A Phase 1, Open-Label, Dose Escalation and Dose Expansion Study to Assess the Safety and Efficacy of Nitric Oxide Injection Into Unresectable Solid Cutaneous/Subcutaneous Primary or Metastatic Tumors

This is a Phase 1, open-label, dose-escalation and dose-expansion study comprised of a screening period, a single treatment session, an evaluation period of 21±3 days, and safety and survival follow-up period of up to 12 weeks post-treatment.

开始日期2022-08-14

申办/合作机构

Beyond Air Ltd.

NCT04685720 / CompletedN/A

A Pilot Study to Assess the Effect of Intermittent Inhaled Nitric Oxide on the Treatment of Nontuberculous Mycobacteria (NTM) Lung Infection in Cystic Fibrosis and Non-Cystic Fibrosis Patients

The purpose of this open-label, multicenter, non-randomized, pilot study is to assess the safety of high dose intermittent iNO for treatment of NTM infection in CF and non-CF patients.

开始日期2020-12-07

申办/合作机构

Beyond Air Ltd.

NCT04606407 / CompletedN/A

Prospective, Open-label, Randomized, Multi-Center Study for Safety and Efficacy Evaluation of Inhaled Nitric Oxide (NO) Given Intermittently to Adults With Viral Pneumonia

The purpose of this multi center, open label, randomized, study is to obtain information on the safety and efficacy of 150 ppm Nitric Oxide given in addition to the standard of care of patients with viral pneumonia

开始日期2020-11-25

申办/合作机构

Beyond Air Ltd.

100 项与 Beyond Air Ltd. 相关的临床结果

登录后查看更多信息

0 项与 Beyond Air Ltd. 相关的专利（医药）

登录后查看更多信息

项与 Beyond Air Ltd. 相关的文献（医药）

2023-04-04·Cancer Research

Abstract 6363: Short-term exposure of cancer cells to ultra-high concentrations nitric oxide induces PDL-1 upregulation

作者: Johnson, Matt ; Chaisson, Selena ; Monson, Jedidiah ; Avniel, Amir ; Confino, Hila ; Goldshtein, Matan ; Lisi, Steve ; Epshtein, Yana

AbstractBackground: We have previously shown that treating mouse colon carcinoma (CT26) tumor-bearing mice with ultra-high concentrations of nitric oxide (UNO) upregulates innate and adaptive immune cells both locally and systemically. As immune-checkpoint molecules, such as the PD-L1 receptor PD-1, are expressed on immune cells, our group assessed the potential synergy of UNO and an anti-PD-1 antibody for treating tumors in vivo. Indeed, primary tumors regressed in 53% of the CT26 tumor-bearing mice treated with UNO and anti-PD-1. Moreover, these mice were primary and distant tumor-free and survived 100 days post-treatment. In the current study, we assessed PD-L1 expression levels on cancer cells in vitro following short-term exposure to UNO.Methods: CT26 cells were exposed to 25,000 - 100,000 ppm NO for 10 - 60 seconds. The percentage of PD-L1-expressing cells was assessed by flow cytometry analysis.Results: 1. Exposing CT26 cells to 100,000 ppm NO for 10 seconds upregulated PD-L1 expression. 85.1% of cells, which are still viable or at early apoptosis, expressed PD-L1 compared to 71% of untreated cells (p<0.0001). Exposure of CT26 cells to 25,000 ppm or 50,000 ppm NO for 10 seconds did not change the level of PD-L1 expression significantly. 2. Exposure to 100,000 ppm NO for 30 seconds further increased the percentage of cells expressing PD-L1 to 96.7% (p<0.0001 compared to untreated cells). For this duration, lower concentrations of NO also increased PD-L1-expression in viable early apoptotic CT26 cells to 82.8% - 92.3% when treated with 25,000 ppm or 50,000 ppm NO, respectively. 3. Finally, a 60 second exposure of CT26 cells to 25,000 ppm, 50,000 ppm, or 100,000 ppm NO resulted in the highest percentage of PD-L1 expressing cells. Approximately 95% of all viable or early apoptotic CT26 cells express PD-L1 under all NO conditions. This finding is significant compared to 71% of cells in the control arm that express PD-L1 (p<0.0001).Conclusion: Short-term exposure (10 - 60 seconds) to UNO upregulates PD-L1 expression on cancer cells in an NO concentration-dependent and exposure-dependent process. A 10-second exposure to 100,000 ppm NO is sufficient to significantly induce PDL-1 expression. Therefore, NO therapy can potentially be combined with anti-PD-L1 antibody treatment to improve therapeutic outcomes.Citation Format: Yana Epshtein, Matan Goldshtein, Selena Chaisson, Jedidiah Monson, Matt Johnson, Amir Avniel, Steve Lisi, Hila Confino. Short-term exposure of cancer cells to ultra-high concentrations nitric oxide induces PDL-1 upregulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6363.

2023-04-04·Cancer Research

Abstract 6327: Intratumoral administration of ultra high-concentration nitric oxide (UNO) is more efficacious than anti-PD1 therapy in 4T1 tumor-bearing mice

作者: Johnson, Matt ; Chaisson, Selena ; Monson, Jedidiah ; Avniel, Amir ; Confino, Hila ; Goldshtein, Matan ; Lisi, Steve ; Epshtein, Yana

AbstractBackground: For the majority of metastatic triple-negative breast cancer (mTNBC) patients, chemotherapy is the standard first-line treatment, however, outcomes in this population are poor. A monoclonal antibody against the immune checkpoint inhibitor anti-programmed death 1 (PD-1) also has antitumor activity in patients with mTNBC. Previously, we reported that delivering ultra-high concentrations of nitric oxide (UNO) to mouse colon tumors stimulated innate and adaptive immune responses leading to the rejection of secondarily-induced tumors. Moreover, adding an anti-PD-1 antibody to UNO treatment resulted in primary tumor regression in 53% of the mice, the rejection of a distant tumors in all mice, and prolonged survival compared to control and anti-PD-1 arms. In this in vivo study, we investigated the ability of UNO to improve the efficacy of anti-PD-1 antibody treatment in the aggressive mouse breast cancer model, 4T1.Methods: We tested two treatment protocols: 4T1 mice tumors were treated with either a single dose of UNO and anti-PD-1 or a repeated dose of UNO and anti-PD-1. In the single dose design, 4T1 tumors were treated with a single administration of UNO combined with Anti-PD1 administration starting one day after UNO treatment (n=9-10 mice per group). In the repeated dosing design, 4T1 tumors were treated with UNO twice combined with Anti-PD-1 administration starting on the first UNO treatment day (n=8 mice per group). • UNO treatment regimen: 50,000 ppm, 10 minutes, flow rate ~0.2 liters per minute • Anti-PD1 treatment regimen: 10 mg/kg antibody was administered every 3 days for a total of 5 treatments.Results (UNO Single Dose): The primary tumors of 4T1 tumor-bearing mice were 13.2% smaller in the combined single-dose UNO group compared to anti-PD-1 alone 15 days post-UNO treatment.Results (UNO Repeated Dosing): The primary tumors of 4T1 tumor-bearing mice were 25.2% smaller in the combined repeated dose UNO group compared to the anti-PD-1 alone group 16 days after the first UNO treatment.Conclusion: Treating 4T1 tumors with single and repeated doses of UNO improved outcomes compared to anti-PD-1 alone. This suggests that local short-term treatment with UNO can serve as a treatment option for cancer patients with tumors that are not amenable to immune checkpoint inhibitor treatment.Citation Format: Yana Epshtein, Matan Goldshtein, Selena Chaisson, Jedidiah Monson, Matt Johnson, Amir Avniel, Steve Lisi, Hila Confino. Intratumoral administration of ultra high-concentration nitric oxide (UNO) is more efficacious than anti-PD1 therapy in 4T1 tumor-bearing mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6327.

2022-06-15·Cancer Research

Abstract 1283: Single intra-tumoral injection of gaseous nitric oxide induces an adaptive immune response in a mouse CT-26 solid tumor model

作者: Malka, Lidor ; Lisi, Steve ; Levi, Yakir ; Goldshtein, Matan ; Wolf, Ido ; Confino, Hila ; Avniel, Amir

AbstractBackground: Metastases are responsible for a significant portion of the morbidity and mortality in cancer patients. In situ destruction of tumor mass has been reported to provide the immune system with an antigen source for the induction of antitumor immunity, which can then attack distant metastases. Nitric oxide (NO) acts as a signaling molecule in multiple disease states, including cancer. NO has been shown to activate innate and adaptive responses of the immune system against tumors. In a previous Beyond Air study, 89% of CT26 tumor bearing mice treated with 50,000 parts per million (ppm) gaseous NO (gNO), rejected a secondary tumor induction. Here, we assessed the effects of a single intra-tumoral injection of gNO at concentrations of 20,000-50,000 ppm on immune cell recruitment in the tumor, spleen, and blood.Methods: Mouse colon carcinoma (CT26) tumor bearing Balb/c mice underwent a single intra-tumoral treatment with 20,000 (n=3) or 50,000 (n=4) ppm gNO for 5 minutes. Mice treated with N2 (n=3), under the same conditions, served as a control. Tumors were removed 14 days post treatment and were histologically analyzed to test for immune cell penetration, inflammation, and necrosis. Immune cells from the spleen and blood were harvested 21 days post treatment and assessed via flow cytometry.Results: 1. Treatment with 50,000 ppm gNO resulted in higher levels of inflammation, lymphocytes and T-cell infiltration, and necrosis within the tumor compared to both N2 and 20,000 ppm NO, as viewed histologically. 2. Flow cytometry analysis of immune cells from the spleen revealed a 1.3-fold increase of both B cells and IFN-γ expressing T cells with 50,000 NO treatment, and a 1.3-fold increase of B cells and 1.1-fold increase of IFN-γ expressing T cells with 20,000 NO treatment, compared to N2. 3. A 29% reduction of myeloid-derived suppressor cells (MDSCs) was detected in spleens of mice treated with 50,000 ppm gNO, and 40% for 20,000 ppm, compared to mice treated with N2.Conclusion: Intra-tumoral injection of ultra-high doses of NO at 20,000 and 50,000 ppm gNO led to an increased recruitment and concentration of T and B cells. Additionally, 50,000 ppm NO led to an increase of lymphocyte infiltration to the tumor. Taken together, the data suggest that the increase in lymphocyte infiltration, B and T cell population, and the reduction of MDSCs, are indicative of an adaptive immune response that results in rejection of secondary tumors in gNO-treated mice.Citation Format: Hila Confino, Matan Goldshtein, Yakir Levi, Lidor Malka, Amir Avniel, Steve Lisi, Ido Wolf. Single intra-tumoral injection of gaseous nitric oxide induces an adaptive immune response in a mouse CT-26 solid tumor model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1283.

100 项与 Beyond Air Ltd. 相关的药物交易

登录后查看更多信息

100 项与 Beyond Air Ltd. 相关的转化医学

登录后查看更多信息