AUM302

AUM302 (formerly IBL-302) is a first-in-class oral kinase inhibitor rationally designed to uniquely combine pan-PIM kinase, pan-PI3K and mTOR inhibition in a single agent. AUM302 is a product of the company’s dual mechanism kinase inhibitor program.

The data for AUM302 indicates potent efficacy, good tolerability and favourable drug properties. AUM302 has been tested in over 700 cell lines with activity shown across a broad range of tissue types including breast cancer, leukemia, lymphoma and neuroblastoma. Initial analysis of this cell line panel identifies PIK3CA mutation, high PIM kinase expression and elevated MYC expression as factors indicating sensitivity to AUM302, markers which may be supportive in selecting patient subgroups in clinical trials.

We have generated a pre-clinical data package on AUM302 which supports the commencement of IND enabling studies. This includes proof-of-concept in several xenograft models (breast, lung, neuroblastoma, AML) and in patient tissue samples (prostate).

The potential for AUM302 to treat neuroblastoma was published in peer reviewed EMBO Molecular Medicine in 2019 (see publications below).

In July 2019, the global development and commercialisation rights to AUM302 were licensed to AUM Biosciences, Singapore.

AUM 302 in breast cancer

Approximately one million people globally are diagnosed with breast cancer each year and, of these, one third have a mutated PI3K pathway. Additionally, PIM kinase expression is elevated in triple negative breast cancer tumours and is associated with poor prognosis in patients with hormone - and HER2-negative tumours (A Goga; Nature; October 2016).

Researchers at the Dana Faber Cancer Institute explored the causes of resistance to PI3K inhibition in breast cancer. They noted that high PIM expression confers resistance and so co-targeting of PIM kinase and PI3K may be warranted in a subset of breast cancers (L. Garraway; Cancer Discovery; October 2016).

As a result of our proof-of concept data with our dual mechanism program, we established a research collaboration with the Royal College of Surgeons of Ireland to refine the potential clinical setting in breast cancer for AUM302, specifically in treatment-resistant breast cancer, including triple negative breast cancers. Results of the collaboration were presented at AACR in 2018, (see Poster Presentations below).

AUM302 indication Expansion

Beyond potential lead target indication in breast cancer, we also see potential for AUM302 in other cancers including lung cancer, AML, lymphoma, neuroblastoma and pancreas cancer. Positive pre-clinical results with AUM302 in neuroblastoma, in collaboration with Lund University, were published in EMBO Molecular Medicine (see Publications below).

Peer Review Publications:

Anti‐tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL‐302 in neuroblastoma

Sofie Mohlin, Daniel Bexell, EMBO Molecular Medicine, 16 July 2019. Link here.

Poster Presentations:

"Co-targeting PIM kinase to overcome MET amplified resistance to EGFR TKIs in NSCLC"

2019 IASLC World Conference on Lung Cancer, Barcelona, September 7-10, 2019. Link to abstract here.

"Activation of the MACC1/PIM/cMyc axis confers resistance to PI3K/mTOR inhibition in PIK3CA mutant NSCLC"

2018 AACR Targeting PI3K/mTOR Signaling Conference, November 30-December 3, 2018, Boston MA.

"Evaluation of dual-acting PIM/PI3K inhibitor IBL-302 in preclinical breast cancer models"

2018 American Association for Cancer Research (AACR) Annual Meeting, April 14-18, 2018 in Chicago. Link to abstract here.

"Elucidating the Role of PIM Kinase and Its Therapeutic Potential in NSCLC" and "Resistance Mechanisms to PI3K-mTOR Inhibition in NSCLC"

17th IASLC World Conference on Lung Cancer, Vienna, December 4-7, 2016. Link to abstracts here.

"Targeting PIM kinase in NSCLC"

International Association of Lung Cancer (IASLC) 16th World Conference on Lung Cancer in Denver, CO September 6-9, 2015. Link to abstract here.

"Initial Evaluation of Novel Dual PIM/PI3K and Triple PIM/PI3K/MTOR inhibitors in multiple myeloma"

20th Congress of the European Hematology Association (EHA) June 11 – 14, 2015, Vienna. Link to abstract here.

“Cotargeting of PIM, PI3K and Mtor in Mantle Cell Lymphoma (MCL)”

57th ASH Annual Meeting, Orlando, December 5-8, 2015. Link to abstract here

 “Combined inhibition of PIM and PI3 kinases shows an enhanced efficacy in a number of solid tumour cell lines”

American Association for Cancer Research (AACR) Annual Meeting 2014, April 5-9, San Diego, California. Link to abstract here

 “Co-targeting PIM and PI3K/mTOR pathways with a single molecule: Novel orally available combined PIM/PI3K and PIM/PI3K/mTOR kinases inhibitors”

2013 AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics Conference, Boston, USA. . Link to abstract here.

 

To request a copy of the corresponding poster please email the company at bd@inflectionbio.com

 

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