma (EU + US)Phase IINCT07228442
A fully human immunomodulatory product combining the L19 antibody, which targets EDB fibronectin, with TNF.
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Fibromun is a fully human immunomodulatory product consisting of the L19 antibody fused to TNF. L19 targets the EDB domain of fibronectin, allowing the fusion protein to localise preferentially at the disease site while sparing healthy organs.
Fibromun has shown potent activity as a single agent and in combination in immunocompetent preclinical models, including long-lasting complete responses. In sarcoma models, combinations with doxorubicin or dacarbazine cured the treated animals. Fibromun has also been studied as systemic monotherapy in solid tumours and through isolated limb perfusion in melanoma.
Clinical development spans soft-tissue sarcoma and glioma or glioblastoma. Encouraging Phase Ib results in metastatic soft-tissue sarcoma supported trials with registration potential, while preclinical and early clinical glioma results supported studies in newly diagnosed and recurrent disease. The program is partnered with Sun Pharma.
Selected references
- Targeted delivery of tumor necrosis factor in combination with CCNU induces a T cell-dependent regression of glioblastoma.Look et al., Sci Transl Med. 2023 May 24;15(697):eadf2281 · PubMed
- Dose escalation and expansion phase I studies with the tumour-targeting antibody-tumour necrosis factor fusion protein L19TNF plus doxorubicin in patients with advanced tumours, including sarcomas.Schliemann et al., Eur J Cancer. 2021 Jun;150:143-154 · PubMed
- The immunocytokine L19-TNF eradicates sarcomas in combination with chemotherapy agents or with immune check-point inhibitors.Corbellari et al., Anticancer Drugs. 2020 Sep;31(8):799-805 · PubMed
- Indication
- Glioblastoma and Soft Tissue Sarcoma
- Payload
- TNF
- Composition
- L19TNF
- Partner
- Sun Pharma
Indications
- + Doxorubicin - 1st line Soft-Tissue Sarcoma (EU)Phase IIINCT04650984EudraCT 2016-003239-38
- + Doxorubicin - 1st line Leiomyosarcoma (US)Phase IINCT03420014
- + Dacarbazine - pre-treated Soft-Tissue Sarcoma (EU)Phase IINCT04733183EudraCT 2018-004104-19
- + Lomustine - recurrent Glioma (EU)Phase IINCT04573192
- + Lomustine - recurrent Glioma (US)Phase IINCT06336291
- + Radiation + Temozolomide - 1st line Glioma (EU)Phase INCT04443010
The L19 antibody fused to IL-2, in clinical development for advanced non-small cell lung cancer in combination with radiation and anti-PD-1.
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Darleukin is a fully human immunostimulatory product consisting of the L19 antibody fused to IL-2. By targeting the EDB domain of fibronectin, it localises IL-2 at the disease site while sparing healthy organs.
The product activates tumour-specific T cells and NK cells at the disease site and has shown strong activity particularly in combination with other treatment modalities. It has been evaluated in several clinical studies as monotherapy and in combinations, with promising Phase I results reported when combined with stereotactic ablative radiotherapy.
Darleukin is being studied by the IMMUNOSABR consortium in advanced non-small-cell lung cancer in combination with stereotactic ablative radiotherapy and anti-PD-1 therapy.
Selected references
- Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial.Lieverse et al., BMC Cancer. 2020 Jun 15;20(1):557 · PubMed
- Radiotherapy combined with the immunocytokine L19-IL2 provides long-lasting antitumor effects.Zegers et al., Clin Cancer Res. 2015 Mar 1;21(5):1151-60 · PubMed
- Indication
- Various solid tumors
- Payload
- IL-2
- Composition
- L19IL2
Indications
- + Radiation - Non-Small Cell Lung Cancer (IMMUNOSABR, + anti-PD-1)Phase IINCT03705403
A vascular-targeting antibody fused to IL-12, in Phase I development for advanced solid tumours and DLBCL.
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Dodekin is a fully human immunostimulatory product consisting of a vascular-targeting antibody fused to IL-12. The construct is designed to localise at the disease site while sparing healthy organs.
It has shown activity as a single agent and in combination with checkpoint inhibitors in immunocompetent preclinical models, including long-lasting complete responses. In orthotopic glioblastoma models, single-agent treatment produced long-term tumour eradication in a proportion of treated animals.
The program entered clinical development in patients with advanced solid tumours and DLBCL whose disease had progressed after immune-checkpoint therapy.
Selected references
- The antibody-based delivery of interleukin-12 to solid tumors boosts NK and CD8+ T cell activity and synergizes with immune checkpoint inhibitors.Puca et al., Int J Cancer. 2020 May 1;146(9):2518-2530 · PubMed
- A novel anti-cancer L19-interleukin-12 fusion protein with an optimized peptide linker efficiently localizes in vivo at the site of tumors.Ongaro et al., J Biotechnol. 2019 Feb 10;291:17-25 · PubMed
- Indication
- Various Solid tumors
- Payload
- IL-12
- Composition
- Vascular-targeting antibody fused to IL-12
Indications
- Various Solid Tumors (and DLBCL, post immune-checkpoint blockade)Phase INCT04471987
The F8 antibody fused to IL-10, designed to localise the anti-inflammatory cytokine in inflamed tissue for rheumatoid arthritis.
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Dekavil is a fully human anti-inflammatory product consisting of the F8 antibody fused to IL-10. F8 targets the EDA domain of fibronectin, directing the product to inflamed tissue.
Dekavil has shown activity in models of chronic inflammation and in a Phase I study in last-line patients with rheumatoid arthritis. It was also evaluated by subcutaneous administration in a randomised, placebo-controlled Phase II study.
The program is partnered with Pfizer and includes intra-articular development for rheumatoid arthritis.
Selected references
- F8-IL10: A New Potential Antirheumatic Drug Evaluated by a PET-Guided Translational Approach.Bruijnen et al., Mol Pharm. 2019 Jan 7;16(1):273-281 · PubMed
- Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis.Schwager et al., Arthritis Res Ther. 2009;11(5):R142 · PubMed
- Indication
- Chronic Inflammation
- Payload
- IL-10 (anti-inflammatory)
- Composition
- F8IL10
- Partner
- Pfizer
Indications
- Chronic Inflammation - Rheumatoid Arthritis (intra-articular, DekaJoint)Phase IINCT07245992
Small-molecule therapeutics
PreIIIIII
+PreclinicalPhase IPhase IIPhase III
Small-molecule radio conjugates
Small organic ligands coupled to radionuclides for imaging or therapy.
A small-molecule FAP-targeting radiotracer labelled with 68Ga for PET imaging.
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68Ga-OncoFAP is a small-molecule radiotracer with ultra-high affinity for FAP. It combines a small organic FAP ligand, a spacer and a DOTAGA chelator labelled with 68Ga.
FAP is overexpressed in more than 90% of epithelial cancers, supporting the development of 68Ga-OncoFAP for non-invasive detection across multiple FAP-positive tumour types. Preclinical studies showed rapid, selective tumour accumulation and exceptionally low kidney uptake.
PET imaging has confirmed targeting activity in more than 200 patients, and a Phase I imaging study has been completed. The program is partnered with Blue Earth Diagnostics, part of the Bracco Group.
Selected references
- An ultra-high-affinity small organic ligand of fibroblast activation protein for tumor-targeting applications.Millul et al., Proc Natl Acad Sci U S A. 2021 Apr 20;118(16):e2101852118 · PubMed
- Automated Radiosynthesis, Preliminary In Vitro/In Vivo Characterization of OncoFAP-Based Radiopharmaceuticals for Cancer Imaging and Therapy.Bartoli et al., Pharmaceuticals (Basel). 2022 Aug 2;15(8):958 · PubMed
- Indication
- Various Solid Tumors
- Payload
- 68Ga (DOTAGA chelator), PET imaging tracer
- Partner
- Bracco (Blue Earth Diagnostics)
Indications
- Colorectal cancer, gastric cancer, pancreatic ductal adenocarcinoma, invasive lobular breast cancer, and epithelial ovarian cancerPhase IINCT07702292
A 177Lu-labelled FAP-targeting small-molecule radioconjugate designed to deliver therapeutic radiation to FAP-positive solid tumours.
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177Lu-OncoFAP-23 is a small-molecule radioconjugate with ultra-high affinity for FAP. It combines a small organic FAP ligand, a spacer and a DOTAGA chelator labelled with 177Lu.
Because FAP is overexpressed in more than 90% of epithelial cancers, 177Lu-OncoFAP-23 is being developed to treat multiple FAP-positive solid-tumour types. Preclinical models showed rapid and selective tumour accumulation with an exceptionally long tumour residence time.
Preclinical studies showed potent anti-tumour activity both as a single agent and in combination with L19IL2/Darleukin. The program is in Phase I development for solid tumours.
Selected references
- Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors.Galbiati et al., J Nucl Med. 2024 Oct 1;65(10):1604-1610 · PubMed
- Molecular Evolution of Multivalent OncoFAP Derivatives with Enhanced Tumor Uptake and Prolonged Tumor Retention.Galbiati et al., J Med Chem. 2024 Aug 8;67(15):13392-13408 · PubMed
- Indication
- Various Solid Tumors
- Payload
- 177Lu (therapeutic radionuclide)
Indications
- Various Solid TumorsPhase INCT06640413
A small-molecule ACP3-targeting radiotracer labelled with 68Ga for PET imaging.
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OncoACP3 is a small-molecule radiotracer with ultra-high affinity for Acid Phosphatase 3, a target abundantly expressed in prostate cancer and largely undetectable in normal organs outside the healthy prostate.
A side-by-side comparison reported higher ACP3 abundance in prostate cancer than PSMA, with a cleaner distribution in normal organs. Preclinical models showed rapid and selective tumour accumulation with extraordinarily low uptake in normal organs, including kidneys and salivary glands.
OncoACP3 labelled with 18F or 68Ga is being developed for non-invasive detection and staging of metastatic prostate cancer. The program is partnered with RayzeBio, a Bristol Myers Squibb company.
- Indication
- Prostate Cancer
- Payload
- 68Ga (PET imaging)
- Partner
- RayzeBio (a Bristol Myers Squibb company)
Indications
- Prostate CancerPhase I/IINCT07862582
A high-affinity ACP3-targeting radioconjugate for metastatic prostate cancer therapy.
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OncoACP3 is a small-molecule radiotracer with ultra-high affinity for Acid Phosphatase 3, a target abundantly expressed in prostate cancer and largely undetectable in normal organs outside the healthy prostate.
A side-by-side comparison reported higher ACP3 abundance in prostate cancer than PSMA, with a cleaner distribution in normal organs. Preclinical models showed rapid and selective tumour accumulation with extraordinarily low uptake in normal organs, including kidneys and salivary glands.
OncoACP3 showed potent single-agent activity in tumour-bearing mice at low and very low tested doses. OncoACP3 is being developed for metastatic prostate cancer and is partnered with RayzeBio, a Bristol Myers Squibb company.
- Indication
- Prostate Cancer
- Payload
- 225Ac (therapeutic radionuclide)
- Partner
- RayzeBio (a Bristol Myers Squibb company)
Indications
- Prostate CancerPreclinical
A small-molecule radiotracer targeting Carbonic Anhydrase IX, with 68Ga for imaging.
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68Ga-OncoCAIX is a small-molecule radiotracer with ultra-high affinity and specificity for Carbonic Anhydrase IX. CAIX is expressed in the vast majority of renal cell carcinomas and in other hypoxic tumours, including proportions of colorectal carcinoma and high-grade glioma.
The molecule combines a small organic CAIX ligand, a spacer and a DOTAGA chelator for incorporation of 68Ga for imaging.
Preclinical models showed rapid and selective tumour accumulation with extraordinarily low kidney uptake. A Phase I clinical trial with 68Ga-OncoCAIX in patients with clear cell renal cell carcinoma (ccRCC) and renal lesions has been completed. The Group is currently planning registration trials.
Selected references
- Small Organic Carbonic Anhydrase IX Ligands from DNA-Encoded Chemical Libraries for Tumor-Targeted Delivery of Radionuclides.Müller et al., J Am Chem Soc. 2025 May 28;147(21):18230-18239 · PubMed
- Selection of Carbonic Anhydrase IX Inhibitors from One Million DNA-Encoded Compounds.Buller et al., ACS Chem Biol. 2011 Apr 15;6(4):336-44 · PubMed
- Indication
- Renal Cell Carcinoma
- Payload
- 68Ga (imaging), DOTAGA chelator
Indications
- Renal Cell CarcinomaPhase INCT06840548
Small-molecule drug conjugates
Small organic ligands coupled to cytotoxic drug payloads.
A FAP-targeting small-molecule drug conjugate with a cleavable Glycine-Proline linker and MMAE payload.
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OncoFAP-GlyPro-MMAE is a small-molecule drug conjugate composed of a high-affinity FAP ligand, a cleavable Glycine-Proline linker and the cytotoxic payload MMAE.
MMAE is inactive while attached to OncoFAP. Proteases in the tumour microenvironment, including FAP itself, cleave the linker and release the active payload.
Mass-spectrometry studies in mouse models confirmed selective MMAE delivery to tumours with extremely low uptake and release in healthy organs, accompanied by potent anti-tumour activity. The molecule has also shown single-agent activity in animal patients with spontaneous tumours. Preparations for a first-in-human study are ongoing.
Selected references
- Development of multivalent FAP-targeted Small Molecule-Drug Conjugates with tailored MMAE release kinetics.Bocci et al., Mol Cancer Ther. 2025 Jun 30 · PubMed
- Fibroblast Activation Protein Triggers Release of Drug Payload from Non-internalizing Small Molecule Drug Conjugates in Solid Tumors.Zana et al., Clin Cancer Res. 2022 Dec 15;28(24):5440-5454 · PubMed
- Indication
- Various Solid Tumors
- Payload
- MMAE (monomethyl auristatin E) via cleavable Glycine-Proline linker
Indications
- Various Solid TumorsPhase I (animal patients)
Integrated platform
From platform to pipeline
These programs emerge from the same target-discovery, ligand-discovery and in-house manufacturing platform.