Elraglusib combination Phase 2 trial with retifanlimab based on observed synergy with immune checkpoint inhibitors, and preclinical and early clinical data supporting immunomodulatory activity of GSK- inhibitors 

CHICAGO, IL and FORT WORTH, TX – March 1, 2022 – Actuate Therapeutics and The University of Kansas Cancer Center today announced the enrollment of the first patient on a Phase 2 study of elraglusib (9-ING-41) plus retifanlimab combined with gemcitabine/nab-paclitaxel for the treatment of patients with advanced pancreatic cancer in the first-line setting (NCT05239182). The study will enroll up to 32 evaluable patients in a Simon two-stage design, with the primary objective of assessing the disease control rate of the combination regimen. 

“The pre-clinical data generated with elraglusib, as a single agent and in combination with checkpoint inhibitors, along with clinical data supporting its immunomodulatory activity is increasingly compelling,” said Daniel M. Schmitt, Actuate President & CEO. “In addition to elraglusib’s established anticancer activity via direct cytotoxicity and reversal of chemoresistance, its immunomodulatory actions may be particularly synergistic with those of anti-PD-1 checkpoint inhibitors. Driven by these synergistic mechanisms of action, we are very excited to include this clinical study in our program for patients with pancreatic cancer and as a template for studies of immunomodulatory combinations for patients with other refractory cancer types.” 

Elraglusib is Actuate’s proprietary small molecule glycogen synthase kinase-3 beta (GSK-) inhibitor which is being developed for adults and children with advanced refractory cancers. Retifanlimab, Incyte Corporation’s (NASDAQ:INCY) investigational intravenous PD-1 inhibitor, is currently under evaluation for patients with microsatellite instability-high endometrial cancer, Merkel cell carcinoma, squamous cell carcinoma of the anal canal, and non-small cell lung cancer. 

“We are very excited to launch this first study of elraglusib combined with retifanlimab as a potentially synergistic immune-modulatory approach for patients with advanced pancreatic cancer,” said Anwaar Saeed, MD, study principal investigator. “The first generation of immune checkpoint (PD-1, PDL-1, CTLA-4) inhibitors including retifanlimab address a key subset of the cancer-created blockade of anti-cancer effector cells in our immune system. We are now beginning to study novel therapies that will modulate other checkpoints and thus be synergistic with the current agents – elraglusib is such an agent. We are very focused on elraglusib in this context as the increasing data on its role as an immune-modulator, including its ability to stimulate NK/T-cell anticancer effector functions, has been generated against a background of it showing meaningful clinical activity in a spectrum of cancers, particularly advanced pancreatic cancer. I am thus delighted to open our investigator-initiated study of elraglusib, retifanlimab and gemcitabine/nab-paclitaxel and am very grateful for all the support I have received for this initiative.” 

“GSK- inhibition has been an increasingly important goal in developmental therapeutics for patients with cancer, pathological fibrotic conditions, and neuro-degenerative disease over the last few decades,” said Razelle Kurzrock, Chair of Actuate’s Scientific Advisory Board. “Elraglusib is the first clinically viable agent with which we can modulate this target in patients with cancer and the initial clinical data is very encouraging. Recently we have gained a very important appreciation for GSK- inhibition as a potential immune-modulatory approach. As the limits of what we can achieve with first-generation targets have become evident, we are studying other inhibitory receptor targets, including TIM3, TIGIT and LAG-3, with data on the latter being particularly encouraging. GSK- inhibition is a means to decrease both PD-1 expression and LAG-3. The initiation of Dr Saeed’s retifanlimab plus elraglusib in combination with gemcitabine/nab-paclitaxel study is a milestone for patients with advanced pancreatic cancer and will guide us in the design and execution of further studies of these important novel agents.” 

Based on positive data from a prior Phase 2 open-label single arm study of elraglusib plus gemcitabine/nab-paclitaxel, Actuate has also initiated an international randomized controlled study of gemcitabine/nab-paclitaxel versus elraglusib in combination with gemcitabine/nab-paclitaxel, in patients with advanced pancreatic cancer in the first-line setting (NCT03678883, EudraCT#:2018-003739-32). Actuate also recently announced the initiation of a randomized study of elraglusib plus FOLFIRINOX alone or with Losartan also for patients with advanced pancreatic cancer in the first-line setting (NCT05077800). 

About Actuate Therapeutics, Inc. 
Actuate is a clinical stage pharmaceutical company focused on the development and commercialization of novel therapeutics for cancers and inflammatory diseases. For additional information, please visit the Company’s website at