AUNP-12 / Pierre Fabre, Dr. Reddy’s - LARVOL DELTA

PD-1 blockade in combination with epigenetic therapy to antagonize tumor mesenchymal program and drive therapeutic efficacy in an esophageal adenocarcinoma model. (ASCO 2025) - "One dose of 3 mpk PD1 inhibitor (AUNP-12) or placebo was given each cycle... This study establishes antitumor efficacy and molecular correlates associated with response for epigenetic therapy with ICB and radiation, to treat EAC. All treatment groups enhanced CD3CD8+ T-cell tumor infiltration and interferon signaling. Dual therapy ± radiation, downregulated EMT and hypoxia-related gene sets, both having a role in modulation of cancer hallmarks, including the acquisition of an immune suppressive tumor microenvironment, tumor invasion, and metastasis."

Clinical • Combination therapy • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gene Therapies • Oncology • Solid Tumor

PD-1 BLOCKADE IN COMBINATION WITH EPIGENETIC THERAPY ANTAGONIZES TUMOR MESENCHYMAL PROGRAM AND DRIVES THERAPEUTIC EFFICACY IN AN ESOPHAGEAL ADENOCARCINOMA MODEL. (DDW 2025) - "One dose of 3mpk PD1 inhibitor (AUNP-12) or placebo was given each cycle...All treatment groups enhanced CD3CD8+ T-cell tumor infiltration and interferon signaling. Dual therapy ± radiation downregulated EMT and hypoxia-related gene sets, both having a role in modulation of cancer hallmarks, including the acquisition of an immune suppressive tumor microenvironment, tumor invasion, and metastasis."

Clinical • Combination therapy • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gene Therapies • Oncology • Solid Tumor

AUNP-12 Near-Infrared Fluorescence Probes across NIR-I to NIR-II Enable In Vivo Detection of PD-1/PD-L1 Axis in the Tumor Microenvironment. (PubMed, Bioconjug Chem) - "These probes have proven to be effective in mapping PD-L1 expression across various mouse tumor models, offering insights into tumor-immune interactions. This study highlights the potential of AUNP-12-Cy5.5 and AUNP-12-CH1055 for guiding clinical immunotherapy through precise patient stratification and dynamic monitoring, supporting the shift toward molecular imaging for personalized cancer care."

IO biomarker • Journal • Preclinical • Tumor microenvironment • Oncology

Effect of sitravatinib combined with PD-1 blockade on cytotoxic T-cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. (ASCO-GI 2024) - "All tumor bearing animals were randomized to a dose of 10mg/kg of sitravatinib (S) or vehicle control (VC) for three cycles, and PD-1 inhibitor, AUNP-12 (IO), was administered on day 12 of each 14 day cycle, at a dose of 3mg/kg. This study establishes a favorable combinational strategy using sitravatinib to overcome immunosuppression in the TME, providing strong rationale for future clinical strategies in the treatment of EAC."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • AXL • CD8 • IFNG • IL10 • IL12A • IL13 • IL1B • IL4 • IL6 • MERTK • PD-L1 • TGFB1 • TNFA

Trans-oral Delivery of Oncolytic Vaccinia Virus expressing Membrane-Bound IL2 for Esophageal Cancer Treatment. (SSO 2024) - "They received two treatments with the 1E9 vaccinia virus containing membrane-bound IL2 administered via oral gavage (OG) or tail vein (TV), +/- the PD-1 inhibitor AUNP-12 (n=5/group)... Conclusion 12/7 In conclusion, our investigation into the trans-oral delivery of oncolytic vaccinia virus expressing membrane-bound IL2 for EAC treatment presents compelling evidence of its therapeutic potential. Notably, OG and TV administrations, with the PD-1 inhibitor, demonstrated distinct effects on median tumor weights and percent total change in tumor volume by MRI. Future work addressing immunomodulatory mechanisms, viral replication dynamics and immune memory and long-term immune responses will bolster the scientific rationale for this therapeutic approach."

Oncolytic virus • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • IL2

Sitravatinib combined with PD1 blockade enhances cytotoxic T-Cell infiltration by M2 to M1 tumor macrophage repolarization in esophageal adenocarcinoma. (PubMed, Carcinogenesis) - "Additionally, pre-treatment gene expression of TAM receptors and PD-L1 were significantly higher in major responders compared to the non-responders, in animals that received sitravatinib and AUNP-12 (P < 0.02), confirming that TAM suppression enhances the efficacy of PD-1 blockade. In conclusion, this study proposes a promising immunomodulatory strategy using a multi-gene TKI to overcome developed resistance to an ICI in EAC, establishing rationale for future clinical development."

IO biomarker • Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CASP3 • CD8 • KIT • PD-L1

The GSH responsive indocyanine green loaded PD-1 inhibitory polypeptide AUNP12 modified MOF nanoparticles for photothermal and immunotherapy of melanoma. (PubMed, Front Bioeng Biotechnol) - "Under 808 nm near-infrared (NIR) irradiation, ICG-MOF-SS-AUNP12 effectively promoted the maturation of DC cells and activated immune responses. This study presents a novel method for constructing MOF-based nanodrugs and offers new possibilities for the synergistic treatment of tumors involving photothermal combined with immunotherapy."

Journal • Melanoma • Oncology • Solid Tumor

[Ga]Ga-AUNP-12 PET imaging to assess the PD-L1 status in preclinical and first-in-human study. (PubMed, Eur J Nucl Med Mol Imaging) - "[ Ga]Ga-AUNP-12 was successfully developed as a PD-L1-specific PET imaging tracer in preclinical and first-in-human studies."

IO biomarker • Journal • P1 data • Preclinical • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • IFNG • PD-L1

Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome. (PubMed, Acta Pharm Sin B) - "Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer."

Journal • Breast Cancer • Oncology • Solid Tumor • MMP2

CSF-1R inhibitor, pexidartinib, sensitizes esophageal adenocarcinoma to PD-1 immune checkpoint blockade in a rat model. (PubMed, Carcinogenesis) - "Here, we showed limited toxicity with significant tumor shrinkage in pexidartinib treated animals compared to controls, single agent and in combination with a PD-1 inhibitor, AUNP-12. Moreover, a post-treatment serum cytokine assay exhibited similar systemic trends as the gene expression in the TME, depicting increases in pro-inflammatory cytokines and decreases in anti-inflammatory cytokines. In conclusion, our study established a promising combinatorial strategy using a CSF-1R inhibitor to overcome resistance to PD-1/PD-L1 axis blockade in an EAC model, providing the rationale for future clinical strategies."

Checkpoint inhibition • IO biomarker • Journal • Preclinical • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • BAX • CD8 • IFNG • IL10 • IL13 • IL6 • TGFB1 • TNFA

CSF-1R inhibitor, pexidartinib, sensitizes esophageal cancer to PD-1 immune checkpoint blockade in a rat model. (ASCO-GI 2022) - "A PD-1 inhibitor, AUNP-12, at a dose of 3mg/kg or placebo, was administered on day 12 of each cycle. Overall, this study established a promising combinatorial strategy using a CSF-1R inhibitor to overcome resistance to PD-1/PD-L1 axis blockade in an esophageal cancer model, providing the rationale for future clinical strategies."

Checkpoint inhibition • IO biomarker • Preclinical • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • CD8 • CD86 • FLT3 • IFNG • IL10 • IL13 • IL4 • IL6 • MRC1 • MRI • TGFB1 • TNFA

M2-Like TAMs Function Reversal Contributes to Breast Cancer Eradication by Combination Dual Immune Checkpoint Blockade and Photothermal Therapy. (PubMed, Small) - "Its photothermal therapy can promote the infiltration of T lymphocytes in addition to ablating tumor cells and AUNP-12 and PQ912 further boost both the innate and adaptive immune reactions by cutting off PD-L1 and CD47 signals, respectively. In contrast to earlier single immunotherapy, the nanocomposites exhibit a stronger anti-tumor immune effect without obvious autoimmune side effects, promoting infiltration of T lymphocyte into the tumor site and strengthening phagocytosis of macrophages, even more exciting, significantly reversing pro-tumor M2-like tumor-associated macrophages (TAMs) to anti-tumor M1-like TAMs. The research may provide a promising strategy to develop high-efficient and low-toxic immunotherapy based on nanotechnology."

Checkpoint inhibition • IO biomarker • Journal • Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • CD47 • PD-1 • PD-L1

An Intelligent Biomimetic Nanoplatform for Holistic Treatment of Metastatic Triple-Negative Breast Cancer via Photothermal Ablation and Immune Remodeling. (PubMed, ACS Nano) - "Tumor antigens thus generated and increasingly released R848 by response to the photothermal effect, combined with AUNP-12 detached from AM@DLMSN@CuS/R848 in the weakly acidic tumor microenvironment, synergistically exerted tumor vaccination, and T lymphocyte activation functions on immune remodeling to prevent TNBC recurrence and metastasis. Taken together, this study provides an intelligent biomimetic nanoplatform to enhance therapeutic outcomes in metastatic TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Aurigene and Pierre Fabre Pharmaceuticals announce a licensing agreement for a new cancer therapeutic in immuno-oncology: AUNP12, an immune checkpoint modulator targeting the PD-1 pathway (PRNewswire) - "Pierre Fabre...and Aurigene...announced that the two companies have entered into a collaborative license, development and commercialization agreement granting Pierre Fabre global Worldwide rights (excluding India) to a new immune checkpoint modulator, AUNP-12."

Licensing / partnership • Oncology

CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not? (PubMed, Molecules) - "To strengthen our reasoning, we performed control experiments on AUNP-12 - a 29-mer peptide, which is a precursor of CA-170. Positive controls consisted of the well-documented small-molecule PD-L1 inhibitors: BMS-1166 and peptide-57."

Journal

Laser Immunotherapy in Combination with Perdurable PD-1 Blocking for Treatment of Metastatic Tumor. (PubMed, ACS Nano) - "Hollow gold nanoshells (HAuNS, a photothermal agent) and AUNP12 (an anti PD-1 peptide, APP) were co-encapsulated into poly(lactic- co-glycolic) acid (PLGA) nanoparticles...Our data demonstrated that the PTA combined perdurable PD-1 blocking could efficiently eradicate the primary tumors, and inhibit tumor metastasis. The present study provides a promising therapeutic strategy for the treatment of advanced cancer with metastases and presents a valuable reference for obtaining better outcomes in clinical cancer immunotherapy."

Combination therapy • Journal