Kitov Pharma Presents Newly Released Data for Reversing Pancreatic Cancer Drug Resistance

Kitov Pharma Ltd. recently presented newly released proof-of-concept data showing evidence of NT-219 mechanism of action in reversing cancer drug resistance in PDX models. The data was presented in a poster at the American Association for Cancer Research’s (AACR) Pancreatic Cancer: Advances in Science and Clinical Care conference in Boston on September 8, 2019.

NT-219 is a first-in-class small molecule bi-specific inhibitor of two key cancer resistance pathways STAT3 and IRS1/2. As previously disclosed, the preclinical study initially evaluated the efficacy of NT-219 in combination with the approved chemotherapy agent gemcitabine on four PDX models of mutated KRAS pancreatic cancer. Data demonstrated reversal of gemcitabine-resistant tumors in all PDX models following treatment with NT-219 and gemcitabine. One of these models demonstrated complete response in about half of the animal group upon addition of NT-219 to gemcitabine. The study was then extended to define an optimal dose regimen and future clinical protocol.

Newly released data from the NT-219 poster showed:

-The combination of NT-219 with the targeted therapies trametinib (MEK inhibitor) or folfirinox (chemotherapy) reversed tumor resistance to the treatments.

-Administering NT-219 prior to chemotherapy suppressed activation of two key cancer survival pathways, STAT3 and IRS.  The sequence of administering the therapies had a remarkable impact on the efficacy of NT-219 in reversing resistance.

-Gene expression analysis of the tumors in a PDX model of KRAS mutated pancreatic cancer revealed an average 80% reduction in IRS1 levels compared to the control group following a single treatment with NT-219 and gemcitabine combined therapy. Similar reductions were observed in the expression of STAT3-regulated genes and the proliferation marker Ki67, confirming NT-219 mechanism of action.

-A dose-dependent therapeutic effect of NT-219 was demonstrated on tumor-growth and correlated with NT-219 levels in plasma.

“STAT3 and IRS play an important role in KRAS-induced pancreatic tumorigenesis and drug resistance. Demonstrating efficacy of NT-219 in pancreatic cancer models is in line with previous results in other cancer types. We believe that targeting IRS and STAT3 may be a tumor-agnostic solution to combat resistance to multiple oncology drugs,” said Hadas Reuveni, PhD, VP Research and Development of Kitov. “NT-219 is a first-in-class small molecule which suppresses both targets using a unique mechanism of action, and is crucial for overcoming cancer drug resistance.”

“We are encouraged by the results of the study which demonstrate the potential of NT-219 to reverse resistance to oncology therapies in a wide range of PDX models. We plan to clinically explore its efficacy in multiple hard-to-treat oncology indications including squamous cell carcinoma of the head and neck in a planned clinical study to be launched soon. We are also exploring its potential in pancreatic cancer,” said Isaac Israel, CEO of Kitov. “Resistance to chemotherapy and targeted therapies is a major problem facing oncology patients. Kitov is now strategically focused on developing first-in-class oncology therapies, including such which are targeted to overcome drug resistance and tumor immune evasion, and to ultimately provide patients long-lasting treatment alternatives.”

Kitov plans to submit an Investigational New Drug Application (IND) to the US FDA for a clinical study on NT-219 in combination with cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck before the end of 2019, and to initiate the trial immediately following FDA’s clearance.

Kitov Pharma is a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, to create successful long-lasting treatments for people with cancer. Kitov’s oncology pipeline includes NT-219, a small molecule targeting the novel cancer drug resistance pathways IRS1/2 and STAT3. Kitov is currently advancing NT-219 in combination with cetuximab as a third-line or second-line treatment option for the treatment of recurrent and metastatic squamous cell carcinoma of head and neck cancer (SCCHN).

Kitov is also under contract to acquire 100% of FameWave Ltd. which owns CM-24, a monoclonal antibody blocking CEACAM1, a novel immune checkpoint that supports tumor immune evasion and survival through multiple pathways. Kitov will advance CM-24 as a combination therapy with anti-PD1 checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC). Following the receipt of the approval of Kitov’s shareholders for the acquisition of FameWave, and the finalization of a clinical collaboration agreement between FameWave and Bristol Myers Squibb for their planned Phase 1/2 clinical trials to evaluate the combination of CM-24 with the PD-1 inhibitor nivolumab (Opdivo), the acquisition is expected to close during the third quarter of 2019, subject to fulfillment of certain additional closing conditions. Consensi, a fixed-dose combination of celecoxib and amlodipine besylate, for the simultaneous treatment of osteoarthritis pain and hypertension was approved by the FDA for marketing in the US in May 2018 and is expected to be launched in the US at the end of 2019 by its partner Coeptis Pharmaceuticals. Kitov has also partnered to commercialize Consensi in China and South Korea. The company is headquartered in Tel Aviv, Israel. For more information, visit http://www.kitovpharma.com.