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Innovative drug, Carrimycin, Receives FDA Approval for International, Multi-country Phase III Clinical Trial for the treatment of severe COVID-19 in hospitalized patients

By Alex

Posted on December 23, 2020

�Shenyang Tonglian Group Co., Ltd. announces FDA approval for a randomized, multicenter, placebo-controlled, double-blind clinical study of the safety and efficacy of Carrimycin for the treatment of severe COVID-19 in hospitalized patients
International 300-patient study, to start in January 2021 and run for ~6 months in the USA, Mexico, Brazil, Philippines, Ukraine, Argentina, Peru, Colombia and India
Carrimycin is an innovative drug marketed in China, shown in China to have a positive impact on outcome for hospitalized COVID-19 patients with potential significant advantages
Carrimycin is an innovative, safe and effective compound, administered as film-coated tablet

SHENYANG, China--(BUSINESS WIRE)--Shenyang Tonglian Group Co., Ltd. (�Tonglian Group� or the company), a company innovating and producing specialty pharmaceuticals including anti-infective treatments, today announces that the U.S. Food & Drug Administration (FDA) has approved a randomized, multicenter, placebo-controlled, double-blind clinical study of the safety and efficacy of Carrimycin for the treatment of severe COVID-19 in hospitalized patients.

The trial (�Study to Evaluate Safety and Efficacy of Carrimycin for Treatment of Severe Coronavirus Disease 2019 (COVID-19) in Hospitalized Patients� NCT04672564) is estimated to start in early January 2021 and will be conducted in the USA, Mexico, Brazil, Philippines, Ukraine, Argentina, Peru, Colombia and India. The primary endpoints for the study will be efficacy and safety, being the recovery rate defined as the proportion of patients alive without need for supplementary oxygen and ongoing medical care at Day 28. A number of secondary efficacy and safety endpoints will also be evaluated. The study protocol is available online at clinicaltrials.gov.

Carrimycin is a member of the macrolide family of antibiotics produced from a genetically engineered strain of S. spiramyceticus, using synthetic biology. It received marketing approval in China in June 2019 to treat bacterial infections. Early in the SARS-CoV-2 outbreak in China, Carrimycin was shown in three sequential clinical trials to effectively eliminate SARS-CoV-2 virus in a timely fashion, significantly improve clinical symptoms and pulmonary inflammation, shorten hospitalization time, and improve patient prognosis.

The Ministry of Science and Technology of the People's Republic of China has mentioned Carrimycin as a safe and effective domestic drug for treating COVID-19.

The International trial will enrol 300 hospitalized patients ?18 years including 150 patients in the experimental group and 150 patients in the control group. Anticipated to last about six months, an interim analysis is planned to be conducted when half (~150) patients have completed the 28-day assessment period. Under the study protocol, Carrimycin will be administered as 2x 200mg film-coated tablets once daily for 14 days.

Carrimycin is China's first innovative drug independently developed by the Institute of Medical Biotechnology, Chinese Academy of Medical Sciences and Tonglian Group using synthetic biology. It is the only FDA-approved synthetic biology drug in the world for phase III clinical studies of severe coronavirus disease.

Commenting on the forthcoming FDA-approved International trial of Carrimycin Jiang Enhong, CEO at Tonglian Group said:

�Our company is proud to have been actively supporting the anti-SARS-CoV-2 pre-clinical and clinical emergency initiatives in China. In view of the seriousness of the pandemic, Tonglian Group is keen to explore the potential of Carrimycin on the international stage to contribute to the global fight against COVID-19.

�We are delighted that having completed its safety review, the FDA has approved our application for a clinical study of the safety and efficacy of Carrimycin for the treatment of severe COVID-19 in hospitalized patients.�

Zhao Xiaofeng, Head of New Drug Development Department at Tonglian Group added:

�Carrimycin is cost effective to produce at scale, and easily administered as a simple tablet. Based on the very positive Chinese studies to date, and our understanding of the potential mode of action of Carrimycin, we believe it could have a very important role to play in improving the outcome of patients with moderate to severe COVID-19.�

According to research by the Chinese Academy of Medical Sciences and other research institutes, the anti-replication effect of Carrimycin on coronavirus in vitro is much stronger than that of Azithromycin. It has also found the target for the protein synthesis inhibition effect of Carrimycin, via the mTOR pathway, and the inhibitory effect of Carrimycin on this protein, is stronger than those of other macrolide drugs and that Carrimycin has a good antifibrosis effect.

�Carrimycin will be used in the clinical trial of COVID-19 as a single drug application, rather than combined with other antiviral drugs, it may avoid drug interaction caused by drug combination� Dr. Xia Mingyu from Shenyang Pharmaceutical University added.

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Notes to editors

1. About Tonglian Group - www.tonglian-group.com

Shenyang Tonglian Group Co., Ltd. (�Tonglian Group�) was established in 1995 and has more than 5,000 employees, with group headquarters located in Shenyang, China. It is an innovative large-scale private enterprise group integrating research, production and marketing of large-scale biochemical active pharmaceutical ingredients (APIs) and multi-dosage forms of Chinese and Western medicine preparations across many industries and regions, such as energy, chemical industry and environmental protection. Its core biopharmaceutical business has R&D and production bases in Shanghai, Shenyang, Hulunbeier (Inner Mongolia), Yueyang (Hunan), and Jingdezhen (Jiangxi).

Anti-infectives R&D, manufacturing, and sales

Tonglian Group is one of the largest pharmaceutical manufacturers with the most comprehensive ranges in the field of antibiotics and vitamins in the world, including Vitamin C, Penicillin industrial potassium salt, 6-APA, Erythromycin thiocyanate, 7-ACA, Rifamycin, and its national first-class new drug Carrimycin, with a production capacity covering over 50% of international demand.

It has established independent R&D capabilities through the Tonglian Pharmaceutical Research Institute and Shanghai Tonglian Pharmaceutical Technology Co., Ltd. Shenyang Tonglian Institute of Life Sciences, which is under construction, has a key research focus on anti-infective drugs. Its goal is to build an international R&D and cooperation infrastructure for independent R&D, technology transfer and cooperative development, and a complete workflow of project establishment, preclinical research, clinical research, and registration application support.

Tonglian Group and COVID-19

Tonglian Group is an active player in the global efforts to address the COVID-19 pandemic. In March 2020, its CRO team formed an �Anti-epidemic Taskforce�. In Wuhan, Huangshi, Harbin, and Mudanjiang in China it supported clinical trial projects and medical workers, delivering first-aid drugs and materials to hospitals. As part of this effort, it donated 21.1456 million yuan (>USD 3,000,000) of Carrimycin to hospitals in China to support the treatment of COVID-19 pneumonia.

2. About Carrimycin

Carrimycin is the first innovative drug in the world developed by using synthetic biology, produced via fermentation in a genetically engineered strain S. spiramyceticus. bacterium.

A 16-membered cyclic macrolide antibiotic, Carrimycin is a physiologically active substance in the class of macrolide antibiotics with a variety of medicinal properties developed jointly by Shenyang Tonglian Group Co., Ltd. and Institute of Medical Biotechnology, Chinese Academy of Medical Sciences.

It received marketing approval in China in June 2019 by the National Drug Administration of China for the treatment of adult mild and moderate community acquired bacterial infection.

Patents

Carrimycin is the subject of 24 invention patents in China and Internationally (11 authorized; 13 in application). Up to now, Carrimycin has been granted 25 patent certificates in 15 countries and regions (including China) (11 domestic and 14 international).

Carrimycin as a potential treatment for COVID-19

During the pandemic in China, the potential of Carrimycin as a treatment for COVID-19 was explored in humans successively in three clinical studies, including the emergency research project of Carrimycin against coronavirus disease initiated by the Ministry of Science and Technology of China, which achieved remarkable clinical results.

On February 15, with the support of the Emergency Research Project of the Ministry of Science and Technology of China, Carrimycin was investigated in a randomized, open, positive drug controlled multicenter clinical study, which was jointly completed by 9 clinical research centers, including Beijing Youan Hospital, Huangshi Central Hospital, and Affiliated People's Hospital of Wuhan University. All the patients were discharged from hospital without any serious adverse reactions. On April 26, another randomized, open, controlled, multi-center clinical study was completed in three hospitals, including Kang'an Hospital of Mudanjiang City. All patients in the test group were deemed cured and discharged from hospital without any deaths or serious adverse reactions.

Through the above clinical trials, it was demonstrated that Carrimycin could effectively eliminate SARS-CoV-2 virus in a timely fashion, significantly improve clinical symptoms and pulmonary inflammation, shorten hospitalization time, and improve patient prognosis. Especially for patients with viral relapse and failure of antiviral treatment, the effect was apparent with no obvious adverse reactions. Through specific target proteins, Carrimycin can regulate inflammation and immune response, significantly improve the pathological changes of inflammation and edema in important organs such as lung and heart and has obvious antipyretic effect.

Potential advantages of Carrimycin as a treatment for COVID-19 vs other anti-COVID-19 drugs

A recent article in the Lancet (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30080-1/fulltext) highlighted that macrolides have anti co-infection, anti-fibrosis, anti-inflammatory and immunomodulatory effects. The potential of members of the macrolide group of antibiotics as a treatment for COVID-19 has thus been proposed. It is postulated that macrolide compounds, notably rapamycin, may have anti-inflammatory effects by inhibiting the mTOR signaling pathway.

Carrimycin shares the same mechanism of inhibiting the mTOR signal pathway with rapamycin, and has shown promising results in clinical trials in China, including higher negative conversion rate and lower pulmonary inflammation scores.

While inhibiting the intracellular replication of coronavirus directly, Carrimycin can regulate the body's inflammatory factors, protect important organs of the body, and has good safety, thus playing an important role in the treatment of coronavirus disease. Patients with severe coronavirus disease are more likely to produce a large number of cytokines and chemokines of different races, which play a pathological role in the development of acute severe systemic inflammatory complications. Carrimycin has been found in studies to inhibit the mTOR pathway, thereby reducing the expression of IL-6 and IL-8. In animal experiments, it has also been observed that Carrimycin can significantly reduce the expression of IL-1? and IL-4. Meanwhile, T cell studies have also found that it can significantly promote the increase of total T cells (CD3 positive cells), in which both CD4 and CD8 positive cells are increased. It was observed in animal models of severe infection that Carrimycin could significantly improve the pathological changes of inflammation and edema in vital organs, especially in lung, liver, kidney, heart, brain, stomach and intestine. It has a good anti-inflammatory effect and immune regulation. Good inhibitory effect on clinical manifestations such as high fever, redness and swelling, and it is safe to use. Therefore, it is speculated that Carrimycin may have a better protective and immunomodulatory effect on severe patients.

It is now known that COVID-19 leads to pulmonary inflammation and bacterial infection and may cause pulmonary fibrosis. Carrimycin�s potential mode of action and advantages include:

Anti-bacterial infection: the results of preclinical and clinical studies of Carrimycin show that the antibacterial effect of Carrimycin is stronger than or equivalent to Azithromycin.

Anti-inflammatory effect: clinical trials of Carrimycin has shown that the improvement effect of Carrimycin on pulmonary inflammation is stronger than Azithromycin.

Antiviral-effect: according to the research of Chinese Academy of Sciences, the anti-replication effect of Carrimycin on coronavirus in vitro is much stronger than that of Azithromycin. It has also found the target for the protein synthesis inhibition effect of Carrimycin, via the mTOR pathway, and the inhibitory effect of Carrimycin on this protein, is stronger than those of other macrolide drugs

Anti-fibrosis effect: the research of Chinese Academy of Medical Sciences shows that Carrimycin has a good antifibrosis effect.

Therefore, in view of the above aspects and the results of the clinical trial of Carrimycin against COVID-19 carried out in China, the therapeutic effect of Carrimycin on COVID-19 is considered to be better than those of other macrolide drugs. Moreover, Carrimycin has been used in the treatment of COVID-19 as a single drug application, rather than combined with other antiviral drugs. Therefore, Carrimycin may avoid drug interaction caused by drug combination.

3. International Clinical Study of Carrimycin as a treatment for Covid-19

Tonglian Group submitted Pre-IND application to the US Food and Drug Administration (FDA) for a phase III clinical study on the indications of Carrimycin for severe coronavirus disease in June 2020 and submitted an IND application in October 2020. It has now received written approval from the FDA for the Carrimycin phase III clinical study against severe coronavirus disease in the United States.

The study protocol is available online at https://www.clinicaltrials.gov (https://clinicaltrials.gov/ct2/show/NCT04672564 )