Immvira: Immuno-Oncology: Conquering the Next Frontier

Dr Grace Zhou, Chairman & CEO, Immvira Dr Grace Zhou, Chairman & CEO If 2020 has taught us anything, it’s about what a ‘virus’ is capable of— shutting down the entire world! Yet, despite their role as a causative agent of diseases, viruses can be an unlikely ally in the war against cancer. Viruses engineered to kill various types of cancer cells are undergoing clinical trials already. The FDA and the AMA approved the first such virus known as oncolytic virus for treating late-stage melanoma in 2015.

Tracing back on the timeline, it was at the beginning of the 20th century that viruses as possible agents of tumour destruction started to attract attention with discoveries pointing to certain cancers regressing in patients following viral infections. Although the use of viruses as anticancer agents sprung from serendipity, revolutions in molecular biology accelerated the idea, and today oncolytic viruses are proving to be innovative tools in the anticancer armamentarium.

The Shenzhen-based Immvira, a company focused on developing a broad range of anticancer therapies based on genetically engineered viruses, is uniquely poised to accelerate discoveries and unveil possibilities. In 2015, six scientists in the field of ‘tumor’s oncolytic immunity’ from the U.S., came together to establish the company that develops innovative drugs for immunotherapy and targeted treatment of herpes oncolytic virus (oHSV), including five product lines, covering all types of cancers.

Oncolytic Virus: The Foundational Phrase

While taking the first step to knowing the potential of oncolytic virus therapies, it is worth understanding oncolytic virus action mechanisms. An oncolytic virus is a product that uses a virus as an immune-oncology treatment factor to initiate a human host immune response specifically to the tumour. The antitumour factor of the oncolytic virus battles on two fronts. In its dual function role, the virus starts to replicate inside cancer cells and in turn stimulates the microenvironment of the tumour to promote immune response first locally and then systemically to cure the tumour.

Building on science that started several decades ago, Immvira, a biotechnology company, develops product pipelines of the engineered oncolytic virus, which carry a single or combination of immunostimulatory agents. The various product pipelines are focused on different indications with an emphasis on drug discovery, preclinical study, and early phase 1 and phase 2 clinical trials. “We develop products based on novel ideas that encapsulate our combined knowledge of immuno oncology, molecular biology, and cancer biology,” says Dr Grace Zhou, Chairman & CEO of Immvira.

Power of Blended Teams

Power of Blended Teams Dr Grace’s experience as a virologist perfectly dovetails with that of Dongyao Ni, the CDO of Immvira, who brings in immense expertise as an immunologist. The amalgamation of knowledge and experience of the former scientists from the University of Chicago underpins the company’s core work on the oncolytic virus, which is a perfect combination of virology and immunology. Immvira, right from its genesis, has been focused on science, research, and product development. To this end, the company has been recruiting industry experts to take the road of drug development. The Immvira team comprises specialists with extensive experience in chemistry, manufacturing, and control (CMC), and pharm/tox to help advance the oncology virus as an industrial product.

Onboard are senior scientific advisors who can guide the development of the product from a pharmaceutical angle.
The company also has the top experts in the molecular mechanism of the virus infection. “This is extremely important because we always need to look at how the virus and the host cell interact or fight each other,” points out Dr Grace. “Alongside, our focus is on having people well versed in designing the protocols such that our product can combine with suitable combination therapies and successfully complete the phase one and phase two clinical studies.” Besides, one of Immvira’s co-founders was instrumental in developing the first oncolytic virusimmunotherapy for the treatment of cancer—T-VEC, the firsthand experience strengthening their scientific stronghold to develop targeted treatment of herpes oncolytic virus.

We aim to cover all solid tumours and haematological malignancies through the various pipelines


“Our success stems from our corporate culture where everybody is encouraged to contribute their ideas openly,” says Ni. In this novel development landscape before any decision springs from the drawing board, the Immvira team actively participates in numerous discussions and brainstorming sessions contributing their ideas, experience, and understanding of regulations before fully committing to its execution.

Immvira’s drug discovery group has developed a viable technology to perform precise gene modification to create important viral vectors. The proficiency is in predictably making the right combinations of the genetic elements and inserting the useful genes into different locations of the viral gene. This makes the oncolytic virus effective in not just replication but in terms of immune therapy. The Immvira team has also developed a key therapeutic platform, which is not only suitable for a single product but also for use in combination with other agile therapies. They also have an efficient gene engineering process to facilitate the oncolytic virus for specific indications.

An Impressive Product Lineup

Immvira’s very first product in the pipeline, Intratumoral injection of oHSVT3011, is designed to use an oncolytic virus armed with IL12 and PD-1 Ab to treat cancers that are accessible by intratumoral injections. In the global oncolytic virus field, the majority of clinical applications are intended as intratumoral injections as it is a precision medicine that concentrates the anticancer agents inside the tumour. In the instance of cancer that has spread in the body, Ni explains that the objective of using an intratumoral injection is not just to treat the lesion but stimulate the body to generate a robust antitumour immune response toward cancer systemically. “We have developed combination therapies, where along with the localized intratumoral injection that triggers the immune response, systemic drugs such as immunotherapy, target therapy, biological therapy and chemotherapy can be administered.”

Emphasizing on the efficacy of combination therapies, Ni draws attention to patients who are not responding to immunotherapy, probably due to an immunosuppressive microenvironment. Even as anti-PD-1 inhibitors provide a survival advantage to patients who are responding, statistics reveal that the percentage in each indication is only a maximum of 30 per cent. Moreover, some patients are generally resistant to PD-1 antibody. Against this backdrop, combining PD-1 with oncolytic virus proves to be successful because the oncolytic virus can turn the tumour environment from ‘cold to hot’, meaning into an immune friendly environment, which is completely changing the world of immunotherapy. It enables the cytotoxic T cells to infiltrate into the local environment to change the immune suppression and get activated to kill the tumour cells. “We believe that in the future all tumor therapies will become combination therapies,” adds Dr Grace.
Dongyao Ni, CDO“Furthermore, with intratumoral injections becoming very advanced, the combination drugs can be administered by direct injection into the tumor mass while keeping the toxicity levels under check.”

“We have developed combination therapies, where along with the localized intratumoral injection that triggers the immune response, systemic drugs such as PD-1 antibody, MEK inhibitor, and chemotherapy are administered”

Immvira’s second pipeline targets those cancers such as lung cancer, liver cancer, and pancreatic cancer where the lesions are difficult to access to administer the intratumoral injection. Active studies are on to deliver the oncolytic virus by IV injection. The product is being developed to be as effective as an intratumoral injection and is expected to reach the clinical stage by the first quarter of next year. The third pipeline is targeted at the most important organ—the human brain. According to Ni, the oncolytic product available in the market currently is approved to treat melanoma but is ineffective toward treating malignant glioma. The five-year survival rate from glioblastoma (GBM) is less than five per cent with most of the GBM patients dying within 15 to 18 months. “We are developing an oncolytic virus that is safe for the normal brain cells and very effective to treat brain cancer,” he states.

In their fourth product pipeline, the Immvira team is developing an oncolytic partner virus that will work in conjunction with new cancer treatments such as chimeric antigen receptor (CAR) T cell therapy and antibody-drug conjugates to generate a better response and overall survival rate. The final product Immvira’s pipeline is a retarget virus, which will specifically target blood cancer. “We aim to cover all solid tumors and hematological malignancies through the various pipelines,” remarks Dr Grace.

Beyond the Horizon

While the various products are under development in China, the company is actively talking with the FDA to ensure that the products meet the FDA’s criteria as well. In May 2019, Immvira received IND clearance for their first product T3011 from FDA, for which the trial is under progress. As per Ni, most of the patients recruited for the study have been part of other clinical trials and treated with PD1 antibody previously, with five patients who have undergone chemotherapy. “Though it is early to conclude on efficacy, we are seeing patients responding well to T3011 clinically even those who were treated previously with PD1 antibody.” The company is conducting phase 1 trials for T3011 in three countries. “Globally this is the only clinical study to be initiated simultaneously in three countries,” extols Dr Grace.

On the business front, Immvira has completed three rounds of fundraising and has numerous accolades and awards under its belt. As the company looks forward to international collaborations with pharmaceutical companies, the company added another feather to its cap, in August. Immvira successfully licensed their first product—MVR-T301—to Shanghai Pharmaceuticals, one of the biggest pharmaceutical management companies in China for 1.1 billion RMB for commercialization in Greater China. This is by far the largest deal for Shanghai Pharmaceuticals and within China in the last five years.

As oncolytic virus therapy is en route to becoming a standard therapeutic option for all cancer patients, representing a watershed moment, Immvira is steadily progressing toward engineering more effective and safer remedies.
- Kenneth Thomas
    November 27, 2020
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Company
Immvira

Headquarters
Shenzhen, China

Management
Dr Grace Zhou, Chairman & CEO and Dongyao Ni, CDO

Description
Immvira develops a broad range of anticancer therapies based on genetically engineered viruses. Immvira, a biotechnology company, develops product pipelines of the engineered oncolytic virus, which carry a single or combination of immunostimulatory agents. The various product pipelines are focused on different indications with an emphasis on drug discovery, preclinical study, and early phase 1 and phase 2 clinical trials .Immvira’s very first product in the pipeline, Intratumoral injection of oHSVT3011, is designed to use an oncolytic virus armed with IL12 and PD-1 Ab to treat cancers that are accessible by intratumoral injections. The company has developed combination therapies, where along with the localized intratumoral injection that triggers the immune response, systemic drugs such as immunotherapy, target therapy, biological therapy and chemotherapy can be administered. The various pipelines are aimed at covering all solid tumors and hematological malignancies