Founded in June 2015 in the PRC, we are a clinical-stage biotechnology company dedicated to the development of immuno-oncology therapies. We have developed our Core Product, IMM01, an innovative clinical-stage CD47-targeted molecule. Including IMM01, our pipeline consists of 14 drug candidates featured by a comprehensive innate-immunity-based asset portfolio targeting CD47 and other novel immune checkpoints, with eight ongoing clinical programs.
WE MAY NOT ULTIMATELY BE ABLE TO DEVELOP OR MARKET OUR CORE PRODUCT SUCCESSFULLY.
Our Key Products, namely IMM0306 (CD47×CD20), IMM2902 (CD47×HER2) and IMM2520 (CD47×PD-L1), are three CD47-based bispecific molecules. Both of IMM0306 and IMM2902 are the first bispecific molecules with their respective targets globally to enter clinical trials. IMM2520 is also a highly differentiated molecule with the potential to treat a broad spectrum of cancers and has demonstrated promising efficacy targeting solid tumors in preclinical studies. In addition, our pipeline also includes ten other drug candidates that address key innate and adaptive immune targets at various development stages, including CD24 antibody, CD24-targeted bispecific molecules, and three clinical and IND stage adaptive immunity-based drug assets. Our pipeline reflects our grasp of the frontiers of cancer biology and immunology, and our expertise in turning scientific research into drug candidates. Our founder, Dr. Wenzhi Tian, began to explore the therapeutic potential of CD47 blockade in 2010, long before this innate immune checkpoint became widely recognized and clinically validated in the biopharmaceutical industry. Based on our understanding of the biology underlying CD47-SIRPα interaction and its potential synergy with other tumor targets and/or immune checkpoints, we have built a differentiated CD47-based portfolio with favorable safety and efficacy profiles since our inception in 2015. In addition to CD47, we have selected and validated another innate immune checkpoint, CD24, in recent years. Around CD24, we are developing one IND-enabling-stage and several discovery- and preclinical-stage drug candidates, each with the potential to become the first few of its class to enter into clinical stage around the world. Moreover, we are also developing drug candidates that target other promising innate and adaptive immune checkpoints, including IL-8, NKG2A and PSGL-1, to maximize the clinical and commercial value of our platform.
OUR KEY PRODUCTS REMAIN IN EARLY-STAGES OF CLINICAL DEVELOPMENT, AND IN PARTICULAR, WE MAY OR MAY NOT DEVELOP OR MARKET THEM SUCCESSFULLY.
Our continuous innovation is driven by an experienced and stable R&D team led by Dr. Tian. Core members of our R&D team have been working with Dr. Tian for over 10 years and possess multi-disciplinary expertise in drug discovery, design and development. Emulating the “Quality-by-Design (QbD)” concept that is intended to improve drug product quality by using analytical and risk-management methodologies, we created the “Drug-by-Design (DbD)” concept that emphasizes the fundamental role of molecule design rationale in the process of large molecule drug development. This concept requires that the structure of every drug molecule be deliberately designed with a sound scientific rationale predicated on target-specific biological functions and validated in preclinical studies. Under the guidance of our “DbD” concept and the leadership of Dr. Tian, we have built a fully-integrated R&D platform. It features our proprietary technologies and know-how (including our mAb-Trap bispecific antibody platform technology) and encompasses all key functionalities throughout the drug development process. For 2021, 2022 and the four months ended April 30, 2023, our R&D expenses (including share-based payments) were RMB176.0 million, RMB277.3 million and RMB75.0 million, respectively. The R&D expenses attributable to our Core Product (including share-based payments) were RMB43.4 million, RMB116.8 million and RMB22.9 million in the same periods, respectively.
Our Business Model
Our core business model is to in-house discover, develop and commercialize novel immuno-oncology therapies to address highly unmet medical needs. To complement our internal efforts, we may also collaborate with third parties on the clinical development and commercialization of our drug candidates to better capture tremendous market opportunities through out-licensing, co-commercialization or other strategic collaborations. We are collaborating with Sunshine Guojian to conduct clinical trials evaluating a combination therapy using CIPTERBIN (inetetamab, a HER2 mAb) and IMM01 for HER2-positive solid tumors in mainland China, and Sunshine Guojian will drive and fund relevant clinical trials.
Our Core Product and Key Products
Our Core Product — IMM01 (SIRPα-Fc fusion protein)
IMM01, our Core Product, is an innovative CD47-targeted molecule. It is the first SIRPα-Fc fusion protein to enter into clinical stage in China. IMM01 is being developed for the treatment of various blood cancers and solid tumors in combination with other agents. We (i) have completed the Phase I dose-escalation study of IMM01 in relapsed or refractory (R/R, a condition of a disease that is not being effectively managed or improved with previous treatments) lymphoma patients, (ii) have completed a Phase Ib trial to evaluate IMM01 in combination with azacitidine for the treatment of certain R/R blood cancers, and initiated a Phase II trial mainly for the first-line treatment of higher-risk (HR) MDS, unfit AML and chronic myelomonocytic leukemia (CMML, a rare type of blood cancer) in June 2022, and (iii) have completed a Phase Ib clinical trial and initiated a Phase II trial in December 2022 to evaluate IMM01 in combination with tislelizumab for the treatment of solid tumors, including among others, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and head and neck squamous cell carcinoma (HNSCC), which are all advanced solid tumors that failed to respond to or relapsed from the standard of care such as PD-1/PD-L1 inhibitors, as well as R/R classical Hodgkin lymphoma (cHL). We have also obtained an IND approval for the Phase Ib/IIa clinical trial to evaluate the combination of IMM01 with bortezomib and dexamethasonum for the treatment of MM from the NMPA in January 2023. With preliminary efficacy and favorable safety in monotherapy clinical trials and preclinical data of its combination studies, IMM01 is expected to achieve strong synergistic effects used in combination with other cancer agents.
IMM01 can fully activate macrophages via a dual mechanism — simultaneously blocking the “don’t eat me” signal and delivering the “eat me” signal and delivering the “eat me” signal. Furthermore, the CD47-binding domain of IMM01 was specifically engineered to avoid human red blood cell (RBC) binding. With the differentiated molecule design, IMM01 has achieved a favorable safety profile and demonstrated its ability to activate macrophages. Among numerous drug developers of CD47-targeted molecules globally, we are one of the only two companies1 to have observed complete response (CR) in monotherapy clinical trials with a well tolerated safety profile, according to Frost & Sullivan. For the details on the mechanism of action, please refer to the paragraphs headed “Business — Our Innate Immune Checkpoint-Targeted Drug Candidates — IMM01 — Mechanism of Action.” IMM01 was discovered, designed and developed by key R&D personnel of our Company, Dr. Wenzhi Tian and Dr. Deqiang Jing, when they worked at their respective former employers. For details, please refer to “Business — Intellectual Property.” We acquired full ownership and related interests in IMM01 after our establishment in 2015, and since then we have continued the preclinical research and are conducting clinical trials to develop IMM01 with our internal team and resources during the Track Record Period and up to the Latest Practicable Date. We are the sole owner of the intellectual property rights and global commercial rights in relation to IMM01. For details of key personnel for the R&D of IMM01, please refer to “Business — Our Platform — Drug Discovery and Preclinical Development” and “Business — Our Platform — Clinical Development.”
The currently approved immunotherapies primarily target T-cell immune checkpoints, including PD-1/PD-L1, CTLA-4 and LAG-3. However, only about 10% to 25% of patients across almost all major cancer types can benefit from PD-1/PD-L1 monotherapy treatment. To overcome the limitations of the current immunotherapies, mounting research highlights the potential to deploy innate immunity-targeted strategies for the treatment of a wide range of cancer indications. Among those, the CD47/SIRPα pathway has been clinically validated and became one of the most attractive and innovative immune targets for cancer treatment.
Addressable markets and competitive landscape
Given the potential broad-spectrum clinical application of CD47/SIRPα-targeted therapies, this new class of therapies presents vast market opportunities globally. 53 CD47/SIRPα-targeted drug candidates are currently under clinical development in China and globally, including fusion proteins, monoclonal antibodies, and bispecific molecules by 24 drug developers in China and 22 worldwide outside of China. As of the Latest Practicable Date, there were six CD47-targeted fusion proteins and 19 CD47-targeted monoclonal antibodies under clinical development globally. As of the Latest Practicable Date, there were no CD47-targeted therapies approved for marketing in China or the rest of the world. For details of competitive landscape of CD47/SIRPα-targeted fusion proteins and monoclonal antibodies, please refer to the paragraphs headed “Industry Overview — Promising Immunotherapies Targeting Innate Immune Checkpoints — Overview of CD47/SIRPα-targeted Drugs — Global and China CD47/SIRPα-targeted drugs competitive landscape — CD47-targeted fusion proteins and monoclonal antibodies.” According to Frost & Sullivan, the global market size of CD47/SIRPα-targeted therapies is expected to reach US$12.6 billion and US$35.4 billion in 2030 and 2035, respectively. China’s CD47/SIRPα-targeted therapy market is expected to grow to US$2.2 billion in 2030 and US$6.7 billion in 2035, with a higher growth rate compared to that of the global market. The prospect promised by CD47-targeted therapies was also validated by several multi-billion dollar take-over transactions of CD47 focused biotechnology companies as well as licensing deals for CD47-targeted agents backed by leading multinational pharmaceutical companies, including Gilead, Pfizer and AbbVie. Nonetheless, such growing market trend signifies that we face the intense competition in the development of CD47-targeted molecule. Globally, in addition to those large multi-national pharmaceutical firms that ventured into this realm through acquisitions, multiple companies are also developing CD47-targeted therapies, such as ALX Oncology, I-MAB and Innovent. Potential competitors also include academic institutions, government agencies, other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization. We anticipate that we will face intense and increasing competition as new drugs enter the market and advanced technologies become available.
According to Frost & Sullivan, as of the Latest Practicable Date, there were no commercialized CD47/SIRPα-targeted drugs globally. Barriers to the design and development of effective and safe CD47-targeted drugs include blood toxicity, antigenic sink, Fc isotype selection and resulting efficacy, as well as T-cell toxicity. Failures to overcome these barriers may result in compromised efficacy, drug resistance and severe side effects. For details, please refer to the paragraphs headed “Industry — Promising Immunotherapies Targeting Innate Immune Checkpoints — Overview of CD47/SIRPα-targeted Drugs — Scientific barriers to CD47/SIRPα-targeted drug development.” To address these potential issues, we carefully designed IMM01 with the specific engineered CD47-binding domain and IgG1 Fc to achieve enhanced efficacy balanced with well-tolerated safety profile.
We are developing the combination therapy of IMM01 and azacitidine for the first-line treatment of various blood cancers, including HR MDS, unfit AML, and CMML. According to Frost & Sullivan, the total incidence of MDS/CMML and AML was 470.1 thousand and 54.2 thousand in 2022 globally and in China, respectively, and is expected to increase to 553.2 thousand and 61.6 thousand in 2030 globally and in China, respectively. MDS/CMML and AML are two types of hematologic cancers that lack effective options for first-line treatments as current first-line treatments are still limited to conventional chemotherapy. Please refer to “Industry Overview — Selected Indications Analysis — Hematologic Malignancies” for further details on current treatment paradigm and unmet medical needs of MDS/CMML and AML.
Our combination therapy of IMM01 and tislelizumab is being evaluated in the ongoing clinical trials for the treatment of various advanced solid tumors that are not responsive to or relapsed from the standard of care such as PD-1/PD-L1 inhibitors, including among others, lung cancer (NSCLC and SCLC) and HNSCC. The total incidence of solid tumors, including among others, NSCLC, SCLC, and HNSCC was 7.0 million and 2.3 million in 2022 globally and in China, respectively, and is expected to increase to 8.6 million and 2.9 million in 2030 globally and in China, respectively. We are also evaluating this combination therapy in R/R cHL patients. The total incidence of cHL was 6.7 thousand and 81.0 thousand in 2022 globally and in China, respectively, and is expected to increase to 7.1 thousand and 90.3 thousand in 2030 globally and in China. Please refer to “Industry Overview — Selected Indications Analysis — Solid Tumors” for further details on current treatment paradigm and unmet medical needs of NSCLC, SCLC, and HNSCC.
Monotherapy
IMM01 single agent has demonstrated encouraging results in safety and efficacy in our Phase I dose-escalation study targeting R/R lymphoma. For details, please refer to “Business — Our Innate Immune Checkpoint-Targeted Drug Candidates — IMM01 — Summary of Clinical Trial Results.”
We initiated our clinical development of IMM01 through its monotherapy trial, and subsequently expanded our focus to encompass combination therapy programs, driven by the safety profile of IMM01 monotherapy and its observed synergistic effects with other cancer agents. With positive efficacy signals obtained from the Phase I monotherapy trial, we commenced a Phase II cohort-expansion study for IMM01 monotherapy in October 2021, with the primary goal of developing this monotherapy for one or two niche lymphoma indications. In light of the emerging data from our various clinical programs and prevailing industry trends, we observed that IMM01 combination therapies and CD47-based bispecific molecules exhibited stronger clinical activity for the indications initially targeted by IMM01 monotherapy, suggesting a higher probability of obtaining marketing approval. As a result, we strategically reallocated our resources to prioritize the development of combination and bispecific therapies, and subsequently terminated the Phase II monotherapy trial in October 2022, following consultation with principal investigators. On April 26th, 2023, we informed the NMPA through the chinadrugtrials platform (藥物臨床試驗登記與信 息公示平臺, a trial registration and publicity platform operated by CDE) of the termination of the Phase II monotherapy clinical trial for IMM01 and have not received any material objections or requests for additional information. The NMPA did not and will not revoke the existing IND approvals due to the termination of the Phase II monotherapy trial.
IMM01 will be regulated as the same drug product by the NMPA under the currently effective Drug Registration Administration Measures, regardless of whether IMM01 is used as monotherapy or in combination therapies. The Company conducted a formal consultation with the CDE of the NMPA through the NMPA’s official communication and consultation channel “Drug Registration Applicant’s Window” (藥品註冊申請人之窗) between March 28 and March 31, 2022. Based on the consultation and as confirmed by the Company’s PRC legal advisor, a cancer drug (first approved in combination therapies, as is the expected case with IMM01) will remain registered with the NMPA under the same drug approval number when additional supplemental NDA approvals for new indications are obtained through the use of such drug in various combination therapies (if such indication has previously been approved by the NMPA) after the first NDA approval of that drug, as long as the structure, preparation, formulation, and route of administration of such cancer drug remain unchanged in the various newly approved combination therapies. Therefore, under the NMPA’s regulatory regime, once IMM01 receives initial approval for use in one combination therapy, IMM01, the single drug product itself, will be registered under a drug registration certificate with a designated drug approval number. Subsequent approvals for IMM01, when used in other combination therapies for other indications which have obtained competent authorities’ regulatory approvals, will remain registered and regulated as the same single product under the same drug registration certificate with the same drug approval number.
In light of the termination of the Phase II monotherapy trial and the suspension or termination of clinical trials of CD47-targeted drug candidates by other drug developers, the Company conducted another formal consultation with the CDE of the NMPA through the Drug Registration Applicant’s Window between April 25 and May 17, 2023. During this consultation, the Company (the trial sponsor for clinical trials of IMM01) summarized and presented the relevant facts and circumstances related to the development status of IMM01. Based on this factual summary, the Company sought confirmation from the CDE as to whether the trial sponsor may, after termination of the Phase II monotherapy trial or after the suspension or termination of clinical trials of same-target drug candidates by other drug companies, continue to advance the various combination therapy clinical trials according to previously approved trial designs and protocols. The CDE, during this consultation, reviewed the Company’s factual summary and consultation questions and confirmed that the trial sponsor itself may choose to suspend or terminate any of its clinical trials. In the consultation, the CDE did not question the Company’s discretion to proceed with the (monotherapy or combination therapy) trials of its own drug candidate (including to advance its combination therapy trials in accordance with previously-approved trial designs and protocols); nor did the CDE require any modification to the previously-approved trial designs and protocols for the combination therapy trials, despite termination of the Phase II monotherapy trial or suspension or termination of other companies’ clinical trials of drug candidates with the same target. The CDE reminded the Company that, in the event of any serious safety issues with any of the trials, the trial sponsor needs to timely report to, and communicate with, the regulatory authority. As of the Latest Practicable Date, the Company has not received any queries, limitations or requirements regarding its combination therapy trials and previously-approved trial designs and protocols, and the Company remains committed to complying with the applicable reporting and other obligations under the relevant rules and regulations.
Source: ImmuneOnco-B (01541) Prospectus (IPO Date : 2023/08/24) |