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Omicron is more contagious than any of its predecessors yet the ratio of patients in critical condition and those hospitalized is relatively low. We would like to know:
1. Is COVID-19 turning flu-like?
2. With the reduced ratio of COVID-19 severity and patients in critical conditions, is SNS812 still of value for continued research and development? Thank you!
1. Given the developments around the world, it is inevitable for COVID-19 to turn flu-like.
2. Nucleic acid drug have become the most important type of new drug after small molecular and antibody drugs. They can be used in traditional disorders such as chronic conditions, cancers, and infections and can also overcome the medical limits in terms of rare diseases and other gene-related disorders. Oneness Biotech and Microbio (Shanghai) decided to devote themselves to the development of SNS812 not just because of the current pandemic. Considering the fact that once COVID-19 turns flu-like, there will be huge and long-lasting demand, it will also help deepen the R&D platform technology for Nucleic acid drug and expedite the development of new drugs in this blue ocean.
Now there is also the South African variant of the virus.
1. How is the treatment effect of SNS812 in the said variant?
2. What is the R&D status of SNS812?
1. DNA sequencing results show that the Omicron (NU) variant does not go through any mutation where SNS812 binds to. In other words, SNS812 should be inhibitive towards this variant. The actual effect is pending confirmation after the viral cell strain is qualified.
2. SNS812 has entered pre-clinical development and contract production has begun. The IND application is scheduled to be submitted by the end of June 2022.
The new COVID-19 drugs of both Pfizer and Merck are to be introduced to the market soon. Will it be a threat for SNS812, which is yet to enter Phase I? If it is impossible to obtain EUA, clinical R&D needs to consist of three phases in order for it to be available on the market, which may then take years before it is available on the market. Although it is a new COVID-19 drug that works differently, will SNS812 have the sufficient efficacy to compete with its counterparts developed by Pfizer and Merck? Given so many new competitors on the market for COVID-19 drugs around the world, will Oneness Biotech continue with the R&D of SNS812? Thank you!
The UK Medicines & Healthcare Products Regulatory Agency (MHRA) already approved the marketing of the oral COVID-19 drug Molnupiravir developed by Merck on November 4, 2021; the drug, however, may only be used in patients with symptoms of mild to moderate COVID-19 and with at least one risk factor of progression to severe ones, including obesity and diabetes, among others. Molnupiravir works to trigger gene mutation in replication of the virus. Experts warn on the basis of prior animal studies that the mechanism can result in animal cell variance and possibly cancer or teratogenicity. In other words, there are concerns about limitation and safety with its use.
The drug developed by Pfizer, on the other hand, is a protease inhibitor. It was already found during the R&D of HCV and HIV drugs in the past that protease inhibitors could lose their efficacy as a result of viral mutation. SARS-CoV-2 is a highly mutant RNA virus. Whether the Pfizer drug can successfully overcome drug resistance of the virus or not is pending continuous observation.
SNS812 is designed specifically against the high variance of the coronavirus and hence does not easily lose its efficacy as a result of viral mutation; it covers 99.8% of the SARS-CoV-2 strains that have been found so far. Given the characteristics of the above two drugs and SNS812, aiming to meet the demand while COVID-19 becomes flu-like in the future, SNS812 targets not only the COVID-19 virus. With a reasonably controlled R&D budget, it shall still be of developmental value.
The Animal Challenge Study showed that the aerosol administration of SNS812 had a good preventive effect (administration before infection). Since this preventive effect is good, can it be made into a COVID-19 preventive drug? How long is the effect limitation that hits the common vaccine? And how long is the preventive validity of SNS812? Is the preventive effect of SNS812 economically beneficial?
SNS812 can significantly reduce the amount of lung virus of the original virus strain in the Animal Challenge Study before (after) administration, and has the chance to become a novel coronavirus preventive (treatment) drug with the method of administration of taking once a day. Unlike a vaccine, SNS812 attacks parts of the virus that are not easily mutated, fighting all mutant strains. Trials are ongoing to verify the efficacy and safety of the drug. It is expected to contribute to the increasingly serious problem of vaccine breakthrough caused by mutant strains in the world.
The news said that NTU has developed a “nasal-spray COVID-19 vaccine” with remarkable results in animals! Human trials may be conducted at the end of the year! Does NTU also adopt the aptamer technology? Can SNS812 be developed as a “nasal-spray COVID-19 vaccine”?
Vaccines protect the human body by producing antibodies. SNS812 is a nucleic acid therapy drug developed by OnenessBiotech. The two mechanisms of action are different and there is no correlation between them.
Have you obtained the test results of SNS812? What is the follow-up research and development?
1. The results of the fourth challenge of ACE2 transgenic mice showed that the expression level of virus genes in the lungs of the mice in the administration group was reduced by more than 99.9%, and the quantitative difference of living virus reached 105.
2. Animal challenge experiments show that aerosol administration of SNS812 has a good preventive effect through administration first before infection. The R&D team is exploring the therapeutic effect through infection first before administration, and different dosages shall be given to determine the effective dose range.
3. We confirm that SNS812 can completely inhibit various mutant strains currently known, including Delta strains through new cell experiments.
What is the pharmacological effect of the experimental drug FB704A the company expected to be used this year for patients of severe COVID-19 pneumonia? Give an injection or take medicine orally? What is the cost? What is the advantage over the current EUA drugs for COVID-19 pneumonia? What are the advantages compared with domestic competing companies?
1. FB704A is a fully humanized anti-IL6 monoclonal antibody by neutralizing IL6 cytokine and inhibiting the immune trans-signaling pathways of IL6/IL6R to suppress the cytokine storm. The excessive activation of the immune trans-signaling pathways of IL6/IL6R triggers a cytokine storm, which is the main reason for the deterioration of the severe patients. Therefore, it is expected that FB704A can alleviate the deterioration of severe COVID-19 pneumonia.
2. FB704A is currently administered by intravenous infusion, and the dosage form for subcutaneous injection is under development.
3. FB704A is a drug in research and development without the price released yet.
4. Among the EUA drugs currently approved by FDA, Roche’s Actemra (Tocilizumab), already on the market, has the same mechanism of action as FB704A. Preclinical experiments have shown that the advantages of FB704A include: it is a fully humanized antibody with high immunocompatibility; it targets free IL6, ensuring highly safety of human cells; it has a stronger ability to inhibit the immune trans-signaling pathways of IL6/IL6R than Tocilizumab in cell experiments.
The mechanism of action of FB704A is different from that of other drugs, but it is impossible to contrast without clinical data available at present.
Does the company have other development plans after the Phase IIa clinical trial of FB825?
After the Phase IIa clinical trial of FB825, LEO Pharma is solely responsible for the development planning with Oneness’s assistance in product knowledge. In order to improve the value of FB825, LEO Pharma is actively trying to determine its other potential indications. Currently, 7 potential indications have been evaluated and further research will be made based on the results. At the same time, the company is looking for a drug in combination with FB825 to develop a more economical dual-effect antibody with good efficacy.
1. What is the effect of the FB704a+, a traditional Chinese medicine formula NRICM101, developed by the company on acute respiratory distress syndrome (ARDS)? Similar IL6 drugs abroad have little effect when combined with concomitant drugs such as steroids, antibiotics, and remdesivir. If it is combined with traditional Chinese medicine, it may have a surprising effect.
2. Does the company believe that the best way to treat severe symptoms of Covid-19 is FB704a (resolvable side effects of RNA drugs) + antiviral drug SNS812 (under development, the schedule will take some time). Or is it sufficient to rely on SNS812 alone?
3. Nucleic acid-based drugs not only attack viruses but also destroy cancer cells. In addition to the treatment of COVID-19, will SNS812 of the company direct towards the treatment of cancer and other indications in the future?
4. Will there be a combined treatment of FB704a+SNS812 in a. coronavirus; b. cancers such as lung cancer, liver cancer, and kidney cancer in the future?
1.The mechanism of action of FB704A is to neutralize IL6, the source of ARDS, and block the cytokine storm. In the guidelines issued by the NIH in the United States on May 27, 2021, it is recommended that patients who are hospitalized and who used High Flow Nasal Cannula (HFNC) or Noninvasive positive pressure ventilation (NPPV) can be treated with tocilizumab + dexamethasone, or tocilizumab + dexamethasone + remdesivir. Taiwan Centers for Disease Control also recommended in the tenth edition of Clinical Management of Covid-19 Interim Guidance that patients with severe pneumonia or higher and CRP≥7.5 mg/dL can be treated with concomitant drugs such as Remdesivir, Dexamethasone (steroid), and Tocilizumab (Roche Anti-IL6 receptor antibody drug). Therefore, the combined treatment of severe COVID-19 with Remdesivir, Dexamethasone, and Tocilizumab has currently become the guidelines for international standard treatment.
To use it with the traditional Chinese medicine formula NRICM101, it is necessary to fully understand the mechanism of action and make a decision only after the experiment.
2.According to the mechanism of action of the drug, SNS812 directly eliminates the virus and accelerates the recovery of the patient. However, critically ill patients are mainly caused by the secondary excessive immune response and cytokine storm, which cannot be cured simply by removing the virus alone. IL-6 plays a key role in the cytokine storm caused by COVID-19. However, a number of clinical trials in 2020 show that no significant difference in mortality reduction between Tocilizumab and the control group could be observed. According to the clinical trials published in scientific journals this year, administering drugs that inhibit IL-6 at the right time can indeed reduce the mortality rate and length of hospitalization days in critically ill patients. That is, by inhibiting IL-6, there is a chance to improve the symptoms of severely ill patients and relieve the pressure of ICU resources.
3.SNS812 specifically targets the coronavirus gene without anti-cancer effects.
4.There is currently no experiment on the combined treatment of SNS812 and FB704A.
Is it feasible to inhale SNS812 directly into the lungs through ultrasonic vibration atomization?
The drug administration of SNS812 in the form of ultrasonic vibration atomization should take into account the uniformity of the size of the atomized particles, and whether the atomized particles can be inhaled deep into the tissues of the lungs and be evenly distributed to achieve the effect of virus inhibition (still underway). However, ultrasonic vibration atomization may cause damage to nucleic acid-based drugs and still need to be evaluated.