On April 27, 2022 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immune-oncology technologies for the treatment of hard to treat cancers, reported that it has entered into exclusive license and sublicense agreements with CLS Therapeutics ("CLS") to develop its interventional DNase based oncology platform, which is aimed at improving outcomes of existing treatments, including immunotherapies (Press release, Xenetic Biosciences, APR 27, 2022, View Source [SID1234613017]). Xenetic will host a conference call and webcast, today, April 27, 2022, at 8:30 a.m. ET (details below).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Xenetic Biosciences, Inc., Tuesday, April 26, 2022, Press release picture
Under the terms of the agreements, Xenetic has an exclusive license to CLS’ intellectual property, for uses of DNases in cancer, including systemic co-administration of DNases along with standard therapies, including chemotherapy, radiation and checkpoint inhibitors, or along with conventional chimeric antigen receptor (CAR) T therapies. In addition, the licenses cover "DNase-armored" CAR T therapies in which novel CAR T products are engineered to secrete DNases into the tumor microenvironment to potentially improve T-cell infiltration, activity and persistence. As part of the agreements, Xenetic will make an upfront payment of $500,000 in cash and issue 875,000 shares of common stock, and will make future payments based on the achievement of certain clinical and regulatory milestones of up to $13 million per program, as well as issue up to an additional 950,000 shares of common stock based on the achievement of certain milestones. Additionally, Xenetic will pay tiered royalty payments ranging from mid-single to low-double digits on any potential future sales, as well as a percentage share of certain consideration received by Xenetic from sublicensees.
The licensed DNase platform is designed to target Neutrophil Extracellular Traps ("NETs"), which are weblike structures composed of extracellular chromatin coated with histones and other proteins. NETs are expelled by activated neutrophils, in response to microbial or pro-inflammatory challenges. However, excessive production or reduced clearance of NETs can lead to aggravated inflammatory and autoimmune pathologies, as well as creation of pro-tumorigenic niches in the case of cancer growth and metastasis.
A substantial amount of scientific literature has implicated NETs in the context of cancer pathogenesis and resistance to cancer therapies (including chemo, radio, and immunotherapies such as checkpoint inhibitors and cell therapies). In published reports, elevated levels of NETs have been a biomarker associated with poor prognosis in patients with a variety of cancers.
In addition, resistance to existing therapeutic agents can involve the release of immunosuppressive signaling factors from NETs, or physical barriers created by NETs which can impede the infiltration, activity, and survival of cytotoxic T cells in the tumor microenvironment.
Published pre-clinical models have demonstrated the effectiveness of systemically administered DNase, alone or in combination with other agents, for the elimination of NETs and prevention of tumor growth and metastasis.
"We are excited to in-license this oncology platform. Based on the compelling pre-clinical efficacy data seen to date, we believe the DNase-based oncology platform has the potential to improve the outcomes of chemotherapy and immunotherapy treatments in multiple solid tumor indications," commented Jeffrey Eisenberg, Chief Executive Officer of Xenetic. "This transaction provides Xenetic with near term opportunities for value-driving milestones, and an anticipated timeline to clinic that now positions us as an emerging clinical-stage company. This gives us the confidence to focus our capital and human resources on advancing the DNase pipeline. Our primary efforts are now aimed at advancing the systemic DNase program into the clinic as an adjunctive therapy for locally advanced or metastatic cancers. Our goal is to provide solutions in the treatment of solid tumors by improving response and overcoming resistance to checkpoint inhibitors or chemotherapy. Ultimately, we expect these programs to drive value for shareholders in the near and long term."
Adoptive transfer of CAR T cells has emerged as one of the most promising advances in cancer immunotherapy. Engineered CAR T cells, designed to recognize cancer-associated antigens, are capable of sustained and selective killing of tumor cells, with substantial reduction of tumor burden. CAR T therapies have exhibited remarkable clinical success against hematological malignancies but thus far have failed to demonstrate success in the context of solid tumors. Published evidence suggests that in addition to immunosuppressive factors, mechanical barriers formed by NETs can impede T-cell penetration and occlude T-cell contact with tumor cells.
"To successfully treat solid tumors, CAR T cells must be able to infiltrate, persist, and maintain anti-tumor function in a hostile tumor microenvironment that is itself adept at immunosuppression and conducive to tumor cell survival. Recent approaches to CAR T design include "armored" CAR-T cells, so named because they can express additional factors to resist immunosuppression or degrade physical components of the tumor’s extracellular matrix, including NETs. We intend to conduct pre-clinical research with the goal of demonstrating that armoring CAR T cells to secrete DNase can support depth and durability of response against solid tumor indications," said Curtis Lockshin, Chief Scientific Officer of Xenetic.
Conference Call and Webcast
Xenetic management will host a conference call and webcast presentation for investors, analysts, and other interested parties to discuss the in-licensing today, April 27, 2022, at 8:30 AM ET.
Interested participants and investors may access the conference call by dialing (877) 407-9708 (domestic) or (201) 689-8259 (international). The live webcast will be accessible on the Events page of the Investors section of the Xenetic website, xeneticbio.com, and will be archived for 90 days.