SHANGHAI, April 20, 2026 /PRNewswire/ -- Nuance Pharma ("Nuance" or the "Company") announces that CHEST, the official journal of the American College of Chest Physicians, has published results from the Phase 3 ENHANCE-CHINA trial evaluating Ohtuvayre® (ensifentrine) in chronic obstructive pulmonary disease ("COPD").

The publication reports results from Nuance's successful ENHANCE-CHINA trial demonstrating improvements with ensifentrine in lung function and dyspnea, with a demonstrated safety profile. The manuscript, entitled "Efficacy and Safety of Ensifentrine in Chinese Patients with Chronic Obstructive Pulmonary Disease: The ENHANCE-CHINA Randomized Clinical Trial," is available online here and will be published in an upcoming issue of CHEST. It follows the announcement of top-line data from the ENHANCE-CHINA trial in May 2025.

Data from the ENHANCE-CHINA program formed the basis of Nuance Pharma's New Drug Application ("NDA"), which was submitted in December 2025 to the National Medical Products Administration ("NMPA") for the approval of ensifentrine for the maintenance treatment of patients with COPD.

Ensifentrine is FDA-approved in the United States as maintenance treatment for adult patients with COPD with a selective dual inhibitor of the enzymes phosphodiesterase 3 and 4, combining bronchodilator and non-corticosteroid anti-inflammatory activities in one molecule. If approved in China, it is expected to be the first novel mechanism of action available for the treatment of COPD in more than 10 years.

Mark Lotter, founder and Chief Executive Officer of Nuance Pharma, said: "We are delighted to see the full results from our Phase 3 ENHANCE-CHINA trial published in CHEST, a highly respected peer-reviewed journal in pulmonary medicine. These data reinforce the robust clinical profile of ensifentrine, demonstrating meaningful improvements in lung function. With our New Drug Application already submitted and accepted for review by the NMPA, we are one step closer to bringing this first-in-class inhaled therapy to patients in China. We extend our sincere gratitude to the patients, investigators, and clinical site teams who made this program possible."

In March 2026, Ohtuvayre was approved by the Hong Kong Drug Office under the "1+"mechanism. In February 2025, Ohtuvayre was approved by the Pharmaceutical Administration Bureau Macau, and was introduced in the Greater Bay Area in November 2025 through the "Hong Kong and Macau Medicine and Equipment Connect" policy and can be used in designated medical institutions. In January 2026, Nuance Pharma announced acceptance for review of the new drug application for Ohtuvayre by the National Medical Products Administration of China. In November 2024, Nuance Pharma launched Ohtuvayre in China's Hainan Boao Pilot Zone through an early access program.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre in Greater China (mainland China, Hong Kong, Macau and Taiwan).

In October 2025, Merck & Co., Inc., Rahway, N.J., USA, known as MSD outside the United States and Canada, announced the completion of the acquisition of Verona Pharma plc. MSD holds the exclusive rights to develop and commercialize Ohtuvayre in all markets outside of Greater China.

About the ENHANCE-CHINA Program

The randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of nebulized ensifentrine as monotherapy and added onto either a LAMA or a LABA, or a LABA+ICS compared to placebo.

• Patient Population: 526 moderate to severe, symptomatic, COPD patients at 46 sites in China.
• Dose/Duration: subjects were randomized to receive a 3mg nebulized dose of ensifentrine or nebulized placebo twice daily for 24 weeks
• Primary Endpoint: Improvement in lung function with ensifentrine as measured by average FEV1 AUC 0-12 hours post dose at week 12.
• Secondary Endpoints: lung function endpoints including peak and morning trough FEV1, COPD symptoms and health related quality of life through 24 weeks via SGRQ and E-RS, and exacerbation at 24 weeks, and others
• Safety: Assessed over 24 weeks

Further information about the ENHANCE-CHINA program can be found at www.clinicaltrials.gov (NCT05743075).

About Ensifentrine (Ohtuvayre®)

Ohtuvayre® is the first inhaled therapy for the maintenance treatment of COPD in adult patients that combines bronchodilator and non-corticosteroid anti-inflammatory activities in one molecule. Ohtuvayre was evaluated in a Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function.

Ohtuvayre Indication and Important Safety Information

INDICATION

Ohtuvayre is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

IMPORTANT SAFETY INFORMATION

Contraindication: Ohtuvayre is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.

Warnings and Precautions:

Acute Episodes of Bronchospasm Ohtuvayre should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting bronchodilator.

Paradoxical Bronchospasm As with other inhaled medicines, Ohtuvayre may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with Ohtuvayre, it should be treated immediately with an inhaled, short-acting bronchodilator. Ohtuvayre should be discontinued immediately and alternative therapy should be instituted.

Psychiatric Events Including Suicidality Before initiating treatment with Ohtuvayre, healthcare providers should carefully weigh the risk and benefits of treatment with Ohtuvayre in patients with a history of depression and/or suicidal thoughts or behavior. Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts, or other mood changes, and if such changes occur to contact their healthcare provider. Healthcare providers should carefully evaluate the risks and benefits of continuing treatment with Ohtuvayre if such events occur.

Treatment with Ohtuvayre is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received Ohtuvayre (1 suicide attempt and 1 suicide). Additionally, the most commonly reported psychiatric adverse reactions in the pooled 24-week safety population were insomnia (6 patients [0.6%] Ohtuvayre 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] Ohtuvayre 3 mg; 1 patient [0.2%] placebo). Depression-related reactions including depression, major depression, and adjustment disorder with depressed mood occurred in 4 patients [0.4%] receiving Ohtuvayre and no patients receiving placebo.

Adverse Reactions: The most common adverse reactions ≥1% in Ohtuvayre and greater than placebo in the pooled population were back pain 1.8%, hypertension 1.7%, urinary tract infection 1.3%, and diarrhea 1.0%.

These are not all of the possible risks associated with Ohtuvayre.

Please see Prescribing Information for Ohtuvayre (ensifentrine) at: https://ohtuvayrehcp.com/wp-content/uploads/sites/2/2024/11/Ohtuvayre-US-Prescribing-Information.pdf, Patient Information for Ohtuvayre at: https://ohtuvayre.com/wp-content/uploads/2024/11/Ohtuvayre-US-Prescribing-Information.pdf.

About Nuance Pharma

Nuance Pharma is an innovation-focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

Forward-looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

SHANGHAI, March 12, 2026 /PRNewswire/ -- Today, Nuance Pharma ("Nuance") announced that the Hong Kong Drug Office approved Ohtuvayre® (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients under the "1+ mechanism."

Ohtuvayre® is the first novel inhaled mechanism for the treatment of COPD in more than 20 years and combines bronchodilator and non-steroidal anti-inflammatory effects. The U.S. Food and Drug Administration approved Ohtuvayre in June 2024 for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

The approval of Ohtuvayre in Hong Kong SAR, China, was based on the Global Phase 3 ENHANCE trials and referencing the completed ENHANCE-CHINA trial. In the ENHANCE trials, Ohtuvayre demonstrated clinical benefits both alone and when used in combination with a LABA, a LABA+ICS, a LAMA, or a LAMA+ICS.

Mark Lotter, founder and Chief Executive Officer of Nuance Pharma, said: "We are pleased to announce that the Hong Kong regulatory authority has approved the registration of Ohtuvayre under the "1+ mechanism," which also marks the second regulatory approval outside of the U.S. We are proud to provide access to this highly innovative COPD treatment to patients in Hong Kong and Macau."

Ohtuvayre was approved by the Pharmaceutical Administration Bureau Macau in February 2025, and was introduced in the Greater Bay Area in November 2025 through the "Hong Kong and Macau Medicine and Equipment Connect" policy and can be used in designated medical institutions. In November 2024, Nuance Pharma launched Ohtuvayre in China's Hainan Boao Pilot Zone through an early access program. in January 2026, Nuance Pharma announced acceptance for review of the new drug application for Ohtuvayre by the national medical products administration of China.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre in Greater China (mainland China, Hong Kong, Macau and Taiwan).

In October 2025, Merck & Co., Inc., Rahway, N.J., USA, known as MSD outside the United States and Canada, announced the completion of the acquisition of Verona Pharma plc. MSD holds the exclusive rights to develop and commercialize Ohtuvayre in all markets outside of Greater China.

About Ohtuvayre® (ensifentrine)

Ohtuvayre® is the first inhaled therapy for the maintenance treatment of COPD in adult patients that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule.  Ohtuvayre was evaluated in a Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function.

Ohtuvayre Indication and Important Safety Information

INDICATION

Ohtuvayre is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

IMPORTANT SAFETY INFORMATION
Contraindication: Ohtuvayre is contraindicated in patients with hypersensitivity to ensifentrine or any component of this product.

Warnings and Precautions:
Acute Episodes of Bronchospasm Ohtuvayre should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting bronchodilator.

Paradoxical Bronchospasm As with other inhaled medicines, Ohtuvayre may produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with Ohtuvayre, it should be treated immediately with an inhaled, short-acting bronchodilator. Ohtuvayre should be discontinued immediately and alternative therapy should be instituted.

Psychiatric Events Including Suicidality Before initiating treatment with Ohtuvayre, healthcare providers should carefully weigh the risk and benefits of treatment with Ohtuvayre in patients with a history of depression and/or suicidal thoughts or behavior. Patients, their caregivers, and families should be advised of the need to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts, or other mood changes, and if such changes occur to contact their healthcare provider. Healthcare providers should carefully evaluate the risks and benefits of continuing treatment with Ohtuvayre if such events occur.

Treatment with Ohtuvayre is associated with an increase in psychiatric adverse reactions. Psychiatric events including suicide-related adverse reactions were reported in clinical studies in patients who received Ohtuvayre (1 suicide attempt and 1 suicide). Additionally, the most commonly reported psychiatric adverse reactions in the pooled 24-week safety population were insomnia (6 patients [0.6%] Ohtuvayre 3 mg; 2 patients [0.3%] placebo), and anxiety (2 patients [0.2%] Ohtuvayre 3 mg; 1 patient [0.2%] placebo). Depression-related reactions including depression, major depression, and adjustment disorder with depressed mood occurred in 4 patients [0.4%] receiving Ohtuvayre and no patients receiving placebo.

Adverse Reactions: The most common adverse reactions ≥1% in Ohtuvayre and greater than placebo in the pooled population were back pain 1.8%, hypertension 1.7%, urinary tract infection 1.3%, and diarrhea 1.0%.

These are not all of the possible risks associated with Ohtuvayre.

Please see Prescribing Information for Ohtuvayre (ensifentrine) at: https://ohtuvayrehcp.com/wp-content/uploads/sites/2/2024/11/Ohtuvayre-US-Prescribing-Information.pdf, Patient Information for Ohtuvayre at: https://ohtuvayre.com/wp-content/uploads/2024/11/Ohtuvayre-US-Prescribing-Information.pdf.

About Nuance Pharma

Nuance Pharma is an innovation-focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

Forward-looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

Ohtuvayre^® is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 ("PDE3 and PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule, delivered directly to the lungs through a standard jet nebulizer.

Mark Lotter, founder and Chief Executive Officer of Nuance Pharma, said: "We are very pleased to see the NDA for Ohtuvayre^® has been officially accepted in mainland China. This exciting milestone affirmed our confidence in ensifentrine's potential to re-define the COPD treatment in China. We are committed to expanding access to Ohtuvayre^®, if approved, with the goal of benefiting millions of patients battling with COPD."

Charlie Chen, Chief Operating Officer of Nuance Pharma added: "The NDA submission was completed as planned following the positive results from the Phase 3 registrational ENHANCE-CHINA study. Following our ongoing early access programs in Hainan BoAo and Greater Bay Area, as well as regulatory approval in Macau, we look forward to accelerating patient access to this innovative medicine in China."

Ohtuvayre^® was approved by the Pharmaceutical Administration Bureau Macau in February 2025, and was introduced in the Greater Bay Area in November 2025 through the "Hong Kong and Macau Medicine and Equipment Connect" policy and can be used in designated medical institutions. In November 2024, Nuance Pharma launched Ohtuvayre^® in China's Hainan Boao Pilot Zone through an early access program.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre^® in Greater China (mainland China, Hong Kong, Macau and Taiwan).

In October 2025, Merck & Co., Inc., Rahway, N.J., USA, known as MSD outside the United States and Canada, announced the completion of the acquisition of Verona Pharma plc.

About Ohtuvayre^® (ensifentrine)

Ohtuvayre^® is the first inhaled therapy for the maintenance treatment of COPD in adult patients that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona has evaluated nebulized Ohtuvayre^® in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre^® met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function.

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

Forward-looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

SHANGHAI, May 16, 2025 /PRNewswire/ -- Nuance Pharma ("Nuance") today announces its top-line Phase 3 ENHANCE-CHINA (NCT05743075) trial results evaluating nebulized ensifentrine for the maintenance treatment of chronic obstructive pulmonary disease ("COPD"). The ENHANCE-CHINA trial has successfully met its primary endpoint, as well as secondary endpoints demonstrating improvements in lung function.

The investigational study drug, ensifentrine is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 ("PDE3; PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule, delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination.

Highlights

- Study population (n = 526 randomized):

• Subject demographics and disease characteristics were well balanced between treatment groups
• Approximately 46% of subjects received background COPD therapy, either a long-acting muscarinic antagonist ("LAMA") or a long-acting beta-agonist ("LABA"). Additionally, approximately 38% of all subjects received inhaled corticosteroids ("ICS") with concomitant LABA.

- Primary endpoint met (FEV₁ AUC 0-12hr):

• Placebo corrected, change from baseline in average FEV₁ area under the curve 0-12 hours post dose at week 12 was 110 mL (p<0.0001) for ensifentrine
• Statistically significant and clinically meaningful improvements with ensifentrine demonstrated across key subgroups including age, smoking status, COPD severity, background medication, ICS use, chronic bronchitis, FEV₁ reversibility

- Secondary endpoints of lung function:

• Placebo corrected, increase in peak FEV₁ of 174 mL (p<0.0001) at week 12
• Placebo corrected, increase in morning trough FEV₁ of 36 ml (p=0.0533) and evening trough FEV₁ of 65 ml (p=0.0038) at week 12, confirming twice daily dosing regimen.
• Placebo corrected, increase in average FEV₁ of 162 ml (p<0.0001) 0-4 hours post dose and 77 mL (p=0.0003) 6-12 hours post dose at week 12

- COPD symptoms and quality of life (QoL):

• Clinically meaningful improvements in dyspnea as measured by Transition Dyspnea Index (TDI) in the ensifentrine group were observed at all weeks (6, 12 and 24) with a statistically significant improvement of 0.8 unit compared to placebo at week 24.
• Quality of Life (QoL) as measured by St George's Respiratory Questionnaire (SGRQ) Total Score in the ensifentrine group improved from baseline to greater than the MCID of -4 units with a significant improvement of -2.9 units compared to placebo at week 24.
• Daily symptoms as measured by Evaluating Respiratory Symptoms (E-RS) Total Score in ensifentrine group showed improvement from baseline as early as 6 weeks and continued improvement at 12 and 24 weeks, numerically exceeding placebo at each measurement. 

- Exacerbation rate reduced

• Subjects receiving ensifentrine demonstrated a 28% reduction in the rate of moderate/severe COPD exacerbations over 24 weeks compared to those receiving placebo (RR = 0.72, 95% CI: (0.43, 1.22))
• Treatment with ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 25% (HR = 0.75, 95% CI: (0.44, 1.28))

- Favorable safety profile:

• Ensifentrine was well-tolerated with treatment related AE incidence similar to placebo

Mark Lotter, founder and Chief Executive Officer of Nuance Pharma, said:"We are very pleased by the successful outcome of our Phase 3 ENHANCE-CHINA study, bringining us another step closer to providing a much needed novel therapy for COPD patients in China. These promising results demonstrate ensifentrine's strength as a first-in-class bronchodilator and non-steroidal anti-inflammatory therapy for COPD, as an advance to existing treatment options. We plan to submit a New Drug Application to the China NMPA in the second half of 2025. We would like to thank all the patients and investigators for their participation in the ENHANCE-CHINA program. "

Charlie Chen, Chief Operating Officer of Nuance Pharma added:"The totality of ENHANCE data including improvements in lung function, symptoms, quality of life measure and reduction in exacerbations, coupled with favorable safety profile, support our belief that ensifentrine will change the treatment paradigm for COPD. Following our ongoing early access programs in Hainan BoAo and Greater Bay Area, as well as regulatory approval in Macau, we look forward to bringing this medicine to patients in Greater China."

David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma, said:"we look forward to Nuance Pharma's continued progress and having Ohtuvayre® available for the millions of symptomatic patients needing additional treatment."

Nuance Pharma plans to release additional information from ENHANCE-CHINA at upcoming scientific conferences.

In Feb 2025, the Pharmaceutical Administration Bureau Macau approved Ohtuvayre™ (ensifentrine) for the maintenance treatment of COPD in adult patients. In Nov 2024, Nuance Pharma launched Ohtuvayre™ in China's Hainan Boao Pilot Zone through early access program. In Sep 2024, Nuance Pharma completed recruitment for ENHANCE-CHINA, the phase 3 clinical trial of Ohtuvayre™ (ensifentrine) for the maintenance treatment of COPD.

In June 2024, Nuance Pharma's global partner Verona Pharma plc (Nasdaq: VRNA), announced the US Food and Drug Administration ("FDA") approved Ohtuvayre™ (ensifentrine) for the maintenance treatment of COPD in adult patients.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre™ (ensifentrine) in Greater China (mainland China, Hong Kong, Macau and Taiwan).

About Ohtuvayre ™ (ensifentrine)
Ohtuvayre™ is the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona has evaluated nebulized Ohtuvayre™ in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre™ met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function.

About the ENHANCE-CHINA program
The randomized, double-blind, placebo-controlled study evaluate the efficacy and safety of nebulized ensifentrine as monotherapy and added onto a single bronchodilator, either a LAMA or a LABA, compared to placebo, and subjects may receive ICS.

Patient Population: 526 moderate to severe, symptomatic, COPD patients at 46 sites in China.

Dose/Duration: subjects were randomized to receive a 3mg nebulized dose of ensifentrine or nebulized placebo twice daily for 24 weeks

Primary Endpoint: Improvement in lung function with ensifentrine as measured by average FEV₁ AUC 0-12 hours post dose at week 12.

Secondary Endpoints: lung function endpoints including peak and morning trough FEV₁, COPD symptoms and health related quality of life through 24 weeks via SGRQ and E-RS, and exacerbation at 24 weeks, and others

Safety: Assessed over 24 weeks

Further information about ENHANCE-CHINA program can be found at www.clinicaltrials.gov (NCT05743075)

About Verona Pharma
Verona Pharma is a biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs. Ohtuvayre™ (ensifentrine) is the Company's first commercial product and the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Ohtuvayre™ (ensifentrine) has potential applications in non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com. 

About Nuance Pharma
Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com. 

Forward-looking Statements
This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

First inhaled COPD treatment providing bronchodilation and non-steroidal anti-inflammatory effects

SHANGHAI, Feb. 7, 2025 /PRNewswire/ -- Today, Nuance Pharma ("Nuance") announced that the Pharmaceutical Administration Bureau Macau approved Ohtuvayre™ (ensifentrine) for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.

In June 2024, Ohtuvayre™ was approved in the United States and became commercially available in August. Ohtuvayre™ is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 ("PDE3; PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule, delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination.

The approval of Ohtuvayre™ in Macau SAR, China, was based on extensive data including the Global Phase 3 ENHANCE trials, the results of which were published in the American Journal of Respiratory and Critical Care Medicine. In the ENHANCE trials, Ohtuvayre^TM demonstrated clinical benefits both alone and when used with other maintenance therapies. Ohtuvayre^TM was well-tolerated in a broad population of subjects with moderate to severe COPD.

Mark Lotter, founder and Chief Executive Officer of Nuance Pharma, said: "We are pleased to announce that the Macau regulatory authority has approved the NDA of Ohtuvayre™, which also marks the first regulatory approval outside of the US. We are proud to provide access to this highly innovative COPD treatment to patients in Macau and beyond, for example through innovative policy in the Greater Bay Area (GBA). Respiratory disease is among Nuance's core areas of focus, and through approval in Macao SAR and early access programs in Hainan BoAo and GBA, Nuance Pharma is looking forward to providing this novel, first-in-class treatment to patients in China, prior to our expected NDA submission in 2025 upon completion of the ENHANCE-CHINA trial."

David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma, said: "We are very pleased that Ohtuvayre^TM is available to help patients still experiencing daily COPD symptoms. We are encouraged by the initial impact of Ohtuvayre^TM and believe its novel profile can re-define the COPD treatment paradigm."

In Nov 2024, Nuance Pharma launched Ohtuvayre™ in China's Hainan Boao Pilot Zone through early access program. In Sep 2024, Nuance Pharma completed recruitment for ENHANCE-CHINA, the phase 3 clinical trial of ensifentrine for the maintenance treatment of COPD.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre™ in Greater China (mainland China, Hong Kong, Macau and Taiwan).

About Ohtuvayre™ (ensifentrine)

Ohtuvayre™ is the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona has evaluated nebulized Ohtuvayre™ in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre™ met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function.

About Verona Pharma

Verona Pharma is a biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs. Ohtuvayre^TM (ensifentrine) is the Company's first commercial product and the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Ensifentrine has potential applications in non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com.

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

Forward-looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

SHANGHAI, Sept. 23, 2024 /PRNewswire/ -- Nuance Pharma (the "Company") today announced that it has agreed with Altamira Medica Ltd., an associate company of Altamira Therapeutics Ltd. (Nasdaq:CYTO), to extend the territory covered by the exclusive license and distribution agreement for Bentrio® nasal spray by several countries across South East and East Asia. Under the amended agreement, Nuance's territory will expand from China (Mainland, Hong Kong, Macau) and South Korea to also include Singapore, Malaysia, Thailand, Philippines, Indonesia, Vietnam and Taiwan, with a combined population of greater than 630 million people. Nuance has been marketing Bentrio in Hong Kong since late 2022 and recently submitted the request for marketing approval for Mainland China.

"We are excited to reinforce and expand our successful collaboration with Altamira on Bentrio," stated Mark Lotter, founder and CEO of Nuance Pharma. "Bentrio offers some unique features such as immediate onset and long duration of protection against airborne particles, strong efficacy and good tolerability thanks to its drug-free and preservative-free formulation. They resonate well with medical professionals and consumers, and we look forward to rolling out the product in additional countries and marketing it through our large sales force and growing network of partners."

"We are very satisfied with the collaboration with our partner Nuance who has shown great dedication and launched Bentrio successfully in Hong Kong," commented Thomas Meyer, Altamira Medica's Chairman and CEO. "Together with Nuance we look forward to making Bentrio available in further countries, first in the existing license territory and subsequently also in the newly added countries to provide relief to the growing number of allergic rhinitis patients in East and South East Asia."

About Bentrio

Bentrio is a drug-free nasal spray for personal protection against airborne allergens and, where approved, against airborne viruses. Upon application into the nose, Bentrio forms a protective gel layer on the nasal mucosa. This thin film is designed to prevent the contact of airborne particles with cells; in addition, the composition serves to bind such particles and help with their discharge. The efficacy and safety of Bentrio has been demonstrated in a total of four clinical trials, of which the largest one ("NASAR" study) enrolled 100 patients suffering from seasonal allergic rhinitis. In NASAR, participants self-administered either Bentrio or saline nasal spray for two weeks 3 times per day. The study showed a statistically significant reduction in the mean daily reflective Total Nasal Symptom Score (rTNSS) for Bentrio compared to saline (p = 0.013), as well as a statistically highly significant improvement in health-related quality of life (Rhinoconjunctivitis Quality of Life Questionnaire, p < 0.001) and superior global ratings of efficacy by patients and investigators alike (p < 0.001). In addition, Bentrio showed good safety and tolerability, similar to saline controls, and fewer Bentrio treated patients used relief medication and more of them enjoyed symptom-free days compared to saline treatment. For more information, visit: www.bentrio.com.

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

About Altamira Therapeutics

Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a 49% stake (with additional economic rights) in Altamira Medica AG, which holds its commercial-stage legacy asset Bentrio®, an OTC nasal spray for allergic rhinitis. Further, the Company is in the process of partnering / divesting its inner ear legacy assets. Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/.

Forward-Looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

The investigational study drug, Ensifentrine (Ohtuvayre™) is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 ("PDE3; PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule, delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination.

In June 2024, Nuance Pharma's global partner Verona Pharma plc (Nasdaq: VRNA), announced the US Food and Drug Administration ("FDA") approved Ohtuvayre™ for the maintenance treatment of COPD in adult patients.

Mark Lotter, founder and CEO of Nuance Pharma, said: "We are pleased to announce that the pivotal phase 3 trial recruitment is completed, as this means that the results and outcome will be soon available in 2025. We are excited about the possibility of offering the new treatment for the COPD patients group in China, following the successful approval by US FDA earlier this year.

The introduction of Ohtuvayre™ will represent a material milestone in offering Chinese patients a new option in the treatment of COPD. The company appreciates the efforts of the leading PI Professor Zhong Nanshan and all the sites for their contribution in completion of the study and in bringing the drug one step closer to patients in China."

"We are pleased with Nuance Pharma's progress and completion of enrollment in ENHANCE-CHINA. We look forward to the study results in 2025 and continued progress to bring Ohtuvayre™ to the millions of COPD patients needing additional treatment." said David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre™ in Greater China (mainland China, Hong Kong, Macau and Taiwan).

About Ohtuvayre™ (ensifentrine)

Ohtuvayre™ is the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona Pharma evaluated nebulized Ohtuvayre™ in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre™ met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function. Ohtuvayre™ has potential applications for development in non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases.

About Nuance pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com. 

About Verona Pharma

Verona Pharma is a biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs, including COPD, non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com. 

Forward-Looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

Ohtuvayre is a first-in-class selective dual inhibitor of the enzymes phosphodiesterase 3 and phosphodiesterase 4 ("PDE3 and PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule. Ohtuvayre is delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination.

The US approval of Ohtuvayre was based on extensive data including the Phase 3 ENHANCE trials, the results of which were published in the American Journal of Respiratory and Critical Care Medicine. In the ENHANCE trials, Ohtuvayre demonstrated clinical benefits both alone and when used with other maintenance therapies. Ohtuvayre was well-tolerated in a broad population of subjects with moderate to severe COPD. 

"The approval of Ohtuvayre is a significant advance in COPD care, and we believe Ohtuvayre's novel profile can change the treatment paradigm for COPD," said David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma. "We plan to launch Ohtuvayre in the third quarter 2024, ensuring Ohtuvayre is available to help the millions of patients who still experience daily COPD symptoms."

Mr. Mark Lotter, founder and CEO of Nuance Pharma, commented: "We are pleased to see ensifentrine's approval with FDA and the planned commercial launch in the US, and we are excited about ensifentrine's potential to re-define the COPD treatment globally as the first-in-class novel therapy. With the largest patient pool globally, COPD in China represents significant disease burden for the public, we are committed to bringing this first-in-class therapy to patients in Greater China as soon as possible, through propelling the ENHANCE-China Phase 3 clinical study, as well as a range of early access programs in the region. Today marks an important milestone for the molecule, we are excited about the potential in expanding opportunities including new indications."

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize ensifentrine in Greater China (mainland China, Hong Kong, Macau and Taiwan). On April 6th 2023, Nuance Pharma announced dosing of first patient for the ENHANCE-China Phase 3 clinical trial.

About Ohtuvayre (ensifentrine)

Ohtuvayre is the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona has evaluated nebulized Ohtuvayre in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function. Ensifentrine has potential applications for development in non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases.

About Verona Pharma

Verona Pharma is a biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs, including COPD, non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com. 

About Nuance pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com. 

Forward-Looking Statements

This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law.

Ensifentrine is a selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 combining bronchodilator and non-steroidal anti-inflammatory activities in one molecule. If approved, it is expected to be the first novel mechanism available for the treatment of COPD in over 10 years.

Mr. Mark Lotter, founder and CEO of Nuance Pharma, commented: "We are immensely proud to see ensifentrine's progress with the FDA. This exciting milestone affirmed our confidence in ensifentrine's potential to re-define the COPD treatment globally. Like our partner Verona, we are highly committed to bringing this first-in-class therapy to patients in Greater China. Together, we aim to significantly improve the lives of millions coping with this challenging disease."

"Millions of symptomatic COPD patients in the US are in urgent need of new treatment options," said David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma. "The NDA submission for ensifentrine is a significant milestone towards our goal of bringing this potential first-in-class therapy to COPD patients and we look forward to working with the FDA during their review." The NDA contains data from the positive Phase 3 ENHANCE studies and other ensifentrine clinical studies including data from approximately 3,000 subjects.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize ensifentrine in Greater China. On April 6th 2023, Nuance Pharma announced first patient in (FPI) for the ENHANCE-China Phase III clinical trial.

About Ensifentrine

Ensifentrine (RPL554) is a selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 that combines bronchodilator and anti-inflammatory activities in one compound. In Phase 2 clinical studies in COPD, ensifentrine has shown significant and clinically meaningful improvements in lung function, symptoms and quality of life as a monotherapy or added onto a maintenance bronchodilator. In the Phase 3 ENHANCE-1 and ENHANCE-2 clinical trials, ensifentrine showed significant and clinically meaningful improvements in lung function measures and reduced the rate of COPD exacerbations. Ensifentrine has been well tolerated in clinical trials involving approximately 3,000 subjects to date.

About Verona Pharma

Verona Pharma is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs. If successfully developed and approved, Verona Pharma's product candidate, ensifentrine, has the potential to be the first non-steroidal therapy for the treatment of respiratory diseases that combines bronchodilator and anti-inflammatory activities in one compound. Ensifentrine met the primary endpoint in its Phase III trial, demonstrating statistically significant and clinically meaningful improvements in lung function and substantially reduced the rate and risk of COPD exacerbations. Two additional formulations of ensifentrine have been evaluated in Phase 2 studies for the treatment of COPD: dry powder inhaler ("DPI") and pressurized metered-dose inhaler ("pMDI"). Ensifentrine has potential applications in cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com.

About Nuance pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia.

With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

Forward-looking statements

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.

SHANGHAI, May 26, 2023 /PRNewswire/ -- Altamira Therapeutics Ltd. (Nasdaq: CYTO), a company dedicated to developing therapeutics that address important unmet medical needs, today announced positive and statistically significant top-line results from the randomized controlled NASAR clinical trial evaluating its Bentrio nasal spray in patients with seasonal allergic rhinitis (SAR). Bentrio nasal spray is formulated as a drug-free and preservative-free gel emulsion designed to help protect against airborne allergens such as pollen or house dust mites. 

The NASAR trial enrolled 100 SAR patients in Australia who were randomized at a 1:1 ratio to receive either Bentrio or saline nasal spray for two weeks via self-administration three times per day, or as needed. For eligibility, patients had to have a baseline reflective Total Nasal Symptom Score (rTNSS) of at least 5 points out of 12, referring to the worst level of nasal congestion, sneezing, nasal itching, and rhinorrhea (runny nose) within the past 24 hours averaged over a one-week treatment-free run-in period. The primary efficacy endpoint was defined as the difference in the average rTNSS over the subsequent 2-week treatment period between Bentrio and saline nasal spray, the current standard of care in drug-free SAR management. The change in mean rTNSS over two weeks is generally accepted as a primary efficacy endpoint for SAR trials and is also recommended by the FDA.

The rTNSS decreased in the Bentrio group from 6.9 points in the pre-treatment period to an average of 5.0 points over the 14-day treatment period (i.e. -1.9 points), while the saline spray group showed a decrease from 6.9 to 6.2 points (i.e. -0.8 points) (see 'Mean rTNSS' graph). The reduction in nasal symptoms conferred by Bentrio was thus 2.5 times larger than with saline nasal spray. The difference in rTNSS reduction of 1.1 points in favor of Bentrio was statistically significant in the ANCOVA model (LSmeans; p = 0.012; 95% confidence interval -2.0 to -0.3), and the study thus met the primary efficacy endpoint.

The treatment effect shown with Bentrio was well above the minimal clinically important difference of 0.28 points. 63.3% of Bentrio-treated study participants rated treatment efficacy as either good or very good vs. 29.2% of saline-treated participants (see 'Patient Rating' graph). Among the latter, 45.8% reported efficacy as poor vs. only 8.2% in the Bentrio group. 73.5% of Bentrio-treated study participants rated tolerability of the treatment as either good or very good vs. 85.5% of saline-treated participants. Among the latter, 10.4% reported tolerability as poor vs. only 6.1% in the Bentrio group.

"We are thrilled with the strong outcomes from the NASAR trial, which we obtained under real-life conditions during the allergy season in Australia," commented Thomas Meyer, Altamira Therapeutics' founder, Chairman, and CEO. "The large magnitude of the reduction of nasal symptoms demonstrates that effective protection against seasonal allergic rhinitis is very well possible with a drug-free treatment. There are many patients who do not respond well to medicated nasal sprays either for lack of efficacy or due to tolerability issues with preservatives or other ingredients. I would like to extend my sincere appreciation to all the patients and investigators involved in the NASAR trial who helped us to reach this important clinical milestone.

"Further, the NASAR results show for Bentrio a statistically significant and clinically highly relevant improvement in efficacy over the current standard of care saline nasal spray treatment," Mr. Meyer added. "Whereas a saline nasal spray aims to rinse out allergen particles, Bentrio forms a thin protective layer which prevents contact of those particles with the nasal mucosa and helps to remove them through natural mucociliary clearance. As already demonstrated in a previous trial, Bentrio stays for about 3.5 hours within the nasal cavity where it can exert its protective effects. In contrast, saline spray is present for only about one hour and provides narrower distribution and less coverage within the nasal cavity.

"With the completion of the NASAR trial, Altamira has concluded its clinical development of Bentrio in allergic rhinitis management. In 2023, the US sales of over-the-counter allergy remedies are estimated to reach close to $4 billion which represents a major opportunity in the non-medicated, preservative-free treatments category. Together with its marketing and distribution partners, Altamira is looking forward to making Bentrio available as an effective and safe treatment option to help patients deal with the daily burden and discomfort associated with allergic rhinitis."

"We are pleased to see our partner, Altamira Therapeutics, has achieved this significant milestone for the Bentrio clinical study. Based on the positive top-line results, we are excited about the potential of Bentrio to address the urgent global need for a novel non-medicated, preservative-free treatment for allergic rhinitis patients." said Mark G. Lotter, CEO and Co-Founder of Nuance Pharma. "We look forward to a successful and strong partnership with Altamira, while delivering this innovative therapy to meet the high unmet medical need in further countries within the APAC region."

In March 2022, Nuance Pharma and Altamira Therapeutics entered into an exclusive licensing and distribution agreement for Bentrio in mainland China, Hong Kong, Macau and South Korea. In November 2022, Nuance Pharma announced to launch Bentrio nasal spray in Hong Kong, China.

About Bentrio

Bentrio is an OTC drug-free nasal spray for personal protection against airborne allergens and, where approved, against airborne viruses. Upon application into the nose, Bentrio forms a protective gel layer on the nasal mucosa. This thin film is designed to prevent the contact of allergens (or virus particles) with cells; in addition, the composition serves to bind such particles and help with their discharge. Together, this is designed to promote alleviation of allergic symptoms (or mitigate upper respiratory tract viral infections). For more info, visit: https://www.aurismedical.com/legacy-programs/bentrio 

About Altamira Therapeutics

Altamira Therapeutics (Nasdaq: CYTO) is dedicated to developing and commercializing RNA delivery technology for extrahepatic targets (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs in preclinical development beyond in vivo proof of concept: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis. The versatile delivery platform is also suited for mRNA and other types of RNA therapeutics and is planned to be leveraged via out-licensing to pharma or biotech companies. In addition, Altamira is in the process of divesting and/or out-licensing its legacy assets in allergology and viral infection (Bentrio® OTC nasal spray; commercial) and inner ear therapeutics (AM-125 nasal spray for vertigo; post Phase 2; Keyzilen® and Sonsuvi® for tinnitus and hearing loss; Phase 3). Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia.

With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

Forward-Looking Statement

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.

Ensifentrine is a first-in-class, selective, dual inhibitor of the enzymes phosphodiesterase 3 and 4 ("PDE3" and "PDE4") combining bronchodilator and non-steroidal anti-inflammatory activities in one compound. This activity has the potential to alleviate respiratory symptoms such as breathlessness and cough, as well as providing anti-inflammatory benefits for those with COPD.

Ensifentrine Study in China

On August 17^th, 2022, Nuance Pharma announced the IND approval from the Center for Drug Evaluation (CDE) for supporting its pivotal Phase I and Phase III clinical trials of Ensifentrine in the maintenance treatment of COPD.

March 9^th, 2023, Nuance Pharma completed first dosing of the first healthy subject in the Phase I trial (RPL554 - AHC001; NCT05758428), a PK, safety and tolerability study of nebulized Ensifentrine on healthy Chinese volunteers.

April 6^th, 2023, Nuance Pharma announces the first COPD patient dosed in the ENHANCE - CHINA Phase III trial (RPL554 - CPC001; NCT05743075), a randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of Ensifentrine over 24 weeks in patients with moderate to severe COPD.

"It gives me great pleasure to announce the first dosing of ENHANCE-China Phase III trial. This represents a crucial milestone for our collaboration with Verona Pharma and is indicative of a strong opening to the China clinical development program. Ensifentrine combines bronchodilator and non-steroidal anti-inflammatory properties in one compound, differentiating it from existing drug classes used to treat COPD" commented Mark G. Lotter, CEO and Co-Founder of Nuance Pharma. "We are looking forward to introducing this novel drug in Greater China to address unmet needs in the COPD market."

"We are pleased our development partner, Nuance Pharma, has begun pivotal studies in COPD with ensifentrine in mainland China," said David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma. "This is a significant milestone and, based on our recent highly positive Phase III results in COPD, we are excited about the potential of ensifentrine to address the urgent global need for a novel treatment for COPD."

December 20^th, 2022, Nuance's global partner Verona Pharma announced Ensifentrine met primary and key secondary endpoints in Phase III ENHANCE-1 trial for COPD, after positive readout for Phase III ENHANCE-2 trial for COPD in August 2022, another step closer to providing a much-needed novel therapy for COPD patients. Verona Pharma plans to submit a New Drug Application to the US Food and Drug Administration in the second quarter of 2023.

About Ensifentrine

Ensifentrine (RPL554) is an investigational, first-in-class, selective dual inhibitor of the enzymes phosphodiesterase 3 and 4 that combines bronchodilator and anti-inflammatory activities in one compound. In Phase II clinical studies in COPD, ensifentrine has shown significant and clinically meaningful improvements in lung function, symptoms and quality of life as a monotherapy or added onto a maintenance bronchodilator. In the Phase III ENHANCE-1 and ENHANCE-2 clinical trials, ensifentrine showed significant and clinically meaningful improvements in lung function measures and reduced the rate of COPD exacerbations. Ensifentrine has been well tolerated in clinical trials involving approximately 3,000 subjects to date.

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia.

With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, please visit www.nuancepharma.com.

About Verona Pharma

Verona Pharma is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of respiratory diseases with significant unmet medical needs. If successfully developed and approved, Verona Pharma's product candidate, ensifentrine, has the potential to be the first therapy for the treatment of respiratory diseases that combines bronchodilator and anti-inflammatory activities in one compound. The Company has evaluated nebulized ensifentrine in its Phase III clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ensifentrine met the primary endpoint in both ENHANCE-1 and ENHANCE-2 trials demonstrating statistically significant and clinically meaningful improvements in lung function. In addition, ensifentrine significantly reduced the rate and risk of COPD exacerbations in ENHANCE-1 and ENHANCE-2. Two additional formulations of ensifentrine are in Phase II development for the treatment of COPD: dry powder inhaler and pressurized metered-dose inhaler. Ensifentrine also has potential applications in cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com.

Forward-Looking Statement:

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law. 

Company contacts:

Nuance Pharma

Vicky Lin, IR & PR Senior Manager, Email: vicky.lin@nuancepharma.cn

Verona Pharma

Victoria Stewart, Senior Director of Investor Relations and Communications, Email: Victoria.Stewart@veronapharma.com

Under the cooperation agreement, DKSH HK will provide full-agency services including key account management, marketing promotion, supply chain, and distribution for Bentrio^TM Nasal Spray sales operation in Hong Kong and Macau.

Bentrio^TM is an OTC drug-free nasal spray designed for protection against airborne disease-causing agents (including allergens and viruses). It is being marketed in several countries throughout Europe and Asia to help protect against allergic rhinitis. It has received 510(k) clearance from the U.S. Food and Drug Administration (FDA) for the treatment of allergic rhinitis (hay fever). The product, which is intended to help protect against airborne allergens and viruses, is considered a Class I medical device in the UK. Bentrio^TM nasal spray is also marketed in Europe, including Germany, for helping to prevent onset and alleviate allergic symptoms caused by airborne allergens such as pollen, house dust mites or animal dander. In other markets such as Singapore, Bentrio^TM is marketed for protecting against airborne viruses and allergens. Bentrio^TM efficacy and protective effects have already been demonstrated through multiple clinical and in vitro studies.

On March 4, 2022, Nuance Pharma and Altamira Therapeutics entered into an exclusive licensing and distribution agreement for Bentrio^TM in mainland China, Hong Kong, Macau and South Korea.

"This is a significant milestone for Nuance Pharma's Asia Expansion strategy as we establish commercial capabilities in two additional key markets, while delivering innovative, safe and effective products to the region." commented Mark G. Lotter, CEO and Co-Founder of Nuance Pharma. "Hong Kong is an important gateway to Asia and represents a critical initial step to expand its presence to the region whilst the Company prepares for the introduction of its innovative pipeline currently in development. We look forward to a successful and strong partnership with the leading regional leader DKSH, while delivering ever more innovative therapies with high unmet needs in the region in the coming years."

Wai Ting Fong, Head of Management and Vice President, Healthcare, DKSH Hong Kong, equally welcomed the partnership: "DKSH is delighted to partner with Nuance Pharma to introduce their innovative product Bentrio^TM. With a broad reach across our different commercial channels, we are committed to driving its expansion in Hong Kong and Macau. Our partnership demonstrates our commitment to offer patients better health and quality of life, in line with DKSH's purpose to enrich people's lives, by providing access to healthcare, goods, services, and insights".

About Bentrio^TM

Bentrio^TM is an OTC drug-free, non-preservatives nasal spray for personal protection against airborne allergens and, where approved, against airborne viruses (including SARS-CoV-2). Upon application into the nose, Bentrio^TM forms a protective gel layer on the nasal mucosa. This thin film is designed to prevent the contact of allergens (or virus particles) with cells. In addition, the composition serves to bind such particles and help with their discharge. Together, Bentrio^TM is designed to promote alleviation of allergic symptoms and to mitigate upper respiratory tract viral infections. For more info, please visit: www.bentrio.com.

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia.

In addition to the Company's commercial base and innovative pipeline in mainland China, Nuance seeks to expand its presence into Asia as a region where it will focus on building its commercial presence for current and pipeline-based portfolio.

With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both mainland China and Asia as a region. For more info, please visit www.nuancepharma.com.

About DKSH

DKSH's purpose is to enrich people's lives. For more than 150 years, we have been delivering growth for companies in Asia and beyond across our Business Units Healthcare, Consumer Goods, Performance Materials, and Technology. As a leading Market Expansion Services provider, we offer sourcing, market insights, marketing and sales, eCommerce, distribution and logistics as well as after-sales services. DKSH is a participant of the United Nations Global Compact and adheres to its principles-based approach to responsible business. Listed on the SIX Swiss Exchange, DKSH operates in 36 markets with 33,100 specialists, generating net sales of CHF 11.1 billion in 2021. The DKSH Business Unit Healthcare distributes pharmaceuticals, consumer health and over-the-counter (OTC) products as well as medical devices. With around 7,920 specialists, the Business Unit generated net sales of CHF 5.6 billion in 2021. For more info, please visit www.dksh.com/hec.

Forward-looking statements

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.

MVA-BN RSV, is being developed for the prevention of respiratory syncytial virus (RSV) in older adults. The vaccine incorporates five distinct RSV antigens to stimulate a broad immune response against both RSV subtypes (A and B), thus mimicking the immune response observed following a natural response to an RSV infection. The vaccine candidate is based on Bavarian Nordic's proven MVA-BN platform technology, which is employed in several approved vaccines.

In April 2022, Bavarian Nordic initiated a global, randomized, double-blind Phase III trial (VANIR) of MVA-BN RSV, planned to enroll 20,000 adults aged 60 years and older, before year end 2022. The trial is being conducted at approximately 115 sites across the U.S. and Germany and is designed to run through the RSV season 2022/2023 with topline results expected mid 2023 if the pre-defined number of lower-respiratory tract disease events has occurred.

Under this MVA-BN RSV Chinese IND approval, conduction of Phase III study in China is granted. According to Dr. Haijin Meng, CMO of Nuance Pharma, the company is planning to conduct the pivotal Phase III study as an extension of the global MRCT in 2023. "We are thrilled to introduce this vaccine to China and give our Chinese investigators and subjects the opportunity to participate in the global clinical development of this novel differentiated vaccine and to evaluate how to apply it to address the unmet needs in RSV prevention," she said.

In 2021, Nuance Pharma entered into an agreement with Bavarian Nordic, granting Nuance Pharma exclusive rights to develop and commercialize MVA-BN RSV in Chinese Mainland, Hong Kong, Macau, Taiwan, South Korea and Southeast Asia.

"This is a significant milestone for Nuance Pharma, and we are confident that we will achieve solid and inspiring progress for the development of MVA-BN RSV vaccine in China. The MVA-BN RSV vaccine holds the potential to become the first to market adult RSV vaccine in China. This is an opportune moment for us to be developing and commercializing the asset, riding the wave of appreciably heightened awareness to the benefits of vaccination in the COVID-era." commented Mark G. Lotter, CEO and Co-Founder of Nuance Pharma. "MVA-BN RSV represents another example of Nuance's capability to bring differentiated solutions to address unmet medical needs in the respiratory space in China and the Asian markets."

About MVA-BN RSV

Bavarian Nordic's vaccine candidate, MVA-BN RSV, is being developed for the prevention of respiratory syncytial virus (RSV) in older adults. The vaccine incorporates five distinct RSV antigens to stimulate a broad immune response against both RSV subtypes (A and B), thus mimicking the immune response observed following a natural response to an RSV infection. The vaccine candidate is based on Bavarian Nordic's proven MVA-BN platform technology, which is employed in several approved vaccines.

In 2021, Bavarian Nordic reported results from a clinical Phase II double-blinded, placebo-controlled human challenge trial (n=61), which enrolled healthy adult volunteers, who were randomized to receive either a single vaccination of MVA-BN RSV or placebo. Volunteers were challenged intranasally with an RSV type A strain 28 days after vaccination. The study demonstrated a significant reduction in viral load in vaccinated subjects (n=30) versus placebo (n=31), thus meeting the primary endpoint. In the vaccinated subjects, clinical symptoms typically associated with RSV infections were significantly reduced. Further, the vaccine demonstrated an efficacy of up to 79% in preventing symptomatic RSV infections ^[1].

Bavarian Nordic has also previously reported strong results from a Phase II trial of MVA-BN RSV in 421 older adults, demonstrating that the vaccine was well-tolerated and induced both broad and durable antibody and T-cell responses against RSV, as well as mucosal immune responses that may be important for protection against RSV. The trial included a revaccination of subjects after one year, following which the immune responses were rapidly and significantly increased, notably in subjects with the weakest immunity prior to the booster vaccination ^[2].

MVA-BN RSV has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration for active immunization for prevention of lower respiratory tract disease caused by RSV in adults aged 60 years or older. It has also been granted access by European Medicines Agency (EMA) to its priority medicines (PRIME) scheme for MVA-BN® RSV in active immunization for the prevention of lower respiratory tract disease (LRTD) caused by Respiratory Syncytial Virus (RSV) in adults ≥60 years of age.

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia.

In addition to the Company's commercial base and innovative pipeline in mainland China, Nuance seeks to expand its presence into Asia as a region where it will focus on building its commercial presence for current and pipeline-based portfolio.

With the mission to address critical unmet medical needs in Asia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in both China and Asia as a region. For more information, visit www.nuancepharma.com.

About Bavarian Nordic

Bavarian Nordic is a fully integrated vaccines company focused on the development, manufacturing and commercialization of life-saving vaccines. We are a global leader in smallpox vaccines and have been a long-term supplier to the U.S. Government of a non-replicating smallpox vaccine, which has been approved by the FDA, also for the protection against monkeypox. The vaccine is also approved in Europe and Canada. Our commercial product portfolio furthermore contains market-leading vaccines against rabies and tick-borne encephalitis. Using our live virus vaccine platform technology, MVA-BN^®, we have created a diverse portfolio of proprietary and partnered product candidates designed to save and improve lives by unlocking the power of the immune system, including an Ebola vaccine, which is licensed to the Janssen Pharmaceutical Companies of Johnson & Johnson. We are also committed to the development of a next generation COVID-19 vaccine. For more information visit www.bavarian-nordic.com.

Forward-looking statements

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.

References

1. https://www.resvinet.org/uploads/2/2/2/7/22271200/abstract_booklet_rsvvw21.pdf
2. Jordan E. et al. 2010. J. Infect, Dis. 28:223(6). 1062-1072

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Ensifentrine is a first-in-class, dual inhibitor of the enzymes phosphodiesterase 3 and 4 ("PDE3" and "PDE4") combining bronchodilator and anti-inflammatory activities in one compound. This activity has the potential to alleviate respiratory symptoms such as breathlessness and cough, as well as providing anti-inflammatory benefits for those with COPD.

On August 9^th, 2022, Verona Pharma announced its ENHANCE-2 Phase III trial evaluating nebulized Ensifentrine for the maintenance treatment of COPD met its primary endpoint, as well as secondary endpoints demonstrating improvements in lung function, and significantly reduced the rate and risk of COPD exacerbations. Verona Pharma expects to report top-line results from its ongoing ENHANCE-1 Phase III trial around the end of the 2022 and, if similarly positive, plans to submit a New Drug Application to the US Food and Drug Administration for Ensifentrine in 1H2023.  

Under this Ensifentrine Chinese IND approval, conduction of both Phase I and Phase III studies in China are granted. According to Dr. Haijin Meng, CMO of Nuance Pharma, the company is planning to conduct a Phase I study to evaluate the detailed pharmacokinetic characteristics of Ensifentrine in healthy Chinese volunteers. Meanwhile, the pivotal Phase III study is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Ensifentrine over 24 weeks in patients with moderate to severe COPD. "We are thrilled to introduce this first-in-class molecule to China and give our Chinese investigators and subjects the opportunity to participate in the global clinical development of this novel molecule and to evaluate how to apply it to Chinese COPD clinical setting properly," she said.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma with a potential value of up to $219 million, granting Nuance Pharma exclusive rights to develop and commercialize Ensifentrine in Greater China (mainland China, Hong Kong, Macau and Taiwan). In return, Verona Pharma received an upfront payment of USD 25 million in cash and an equity interest valued at USD 15 million. Meanwhile, Verona Pharma is eligible to receive future milestone payments as well as double-digit royalties as a percentage of net sales in Greater China.

"This is a significant milestone for Nuance Pharma, and we are confident that we will achieve solid and inspiring progress for the development of Ensifentrine in China," commented Mark G. Lotter, CEO and Co-Founder of Nuance Pharma. "COPD is the fifth leading cause of death in China with a reported prevalence of 8.2% in the population aged 40 years and above. We strongly believe Ensifentrine will be an effective COPD therapy to address the unmet medical needs in mainland China."

"We are pleased our development partner, Nuance Pharma, has received IND approval to begin pivotal studies in COPD with Ensifentrine in mainland China," said David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma. "This is an important milestone and, based on our recent positive Phase 3 results from our ENHANCE-2 trial in COPD, we remain confident about the potential of Ensifentrine to address the urgent global need for a novel treatment for COPD."

About Ensifentrine

Ensifentrine (RPL554) is an investigational, first-in-class, dual inhibitor of the enzymes phosphodiesterase 3 and 4 ("PDE3" and "PDE4") that combines bronchodilator and anti-inflammatory activities in one compound. In Phase 2 clinical studies in COPD, Ensifentrine has shown significant and clinically meaningful improvements in lung function, symptoms and quality of life as a monotherapy or added onto a maintenance bronchodilator. In the Phase 3 ENHANCE-2 clinical trial, Ensifentrine showed significant and clinically meaningful improvements in lung function measures and reduced the rate of COPD exacerbations. Ensifentrine has been well tolerated in clinical trials involving more than 2,200 subjects to date.

About Nuance Pharma

Nuance Pharma is a patient-centric and innovation focused biopharmaceutical company, with both clinical and commercial stage assets. Founded by Mark Lotter in 2014, with the mission to address critical unmet medical needs in Greater China and Asia Pacific, Nuance's portfolio represents a differentiated combination of commercial stage and innovative pipeline assets across respiratory, pain management, emergency care and iron deficiency anemia. Focusing on specialty care, Nuance deploys the Dual Wheel model that incubates a late clinical stage innovative portfolio, while maintaining a self-sustainable commercial operation.

About Verona Pharma

Verona Pharma is a clinical-stage biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of respiratory diseases with significant unmet medical needs. If successfully developed and approved, Verona Pharma's product candidate, Ensifentrine, has the potential to be the first therapy for the treatment of respiratory diseases that combines bronchodilator and anti-inflammatory activities in one compound. The Company is evaluating nebulized ensifentrine in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ensifentrine met the primary endpoint in ENHANCE-2 demonstrating a statistically significant and clinically meaningful improvement in lung function. In addition, Ensifentrine significantly reduced the rate of COPD exacerbations in the ENHANCE-2 trial. Two additional formulations of Ensifentrine are in Phase 2 development for the treatment of COPD: dry powder inhaler ("DPI") and pressurized metered-dose inhaler ("pMDI"). Ensifentrine also has potential applications in cystic fibrosis, asthma and other respiratory diseases. For more information, please visit www.veronapharma.com.  

Forward-looking statements

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, that could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.

Contacts

Nuance Pharma

Vicky Lin, IR & PR Senior Manager, vicky.lin@nuancepharma.cn, Tel: +86 21 3203 5318

Verona Pharma PLC.

Victoria Stewart, Director of Investor Relations and Communications, info@verona.com, Tel: +44 (0)203 283 4200

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SHANGHAI, July 26, 2022 /PRNewswire/ -- Nuance Pharma ("the Company") announces the completion of dosing for all HNVs in the Phase I clinical study of its novel Ketorolac for IV infusion (NTM-001), a non-opioid analgesic drug co-developed with Neumentum. A total of 16 healthy normal volunteers (HNVs) were recruited for the Phase I clinical study. All subjects had completed sample collections up to 96 hours and passed a 15-day safety follow-up period. To date, there have been no serious adverse events or alarming safety concerns reported among any of the subjects. According to Nuance R&D head, sample data clean-up and statistical analysis are in progress. The Phase I clinical study is estimated to be completed later this year.

In late 2020, Nuance Pharma entered into an exclusive license agreement with Neumentum for the rights to develop and commercialize the novel intravenous infusion of ketorolac (NTM-001) in Greater China. The asset is currently in Phase III development in the U.S. for the short-term management of moderately severe pain.

"It gives me great pleasure to announce the smooth completion of Phase I dosing for NTM-001 in Hong Kong. This represents a crucial milestone for our collaboration with Neumentum and is indicative of a grand opening to the China clinical development program. NTM-001 provides injectable non-opioid analgesic to patients and will be a promising alternative candidate for the use of opioid drugs in analgesics," commented Mark G. Lotter, CEO and Co-Founder of Nuance Pharma. "We are looking forward to introducing this novel drug in Greater China to address unmet needs in the pain management market."

"We are very excited to have completed this important study for NTM-001, further demonstrating the safety of the compound," stated Joseph Pergolizzi MD, Executive Chairman of Neumentum. " We believe NTM-001 has the potential to significantly improve the standard of care for many patients experiencing moderately severe, acute pain requiring analgesia at the opioid level. We believe the results of this study further highlight the profile of NTM-001 as a potentially effective and safe short-term pain management solution and provide valuable information for the product's clinical program moving forward."

About Ketorolac (NTM-001)

Ketorolac (NTM-001) is a novel, alcohol-free formulation of ketorolac in a convenient, ready-to-use, pre-mixed bag for continuous 24 hours IV infusion, for the treatment of moderately severe acute pain requiring analgesia at the opioid level, usually in a postoperative setting with the potential benefit of consistent pain relief without the risks associated with opioids, or the disadvantages of bolus short-acting analgesics.

About Pain in Postoperative Period (POP)

In 2020, there was an estimated 66 million inpatient surgical operations in Chinese hospitals. 1) There is significant demand for pain management in the POP setting in China, driven by the huge inpatient surgery volume and double-digit growth rates. 2) In the POP setting, the main goal of pain management is to reduce pain or discomfort to the extent possible and minimize side effects at the same time. However, despite medical advancements in the last decades, opioids remain the backbone of POP pain management in the moderate to severe setting despite the serious side-effects. There is substantial need for a non-opioid pain management option that affords consistent, opioid-level pain relief that is, at the same time, safe to address the significant unmet medical needs in China's pain management market.

About Nuance Pharma

Nuance Pharma is a patient-centric and innovation focused biopharmaceutical company, with both clinical and commercial stage assets. Founded by Mark Lotter in 2014, with the mission to address critical unmet medical needs in Greater China and Asia Pacific, Nuance's portfolio represents a differentiated combination of commercial stage and innovative pipeline assets across respiratory, pain management, emergency care and iron deficiency anemia.

Focusing on specialty care, Nuance deploys the Dual Wheel model that incubates a late clinical stage innovative portfolio, while maintaining a self-sustainable commercial operation.

About Neumentum

Neumentum is dedicated to becoming a leading non-opioid analgesic and neurology specialty pharmaceutical company with product candidates that have the potential to provide the benefits of safe and effective pain management, without the risks for abuse, misuse and diversion seen with opioids or the opioid-induced side effects, including potentially life-threatening respiratory depression. Neumentum is led by an experienced executive team of biotech and pharmaceutical industry leaders who have extensive experience in pain and neurology, from drug development through commercialization. For more information, visit www.neumentum.com.

Forward-looking statements

This announcement includes forward-looking statements that involve risks, uncertainties and other factors, many of which are outside of our control, which could cause actual results to differ materially from the results discussed in the forward-looking statements. Forward-looking statements include statements concerning our plans, objectives, goals, future events, performance and/or other information that is not historical information. All such forward-looking statements are expressly qualified by these cautionary statements and any other cautionary statements which may accompany the forward-looking statements. We undertake no obligation to publicly update or revise forward-looking statements to reflect subsequent events or circumstances after the date made, except as required by law.

Contacts:

Nuance Pharma
Vicky Lin, IR & PR Senior Manager, vicky.lin@nuancepharma.cn, Tel: +86 21 3203 5318
Neumentum Inc.
Melissa Donnelly, Public Relations Manager, melissaanne@neumentum.com Tel: +1 (833) 638-7246

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