About Polaris
Polaris Group is a multinational biotechnology company focused on developing novel anti-cancer therapies.
Our lead drug candidate,
Polaris Group is involved in every stage of the drug development process. Our family of companies harnesses structure-based drug design technology to create novel oncology therapies, conducts clinical studies at top-tier cancer centers worldwide and operates CGMP production facilities in Northern California and China.
Family of Companies
Polaris Pharmaceuticals
San Diego-based Polaris Pharmaceuticals is leading clinical development of Polaris Group’s lead drug candidate, ADI‑PEG 20. Founded in 2006, the company also conducts early-stage drug discovery, translational research and pre-clinical research for a variety of cancer indications and is executing global clinical studies for ADI‑PEG 20.
TDW Pharmaceuticals
TDW, based in Taiwan, is responsible for clinical studies in Asia, outside of China. TDW completed a multi-center Phase 2 clinical study in Taiwan for hepatocellular carcinoma in 2008, and is conducting multiple studies for ADI‑PEG 20 in Taiwan.
DesigneRx Pharmaceuticals – USA
Founded in 2002. Built a cGMP facility for biologics in 2005 and has been providing ADI‑PEG 20 for all clinical studies for over 10 years. As a CMO, manufactured cGMP grade biologics for a biotech company to conduct clinical studies in the USA.
DesigneRx Pharmaceuticals – Chengdu
Founded in 2013. Acquired 68 acres in Chengdu Hightech Industrial Park in 2013. Currently building a world-class large scale cGMP facility for biologics; pilot facility projected to be validated in 2019.
DesigneRx Pharmaceuticals – Shanghai
Founded in 2007, DesigneRx Pharmaceuticals – Shanghai conducts translational research to identify additional cancers that may be suitable for treatment with ADI‑PEG 20. The business also is responsible for the clinical development of ADI‑PEG 20 in China.
Management Team
Chairman and Chief Executive Officer
John Bomalaski, M.D.
Executive Vice President, Medical Affairs
Shaw Chen, M.D., Ph.D.
Executive Vice President, Regulatory Affairs
Wei He, Ph.D.
Senior Vice President, Pharmaceutical Operations
James Thomson, Ph.D.
Senior Vice President, Research & Development
Amanda Johnston, Ph.D.
Senior Vice President, Clinical Affairs
Irene Kuo
Senior Vice President, Finance and Accounting
Peter Posel
Vice President, Finance
Scientific Advisors
Ongoing Clinical Studies
ADI‑PEG 20 is in clinical development for numerous oncology indications.
Drug: ADI‑PEG 20 + Pemetrexed and Cisplatin
Lead Institute: Barts Cancer Institute
ATOMIC Study (Phase 2/3)
Phase 2/3 Study in Subjects with MPM to Assess ADI‑PEG 20 with Pemetrexed and Cisplatin (ATOMIC)
This is a randomized, double-blind, Phase 2/3 study in patients with non-epithelioid (including biphasic and sarcomatoid histologies) malignant pleural mesothelioma (MPM) to assess the effect of ADI‑PEG 20 with pemetrexed and cisplatin, the current first-line standard of care chemotherapies for MPM. The study uses an adaptive biomarker-driven design with an interim analysis to be conducted at the end of Phase 2. Patients in the study are required to have tumor samples submitted for biomarker analysis. This study is being conducted at multiple centers globally and is currently recruiting patients. Learn more
Drug: ADI‑PEG 20 + FOLFOX
Lead Institute: Memorial Sloan-Kettering Cancer Center
FOLFOX Study (Phase 1/2)
Phase 1/2 Study of ADI‑PEG 20 Plus FOLFOX in Subjects with Advanced Gastrointestinal Malignancies
This is a Phase 1/2 study to assess the effect of ADI‑PEG 20 in combination with folinic acid (leucovorin), fluorouracil and oxaliplatin (FOLFOX) in advanced gastrointestinal (GI) malignancies. The already concluded Phase 1 portion established safety and tolerability of combining ADI‑PEG 20 with FOLFOX for the treatment of advanced GI malignancies including hepatocellular carcinoma (HCC), colorectal cancer, and gastric cancer. The Phase 2 portion of the study is being conducted at multiple centers globally, with a focus on HCC patients who have failed at least two lines of prior systemic treatments. The study is open and currently recruiting patients. Learn more
Drug: ADI‑PEG 20 + Pemetrexed and Cisplatin
Lead Institute: Barts Cancer Institute
TRAP Study (Phase 1)
Phase 1 Study in Subjects with Tumors Requiring Arginine to Assess ADI‑PEG 20 with Pemetrexed and Cisplatin (TRAP)
This Phase 1 study is assessing the effect of ADI‑PEG 20 with pemetrexed and cisplatin in tumors that require arginine, as determined by deficiency in argininosuccinate synthetase (ASS1). The study includes a dose-escalation phase (closed) and an ongoing expansion phase including cohorts for malignant plural mesothelioma, non-small cell lung carcinoma, glioma, uveal melanoma and sarcomatoid cancers. The study is open but no longer recruiting patients. Learn more
Drug: ADI‑PEG 20 + Low dose cytarabine
Lead Institute: Taiwan National Cheng Kung University Hospital
AML Study (Phase 1)
Phase 1 Study of ADI‑PEG 20 Plus Low Dose Cytarabine in Older Patients with AML
This is a Phase 1, multicenter, open label study of ADI‑PEG 20 in combination with low-dose cytarabine in older patients with acute myeloid leukemia (AML), who are deemed unfit for intensive chemotherapy with refractory or relapsed disease; or untreated with intermediate or adverse risk karyotypes (MRC risk group). The study is open and currently recruiting patients. Learn more
Drug: ADI‑PEG 20 + Pembrolizumab
Lead Institute: Taiwan National Institute Cancer Research
Pembrolizumab (Phase 1)
Phase 1 Study of ADI‑PEG 20 Plus Pembrolizumab in Advanced Solid Cancers
This is an open-label, Phase 1b study of ADI‑PEG 20 in combination with pembrolizumab in patients with advanced solid cancers who have failed prior treatment. In addition to assessing the safety and tolerability of combining ADI‑PEG 20 and pembrolizumab, this study also intends to explore the effect of ADI‑PEG 20 on tumor immunogenicity focusing on tumor PD-L1 expression and T-cell infiltration, and to explore the effect of this combination in solid tumors. The study is open and currently recruiting patients. Learn more
Completed Clinical Studies
In addition to our ongoing clinical trials, we have evaluated ADI‑PEG 20 in completed studies for a range of oncology indications.
| Tumor Type | ADI-PEG 20 Monotherapy or Combination with Chemotherapy | Lead Clinical Site | Phase |
|---|---|---|---|
| Hepatocellular Carcinoma | Monotherapy | Memorial Sloan-Kettering Cancer Center | Phase 3 |
| Mesothelioma | Monotherapy | Barts Cancer Institute | Phase 2 |
| Melanoma | Monotherapy | Memorial Sloan-Kettering Cancer Center | Phase 2 |
| Acute Myeloid Leukemia | Monotherapy | Tawain NHRI + MD Anderson Cancer Center | Phase 2 |
| Non Hodgkin’s Lymphoma | Monotherapy | Tawain NHRI | Phase 2 |
| Small Cell Lung Carcinoma | Monotherapy | Memorial Sloan-Kettering Cancer Center | Phase 2 |
| Pancreatic Cancer | Nab-paclitaxel Gemcitabine | Memorial Sloan-Kettering Cancer Center | Phase 1 |
| Mesothelioma, Non-Small Cell Lung Carcinoma, Glioma | Pemetrexed Cisplatin | Barts Cancer Institute | Phase 1 |
| Solid Tumors | Cisplatin | MD Anderson Cancer Center | Phase 1 |
| Breast Cancer | Doxorubicin | MD Anderson Cancer Center | Phase 1 |
| Colorectal, Gastric Cancer | FOLFOX | Taiwan National Cheng Kung University Hospital | Phase 1 |
| Prostate Cancer, Non-Small Cell Lung Carcinoma | Docetaxel | UC Davis Medical Center | Phase 1 |
Our Science
Acting on a Metabolic Linchpin of Many Cancers
ADI‑PEG 20 is a novel therapeutic protein being developed for cancers with a unique metabolic trait: their cells are unable to create arginine, an amino acid that is essential for cancer cell proliferation and survival. Because the cells can’t create arginine on their own, they must rely on arginine in the patient’s plasma. But ADI‑PEG 20 deprives the cancer cells of this amino acid by converting plasma-borne arginine into citrulline.
While healthy cells are able to easily convert citrulline back into arginine through a process known as the urea cycle, cancer cells are not. At the core of their deficiency is a down-regulation of argininosuccinate synthase (ASS1), an enzyme needed to synthesize arginine. To survive, the cancer cells must “rewire” their metabolism. This exerts a stress on the cells that renders them more susceptible to conventional chemotherapies.
Polaris is evaluating ADI‑PEG 20 in combination with standard chemotherapies and immuno-oncology drugs. The candidate has gained orphan drug status for hepatocellular carcinoma, melanoma and mesothelioma in the U.S., also for mesothelioma and hepatocellular carcinoma in Europe.
The FDA also has provided Special Protocol Assessment and the EMEA has provided Protocol Assistance, allowing for the potential of expedited market approval.
Polaris Group owns multiple issued and pending patents covering ADI‑PEG 20, including patents on formulation and use.
Research Programs
Second-Generation ADI-PEG
Polaris Group is working to identify and develop the next generation of arginine-depleting therapeutic proteins. ADI-PEG 20 is based on an enzyme, ADI (arginine deiminase), that originates from the micro-organism Mycoplasma hominis. Because ADI is from a foreign source, prolonged treatment will give rise to anti-ADI-PEG 20 antibodies that will reduce the drug’s effectiveness. To minimize the impact of neutralizing antibodies, ADI has been PEGylated using the same technology as is used for other FDA-approved therapeutic proteins.
To further counter neutralizing antibodies, Polaris is developing a follow-up drug based on a protein that is distantly related to M. hominis ADI from M. hominis. Promising enzymes are currently undergoing more extensive characterization and additional genetic engineering. The second-generation drug will be developed with comparable or superior characteristics as the first generation, including enzyme activity under physiological conditions, pharmacodynamics and pharmacokinetic properties. Polaris owns issued or pending patents covering PEGylated ADI originating from new species and chimeric proteins.
Activation of Death Receptor-Signaling
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand, or TRAIL, is a member of the TNF superfamily that can initiate cell death. The ability of TRAIL to selectively induce apoptosis in tumor cells, but not normal cells, renders TRAIL-based therapy a safe and efficacious approach to targeting cancer. Cytokines induce apoptosis through the activation of death receptors via receptor oligomerization, which in turn results in the recruitment of specialized adaptor proteins and activation of caspase cascades.
Polaris has designed and synthesized multiple TRAIL-based biologics and has advanced this project to pre-clinical candidate selection. A representative of these molecules has shown significant efficacy in mouse models. Polaris has filed a provisional patent on this highly novel class of biotherapeutics.
CK2 Dysregulation
Protein kinase CK2 plays a global role in cell growth, death and survival. And in many cancers, this protein is dysregulated and overexpressed, making it an attractive anti-cancer target. Polaris has developed a small-molecule inhibitor of CK2 and owns issued or pending patents covering two different structural classes of CK2 small-molecule inhibitors.
PD-L1/PD-1 Inhibitor
PD-L1/PD-1 interaction inhibitors, often referred to as immune checkpoint inhibitors, have seen much success as cancer therapies in recent years. Polaris has developed small-molecules therapies that seek to block the PD-L1/PD-1 interaction, thereby decreasing tumor-induced immune suppression. Small-molecule drugs have several advantages over antibody-based drugs; they can be administered orally, have a shorter half-life making it easier to manage adverse events, and have lower manufacturing costs. Polaris has filed a provisional patent covering its first structural class of PD-L1/PD-1 interaction inhibitor.
IDO Inhibitor
Polaris is employing rational structure-based drug design to develop a novel structural class of small-molecule inhibitors of indoleamine 2,3-dioxygenase (IDO) for the treatment of cancer.
IDO regulates immune function through control of tryptophan levels. In a healthy person, IDO ensures the immune system does not over-respond to threats. Tumor cells hijack this immunosuppressive process by up-regulating IDO activity. As IDO has been shown to be up-regulated in several types of cancer, it is seen as an emerging target for anti-cancer treatment.
ASS1 IHC Assay
The ASS1 IHC assay is a standard laboratory immunohistochemistry (IHC) assay. Using Polaris’ proprietary mouse monoclonal antibody against ASS1, it is developed for the in vitro semi-quantitative detection of ASS1 antigen in sections of formalin-fixed, paraffin-embedded (FFPE) normal and neoplastic tissues. Visualization of the ASS1 antigen is achieved by sequential application of the anti-ASS1 primary antibody, visualization reagents and chromagen, resulting in a visible reaction at the site of the antigen. Results are evaluated by a pathologist using a light microscope. Polaris mouse anti-ASS1 monoclonal antibodies can be used in detecting ASS1 protein expression in both Western blot and IHC.
Manufacturing
Polaris Group operates state-of-the-art production facilities in California and China to manufacture its therapies for clinical trials and commercialization.
DesigneRx Pharmaceuticals – USA, located in Vacaville, California, manufactures all drugs for Polaris Group’s global clinical studies. The cGMP facility produces novel protein therapeutics to support clinical trials at various stages in the U.S., Europe and the Asian-Pacific region.
DesigneRx Pharmaceuticals – Chengdu, established in 2013, is located in the Hi-Tech Zone of Chengdu in the Sichuan province in China. As a wholly owned subsidiary of Polaris Group, this facility is designed to include a small-scale clinical manufacturing suite and a commercial-scale cGMP manufacturing facility for biologic drugs.