On October 17, 2023 Beyond Cancer, Ltd., an affiliate of Beyond Air, Inc. (NASDAQ: XAIR) that is developing ultra-high concentration nitric oxide (UNO) as an immunotherapeutic for solid tumors, reported the publication of pre-clinical data demonstrating that its proprietary technology reduces immunosuppression and creates a favorable microenvironment that can contribute to immune potentiation (Press release, Beyond Air, OCT 17, 2023, View Source [SID1234636081]).

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!

The data were published in an article entitled, "Intratumoral Administration of High-Concentration Nitric Oxide and Anti-mPD-1 Treatment Improves Tumor Regression Rates and Survival in CT26 Tumor-Bearing Mice," in the peer-reviewed journal Cells. The article is available on the Cells website. (click here).

"The combination of UNO and anti-mPD-1 resulted in a potent, synergistic immune response," stated Dr. Hila Confino, Head of In Vivo Studies. "This work aligns with prior data utilizing UNO to treat solid tumors and has repeatedly demonstrated increased tumor regression rates and improvement in survival."

Dr. Frederick Dirbas, MD, Associate Professor of Surgery, Div of Surgical Oncology, Dept of Surgery, Stanford University School of Medicine and Chair of the Beyond Cancer Scientific Advisory Board commented, "This manuscript details the beneficial effects of UNO alone and in conjunction with immunotherapy in a murine tumor model. The boost seen with the combination of UNO and immunotherapy is important. We look forward to further investigation exploring mechanisms of action of UNO as well as the potential merits of UNO in treating human solid tumors."

The manuscript published in Cells describes several studies elucidating UNO’s effect on both the adaptive and innate immune responses, as well as tumor responses, to a single administration of therapy. Specifically, in vitro studies showed that PD-L1 was upregulated in both CT26 and 4T1 tumor models following exposure to UNO, implying a possible mechanism for overcoming PD-1 resistance (Figure 1).

PD-L1 Upregulation in CT26 and 4T1 Cells after In Vitro Exposure to UNO

Intratumorally, UNO resulted in a substantial and enduring reduction in the T-reg/CD8+ ratio demonstrating a less tumorigenic microenvironment (Figure 2).

T-cell profiling in tumors of CT26 mice treated with UNO

Systemically, the acute effects of UNO treatment included a decrease in MDSC’s and simultaneous increase in M1 macrophages, demonstrating a more immunogenic blood profile (Figure 3).

Myeloid cell profiling in CT26 tumors treated with UNO

Figure 3: Myeloid cell profiling in CT26 tumors treated with UNO

"The publication of our second peer-reviewed manuscript in the journal Cells further demonstrates the acceptance of the science of UNO by an expanding community of researchers," said Dr. Selena Chaisson, Chief Executive Officer. "I am excited for the presentation of our initial clinical data at SITC (Free SITC Whitepaper)."

About Nitric Oxide
Nitric Oxide (NO) is a potent molecule, naturally synthesized in the human body, proven to play a critical role in a broad array of biological functions. In the airways, NO targets the vascular smooth muscle cells that surround the small resistance arteries in the lungs. Currently, exogenous inhaled NO is used in adult respiratory distress syndrome, post certain cardiac surgeries and persistent pulmonary hypertension of the newborn to treat hypoxemia. Additionally, NO is believed to play a key role in the innate immune system and in vitro studies suggest that NO possesses anti-microbial activity not only against common bacteria, including both gram-positive and gram-negative, but also against other diverse pathogens.