Clover’s R&D efforts are ever-expanding, and in addition to our current programs, we are evaluating other trimerization-dependent disease targets to address using our proprietary Trimer-Tag© technology.
At Clover, we are committed to helping to control the world’s most urgent public health challenges. We believe that we can better respond to public health emergencies by rapidly developing protein-based vaccines at a large scale which we aim to make accessible to populations in need. Amid the COVID-19 pandemic, we have quickly enabled our proprietary Trimer-Tag© technology to develop a potentially safe and effective vaccine for the global population. In addition, we are also leveraging the Trimer-Tag© technology to develop rabies, influenza, respiratory syncytial virus (RSV) and human immunodeficiency virus (HIV) vaccines.
Clover has developed recombinant subunit trimer vaccines for Rabies, influenza, RSV and HIV with our Trimer-Tag© technology and has demonstrated that they evoke protective neutralizing antibody responses in multiple animal models.
The rabies vaccine candidate (RABV G-Trimer) is currently in early-stage development. There is a high unmet need for rabies vaccines in developing countries, where animal immunization programs have been unsuccessful.
The influenza vaccine candidate (Hemagglutinin (HA)-Trimer) has demonstrated proof-of-concept HAI immunogenicity and viral-challenge results in vivo in mice (pandemic and seasonal). There is a significant speed of production advantage (shortened lead times) and no use of toxic chemicals such as formaldehyde and preservatives. In addition, the vaccine candidate can potentially be used as a pandemic and universal (HA-stem) flu vaccine.
The RSV vaccine candidate (Fusion (F) Antigen-Trimer) induced strong neutralizing antibody response in a rat immunization model and has sub-picomolar binding affinity to palivizumab. There is a significant unmet need for a safe and effective RSV vaccine worldwide as no RSV vaccines are currently approved.
The HIV/AIDS vaccine candidate (gp120-Trimer) demonstrates strong binding affinity to broadly-neutralizing neutralizing antibodies (bNAbs), suggesting preservation of important antigenic epitopes, and gp120-trimers have induced bNAb responses in vivo in the rabbit immunization model. Current progress made in AIDS vaccine research has revealed that native-like trimeric gp120 is the preferred antigen for eliciting broadly neutralizing antibodies (bNabs) and could hold promise for an effective prophylactic vaccine for the deadly disease.
Clover’s oncology programs hold significant promise in targeting critical pathways that have the potential to provide much-needed options for oncologic therapies to communities around the globe.
The SCB-313 program targets cancer apoptosis for the treatment of intracavitary oncology indictions(including malignant ascites, malignant pleural effusions and peritoneal carcinomatosis). SCB-313 is a novel fusion protein consisting of TRAIL (TNF-related apoptosis-inducing ligand) and the proprietary Trimer-Tag©, allowing TRAIL to form a stable covalently-trimerized complex. TRAIL receptors, which are selectively expressed on many tumors, must be trimerized in order to trigger the programmed cell death signaling pathway. TRAIL has long been considered a tantalizing target for cancer therapy because it can induce apoptosis in a tumor-specific manner across many different tumor types.
SCB-313 is currently being tested in five open-label, dose escalation, multi-center trials in Australia and China (two trials in Australia, three trials in China) to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of intraperitoneally or intrapleurally administered SCB-313 as a single-agent for the treatment of malignant ascites, malignant pleural effusion or peritoneal malignancies.
In preclinical studies, SCB-313 has demonstrated potent ability to induce apoptosis in multiple human tumor models with a favorable safety profile and multi-fold superior potency compared to a dimeric TRAIL agonist.
The SCB-333 program involves a novel fusion protein consisting of 4-1BBL (CD137 Ligand, naturally trimeric) and the proprietary Trimer-Tag©, allowing 4-1BBL to form a stable covalently-bound trimeric fusion protein. Activation of 4-1BB on activated T cells stimulates proliferation and survival of the tumor-specific cytotoxic T cells and promotes development of the innate immune memory response. SCB-333 has a favorable pharmacokinetic profile and natural receptor-activating potency, allowing it to potentially overcome dose-limiting severe hepatic toxicities observed with other 4-1BB targeted candidates. 4-1BB is one of the most promising immune costimulatory targets with the potential to be combined with checkpoint inhibitor therapies (e.g. PD-1) to synergistically stimulate the immune system’s anti-tumor response.
SCB-340 is a trimeric fusion protein consisting of OX40L, engineered using the Trimer-Tag© platform technology and are currently in early stage development.
The development of Fc-Fusion proteins is an important field in the current Clover R&D pipeline. The Fc-Fusion protein program is comprised of SCB-808, SCB-420 and SCB-219.
SCB-808 is a biosimilar to Enbrel® (etanercept) being developed as a ready-for-injection prefilled syringe formulation for use in ankylosing spondylitis and rheumatoid arthritis. All currently available domestically produced etanercept biosimilars in China are approved as freeze-dried powder formulations only. SCB-808 is ready-for-injection and can potentially be self-administered by patients in the convenience of their own homes.
Clover has successfully completed a Phase 1 clinical trial of SCB-808 in China to assess the pharmacokinetics, safety and immunogenicity of subcutaneously administered SCB-808 and originator drug Enbrel® in healthy volunteers. A Phase 3 multi-center clinical trial of SCB-808 is currently being conducted in China to assess the efficacy, safety and pharmacokinetics of SCB-808 and originator drug Enbrel® in patients with ankylosing spondylitis (radiographic axial spondylarthritis) via subcutaneous administration.
SCB-420 is an aflibercept biosimilar currently in preclinical development for the treatment of wet age-related macular degeneration (wAMD). Clinical trials are expected to initiate in 2021.
SCB-219 is a novel TPOR agonist currently in preclinical development for the treatment of immune thrombocytopenic purpura (ITP) and chemo-induced thrombocytopenia (CIT). Clinical trials are expected to initiate in 2021.