Founded in 2009, we are a biopharmaceutical and revenue-generating pre-clinical research services company. We have two Core Products, YH003 and YH001, and 10 other pipeline product candidates. YH003 is a recombinant humanized agonistic anti-Cluster of Differentiation 40 (CD40) Immunoglobulin G2 (IgG2) monoclonal antibody and YH001 is a recombinant humanized anti-CTLA-4, a protein receptor expressed constitutively on T cells that functions as an immune checkpoint and downregulates immune responses, Immunoglobulin G1 (IgG1) monoclonal antibody. Our Core Product YH003 is primarily being developed for pancreatic ductal adenocarcinoma, melanoma and other advanced solid tumors. Our other Core Product YH001 is primarily being developed for hepatocellular carcinoma (HCC), non-small-cell lung carcinoma (NSCLC) and other solid tumors. Most of our clinicalstage drug candidates, including both Core Products, are developed as combination therapies.
WE MAY NOT BE ABLE TO SUCCESSFULLY DEVELOP AND/OR MARKET OUR CORE PRODUCTS.
Our business model consists of drug development business and pre-clinical research services, which are two distinctive business segments. Our drug development business includes (i) research and development of oncology and autoimmune disease therapeutics; and (ii) our antibody development business: we utilize our own antibody discovery platforms to identify antibodies which have the potential to become our drug candidates and out-license or collaborate with partners for potential therapeutic antibody molecules. Our pre-clinical research services include gene editing, pre-clinical pharmacology and efficacy evaluation, and animal models selling. During the Track Record Period, our revenue was mainly generated from our pre-clinical research services and antibody development business.
DRUG DEVELOPMENT BUSINESS
Research and Development of Oncology and Autoimmune Disease Therapeutics
As of the Latest Practicable Date, we had strategically designed and built a selective antibody drug pipeline of 12 drug candidates, including five clinical stage candidates and seven pre-clinical stage candidates. Three out of our drug candidates are with out-licensing arrangements with different collaborators. All of our drug candidates were discovered through our antibody discovery platforms.
Most of our clinical-stage drug candidates, including both Core Products, are developed as combination therapies. In China, the United States and Australia, combination therapies may be subject to certain regulatory requirements:
‧ In China, the development of a combination therapy should have a reasonable basis prior to conducting an exploratory clinical trial of that combination therapy. The reasonable basis may include in-depth exploration and study of the mechanism of action of the single drug prior to combination development, obtaining sufficient single-agent clinical pharmacology, safety and efficacy data for the competent drug and evaluating the preliminary clinical data prior to a confirmatory trial of the combination therapy. The regulatory pathway of combination therapy in China is applicable to our combination therapy studies conducted in China, such as Phase II MRCT of YH003 in combination with toripalimab in patients with advanced solid tumors in China, Phase II MRCT of YH001 in combination with toripalimab for the treatment of advanced NSCLC or HCC in China, and Phase I clinical trial of YH001 in combination with YH002 for the treatment of solid tumors in China.
‧ In the United States, typically, the FDA’s Office of Combination Products assigns a combination product to a specific agency center (“Center”) as the lead reviewer. The FDA determines which Center will lead a product’s review based upon the product’s primary mode of action. Depending on the type of combination product, its approval, clearance or licensure may usually be obtained through the submission of a single marketing application. However, the FDA sometimes will require separate marketing applications for individual constituent parts of the combination product, which may require additional time, effort, and information. The regulatory pathway of combination therapy in the United States is applicable to our combination therapy studies conducted in the Unites States, such as Phase II MRCT of YH003 in combination with toripalimab in patients with advanced solid tumors in the Unites States, and Phase II MRCT of YH001 in combination with toripalimab for the treatment of advanced NSCLC or HCC in the United States.
‧ In Australia, in order to register a new fixed combination medicine, the applicant must submit to the Therapeutic Goods Administration (TGA) a justification for the fixed combination. This justification should address why the particular combination has been created and the type and extent of data to be submitted with the application. After this justification has been accepted by the TGA, the applicant may proceed with the remainder of the application process. The regulatory pathway of combination therapy in Australia is applicable to our combination therapy studies conducted in Australia, such as Phase II MRCT of YH003 in combination with toripalimab in patients with advanced solid tumors in Australia, Phase II MRCT of YH001 in combination with toripalimab for the treatment of advanced NSCLC or HCC in Australia, Phase I clinical trial of YH001 in combination with YH002 for the treatment of solid tumors in Australia, and Phase I clinical trial of YH004 in combination with toripalimab in subjects with advanced solid tumors or relapsed/ refractory non-Hodgkin lymphoma in Australia.
Our strategy to develop combination therapies depends on the safety and efficacy of each component drug within each combination therapy. If the NMPA, the FDA, the TGA or another comparable regulatory agency revokes or denies its approval of a component therapeutic, in either the clinical design, clinical administration, therapy approval or commercialization stage, we will be forced to terminate or redesign the clinical trials, experience significant regulatory delays or stop our commercialization efforts. In addition, we may even fail our commercialization effort because products that facilitate the use of our drug candidates incur safety, efficacy or availability issues. The lack of regulations presents uncertainties to our commercialization efforts and may have an adverse effect on our business and results of operations.
For more details, please see “– Regulatory Overview – Laws and Regulations of Drug Development – Laws and Regulations of New Drugs – Combination Therapies” and “– Risk Factors – Development of product candidates in combination with other therapies could expose us to additional risks”.
Core Products
‧ YH003: YH003 primarily targets for the treatment of pancreatic ductal adenocarcinoma, melanoma and other solid tumors. It is a recombinant, humanized agonistic anti-CD40 IgG2 monoclonal antibody (mAb). We have completed a Phase I clinical trial in Australia to evaluate the safety, tolerability, efficacy and pharmacokinetics of YH003 in combination with toripalimab in patients with advanced solid tumors, which reached the primary end-point of the trial with the recommended Phase II dose (RP2D) identified in April 2021. We have obtained the approval from the ethics committee for a Phase II multi-regional clinical trial (MRCT) of YH003 in the United States and have completed the dosing of the first patient in Australia in December 2021. We received the IND approval for the Phase II MRCT from the FDA in June 2021, the TGA in August 2021, from the New Zealand Medicines and Medical Devices Safety Authority in September 2021, the NMPA in October 2021 and from Taiwan FDA in November 2021. We have commenced (first subject in) the Phase II MRCT in China in March 2022 and expect to commence (first subject in) the Phase II MRCT in the United States by second half of 2022. In addition, we plan to apply for a Phase I dose escalation trial in Australia to evaluate the safety, tolerability, preliminary efficacy and pharmacokinetics of YH001 and YH003 in combination with PD-1 antibody in patients with advanced solid tumors. We will also further explore the expansion of YH003 for the treatment of other solid tumor indications.
‧ YH001: YH001 primarily targets for the treatment of NSCLC, HCC and other solid tumors. It is a recombinant humanized anti-CTLA-4 IgG1 monoclonal antibody. We are conducting a Phase I clinical trial in Australia to evaluate the safety, tolerability and pharmacokinetics of YH001 when combined with toripalimab in patients with advanced solid tumors, which reached the primary end-point of the trial with the RP2D identified in April 2021. Clinical data demonstrate robust anti-tumor activities of YH001 in combination with toripalimab. We expect to initiate a Phase II MRCT of YH001 in combination with toripalimab for the treatment of advanced NSCLC or HCC in the United States, mainland China, Taiwan and Australia. In addition, we intend to conduct a clinical trial of YH001 in combination with YH002 in patients with advanced solid tumors in China and Australia. Moreover, we plan to apply for a Phase I dose escalation in Australia to evaluate the safety, tolerability, preliminary efficacy and pharmacokinetics of YH001 and YH003 in combination with PD-1 antibody in patients with advanced solid tumors.
We entered into an exclusive license agreement with TRACON Pharmaceuticals (“Tracon”) concerning the development and commercialization of YH001, in the regions of the United States, Canada and Mexico (the “Tracon Territories”) and in the field of sarcoma, microsatellite stable colorectal cancer (mssCRC), renal cell carcinoma (RCC), K-ras positive non-small cell lung cancer (K-ras NSCLC) (the “Tracon Field”) only. The Company’s collaboration with Tracon does not and will not conflict with its development of YH001, as the collaboration is limited to the Tracon Territories and within the Tracon Field. Tracon will owe us escalating tiered royalties ranging from the 25% to the 40%, based on the amount of annual net sales (with no more than US$60 million, more than US$60 million and up to US$100 million, more than US$100 million and up to US$200 million, and more than US$200 million as triggering events of tiered royalties) from the Tracon Territories and a one time launch success milestone payment of US$9 million if the net sales for YH001 in the Tracon Territories in the first full calendar year following first commercial launch exceeds US$100 million. We remain the sole owner of all rights, title and interests in and to YH001, and will continue to have the sole rights in relation to and be solely responsible for the preparation, filing, prosecution and maintenance of YH001 related patents and other intellectual property rights. We will co-own inventions, exclusive of certain development data, that are specific to YH001 or its use and are generated in connection with the development of YH001 in the Tracon Field and collaborative territories by or on behalf of Tracon and its affiliates during the collaboration term. See “– Business – Our Drug Development Business – YH001 – Collaboration with TRACON Pharmaceuticals” for further details.
Other Clinical or IND Stage Candidates
‧ YH002: a recombinant humanized IgG1 antibody that targets the human OX40 receptor, which is expressed on activated T cells and gives costimulatory signals to promote T cell division and survival.
‧ YH004: a humanized IgG1 anti-4-1BB agonist. 4-1BB is a receptor expressed on activated T cells and NK cells which gives costimulatory signals to promote T cell division and survival, activate cytotoxic effects and help form memory T cells.
Selective Pre-Clinical Stage Candidates
In addition to our clinical stage candidates, we mainly have six drug candidates at the pre-clinical stage, including YH008, YH009, YH006, YH010, YH012 and YH013. We expect to submit IND applications for these six oncology drug candidates in the next 12 to 18 months.
Selective Collaboration Clinical and Pre-Clinical Stage Candidates
In addition to our clinical stage candidates and pre-clinical stage candidates, we have two main drug candidates under collaboration with third parties at the clinical and pre-clinical stage, namely YH005 ADC, an anti-Claudin 18.2 antibody generated using our Claudin 18.2 knock-out (i.e. the process of having a specific single gene inactivated or removed by genetic manipulation) mice, and YH011, a novel bifunctional molecule. See “Business – Selective Collaboration Clinical and Pre-Clinical Stage Candidates” for further details.
Antibody Development Business
Our antibody development business is based on the antibody discovery technology of our proprietary RenMice platform and our self-developed in vivo drug efficacy screening technology. Together with hybridoma technology and Beacon single-cell photoconduction screening, our antibody discovery platform enables us to generate large amounts of potential antibodies and conduct large-scale in vivo drug efficacy evaluation to screen and obtain antibody molecules with the potential to become drug candidate. Project Integrum (千鼠萬抗) is our unique and innovative large scale antibody drug discovery program that discovers antibody molecules for internal drug development or external monetization. Our antibody development business, including Project Integrum, is integral to our drug development business.
Source: Biocytogen Pharm-B (02315) Prospectus (IPO Date : 19/08/2022) |