HebaBiz Biotech's anti-cancer drug candidate under development Siroquine (JP001) has been approved for IND clinical trials in the United States

BEIJING, Aug. 20, 2021 /PRNewswire/ -- HebaBiz Biotech is pleased to announce, it has come to its knowledge on August 16, 2021, that the U.S. Food and Drug Administration (FDA) had granted clinical trial approval for Siroquine (JP001), an innovative anti-cancer drug under development. Such a clinical trial is to be conducted on newly diagnosed glioblastoma (GBM) -- this marks an important milestone in the ongoing multicenter, open-label, phase II/III clinical trial to evaluate the overall survival benefit and safety of JP001 in combination with standard chemoradiotherapy in newly diagnosed GBM patients. The clinical trial will be conducted in Taiwan, the United States and Mainland China.

Glioblastoma (GBM), the most common type of glioma, has a poor prognosis, with most patients reporting a median survival time of 10 to 15 months. The current standard treatment is surgical resection, followed by synchronous radiotherapy (RT) and temozolomide (TMZ) chemotherapy in the resection cavity, further followed by TMZ adjuvant therapy. The median survival time upon surgical resection alone is about 6 months, and the combination of surgical resection and radiotherapy extends the median survival time to 12.1 months. On this basis, the combined treatment with TMZ further extends the median survival time to 14.6 months. Although the survival time of GBM patients continues to improve slowly, treatment for GBM remains a significant challenge and yet fails to meet patients' needs.

Autophagy is a lysosomal mediated catabolic process that helps maintain cellular homeostasis and cell survival by degrading cytoplasmic components in response to intracellular and extracellular stress. GBM is considered to demonstrate very strong autophagy and is a kind of tumor that is resistant to radiotherapy and chemotherapy, and the tumor microenvironment is immunosuppressed. Autophagy regulation is the main strategy to overcome the resistance of glioblastoma cells to cytotoxic chemotherapy and radiation-induced cell death.

JP001

JP001 is a dual autophagy modulator being developed by HebaBiz Biotech, which can improve tumor microenvironment (TME) and increase tumor cells' sensitivity to chemoradiotherapy. HebaBiz Biotech was granted an exclusive global license for the anti-tumor indications of JP001 from Johnpro Biotech Inc. in November 2019. JP001 has been approved by the Ministry of Health and Welfare of Taiwan (TFDA) for phase I exemption and could directly proceed to clinical phase II/III study for the newly diagnosed GBM; safety and efficacy data of some patients have already been obtained. HebaBiz Biotech also has plans in place to commence concurrent phase II/III clinical trials of the same indication in the United States and Mainland China.

Given JP001's nature as a dual autophagy modulator, it has an effect on a variety of cancers including GBM, such as sarcoma, refractory metastatic solid tumor, multiple myeloma treatment failure, lymphatic fibroids, bladder cancer, renal cell carcinoma, etc and a number of papers on this topic has been published. JP001 will adopt the strategy of used-in-combination with standard treatment, to develop more indications. To this end, preliminary estimates suggest coverage of at least 30% of tumor types by JP001.

The key advantages of JP001 are as follows:

• Anti-cancer sensitizer

JP001 can induce autophagy, inhibit tumor cell proliferation, promote cell apoptosis, and increase the sensitivity of chemoradiotherapy.

• Great development value

JP001 has a therapeutic effect on GBM, sarcoma, refractory metastatic solid tumor, multiple myeloma, lymphangiomyoma, bladder cancer, renal cell carcinoma, etc. It was found that JP001 demonstrate synergistic killing effect in connection with Clevudine (another drug candidate in HebaBiz Biotech's pipeline) in liver cancer cell lines transfected with Hepatitis B virus, and the effect of single drug or used in combination on tumor cell metabolism is under study.

• GBM treatment is significantly more effective than standard treatment

At present, the treatment of newly diagnosed GBM is basically surgical treatment combined with chemoradiotherapy as the standard treatment, and the treatment results are not ideal. The efficacy of JP001 in combination with standard treatment is shown to be significantly more effective than that of standard treatment, and its therapeutic efficacy is highly correlated with a specific Bio-marker.

Summary of JP001 Phase II/III clinical trial (enrolled patients)

The ongoing randomized phase II/III trial of radiotherapy with /without temozolomide for newly diagnosed glioblastoma will involve the enrollment of 370 patients in aggregate, under international multicenter in the United States, Mainland China, and Taiwan. Six patients so far have been randomly recruited into the study arm (standard treatment TMZ/RTZ in combination with JP001).

Of the six patients in the study arm, four are female and two are male, ranging in age from 41 to 58 years, with a median treatment period of 14 months, JP001 was well tolerated with no grade 3 toxicity.

Median progression-free survival (PFS) was observed to be over 14 months (PFS > 21 months in patient 006). Up to now, certain patients are still alive, and the longest overall survival (OS) is more than 29 months. Both PFS and OS are observed to be significantly higher than existing standard treatments and has a 100% correlation with a specific Bio-marker.

Commenting on this milestone, Dr. Zhou stated:

"We have been conducting phase II/III clinical trial in Taiwan on JP001. Preliminary clinical trial results show that JP001 is well tolerated. Four of the six patients in the treatment group responded significantly in positive ways, with two surviving with no signs of recurrence and PFS is >20 months and the longest OS is > 29 months.

Even more exciting is the high correlation between effective cases and a specific Bio-marker, which has important implications for the precision treatment of JP001, reduction of costs of clinical trials, and acceleration of the NDA approval, and gaining of market share. Meanwhile, we found that JP001 when used in combination with PD-1 can enhance the sensitivity of PD-1 to GBM, and we are actively coordinating for the commencement of a clinical trial program in the United States.

We are conducting a phase II/III international multicenter trial in the United States, Mainland China and Taiwan, and we have applied for a pre-IND meeting with CDE (Center for Drug Evaluation, National Medical Products Administration) in China. I am confident that JP001 will be a successful showcase under an innovative drug strategy that will help develop more and in a faster manner, new cancer drugs that truly meet the needs of patients."

Professor Kwan–Hwa Chi, principal investigator (PI) of JP001, also said:

"Autophagy is the subject of a Nobel Prize and is essential to every cell. Therapeutic targets for autophagy exist in every cell class, including tumor cells, cells in tumor microenvironment (TME), and normal cells in the body. Autophagy usually has a cellular protective effect when cells are stressed by starvation or chemotherapy (CT). The protective effect of autophagy is particularly prominent when tumor cells are induced to death via programmed cell death or tumor necrosis  by chemoradiotherapy, so it is becoming an important target for the development of new anticancer drugs in recent years.

It is very effective to use JP001 on a stand-alone basis for lymphangioleiomyomatosis, a rare disease, and it shows better effect when used in combination with various anti-tumor therapies for most other cancers. The basic principle of JP001 also suggests that it has the advantage of sensitizing tumor cells to most anti-cancer drugs, which could demonstrate clinical value in more than 30% of advanced cancers. As an anti-cancer sensitizer, JP001 is not positioned on only one type of cancer, its market potential is much larger, an example is Bevacavastine, which it is claimed to have a global market of $12 billion by 2025 – it shows huge market potential for a used-in-combination strategy despite not being as effective when used on a stand-alone basis.

About Dr. Zhou

Dr. James Zhou is the founder, Chairman and Chief Scientist of HebaBiz Biotech. His academic and research achievements include the following:

• Postdoctoral Fellow, Department of Biology / School of Medicine, Yale University
• Ph.D. in Genetics, Iowa State University
• National "Innovative Talents Promotion Plan" Scientific and Technological Innovation and Entrepreneurship Talents
• Director, National & Local Joint Engineering Research Center for Anti-tumor Drug Development
• 863 Evaluation Expert in Agricultural Biology, Ministry of Science and Technology
• 863 Expert and Host of Special Biological Resources Major Project of Ministry of Science and Technology
• Evaluation Expert in Biopharmacy of Evaluation Center of Ministry of Science and Technology
• Zhongguancun "High-End Leading Talent"

About Professor Kwan–Hwa Chi

Professor Kwan–Hwa Chi has been engaged in cancer treatment for more than 30 years. He is now the principal investigator (PI) of JP001 and holds the following positions: PhD, Tokyo Medical University, Japan, Director of the Department of Cancer Therapy, Shin Kwang Wu Hoshi Memorial Hospital, and Professor, Department of Medicine, Yang-Ming University.

About HebaBiz Biotech

Founded by Yale University scholars and their team returning to China, HebaBiz Biotech is committed to creating personalized, precise and improved solutions for the treatment of cancers and liver diseases, guided by clinical value and patients' needs and systematically improving the quality of traditional Chinese medicines by the use of cutting-edge biotechnology.

HebaBiz Biotech has established a National & Local Joint Engineering Research Center for Anti-tumor Drug Development, systematic technology platforms for small-molecular drugs and innovative traditional Chinese medicines. HebaBiz Biotech has a number of international and domestic patented technologies, and seven new drug candidates in its pipeline under research and development, including China's Category 1.1 Anti-cancer Innovative Drug under the National New Drug Development Major Project. HebaBiz Biotech's pipeline is also strategically positioned to comprehensively cover liver disease indications including liver cancer, chronic hepatitis B, non-alcoholic steatohepatitis, alcoholic liver disease, weight, lipid and other metabolic disorders; at the same time, HebaBiz Biotech is seeking breakthroughs in glioblastoma (GBM), pancreatic cancer and kidney cancer etc.

In parallel with innovative research and development, HebaBiz Biotech adheres to the principle of using the best from both Chinese and Western sources and implements a commercial layout of chemical medicines and natural medicines being mutually complementary. HebaBiz Biotech currently has nine types of production dosage forms, 82 product approvals; it has built and put into operation a modern production base of 68,000 square meters and has a mature sales team, and is strategically positioned as an all-rounded innovative enterprise of "integration of research and development, production and sales".

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