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

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