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The new drug Fespixon (ON101) will gradually enter the international market. Will there be some unknown challenges? The previous announcement has already obtained patent protection in some countries. Whether Oneness Biotech has made a general patent investigation, including (but not limited to) the process, production method, etc. Even for new drugs that are still under development, we should make sure that there are no hidden problems involving patent infringement. Many years ago, the stock king of the mobile phone industry in Taiwan went downhill because of a lawsuit by a major North American cell phone manufacturer. After all, Oneness Biotech is an enterprise intended to enter the international arena.
A well-known U.S. firm is entrusted with the patent of Oneness Biotech’s new drug. The patent has been effectively protecting the innovation of the drug, and multiple protections are provided for subsequent research and development. Also, the patent is the key to international cooperation.
Merck, Pfizer, Roche, or other pharmaceutical companies developing oral drugs for COVID-19 have conducted clinical trials mostly in patients with mild-to-moderate symptoms who are not hospitalized, and have not enrolled patients with severe symptoms or hospitalized patients or have terminated them for business reasons. If the company’s SNS812 successfully enters the IND, what type of patients are expected to be admitted, and will it be willing to take on the challenge of recruiting inpatients or patients with severe symptoms?
In the course of COVID-19, the virus is the virulence factor in the early stages of the disease, after which the main cause of severe symptoms is the over-activated immune system of the host. Therefore, different treatment strategies need to be given to patients in different stages of COVID-19.
Merck has also tried its antiviral drug (Molnupiravir) in inpatients, but it was abandoned because there were no significant effects. SNS812 is designed to target the replication of viral genes, and the IND will focus on patients with mild-to-moderate symptoms and who are not hospitalized with influenza.
If FB825 is up to the standard of AD efficacy at the end of the year, does the company plan to set up a plant further?
Oneness Biotech has evaluated that if FB825 achieves significant efficacy in Phase 2a, the establishment of its own antibody manufacturing plant will not be ruled out. At present, FB825 has two indications: atopic dermatitis and allergic asthma. Oneness Biotech is also actively discussing other potential indications with international partners, and will further explore depending on the evaluation results to expand the product value. In addition, FB704A and other pre-clinical antibodies will be produced by our plant established in the future to control the production cost.
Recently, I have found more and more research reports in the journal were introducing M1/M2 macrophage polarization on chronic wound mechanisms.
1. In the case of a clear mechanism of action, are there any pharmaceutical companies that can develop the biological drugs or molecule drugs different from Fespixon (ON101) in the future?
2. Is it difficult?
The polarization of M1/M2 macrophages is increasingly important for the treatment of chronic wounds, but the research and development of other similar new drugs with the same mechanism would take a long time, often more than 10 years, and it’s difficult to make it successful. ON101 will continue to submit the (approved) new patent applications, with a 20-year advantage of new protection period.
Is ON101 related to gram-positive bacteria and gram-negative bacteria in the pathogen of diabetic foot infection?
In addition, Centaur Pharmaceuticals launched its new NCE drug WOXheal in India last year. What are the advantages of ON101 compared with WOXheal?
1. The mechanism of action of Fespixon (ON101) is to “inhibit M1-type macrophage inflammatory response, promote M2-type macrophage polarization, reshape the balance of M1/M2 microenvironment of the wound, regulate the wound from inflammation to hyperplasia, and accelerate the wound tissue repair and healing. In contrast to the antibacterial effect of antibiotics against gram-positive bacteria and gram-negative bacteria, according to the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the topical antibacterial agents for skin are not listed in DFU clinical recommendation.
2. This product is a small molecule drug DermaPro developed by CytoTools, a German biotechnology company. The active ingredient is Diperoxochloric acid, and its trade name is WoxHeal in India, with the main effect of antibacterial. The product was previously failed in Phase III clinical trial in Europe (2015), and the technology was transferred to India by Centaur Pharmaceuticals for development. The product was approved for marketing in India in 2019. According to the published clinical data of Phase III in India, the incidence of complete wound closure of diabetic foot ulcer was 71.03%, but the incidence of complete wound closure of active control group (only using the normal saline) was also as high as 57.53%, far higher than the general treatment standard, and the difference between the two groups was 13.5%, p = 0.0156. Due to the lack of published Phase III clinical analysis data, the reliability of clinical efficacy cannot be confirmed.
3. ON101 indications do not restrict the DFU types, and Phase III international multi-center clinical efficacy shows that the difference between ON101 and DFU wound care common dressings Aquacel is 25.57%, p = 0.0001; ON101 Phase III related trial data and mechanism of action have been accepted by internationally renowned SCI Journal, and will be officially released internationally at the beginning of next month (September).
Last year, Novo Nordisk spent US$2.1 billion (signing bonus of US$725 million) to merge and acquire a biotech company that completed the new drug IL-6 Phase II trial. Is FB704A also a new drug IL-6 Phase II trial of similar value?
Anti-IL6 is an important target for inhibiting inflammation, and the international licensing transaction amount is large. In 2009, BMS completed the license transfer of IL6 Phase IIa trial to Alder with the signing bonus of US$85 million, and the total licensing fee was US$1 billion; in 2016, Roche licensed Eleven to complete Phase I clinical trial with a total licensing fee of US$270 million; Novo Nordisk at this time, Novo Nordisk directly merged and acquired Corvidia (mainly IL6), and the transaction amount was a new high record, driven by Ziltivekimab fully human monoclonal antibody new drug’s IIb trial of Corvidia, showing the excellent effect (P=0.0001) of reducing hsCRP in the treatment of chronic kidney disease (CKD). There are more than 700 million CKD patients in the world. In the past, no pharmaceutical company used Anti-IL6 drugs for the treatment of CKD. FB704A is a self-developed fully human monoclonal antibody new drug developed by Oneness Biotech, which is currently undergoing the first Phase II trial, mainly for severe neutrophilic asthma. It is also the first time that Anti-IL6 drug is used for this indication in the world. Phase II trial of new target may be executed in the future to enhance the value of drug.
What is the new drug for the production technology of monosaccharide antibody of Chinese patent?
The glycosylation type of the antibody will affect the stability and function of the antibody. It is an important quality indicator of antibody drugs and one of the possible targets of antibody optimization. Nowadays, antibody glycosylation produced through the commonly used cell production technology is diverse and complex, and maintaining the consistency of glycosylation requires accurate and stable production technology. Oneness can produce antibodies with only single glycosyls through its patented production technology of monosaccharide antibody, which can improve the manufacturing process and the consistency and effectiveness of quality, and can produce antibody-drug conjugates (ADC) to improve the competitiveness of antibody drugs.
Nowadays, Mainland China is one of the countries with a large number of DFU patients, and it is also known for counterfeiting. Fespixon is only extracted from 2 kinds of herbs. Is it easy to be counterfeited in the mainland market? Is there any countermeasure in your company for counterfeiting in the mainland or Southeast Asian countries to avoid wasting ten years’ hard work? And if the traditional Chinese medicine method of direct application of Plectranthus amboinicus and Centella Asiatica to the wounds is adopted, will it have some curative effect?
1. Botanical new drug, different from Chinese herbal medicine, requires rigorous scientific and medical research. Starting from planting, the ingredients and activities of medicinal herbs shall be controlled in accordance with Good Agricultural and Collection Practices (GACP) to meet the requirements. The herbs are extracted, analyzed and verified to meet the requirements of quality consistency, significant efficacy and drug safety, which is not the same as the theory that the medicinal materials will have efficacy by mixing them up.
2. The formula patent of Fespixon in major global markets has been applied for and licenses of the United States and Russia have been obtained with a patent period up to 2038 and up to 5 years to be extended. The patent covers extraction methods, extracts, medical uses, formulations and manufacturing processes, which can prevent any generic drug coming into the market. In addition, there are still other trade secrets that constitute technical barriers from planting to the final preparations, and illegal makers cannot make any product consistent with Fespixon.
3. Meanwhile, the mechanism of action of botanicals to be verified or explained clearly is always the most difficult but that of Fespixon has been completed rigorously, which will soon be published in a well-known SCI journal.
How about the current progress of the VLU safety test (ON101CLAS03) on the Clinical Trials Network in Taiwan?
In addition, how about the patent application progress of FB825 biomarker responder?
1.The VLU clinical trial is part of new curative effect exploration and mechanism of action trial of Fespixon. The trial center has been started and subjects have been recruited.
2. A provisional patent application of FB825 responder biomarker was submitted in November 2020. All trials of the biological index clinical research conducted in Taiwan were visited in June 2021, and the sample analysis is in progress. The test report is scheduled to be obtained in September 2021. With complete data collected, the formal patent application will be completed by November 2021.
With the rapid clinical progress and the increasing product lines of Oneness’s antibody products, is the company planning to set up a GMP plant for production on its own?
Getting positive results of the Phase IIa clinical trial of FB825, Oneness will evaluate the plan of building its own production plant, and improve the independent production capacity of antibody drugs for higher profits and lower research and development costs.