Newco news: Oncolytic virus specialist Immvira moves oHSV to China and U.S. phase II trials

By Elise Mak (/authors/46-elise-mak) 

June 18, 2021 

Immvira Group Co. (https://www.cortellis.com/intelligence/qsearch/Immvira?indexBased=true&searchCategory=ALL) presented positive phase I data for MVR-T3011 (https://www.cortellis.com/intelligence/qsearch/MVR-T3011?indexBased=true&searchCategory=ALL) as an intratumoral administration (MVR-T3011 IT) at the 2021 American Society of Clinical Oncology (ASCO) annual meeting this month, drawing attention to oncolytic viruses developed by Chinese scientists. 

Last week, Immvira also completed the first dosing of MVR-T3011 IT in phase II trials in China and the U.S. Next, the biotech is looking to test MVR-T3011 as an intravenous (I.V.) infusion. 

“MVR-T3011 is the first oncolytic herpes simplex virus (oHSV) from Immvira’s pipeline to enter clinical studies,” Immvira’s chief financial officer, Carl Yeung, told BioWorld in an exclusive interview. “Preliminary clinical phase I study results of MVR-T3011 IT demonstrated promising efficacy.” 

Data presented at ASCO were convincing. Subjects with advanced solid tumors that have accessible injectable lesions received MVR-T3011 IT once every other week. MVR-T3011 IT was shown to be safe and well-tolerated at the dose levels tested with no dose-limiting toxicities. 

Preliminary efficacy was encouraging, with stable disease rate reaching 75% in all evaluable subjects. Tumor shrinkage was observed in some early enrolled subjects who had at least one efficacy assessment. One subject had stable disease at week nine and an injected lesion reduction of 27% at week 17. 

“Analysis from biopsy samples taken pre- and post-treatment from subjects with accessible lesions showed significant tumor cell reduction as well as increased lymphocyte infiltration, indicating on-target antitumor activity,” Yeung said. 

MVR-T3011 is Immvira's next-generation, genetically modified oHSV developed on a new virus backbone design and gene recombinant technology. 

“Our genetic edit strategy allows MVR-T3011 to have around three-log higher the replication in tumor cells compared to traditional oncolytic viruses, making it a much more potent candidate with enhanced safety features,” Yeung explained. 

“Selective incorporation of two latest and well-validated payloads encoding immune modulatory genes, namely PD-1 antibody and IL-12, can improve the synergistic antitumor ability and promote immunoreaction in the localized tumor environment,” he added. 

Broadening the MVR-T3011 program

Encouraged by the data, Immvira aims to broaden its first clinical program to more indications and uses. “Responses to MVR-T3011 IT were shown across a broad range of tumor types, including melanoma, sarcoma, cervical cancer and breast cancer,” Yeung said. 

“The ongoing study has also achieved a high stable disease ratio relative to other oncolytic virus programs from published data current available. This well distributed control of disease in late-stage patients, among which many of them were heavily pre-treated and had PD-1/PD-L1 treatments, is a positive signal for potentially a new modality for cancer treatment,” he added. 

In the U.S. phase IIa study, Immvira is testing MVR-T3011 IT as a single agent for melanoma and metastatic solid tumors, and in combination with Keytruda (pembrolizumab, Merck & Co. Inc.) for non-small-cell lung carcinoma. In the China phase IIa study, MVR-T3011 IT is indicated for head and neck cancer, sarcoma and breast cancer. 

The next goal is to study MVR-T3011 as an I.V. infusion targeting advanced solid tumors. 

Yeung said Immvira has initiated the program in the U.S. and is expected to dose the first patient this month. In China, the company is waiting for IND clearance to start a clinical study targeting lung and liver cancer this year. 

“Immvira could become the first company to conduct clinical trials with intravenous administration of oHSVs in the world,” he said. 

“Intravenous administration of oncolytic viruses has long been a challenge, as most oncolytic viruses cannot overcome multiple obstacles such as neutralization by innate immune response, and they can also potentially lead to cytokine storm in the body.” 

OvPENS platform to yield more oHSV 

Founded in 2015, Immvira has a keen interest in oHSV. Back in 2002, its founder Grace Zhou demonstrated that HSV-1 can target cancer cells through genetic modification to viral surface, and those discoveries laid the foundation for targeted oHSV development. 

Immvira relies on its OvPENS platform to develop oncolytic virus with potency, enabling, novelty and safety. It enables viral vector validation, virus discovery and development, CMC know-how and manufacturing. 

The biotech has developed a portfolio of oHSV drug candidates based on the platform. Besides MVRT3011, its pipeline includes single-drug modification candidate MVR-C5252 for brain tumors and MVRT8011 for hematological malignancies. Immvira has submitted INDs for MVR-C5252 in China and the U.S. and expects to begin the trials this year, while MVR-T8011 is in the discovery stage. “We also further completed new design of combo product series MVR-T701X and initiated preclinical studies to validate its potential as an enabler for CAR T, ADC and BiTE therapies,” Yeung said. Immvira has developed three product candidates, MVR-T7011, MVR-T7012 and MVR-T7013, each carrying different combinations of target antigens. 

“Conceptually, we plan to discover oncolytic virus candidates that can enhance therapeutic profiles of prevailing cancer therapies,” he added. “We will explore oncolytic viruses’ combinatorial potentials, including but not limited to direct combination therapies, designed combination therapies, targeted receptors and customized payloads.” 

With its clinical progress, Immvira stands out as one of the forerunners in oncolytic virus in China, racing along with nearly 40 other players. In August 2020, it out-licensed the greater China rights of MVR-T3011 IT to pharma giant Shanghai Pharmaceuticals Holding Co. Ltd. 

“It is the largest domestic transaction in recent years with an aggregate payment amount up to ¥1.15 billion, as well as royalty payments of up to 12% of net sales in the future,” Yeung commented on the landmark deal. 

He said China's oncolytic virus treatment market has not only received support from policies and regulations, but also attracted keen attention from investors to make it a “hot spot for the region’s capital market.” 

Between June 2020 and December 2020, Immvira raised $58 million from series B, $10 million from series B+ and an undisclosed amount from series C round. 

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