tinodasertib (AUM001) / AUM Biosci, Newsoara Biopharma, Experimental Therapeutics Centre - LARVOL DELTA

Safety, tolerability, and preliminary efficacy of tinodasertib as a monotherapy or in combination with pembrolizumab or irinotecan in metastatic colorectal cancer: Interim results from a phase II open-label, dose-finding, run-in and cohort expansion study. (ASCO-GI 2025) - P2 | "Tinodasertib either as monotherapy or combined with irinotecan or pembrolizumab, was well tolerated with no DLTs at the dose levels evaluated. Prolonged median time to progression and OS compared to historical controls were observed even during the dose escalation phase for the study population as a whole and for each of the monotherapy and combination arms. Enrolment in the dose escalation phase continues."

Clinical • Combination therapy • Metastases • Monotherapy • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EIF4E • KRAS

A patent review of mitogen-activated protein kinase-interacting kinases (MNKs) modulators (2019-present). (PubMed, Expert Opin Ther Pat) - "The majority of small-molecule inhibitors developed recently, similarly to the structure of eFT508 and ETC-206. Also, some new skeletons were disclosed and showed novel mechanisms, including non-traditional ATP competition and induced protein degradation by proteolysis targeting chimeras. Ongoing preclinical research and clinical trials will provide us more information on these new compounds and MNKs novel functions beyond cancer."

Journal • Review • Genetic Disorders • Obesity • Oncology • Targeted Protein Degradation • EIF4E

Looking around the corner: predicting synergy or futility to combination of arsenic trioxide plus MNK1 inhibitors in glioblastoma (SNO 2024) - P2 | "Glioblastoma (GBM) is the most prevalent type of malignant tumor within the central nervous system. These signatures could serve to prioritize patient inclusion in clinical trials of ATO in combination with AUM001, enriching the fraction of responsive glioma patients. Such molecular signatures may bring precision medicine in early-stage clinical trials to advance promising new agents and combinations of agents to full FDA approval."

Acute Promyelocytic Leukemia • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor

Immunomodulatory and anticancer effects of cyclical gemcitabine/nab-paclitaxel with continuous dosing of tinodasertib (AUM001) in preclinical KPC model (AACR 2024) - "This study showed that sustained administration of AUM001 alongside cyclical GEM-nPTX is well-tolerated with good anti-tumor outcomes. Additionally, the maintenance of AUM001 may enhance the decrease in pro-oncogenic protein expression and remodel the tumor immune microenvironment. In conclusion, continuous dosing of AUM001 following the cessation of chemotherapy could stabilize the tumor state, potentiating its application in clinical settings as maintenance therapy for PDAC."

Immunomodulating • Preclinical • Neuroendocrine Tumor • Oncology • ANXA5 • EIF4E • MYC • PTPRC

Reclaiming a dirty drug: What is the context of vulnerability to arsenic trioxide in glioblastoma? (AACR 2024) - "Combination therapy with the MNK1 inhibitor, ETC-206, displayed mild to moderate synergy on overall cell viability and strong synergy when observing its effects on the glioma stem cell population. These findings further implicate MNK1 activity and cellular response to oxidative stress as markers of ATO sensitivity, however they are not the sole determinates of response. Understanding of the mechanism of action for idiopathic compounds may allow for the discovery of molecular signatures of sensitivity, improving patient selection for clinical trials and the development of new combination approaches to combat resistance in other tumor types."

Acute Promyelocytic Leukemia • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • EIF4E

Design, synthesis and biological evaluation of MNK-PROTACs. (PubMed, Mol Divers) - "In this study, DS33059, a small-molecule compound modified based on the ongoing clinical trials drug ETC-206, was chosen as the target protein ligand...The protein degradation assay showed that compound II-5 had good capability to degrade MNK1. The MNK-PROTACs strategy represents a new direction in treating tumors and deserves further exploration."

Journal • Oncology • Targeted Protein Degradation • EIF4E

MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: AUM Biosciences Pte Ltd | Trial primary completion date: Aug 2023 ➔ Sep 2024

Combination therapy • Metastases • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • MSI • NTRK

AUM001 potentiates the anti-tumor activity of gemcitabine in an AsPC-1 PDAC model (ESMO-GI 2023) - "This study demonstrated that the addition of AUM001 to standard chemotherapy GEM is well-tolerated and confers a greater anti-tumor effect than single agent GEM. Pharmacodynamic analysis suggests that AUM001 may potentiate the reduction in pro-tumorigenic protein expression and slow the tumor growth kinetics. This is the first study depicting clinical activity of AUM001 in combination with chemotherapy for the treatment of PDAC."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CCND1 • CD31 • EIF4E • PECAM1

Continuous dosing of AUM001 with cyclical gemcitabine/nab-paclitaxel to maintain the tumor growth kinetics in KPC xenograft model. (ASCO 2023) - "This study demonstrated that continuous dosing of AUM001 with cyclical GEM-nPTX is well-tolerated and confers good anti-tumor effect. Pharmacodynamic analysis also suggests that AUM001 may potentiate the reduction in pro-tumorigenic protein expression. This is the first study depicting the continuous dosing of AUM001 after cessation of chemotherapy could help to maintain the tumor state, facilitating its possible use in clinics as maintenance therapy in PDAC."

Preclinical • Oncology • Solid Tumor • ANXA5 • EIF4E • MYC

AUM Biosciences Doses First Patient in Phase 2 Clinical Trial of AUM001 in Metastatic Colorectal Cancer (GlobeNewswire) - "AUM Biosciences Pte. Ltd...announced today that the first patient has been dosed in its Phase 2 clinical trial evaluating AUM001 for the treatment of metastatic colorectal cancer (MSS CRC)....Module 1 is expected to enroll up to forty-eight patients, and top line readout from Module 1 is anticipated in the fourth quarter of 2023. The first patient has been dosed at Pindara Private Hospital in Queensland, Australia."

P2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: AUM Biosciences Pte Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2022 ➔ Apr 2023

Combination therapy • Enrollment open • Metastases • Trial initiation date • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • MSI • NTRK

AUM Biosciences Receives Human Research Ethics Committee Approval to Commence Phase II Clinical Trial of AUM001 for Treatment of Metastatic Colorectal Cancer in Australia (GlobeNewswire) - "AUM Biosciences...announced it has received Human Research Ethics Committee ('HREC') approval to commence a Phase II clinical trial of its selective translation inhibitor AUM001 in Australia. Ethics approval is confirmation that AUM has completed all the necessary pre-clinical safety and efficacy testing of AUM001 required to commence its Phase II clinical trial in Australia....This trial is a Phase II open label, dose-finding run-in and cohort expansion study to evaluate the safety, tolerability and effectiveness of AUM001 in combination with pembrolizumab or irinotecan for the treatment of metastatic colorectal cancer."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • 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

MNK Inhibitor AUM001 in Combination With Either Pembrolizumab or Irinotecan to Treat Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: AUM Biosciences Pte Ltd

Combination therapy • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF • EGFR • HER-2 • MSI • NTRK

AUM Biosciences Announces FDA IND Authorization for Global Phase 2 Trial of Selection Translation Inhibitor AUM001 in Colorectal Cancer (GlobeNewswire) - "AUM Biosciences...announced that it has received authorization from the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for the clinical trial evaluating AUM001, a selective translation inhibitor. As a result, AUM plans to evaluate AUM001, in combination with MSD’s anti-PD-1 therapy KEYTRUDA (pembrolizumab), in a global Phase 2 clinical trial in patients with microsatellite stable colorectal cancer (MSS CRC)."

IND • Colorectal Cancer • Gastrointestinal Cancer • Oncology

AUM Biosciences Enters into Collaboration with Roche for Clinical Development of AUM001 in Combination with anti-PD-L1 Therapy in Solid Tumor Indications (GlobeNewswire) - "AUM Biosciences...announced that it has entered into a clinical trial collaboration and supply agreement with Roche to evaluate AUM001, the Company’s novel, highly selective MNK1/2 inhibitor, in combination with atezolizumab (Tecentriq®), Roche’s anti-PD-L1 therapy, across multiple solid tumor indications, leading with Non-Small Cell Lung Cancer (NSCLC) and Urothelial Cancer (UC)."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

AUM Biosciences Announces Clinical Trial Collaboration and Supply Agreement with MSD to Evaluate AUM001 in Combination with KEYTRUDA (pembrolizumab) in Colorectal Cancer (GlobeNewswire) - "AUM Biosciences...announced that it has entered into a clinical trial collaboration and supply agreement with MSD, a tradename of Merck & Co., Inc., Rahway, NJ, USA, a premier global research-intensive biopharmaceutical company, to evaluate AUM001 in combination with MSD’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in a global Phase 2 trial in patients with microsatellite stable colorectal cancer (MSS CRC)....Enrollment is planned to commence in the second half of 2022, pending positive outcome of an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA) and a Clinical Trial Notification (CTN) with the Australian Therapeutics Goods Administration (TGA)."

Licensing / partnership • New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology