We are a clinical demand-oriented, registrational clinical stage biopharmaceutical company focusing on discovering and developing innovative small molecule therapies for oncology, inflammatory and cardiometabolic diseases. Since our incorporation in 2014, we have internally discovered and developed one Core Product Tinengotinib (TT-00420) and built a pipeline of five clinical stage product candidates and one preclinical stage product candidate with our fully-integrated in-house R&D system.
Our Core Product Tinengotinib is a unique multi-targeted kinase (“MTK”) inhibitor primarily targeting three key pathways (namely, FGFR/VEGFR, JAK and Aurora kinases). As of the Latest Practicable Date, it was undergoing two pivotal/registrational clinical trials for the treatment of cholangiocarcinoma (“CCA”) that has progressed following prior FGFR inhibitor therapy, one being conducted in China and the other as a multi-regional clinical trial (“MRCT”) involving the U.S. Additionally, we are exploring Tinengotinib for the treatment of metastatic castration resistant prostate cancer (“mCRPC”), breast cancer, biliary tract carcinoma (“BTC”), and pan-FGFR solid tumors, and have completed Phase II clinical studies for these indications. Having obtained IND approval from the NMPA, we also intend to evaluate Tinengotinib in combination with Cadonilimab or Ivonescimab for the treatment of hepatocellular carcinoma (“HCC”) in a Phase II trial.
THERE IS NO ASSURANCE THAT WE WILL ULTIMATELY BE ABLE TO DEVELOP AND MARKET OUR CORE PRODUCTS OR ANY OF OUR PIPELINE PRODUCTS SUCCESSFULLY.
Our Business Model
Our core business model involves internally discovering, developing and commercializing small molecule drugs that address the significant medical needs in the fields of oncology, inflammatory and cardiometabolic diseases.
With our global vision and clinical practice, we have formed a strong engine for our continuous innovation of small molecule drug candidates. As a dedicated innovative small molecule drug developers in China, we strive to establish a global clinical development platform aiming to create novel therapies for the global market. We plan to continue executing our global clinical development and marketing strategy through our approach, Adaptive Comprehensive Expandable (“ACE”).
OUR CORE PRODUCT
Tinengotinib (TT-00420), our Core Product, is an internally discovered and developed, registrational clinical stage, unique MTK inhibitor for the treatment of drug-resistant, relapsed or refractory cancers. Tinengotinib targets three key pathways including FGFR/VEGFR, JAK and Aurora. Driven by targeting one or a combination of pathways, Tinengotinib can target a wide range of cancer types. The unique binding mode with FGFR enables Tinengotinib to overcome polyclonal mutations, rendering it target FGFR-driven cancers (such as FGFR altered CCA and pan-FGFR solid tumor), and the distinct combination of the key pathways makes it capable of being efficacious in a broad range of cancer types (including prostate cancer, HCC, breast cancer, and BTC). For details regarding Tinengotinib’s mechanisms of action, see “Business – Core Product: Tinengotinib – Registrational Clinical Stage, Unique MTK Inhibitor – Mechanism of Action.” For more information regarding the ongoing and planned clinical trials of Tinengotinib, see “Business – Core Product: Tinengotinib – Registrational Clinical Stage, Unique MTK Inhibitor – Summary of Clinical Trials – Overview of Clinical Studies of Tinengotinib.” There are known advantages to developing MTK inhibitors compared to highly selective kinase inhibitors, yet there are also challenges in developing MTK inhibitors. For details, see “Industry Overview – Small Molecule Oncology Targeted Therapy – MTK Inhibitors.” As of the Latest Practicable Date, there was one MTK inhibitor targeting FGFR approved by the FDA, namely, erdafitinib. As of the Latest Practicable Date, there were five MTK inhibitors targeting FGFR and one or more of JAK, Aurora and VEGFR at clinical stage globally.
Tinengotinib and AL8326 were under clinical development in the U.S., while four of them, namely Tinengotinib, AL8326, MAX-40279- 01 and TQB2868 were under clinical development in China. Tinengotinib is a unique MTK inhibitor targeting FGFR/VEGFR, JAK and Aurora. No other MTK inhibitor has demonstrated the same target combination and applications, and thus such drug profile of Tinengotinib is unique. For details, see “Industry Overview – Small Molecule Oncology Targeted Therapy – MTK Inhibitors – Competitive Landscape.” Starting in 2018, we received IND approvals from the FDA and the NMPA to conduct clinical trials of Tinengotinib monotherapy in solid tumors. We proceeded with and completed multiple Phase I and Phase II studies for CCA, mCRPC, HER2– breast cancer, and pan-FGFR solid tumors in both China and the U.S. In 2023 and 2024, we received regulatory clearance from the FDA, the NMPA, the EMA, the MHRA, the MFDS and the TFDA to initiate registrational/pivotal clinical trials in FGFR inhibitor-relapsed or refractory CCA patients, and have initiated the trials in these jurisdictions. Additionally, for combination therapy, in November 2020, we received the IND approval from the FDA to conduct Phase I/II trials of Tinengotinib in combination with nab-paclitaxel for breast cancer, and we have completed a Phase Ib trial in the U.S. In May 2021, we obtained the IND approval from the NMPA to conduct Phase I/II trials of Tinengotinib combined with PD-L1 for BTC, and we have completed a Phase Ib/II trial in China. In February 2024, we received the IND approval from the NMPA to initiate a Phase II trial of Tinengotinib with NHT for mCRPC.
CCA
Our Core Product Tinengotinib is the world’s first and only investigational drug that has entered registrational clinical stage to treat FGFR inhibitor relapsed or refractory CCA patients. FGFR inhibitors have been approved for the treatment of CCA patients with FGFR alterations (i.e. FGFR-altered CCA) after chemotherapy. However, disease progression occurs in almost all patients following treatment with an FGFR inhibitor. The absence of recommendations for subsequent treatment options in NCCN or CSCO guidelines has indicated a medical need that is not fully addressed. Researchers have reported that additional changes (i.e. secondary polycloncal mutations) in the FGFR2 kinase domain are a major prominent acquired resistance mechanism. In a pooled analysis of clinical studies in the U.S., as of March 28, 2024, among 43 CCA patients who had progressed on prior FGFR inhibitors, after being treated with Tinengotinib and had at least one tumor scan, the objective response rate (“ORR”) was 30% (13/43), the disease control rate (“DCR”) was 93% (40/43), and the median progression free survival (“PFS”) was 6.0 months. The promising clinical data was also observed in the clinical trial conducted in China. In China, two of three (66.7%) CCA patients who had progressed on prior FGFR inhibitors were treated with Tinengotinib and achieved partial response (“PR”). As of March 28, 2024, one patient lasted for more than 8 months, and the other patient has lasted for 14 months, who is still on treatment. Results of Tinengotinib treating FGFR inhibitor relapsed or refractory CCA patients were presented at 2023 ESMO annual conference and 2024 ASCO GI annual conference as oral presentations and published as poster presentation at 2024 Cholangiocarcinoma Foundation annual conference. Two pivotal/registrational trials in China and certain other regions were initiated in November 2023 and December 2023, respectively. For details regarding Tinengotinib’s competitive advantage for the treatment of CCA, see “Business – Core Product: Tinengotinib – Registrational Clinical Stage, Unique MTK Inhibitor – Competitive Advantages.”
Addressable Market and Competitive Landscape
The market size of CCA is expected to grow at a higher CAGR than the incidence, as the market penetration of innovative therapies, including FGFR inhibitors, is anticipated to increase. These therapies are expected to result in higher per-patient costs compared to traditional treatments such as chemotherapy. According to Frost & Sullivan, the global CCA drug market size reached US$2.0 billion in 2024, with a CAGR of 16.2% from 2019 to 2024. It is projected to grow to US$3.2 billion in 2027, with a CAGR of 17.1% from 2024 to 2027, and further increase to US$4.6 billion in 2030, with a CAGR of 12.8% from 2027 to 2030. China’s CCA drug market size reached RMB3.2 billion in 2024, with a CAGR of 16.4% from 2019 to 2024, and is expected to further grow to RMB5.5 billion and RMB7.6 billion in 2027 and 2030, respectively. Globally, the incidence of CCA increased from 243.4 thousand in 2019 to 290.0 thousand in 2024, representing a CAGR of 3.6%. It is projected to increase to 321.4 thousand and 354.9 thousand in 2027 and 2030, respectively, representing a CAGR of 3.5% from 2024 to 2027 and a CAGR of 3.4% from 2027 to 2030. The incidence of CCA in China increased from 94.4 thousand in 2019 to 106.6 thousand in 2024, representing a CAGR of 2.5%. The number is expected to reach 114.2 thousand and 121.6 thousand in 2027 and 2030, respectively, representing a CAGR of 2.4% from 2024 to 2027 and a CAGR of 2.2% from 2027 to 2030. Around 62% of patients with advanced unresectable or metastatic CCA proceed to second-line treatment, and 32% receive at least third-line therapy. For more details of CCA incidence, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – CCA.” FGFR alterations (including fusion and rearrangement, point mutation and gene amplification) are observed in 25.2% of CCA patients, and FGFR fusions and rearrangements are observed in 7.4% of CCA patients.
CCA is an aggressive type of tumor that can progress rapidly and become fatal due to invasion across all body areas if treatment is not administered at an early stage. Currently, CCA is considered incurable unless fully resected in the early-stage through surgery. CCA is frequently diagnosed at an advanced, unresectable stage because of the late presentation of nonspecific clinical symptoms of the disease and the lack of effective screening modalities. Although surgery and liver transplantation are the primary treatment options for eligible CCA patients, there was a high recurrence rate, perioperative complications and poor patient survival rate among CCA patients treated with surgery and liver transplantation. To be specific, the actual five-year survival rate after the transplantation is approximately 30%, according to the Frost & Sullivan.
In the U.S. and China, surgery is the preferred choice for eligible patients in all types of CCA, facilitated by neo-adjuvant therapy or other pre-operative procedures to achieve surgical eligibility. Liver transplantation was also considered an ideal treatment option for CCA. However, due to difficulty in finding well-matched organs, the treatment was no longer a preferred treatment. For late stage CCA with advanced/metastatic disease, immune checkpoint inhibitor in combination with chemotherapy of gemcitabine and cisplatin is currently the preferred treatment in the first-line setting. For the second-line treatment, FOLFOX regimen is recommended for all types of late stage CCA. Targeted therapies are useful when patients qualify for genetic testing of FGFR2, NTRK, MSI-H/dMMR, and IDH1, providing more precise treatment options. The safety and efficacy of FGFR inhibitors (pemigatinib and futibatinib) approved for the second-line treatment of advanced/metastatic CCA have been validated in early studies. For a chart summarizing the treatment paradigm, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – CCA.”
As of the Latest Practicable Date, the FDA had conditionally approved two FGFR inhibitors for the treatment of CCA, i.e. LYTGOBI (futibatinib) and PEMAZYRE (pemigatinib), and one MTK inhibitor targeting FGFR for the treatment of urothelial cancer, i.e. BALVERSA (erdafitinib). In China, only pemigatinib was conditionally approved by the NMPA for the treatment of CCA. Nonetheless, the approved FGFR inhibitors and the MTK inhibitor are not able to address drug resistance to prior FGFR inhibitors.
As of the Latest Practicable Date, there were 14 FGFR inhibitors under Phase II or later stage clinical development globally, and among which there were two FGFR inhibitors for CCA that had progressed on prior FGFR inhibitor treatment. In China, there were 11 FGFR inhibitors under Phase II or later stage clinical development, and among which there was one FGFR inhibitor for CCA that had progressed on prior FGFR inhibitor treatment. On a global scale, as of the Latest Practicable Date, Tinengotinib stood out as the only drug candidate in registrational clinical stage for treating CCA that has progressed on the prior FGFR inhibitor treatment. For details, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – CCA – FGFR Inhibitor – Competitive Landscape.”
mCRPC
Tinengotinib is also the world’s first and only investigational drug that has the potential to simultaneously inhibit the FGFR/JAK pathway with clinical evidence in the treatment of mCRPC. Currently, novel hormone therapies, including enzalutamide, apalutamide and abiraterone, have been established as the standard of care for mCRPC patients. However, resistance will inevitably develop after a period of hormone therapy treatment. Recent academic discoveries have identified that activation of FGFR and JAK pathways will stimulate the cell state transformation from androgen sensitive cancer cells to neuroendocrine cancer cells and cause drug resistance. Simultaneous inhibition of FGFR and JAK pathways would be able to reverse the cell state transformation, or lineage plasticity, back to androgen sensitive cancer cells and re-sensitize to hormone therapies. In a pooled analysis of patients in the U.S. and China, Tinengotinib monotherapy has shown encouraging antitumor efficacy in heavily pre-treated mCRPC patients. According to our Phase I/II clinical trials of Tinengotinib as monotherapy in 22 efficacy-evaluable heavily pre-treated mCRPC patients who are resistant to hormonal treatments, the preliminary efficacy observed in 13 patients with measurable lesions was promising, showing an ORR of 46% (6/13) and a DCR of 85% (11/13). 43% patients had prostate-specific antigen reduction of more than 50%. The median radiographic PFS was 5.6 months (N=22). The results have been published at 2024 ASCO GU annual conference. Further combination study to explore Tinengotinib and novel hormone therapies has been initiated in the U.S., targeting mCRPC patients who have developed resistance to prior hormone therapy treatment. For details regarding Tinengotinib’s competitive advantage for the treatment of mCRPC, see “Business – Core Product: Tinengotinib – Registrational Clinical Stage, Unique MTK Inhibitor – Competitive Advantages.”
Addressable Market and Competitive Landscape
The market size of prostate cancer is expected to grow at a higher CAGR than its incidence, as the market penetration of androgen receptor-targeted and other innovative therapies, including MTK inhibitors, is anticipated to increase. These therapies are expected to result in higher per-patient costs compared to traditional treatments such as androgen deprivation therapy. According to Frost & Sullivan, the global prostate cancer drug market size reached US$19.3 billion in 2024, with a CAGR of 8.8% from 2019 to 2024. It is expected to reach US$24.9 billion in 2027, with a CAGR of 8.9% from 2024 to 2027, and further increase to US$32.4 billion in 2030, with a CAGR of 9.2% from 2027 to 2030. China’s prostate cancer drug market size reached RMB12.9 billion in 2024, with a CAGR of 19.6% from 2019 to 2024. It is expected to increase to RMB22.4 billion in 2027 and RMB34.1 billion 2030, with respective CAGRs of 20.1% from 2024 to 2027 and 15.1% from 2027 to 2030. The number of new cases of mCRPC around the world increased from 180.5 thousand in 2019 to 209.3 thousand in 2024. It is expected to grow to 225.3 thousand in 2027 and further to 238.0 thousand in 2030. In China, due to the change in dietary habit to high protein and high fat in recent years, the risks of having prostate cancer are increasing. Nevertheless, the diagnosis rate is relatively low due to the insufficient awareness and attention to this disease as well as no obvious specific symptoms in the early stage. The incidence of mCRPC in China increased from 43.8 thousand in 2019 to 52.7 thousand in 2024. The number is expected to grow to 59.7 thousand in 2027 and further reach 67.1 thousand in 2030. Approximately 77% of mCRPC patients receive first-line therapy, of whom around 49% proceed to second-line therapy.
Currently, in both U.S. and China, the main treatment options for mCRPC patients include the second-generation androgen receptor (“AR”) antagonists (enzalutamide), androgen biosynthesis inhibitor (abiraterone), cytotoxic chemotherapy (docetaxel and prednisone), poly ADP ribose polymerase (“PARP”) inhibitors, and immunotherapy (sipuleucel-T). Enzalutamide and abiraterone are an important group of treatment for prostate cancer, also known as novel hormone therapies (“NHT”) and they are also the backbone treatment of current therapies. However, patients who received NHT treatment will become resistant to these treatments. Currently, there is a lack of an effective small molecular targeted therapy that universally addresses mCRPC patients in the second-line setting. Therefore, innovative therapy for mCRPC is still in urgent need. To further enhance the therapeutic effects, future studies on mCRPC need to focus on a deeper understanding of the molecular mechanism of mCRPC, as well as the exploration of relevant targets, in order to address the resistance issues. For a chart summarizing the treatment paradigm, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – mCRPC.”
As of the Latest Practicable Date, there were five small molecule targeted therapies approved for the treatment of mCRPC by the FDA. There were five small molecule targeted therapies for the treatment of mCRPC approved by the NMPA. All of these therapies were AR antagonist, androgen receptor inhibitor or PARP inhibitor. None of these products were MTK inhibitors. As of the Latest Practicable Date, on the global scale, there were 45 small molecule targeted therapies under Phase II or later stage clinical development for mCRPC. In China, there were 16 small molecule targeted therapies under Phase II or later stage clinical development for mCRPC. Among these targeted therapies under development, there were two MTK inhibitors under development in the U.S. and there were only one MTK inhibitor, i.e. Tinengotinib, under development in China for the treatment of mCRPC. For more details of competitive landscape of small molecule targeted therapies for mCRPC, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – mCRPC.”
Other Indications
‧ Hepatocellular carcinoma. Preclinical data indicated that Tingengotinib demonstrated encouraging antitumor activity against hepatocellular carcinoma (“HCC”) . Cadonilimab or Ivonescimab in combination with Tingengotinib is expected to achieve multifaceted tumor eradication through dual immune remodeling of the tumor microenvironment and an innovative mechanism targeting HCC, overcoming the resistance of existing targeted therapy and immunotherapy combinations. This approach holds potential as a first-line treatment for advanced HCC in patients who are unsuitable for curative surgical resection or local therapy, or who have experienced disease progression after surgical resection or local therapy.
‧ Breast cancer. Similar promising efficacy of Tinengotinib has also been observed in heavily pre-treated Hormone receptor-positive (“HR+”)/human epidermal growth factor receptor 2-negative (“HER2”) breast cancer patients and triple-negative breast cancer (“TNBC”) patients.
In a pooled analysis of breast cancer patients in the U.S. and China, Tinengotinib monotherapy demonstrated an ORR of 50% (8/16) and a DCR of 88% (14/16) in patients who were originally diagnosed as HR+/HER2. Notably, among the 16 patients, five transformed TNBC patients reached 60% ORR (3/5) and 100% DCR (5/5). One HR+/HER2 patient has been on the treatment for over 20 months and reached confirmed complete response.
In the U.S. and China, according to the treatment guidelines of breast cancer, the basic therapy of breast cancer is systemic therapies. Once disease progresses, multiple targeted drugs or non-specific drugs are available. For advanced HR+/HER2 breast cancer, hormone therapy and chemotherapy are the main treatments. Aromatase inhibitor (“AI”) combined with CDK4/6 inhibitors is recommended as the first-line standard treatment. When CDK4/6 inhibitors are not available, single-agent hormone therapy, such as fulvestrant, AI, and estrogen receptor modulators, is also feasible. For HR+/HER2 patients resistant to endocrine therapy, single-agent chemotherapy or combined chemotherapy is recommended. The main chemotherapy drugs include anthracyclines (doxorubicin or liposomal doxorubicin), taxanes (paclitaxel), anti-metabolites (capecitabine or gemcitabine), and microtubule inhibitors (vinorelbine or eribulin). For a chart summarizing treatment paradigm of HR+/HER2 breast cancer, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – HER2 Breast Cancer.” In addition to patients initially diagnosed with TNBC, some HR+/HER2– breast cancers are found to be transformed into TNBC after receiving treatment of CDK4/6 inhibitors. For TNBC patients, chemotherapy is currently the primary treatment option. In addition, for PD-L1- positive TNBC patients, the NCCN and CSCO guidelines recommend chemotherapy combined with PD-1 inhibitors. Besides, the ADC drugs, sacituzumab govitecan- hziy and T-DXd, are also recommended for the treatment of TNBC. For details regarding the market size of breast cancer, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – HER2 Breast Cancer.” For more details of competitive landscape of small molecule targeted therapies for breast cancer, see “Industry Overview – Small Molecule Oncology Targeted Therapy – Major Indications of MTK Inhibitors – HER2 Breast Cancer.”
‧ Biliary tract cancer. Preclinical data demonstrates Tinengotinib is capable of modulating tumor microenvironment, indicating its potential to enhance the efficacy of immunotherapy. From our Phase Ib/II clinical trial, among 28 efficacy-evaluable CCA patients treated with Tinengotinib plus atezolizumab, the ORR and the DCR were 25.0% (7/28) and 75.0% (21/28), respectively. The combination therapy is also well tolerated. These encouraging data suggest Tinengotinib’s high potential in combination therapy with immunotherapies.
‧ Pan-FGFR solid tumor. Tinengotinib has unique binding mode to FGFR 1/2/3 kinase proteins, enabling it to be potent to key mutations within FGFR 1/2/3 kinase domains. This differentiated feature has brought good clinical responses to a variety of solid tumor patients with FGFR 1/2/3 alterations, especially point mutations. In a pooled retrospective analysis, 51 patients with documented or detected FGFR 1/2/3 mutations and measurable target lesions have been treated with Tinengotinib and demonstrated an ORR of 33% and a DCR of 88%. The median PFS reached 6.9 months.
Source: TransThera-B (02617) Prospectus (IPO Date : 2025/06/13) |