First-in-human Phase 1 study demonstrates early clinical proof of concept
Positive clinical biomarker data demonstrate evidence of immune system activation and the translation of the immunogenic response previously observed in preclinical studies
Data represent the first successful administration of intratumoral UNO therapy
Additional Phase 1 data for UNO expected in 2024
GARDEN CITY, N.Y. and HAMILTON, Bermuda, Nov. 03, 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, today announced encouraging first-in-human and first-in-class clinical data demonstrating a promising safety profile and clear evidence of immune system activation via biomarker response. The single agent treatment in relapsed or refractory unresectable, primary or metastatic cutaneous and subcutaneous malignancies represents an unprecedented use of ultra-high concentration nitric oxide as an immunotherapeutic. These data were presented today at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2023, which is being held in San Diego, California from November 1st to 5th via a poster presentation of abstract number 733.
“The development of immunotherapy has pushed the frontier of cancer medicine further than ever expected,” stated Dr. Jedidiah Monson, Chief Medical Officer. “Beyond Cancer is thrilled to contribute to this rapidly evolving landscape with a straightforward, minimally invasive procedure that may very well become a part of the immunotherapeutic armamentarium.”
The Company’s abstract presented at SITC includes safety, tolerability, biomarker and initial antitumor activity results from 5 subjects dosed with 25,000 ppm UNO. The data show UNO at 25,000 ppm delivered over 5-minutes upregulates cytotoxic T-cells, T-central memory cells, M1 macrophages, and dendritic cells while downregulating T-regulatory cells and mononuclear-myeloid-derived suppressor cells (M-MDSC).
Specifically, by Day 21, a single UNO administration resulted in an immunostimulatory effect. Dendritic cells increased more than 250%, representing more than a 2-fold increase in the magnitude observed in a murine model utilizing 50,000 ppm UNO. In addition, more than a 150% increase in T-central memory cells was observed, consistent with previously reported murine data (Sela Y et al. AACR/NCI/EORTC 2023). Encouragingly, there was also a greater than 50% increase in M1 macrophages over the same time period.
UNO also had a favorable impact on the inhibitory cells of the immune system. T-regulatory cells decreased by 40% by Day 21 and myeloid derived suppressor cells (M-MDSC) decreased by greater than 30% by Day 7.
Dr. Frederick Dirbas, Head of the Beyond Cancer Scientific Advisory Board, commented, “Prior preclinical data convincingly demonstrated immunostimulatory and anti-tumor effects of UNO compared to control in mice. To see the same immunostimulatory effects from preclinical studies carry over to humans is an important milestone in assessing the potential anti-tumor effects of UNO in humans.”
Of the five heavily pre-treated patients treated as of this data cut, UNO was well tolerated with primarily Grade 1 related toxicities observed with an early clinical response (Day 7) in a highly refractory, salvage population.
The poster presentation detailing the emerging early clinical data titled, “Phase 1 study of ultra-high concentration nitric oxide (UNO) in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies,” at the SITC 2023 Annual Meeting will be made available on the company’s website (click here).
About Beyond Cancer, Ltd.
Beyond Cancer, Ltd., an affiliate of Beyond Air, Inc., is a development-stage biopharmaceutical and medical device company utilizing ultra-high concentration nitric oxide (UNO) via a proprietary delivery platform to treat primary tumors and prevent metastatic disease. Nitric oxide at ultra-high concentrations has been reported to show anticancer properties and to potentially serve as a chemosensitizer and radiotherapy enhancer. A first-in-human study is underway in patients with solid tumors. The Company is conducting preclinical studies of UNO in multiple solid tumor models to inform additional treatment protocols. The company’s Scientific Advisory Board (SAB) includes several prominent key opinion leaders in oncology including Dr. Fred Dirbas, Assoc. Prof. of Surgery, Div. of Surgical Oncology, Stanford University School of Medicine, Dr. Sunil Panchal, President of the National Institute of Spine and Pain, and Dr. Mark Pegram, Susy Yuan-Huey Hung Professor of Medicine (Oncology), Medical Director, Clinical Translational Research Unit, and Associate Dean for Clinical Research Quality at Stanford University. For more information, visit www.beyondcancer.com.
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.
About UNO Therapy for Solid Tumors
Cancer is the second leading cause of death globally, with tumor metastases responsible for approximately 90% of all cancer-related deaths. Current cancer treatment modalities generally include chemotherapy, immunotherapy, radiation, and/or surgery. Ultra-high concentration Nitric Oxide (UNO) therapy is a completely new approach to preventing relapse or metastatic disease. In vitro murine data show that local tumor ablation with UNO stimulates an anti-tumor immune response in solid tumor cancer models. Beyond Cancer, Ltd. believes that UNO has the potential to prevent relapse or metastatic disease with as little as a single 5-minute treatment and with limited toxicity or off-target effects.
About Beyond Air®, Inc.
Beyond Air is a commercial stage medical device and biopharmaceutical company dedicated to harnessing the power of endogenous and exogenous nitric oxide (NO) to improve the lives of patients suffering from respiratory illnesses, neurological disorders and solid tumors. The Company has received FDA approval for its first system, LungFit® PH for the treatment of term and near-term neonates with hypoxic respiratory failure. Beyond Air is currently advancing its other LungFit systems in clinical trials for the treatment of severe lung infections such as viral community-acquired pneumonia (including COVID-19), and nontuberculous mycobacteria (NTM). The Company has also partnered with The Hebrew University of Jerusalem to advance a pre-clinical program dedicated to the treatment of autism spectrum disorder (ASD) and other neurological disorders. Beyond Cancer, Ltd., an affiliate of Beyond Air, is investigating ultra-high concentrations of NO with a proprietary delivery system to target certain solid tumors in the pre-clinical setting. For more information, visit www.beyondair.net.
Forward Looking Statements
This press release contains “forward-looking statements” concerning the potential safety and efficacy of inhaled nitric oxide and the ultra-high concentration nitric oxide product candidate, as well as its therapeutic potential in a number of indications; and the potential impact on patients and anticipated benefits associated with inhaled nitric oxide and the ultra-high concentration nitric oxide product candidate. Forward-looking statements include statements about expectations, beliefs, or intentions regarding product offerings, business, results of operations, strategies or prospects. You can identify such forward-looking statements by the words “expects,” “plans,” “anticipates,” “believes” “expects,” “intends,” “looks,” “projects,” “goal,” “assumes,” “targets” and similar expressions and/or the use of future tense or conditional constructions (such as “will,” “may,” “could,” “should” and the like) and by the fact that these statements do not relate strictly to historical or current matters. Rather, forward-looking statements relate to anticipated or expected events, activities, trends or results as of the date they are made. Because forward-looking statements relate to matters that have not yet occurred, these statements are inherently subject to risks and uncertainties that could cause actual results to differ materially from any future results expressed or implied by the forward-looking statements. These forward-looking statements are only predictions and reflect views as of the date they are made with respect to future events and financial performance. Many factors could cause actual activities or results to differ materially from the activities and results anticipated in forward-looking statements, including risks related to: Beyond Cancer’s ability to raise additional capital; the timing and results of future preclinical studies and clinical trials concerning the ultra-high concentration nitric oxide product candidate; the potential that regulatory authorities, including the FDA and comparable non-U.S. regulatory authorities, may not grant or may delay approval for the ultra-high concentration nitric oxide product candidate; the approach to discover and develop novel drugs, which is unproven and may never lead to efficacious or marketable products; Beyond Cancer’s ability to fund and the results of further preclinical studies and clinical trials of the ultra-high concentration nitric oxide product candidate; obtaining, maintaining and protecting intellectual property utilized by products; obtaining regulatory approval for products; competition from others using similar technology and others developing products for similar uses; dependence on collaborators; broad acceptance of the Company’s conclusive interpretation of its research results, potential delay or disruption in our operations resulting from military activity in and around Israel, and other risks, which may, in part, be identified and described in the “Risk Factors” section of Beyond Air’s most recent Annual Report on Form 10-K and other of its filings with the Securities and Exchange Commission, all of which are available on Beyond Air’s website. Beyond Cancer and Beyond Air undertake no obligation to update, and have no policy of updating or revising, these forward-looking statements, except as required by applicable law.
Corey Davis, PhD
LifeSci Advisors, LLC
Matt Johnson, Head of Corporate Development & Strategy
Beyond Cancer, Ltd.