AUM302 / Inflection Biosci, AUM Biosci - LARVOL DELTA

AUM-302, A NOVEL TRIPLE PIM/PI3K/MTOR INHIBITOR, SYNERGIZES WITH KRAS INHIBITION AND IMPEDES THE GROWTH OF PANCREATIC DUCTAL ADENOCARCINOMA SPHEROIDS AND ORGANOIDS (DDW 2025) - "Single- and dual kinase inhibitors TP-3654, GDC-0941, and BEZ-235, and DMSO were used as controls...Finally, combinatorial assays revealed synergy between AUM-302 and the KRAS inhibitor RMC-6236 in reducing the growth of hT1 and hM1A organoids. By blocking kinase activity, AUM-302 demonstrates potent inhibitory activity in PDAC cell lines and organoids in two different 3D culture formats. Treatment with this novel triple PIM/PI3K/mTOR inhibitor may also sensitize PDAC to other therapies, such as KRAS inhibitors."

Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor. (PubMed, PLoS One) - "In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy."

Journal • Preclinical • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • PIM1

SCREEN: Spatial transcriptomic effects of a panel of pre-clinical and clinical targeted therapeutic combinations in a clinically relevant prostate explant model (EACR 2023) - "These drugs were AZD-1208, a pan-PIM kinase inhibitor; BEZ235/Dactolisib, a pan-PI3K-mTOR dual inhibitor, a combination of both AZD-1208 and BEZ235, and AUM-302 – a preclinical PIM, PI3K, mTOR triple inhibitor. However, AZD-1208 activated PI3K cascade. MKi67 and PIM genes activity switched between different cell types in response to the different treatments, which may be compensatory.ConclusionWe conclude that pre-clinical drug development can and should be carried out not just on cancer cells but on complex models, including epithelium, stroma, and benign areas, and that when such drug screening is carried out, advanced endpoint analyses such as spatial transcriptomics are warranted, in order to properly assess both the promise and the pitfalls of drug candidates in clinically relevant settings."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • PIM1

AUM-302, A NOVEL TRIPLE PIM/PI3K/MTOR INHIBITOR, IS A POTENT PANCREATIC CANCER GROWTH INHIBITOR (DDW 2023) - " We tested the effectiveness of TP-3654, a known PIM inhibitor, and AUM-302, a novel triple PIM/PI3K/mTOR inhibitor, in five human PDAC cell lines. In vitro studies show that the AUM-302 compound strongly inhibits the growth of PDAC cells and has the potential to overcome the gemcitabine-resistant phenotype of pancreatic cancer cell lines, and thus has the potential to be an effective drug for PDAC therapy."

Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • EGFR • MYC • PIM1

AUM Biosciences Receives U.S. FDA Rare Pediatric Disease Designation for AUM302 for Treatment of Neuroblastoma (GlobeNewswire) - "AUM Biosciences Pte. Ltd...announced today that the U.S. Food and Drug Administration (FDA) has granted a Rare Pediatric Disease Designation (RPDD) for its product candidate, AUM302, a potential first-in-class oral kinase inhibitor that targets not only PI3K, but also key resistance mechanisms such as PIM and mTOR, for the treatment of neuroblastoma....'We expect to file an Investigational New Drug (IND) application with the FDA for our first-in-human clinical trial in mid-2023'."

FDA event • IND • Neuroblastoma • Oncology • Solid Tumor

AUM Biosciences Receives FDA Orphan Drug Designation for AUM302 for the Treatment of Neuroblastoma (GlobeNewswire) - "AUM Biosciences...announced today that the U.S. Food and Drug Administration ('FDA') has granted Orphan Drug Designation for AUM302, a potential first-in-class oral kinase inhibitor that targets not only PI3K, but also key resistance mechanisms such as PIM and mTOR, for the treatment of neuroblastoma."

Orphan drug • Neuroblastoma • Oncology • Solid Tumor

Spatial transcriptomics analysis of co-targeted pim and pi3k / mtor in multikinase inhibitor and single kinase inhibitor combination-treated patient-derived prostate cancer explants (AACR-NCI-EORTC 2022) - "The novel preclinical multikinase PIM/PI3K/mTOR inhibitor, AUM302, versus clinical trial investigated - a combination of the PI3K/mTOR inhibitor BEZ235 (Dactolisib) and PIM inhibitor, AZD-1208 has been analyzed in our laboratory using a cohort of cancer explants emanating from our PEOPLE: PatiEnt prOstate samPLes for rEsea ch study and our current SCREEN study. Our findings will contribute to understanding how the spatial landscape of the tumour microenvironment enhances the efficacy of anti-tumour drugs and what subset of patients are more likely to benefit from such therapy. No"

Clinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

AUM Biosciences, a Global Biotechnology Company Developing Precision Oncology Therapeutics, Announces Plans to Become a Public Company via Merger with Mountain Crest Acquisition Corp. V (GlobeNewswire) - "AUM Biosciences Pte. Ltd...and Mountain Crest Acquisition Corp. V...announced that they have entered into a definitive business combination agreement...The transaction reflects a pre-money equity value of $400 million for AUM and is expected to close in the first quarter of 2023...AUM is advancing a broad portfolio of precision oncology therapeutics. AUM001 is a selective and synergistic MNK inhibitor as shown in current studies and expected to begin Phase 2 enrollment in the fourth quarter 2022. AUM601 is a promising therapy for TRK fusions and mutations within the kinase domain and is on track to enter Phase 2...AUM has sub-licensed the Greater China rights (AUM001, AUM302 and AUM003) to Newsoara making it eligible to receive up to $135 million in development, regulatory, and commercial milestones, plus up to double digit royalties."

M&A • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Macrocyclization as a Source of Desired Polypharmacology. Discovery of Triple PI3K/mTOR/PIM Inhibitors. (PubMed, ACS Med Chem Lett) - "We report the medicinal chemistry exploration and biological characterization of a series of thieno[3,2-d]pyrimidine MCXs, which led to the discovery of IBL-302 (31), a potent, selective, and orally bioavailable triple PI3K/mTOR/PIM inhibitor...Additionally, during the course of our experiments, we observed that macrocyclization was essential to obtain the desired multitarget profile. As a matter of example, the open precursors 35-37 were inactive against PIM whereas MCX 28 displayed low nanomolar activity."

Journal • Breast Cancer • Neuroblastoma • Oncology • Solid Tumor

Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer. (PubMed, Oncogene) - "Our results demonstrate in vitro efficacy of IBL-302 in a range of breast cancer cell lines, including lines with acquired resistance to trastuzumab and lapatinib. The combination of trastuzumab and IBL-302 significantly increased the anti-proliferative effect in HER2+ breast cancer cell line, and matched trastuzumab-resistant line, relative to testing either drug alone. We thus believe that the novel PIM and PI3K/mTOR inhibitor, IBL-302, represents an exciting new potential treatment option for breast cancer, and that it should be considered for clinical investigation."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer. (PubMed, Sci Rep) - "The preclinical inhibitor AUM302, used at a lower dose, elicited a comparable or superior functional outcome compared with combined AZD-1208 + BEZ235, which have been investigated in clinical trials, and could help to reduce treatment toxicity in future trials. We believe that a co-targeting approach is a viable therapeutic strategy that should be developed further in pre-clinical studies."

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma. (PubMed, EMBO Mol Med) - "IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma."

Journal • Neuroblastoma • Oncology • Solid Tumor

Co-Targeting PIM Kinase to Overcome MET Amplified Resistance to EGFR TKIs in NSCLC (IASLC-WCLC 2019) - "Background: Currently there are five EGFR tyrosine kinase inhibitors (TKIs) (erlotinib, gefitinib, afatinib, dacomitinib, and osimertinib) available for treatment of EGFR-mutated non-small cell lung cancer (NSCLC). We show here for the first time that PIM kinase is activated in MET amplified EGFR TKI resistant cells. Erlotinib resistant HCC827ER cells are sensitive to pan-PIM inhibitor AZD1208 and the novel triple targeted therapy IBL-302. These data demonstrate that PIM kinase is a pivotal mechanism involved in EGFR TKI resistance and is an ideal target for dual inhibition strategies."

Inflection Biosciences and AUM Biosciences announce global license agreement for PIM/PI3K/mTOR inhibitors (Businesswire) - "Inflection Biosciences...and AUM Biosciences...announced a global license agreement for Inflection’s first-in-class PIM/PI3K/mTOR inhibitors. The agreement will provide AUM with exclusive worldwide rights to develop, manufacture and commercialise these inhibitors with Inflection receiving an upfront payment, milestone payments and royalties on future sales...The agreement will see AUM develop the lead candidate, IBL-302 (hereafter AUM302), which is currently in the pre-clinical stage of development...AUM plans to commence Investigational New Drug (IND) enabling studies for AUM302 by 2020."

IND • Licensing / partnership