Contents:
1. Date of occurrence of the event: 2023/11/13
2. Company name: TaiMed Biologics Inc.
3. Relationship to the Company (please enter "head office" or "subsidiaries"): head office
4. Reciprocal shareholding ratios: N/A
5. Cause of occurrence:
 (1) TaiMed submitted a revised clinical study protocol to the U.S. FDA in early October 2023 for the evaluation of the safety and efficacy of the TMB-365/380 combination in the core group of the Phase 2 clinical study. In the modified protocol, all HIV participants in the core group will be combined and executed injections every two months to obtain a sufficient sample size for the Phase 2 clinical study. The FDA did not raise any concern within the mandatory 30 calendar days review period, and TaiMed initiated the Phase 2 clinical study according to the revised study protocol.
 (2) Summary of clinical study design
  a. Title: A Phase 1b/2 Dose Escalation Study to Evaluate Safety, Pharmacokinetics, and Efficacy of TMB-365/TMB-380 Combination in Virologically Suppressed HIV-1 Infected Patients
  b. Participants and Investigator Sites: A total of 40 Core Group participants from approximately 6-8 sites in North America
  c. Primary Objectives – Core Group:
  (a) Evaluate the safety and tolerability of TMB-365/TMB-380 combination given q8wks in virologically suppressed HIV-1 patients.
(b) Evaluate the antiviral activity of the TMB-365/TMB-380 combination as a complete regimen maintenance therapy in virologically suppressed HIV-1 patients.
  d. Study Phase: 2
  e. Protocol Number: TMB-a21
  f. Clinical Study Design:
    This is an adaptive dose-escalation study of the TMB-365/TMB-380 combination administered intravenously to virologically suppressed HIV-1 patients. The study design comprised three Sentinel Groups and a Core Group. The dose for the Core Group will be based on the results from the Sentinel Groups. The participants of the Core Group are virologically suppressed HIV-1 patients who will receive multiple IV doses of TMB-365/TMB-380 combination q8wks as a stand-alone maintenance regimen for 12 months.
6. Countermeasures: None
7. Any other matters that need to be specified:
 (1) New drug name or code: TMB-365 and TMB-380
 (2) Indication: mainly used to provide long-acting monoclonal antibody drugs for AIDS patients
     website：https://classic.clinicaltrials.gov/ct2/show/NCT05275998
 (3) Planned development stages:
    Phase 2 to Phase 3 clinical studies、Biologics License Application (BLA)
 (4) Current development stage:
  a. Application submission/approval/disapproval/each of clinical trials (include interim analysis):
    Approval
  b. Once disapproved by competent authority or each of clinical trials (include interim analysis) results less than statistically significant sense, the risks & the associated measures the Company may occur: None
  c. After obtaining official approval or the results of statistically significant sense, the future strategy:
    Clinical trials have confirmed TMB-365 as an ultra-long-acting new drug, and its target market of first-line maintenance therapy is completely different from and much greater than that of the company's first-generation product, Trogarzo, which is an orphan drug and targets multi-drug resistant patients. TMB-380(VRC07-523L), another long-acting monoclonal antibody, was licensed by the US National Institutes of Health (NIH). In a separate phase 1 clinical trial, the NIH has successfully demonstrated the efficacy of TMB-380 in HIV patients who received bi-monthly I.V. infusion. The target population for the TMB-365/TMB-380 combination is the early-stage (first-line maintenance therapy) HIV-infected patients. This combination treatment with bi-monthly or quarterly dosing, if successfully developed, provides a full stand-alone regimen and offers patients greater convenience and better tolerability, as well as ensures adherence. At present, the only approved long-acting HIV maintenance therapy is GSK's Cabenuva (containing two small molecule drugs), which needs to be injected intramuscularly once monthly or bimonthly.
  d. Accumulated investment expenditure incurred:
    Because it involves future international cooperation negotiation information or product marketing strategies to protect the rights and interests of investors, it will not be disclosed for the time being.
(5) Upcoming development plan:
  a. Estimated date of completion:
    It is expected to be completed in about one year for the clinical study of the core group.
  b. Estimated responsibilities:
    TMB-365 and TMB-380 will incur development milestone payments to Rockefeller University and NIH, respectively. A certain percentage of sales royalties will be paid according to the sales amount of the new drug in the future. No royalty details can be disclosed due to the confidentiality terms in the contract.
(6) Market situation:
    The global anti-HIV drug market is dominated by Europe and the United States with most of the markets controlled by the top five companies. Among them, the leading company Gilead's product line is first-line (initial) treatment drugs, including two-in-one and three-in-one first-line drugs, with a market share of more than half. However, after years of using the anti-HIV drug, AIDS patients gradually develops resistance to the drugs and has to start receiving the second-line treatment drugs. Under the very different competitive market, the market share is carved up by manufacturers such as Merck, Bristol, ViiV, Johnson & Johnson, etc. It is estimated that, driven by new drugs, the global sales of anti-HIV drugs will grow to more than US$30 billion in 2022.
    In order to overcome the problem of virus resistance, in 1996, Dr. David Ho developed a three-drug combination therapy (HAART), commonly known as cocktail therapy. The basic principle is to use multiple drugs at the same time. When the virus mutation becomes resistant to one of the drugs, the other drugs can also suppress the virus replication and mutation, making the mutation unsuccessful. Due to the emergence of cocktail therapy, the mortality rate of HIV/AIDS virus infections and the morbidity rate of various opportunistic infections have dropped significantly, making AIDS a chronic disease that requires long-term medication to suppress the virus but cannot be cured.
    The HIV/AIDS market can be roughly divided into four lines based on treatment methods. When the patients have no response to the initial therapy and begin to develop drug resistance, they should enter the second-line therapy and use a new HIV drug combination. When the patients develop resistance to second-line therapy, the third-line therapy should be applied. If the treatment fails, the final salvage therapy (i.e., fourth-line therapy) will be performed. At present, the target range of the future application of TMB-365 and 380 combination of the Company is not the first-line patients who received the initial drug, but the first-line patients who have already controlled their viral load, and intend to use long-acting drugs to maintain the disease, no longer daily take medicine stably. The first-line maintenance therapy estimated to have a market size of US$10 billion.
    The TMB-365 is an ibalizumab (TMB-355) based, IgG1-scaffold, anti-CD4 recombinant humanized monoclonal antibody used against HIV infections.  The major medication or medicament of TMB-365 is mainly focused upon treatment and prevention against HIV infections (including opportunistic infections), said therapeutic and prophylactic usages or medical application.  The TMB-365-relevant technology platforms of TMB-365 are licensed from Arron Diamond AIDS Research Center (ADARC). The paper on the development of TMB-365 technology was published in the world-renowned journal Nature Biotechnology. Clinical trials have shown that TMB-365 has a significant improvement in drug resistance, efficacy, and pharmacokinetic profile compared to TMB-355.
    TMB-380 (VRC07-523LS) is the new generation of highly potent and broadly neutralizing HIV-1 antibody. The potent neutralizing activity, breadth, and extended half-life of TMB-380 make this antibody a leading candidate for inclusion in HIV-1 prevention and therapeutic strategies. TaiMed has a non-exclusive licensing agreement of TMB-380 from the National Institute Allergy and Infectious Diseases (NIAID) to develop a combination of TMB-380 and TaiMed’s own monoclonal HIV antibodies for treatment use.
(7) New drug development requires long process, vast investments, and with no guarantee in success which may pose investment risks. The investors are advised to exercise caution and conduct a thorough evaluation