OUR DRUG DEVELOPMENT PIPELINE
All of our compounds are designed to be first-in-class or best-in-class anticancer agents.
- Address unmet clinical needs
- Potent against validated or new cancer targets
- Excellent pharmaceutical characteristics, including:
- oral bioavailability
- blood-brain-barrier permeability
- Effective as single agent and as combination therapies
- Superior efficacy in comparison to current and late stage development drugs
- Highly specific for individual kinase targets
- Unique chemical entities, with strong patentability
Oral CDK9 inhibitor
Haematological malignancies, high-risk myelodysplastic syndrome, MCL1/MYC-dependent cancers
PHASE I: AML
Oral CDK4/6 inhibitor
Glioblastoma/metastatic brain cancers, cyclin D-CDK4/6-amplified cancers, ER+/Rb+ cancers, cancer immunotherapy
PHASE 1: SOLID TUMOUR
Oral CDK4 inhibitor
Brain tumours, cancer immunotherapy, chemo-protective therapy, ER+/Rb+ cancers
Oral CDK8 inhibitor
Haematological malignancies, STAT1/5- and Wnt/ß-catenin-dependent cancers, NK cell-mediated tumour surveillance
Oral CDK2 inhibitor
Cyclin E/B-dependent solid tumours and leukaemia
Oral CDK9/TRK inhibitor
MCL1/MYC-dependent cancers, TRK-positive cancers
Oral FLT3 inhibitor
FLT3-ITD/TKD-mutant haematological malignancies
TAM-dependent malignancies, cancer immunotherapy
SUNACICLIB: A HIGHLY POTENT CDK9 INHIBITOR FOR TREATING HAEMATOLOGICAL MALIGNANCIES AND SOLID TUMOURS
Sunaciclib is an oral, highly potent and selective CDK9 inhibitor that is effective against MCL1- and MYC-dependent cancers, especially in blood cancers. MCL1 and MYC are the common oncogenes that drives leukaemogenesis, where CDK9 has a vital role in regulating the expression of these oncogenes. Sunaciclib did not only kill leukaemic cells derived from AML and CLL patients, but also effective against primary cancer cells from relapsed patients while had no influence on normal blood cells. Furthermore, Sunaciclib is able to restore the resistance of cancerous cells to venetoclax or chemotherapies and enhances the anti-cancer effects of these agents. In Phase I trial in patients with haematological malignancies, Sunaciclib is well tolerated and Phase II study will commence in 2022-23.
AUCELICICLIB: A HIGHLY POTENT AND SELECTIVE CDK4/6 INHIBITOR
CDK4 and CDK6 are fundamental for the initiation and progression of the majority of malignancies. As such, components of the CDK4/6 signalling pathway represent molecular targets for cancer therapy. CDK4/6 inhibitors have been FDA-approved for the treatment of ER+ breast cancer and are demonstrating their success in the market. However, current agents are not specific to CDK4 and CDK6 and also inhibit other kinases, resulting in undesirable toxicity.
Auceliciclib selectively inhibits CDK4 and CDK6 with picomolar potency and is very effective against cancer types that carry the KRAS mutations and/or CDKN2A mutations/deletions. In addition to the superior drug property/pharmacokinetics, its unique feature in crossing the blood-brain barrier efficiently has made it an excellent candidate for the treatment of glioblastoma and other metastatic brain tumours. Auceliciclib has demonstrated anti-cancer immunotherapeutic potential either as a single agent or in combination with anti-PD-L1. Auceliciclib is currently in Phase 1 clinical trial in patients with advanced solid tumour.
AU2-94: A FIRST-IN-CLASS CDK4 INHIBITOR
AU2-94 is a first-in-class, oral inhibitor that specifically targets CDK4 at high potency. It demonstrates 140-fold selectivity for CDK4 over its close analogue CDK6, and only inhibited three other kinases potently when tested against 369 kinases. CDK6 has been implicated in myeloid transcriptional role and inhibition of CDK6 may cause myelosuppressive toxicity. AU2-94 has shown an excellent safety pharmacological profile with little impact on the blood cells in animals. AU2-94 can effectively penetrate the brain and has demonstrated marked anti-tumour efficacy against metastatic and Rb+ cancers including glioblastoma. Interestingly, with its CDK4 inhibition, AU2-94 stimulates the anti-cancer immunity when treated as a single agent and increases anti-tumour efficacy of anti-PD1 antibody when in combination. We aim to commence Phase I study in early 2023.
AU2-85: A HIGHLY POTENT AND SELECTIVE CDK8 INHIBITOR
AU2-85 is an oral, highly potent and selective CDK8 inhibitor that shows high efficacy against haematological malignancies through STAT1/5 pathway. CDK8 regulates transcription of cytokines via this pathway, thereby interfering with the immune responses. Natural killer (NK) cells serve as the first-line defense against transformed and infected cells. Therefore, AU2-85 has been an ideal candidate for promoting NK cells-mediated tumour immune surveillance, apart from increasing the efficacy of chemotherapies. The anticancer efficacy and safety profiles in animal models has been well demonstrated upon treatment with AU2-85. In addition to its single agent anti-tumour efficacy, AU2-85 has demonstrated marked activity when combining with targeted therapy or chemotherapy and has the potential to address their resistance. Currently, AU2-85 is at late stage of preclinical studies aiming to commence Phase I study in 2023.
AU14-5: A HIGHLY POTENT AND SELECTIVE CDK2 INHIBITOR
CDK2 plays a pivotal role in cell cycle regulation and is known to be important in tumourigenesis. Inhibition of CDK2 has been shown to force MYC or RAS expressing cells into senescence. Thus, CDK2 is a potential target for treatment of tumours driven by MYC or RAS. Another important role for CDK2 is the phosphorylation of androgen, estrogen and progesterone receptors, thereby increasing their transcription. Estrogen and progesterone contribute to breast and ovarian cancer progression, and androgen receptor phosphorylation is strongly implicated in prostate cancer. This, combined with the fact that CDK2 overexpression is associated with recurrence and metastases, highlights CDK2 as a promising therapeutic target in hormone dependent cancers. Despite decades of development of CDK2 inhibitors, none have yet been approved for the clinic.
AU14-5 is a highly potent oral CDK2 inhibitor that exhibits an excellent selectivity for CDK2 over a panel of 360 human protein kinases. It inhibits cancer cell proliferation and demonstrates excellent anticancer efficacy without any overt toxicity in animal models including ovarian and triple negative breast cancers, as well as leukaemia. Currently, AU14-5 is at late stage of preclinical testing, and aimed to commence Phase 1 trial in 2023.
AU4-53: A HIGHLY POTENT CDK9/TRK INHIBITOR
CDK9 is a key regulatory enzyme of RNA polymerase II (RNAPII) and as such, enables the excessive production of multiple oncogenes, such as MYC, HOXA9, MCL1, BCL-2 and XIAP. CDK9 inhibitors block the transcription of these oncogenes and induce cancer cell apoptosis. Gene mutations or rearrangements in the tropomyosin receptor kinase (TRK) are an important driver of cancer-cell growth in a wide range of cancers. NTRK genes, which encode for TRK proteins, can fuse abnormally to other genes and enhance cell signals that support tumour growth. NTRK gene fusions are found in a variety of tumour types, including soft-tissue sarcoma, salivary gland cancer, infantile fibrosarcoma, thyroid cancer, and lung cancer.
AU4-53 is an oral inhibitor that targets CDK9 and TRK with picomolar potency and is highly selective. This candidate is cytotoxic against a panel of human cancer cell lines, including leukemia, and cancers of breast, colorectal, lung and ovarian. It has demonstrated strong anticancer efficacy in animal models without any overt toxicity. The dual inhibition of CDK9 and TRK has allowed AU4-53 to treat a broader spectrum of cancers while addressing the resistance issue associated with the current TRK inhibitors. Currently, AU4-53 is at the late stage of preclinical development.
AU5-5: A HIGHLY POTENT AND SELECTIVE FLT3 INHIBITOR FOR TREATING LEUKAEMIA
FMS-like tyrosine kinase 3 (FLT3) is expressed at high levels in a spectrum of haematologic malignancies including 70-100% of AML of all subtypes, ALL, and CML. Patients with FLT3 mutations have a very poor prognosis, experience higher rates of relapse and subsequent death.
AU5-5 is a highly selective FLT3 inhibitor, showing picomolar potencies against FLT3 and all eight possible mutations of FLT3, including FLT3 (ITD), FLT3 (D835Y), FLT3 (F594_R595insR), FLT3 (F594_R595insREY), FLT3 (ITD)-NPOS, FLT3 (ITD)-W51, FLT3 (R595_E596insEY) and FLT3 (Y591V592insVDFREYEYD), in a panel screen of 370 human kinases. AU5-5 is highly cytotoxic in FLT3-positive leukaemic cells and holds the advantage of addressing the resistance issue that has been commonly seen in current FLT3 inhibitor treatment. AU5-5 was highly efficacious against tumour xenografts and caused complete remission in all animals bearing AML cancer cells, translating to a 100% survival rate. Moreover, AU5-5 is highly synergistic to venetoclax, a BCL-1 inhibitor, and has the potential to address venetoclax resistance. AU5-5 is at the late stage of preclinical CMC, DMPK/Tox studies.
AU7-55: A HIGHLY POTENT TAM INHIBITOR FOR THE TREATMENT OF BLOOD CANCERS
TAM kinases are over-expressed in a wide variety of cancers and are often associated with poorer patient survival, drug resistance and metastasis. TAMs act as immune checkpoints, similar to CTLA-4, PD-1 and PD-L1, and inhibition of TAM kinases improves tumour immunity.
AU7-55 is an oral, highly potent and selective inhibitor targeting Tyro3, Axl and Mer (TAM) that demonstrated strong anti-cancer activity against a range of cancer cell lines. In animal models, it has shown marked anti-tumour efficacy and caused tumour regression. Moreover, AU7-55 has the potential to be developed as anti-tumour immunotherapy; it promotes anti-tumour immune responses by increasing the CD3+/CD8+ T cells in murine syngeneic models. AU7-55 is in the preclinical CMC, DMPK/Tox studies