CanVirex
Cancer Vaccination to Activate Anti-Tumor Immune Response

“Cancer is a journey, but you walk the road alone. There are many places to stop along the way and get nourishment—you have to be willing to take it.” (Emily Hollenberg)

These lines by Emily Hollenberg, a cancer survivor, give some semblance to the predicament of cancer patients. The torment of cancer continues to grow at an incredible pace, exerting tremendous physical, emotional, and financial strain on individuals, families, communities, and health systems. The disease is the second leading cause of death globally, accounting for more than nine million deaths in 2018 worldwide with rising incidence according to the World Health Organization (WHO). Significant efforts and resources across the globe are being put into attempt to find an effective treatment for the disease.

In recent years, cancer immunotherapy has come a long way as a transformational methodology in the treatment of cancer patients, establishing itself as a new standard of care besides chemotherapy, radiotherapy, molecularly targeted therapeutics, and surgery. Thereby, cancer immunotherapy has made significant inroads in terms of survival and quality of life of cancer patients. Rather than aiming treatments directly at the tumour, immunotherapy engages the patient’s immune system to recognise and eradicate tumour cells. It also demonstrates the potential for the long-term survival of patients suffering from advanced solid tumours as immunomemory guides the immune system to go after cancer cells if they ever come back. However, despite these advances, many obstacles still exist in the field of cancer immunotherapy. The patients’ response rates vary significantly and, more often than not, only a small subset of the patients within a large cohort responds favourably to the treatment. Besides, patients also may have to deal with systemic toxicity along with the higher cost of treatment.

The discovery that natural virus infections can cause tumour regression led to the development of so-called oncolytic viruses for cancer (immuno) therapy. Although these viruses have garnered considerable interest as possible agents of tumour destruction since the beginning of 20th century, it is in the last two decades that oncolytic virotherapy has emerged as a potential cancer treatment with the opportunities of modern virology and genetic engineering. Efforts in clinical research and development in this field resulted in the approval of the first oncolytic virus therapeutic in 2015 to treat advanced melanoma patients.

Two decades ago, Dr Guy Ungerechts started working on viral vectors for his PhD thesis at the University Hospital Tübingen. He became a medical oncologist trained in the field of oncolytic viruses at Mayo Clinic, Rochester, USA and the Ottawa Hospital Research Institute (OHRI), Ottawa, Canada. With his vast experience, Dr Ungerechts, along with Dr Werner Tschollar, an expert in the pharmaceutical, biotech, and financing industries, founded CanVirex as a spin-off company from the Heidelberg University Hospital. The company offers an innovative and highly promising measles virus vector-based platform for cancer immunotherapy. Dr Tschollar, co-founder, and chairman of the board at CanVirex, says, “Guy and I founded CanVirex with a deep conviction that viro-immunotherapy will inevitably provide a next-generation of safe and highly effective cancer therapeutics.”

Guy and I founded CanVirex with a deep conviction that viro-immunotherapy will inevitably provide a next-generation of safe and highly effective cancer therapeutics

Oncolytic measles viruses— engineered from a measles vaccine strain—have shown great potential as cancer therapeutics, with the potential to circumvent current limitations of cancer immunotherapy. Its firm tumour suppressive potential combined with an excellent safety record as a viral vaccine, makes it an optimal platform for cancer treatment. Upon infecting their tumour target cells, oncolytic viruses—referred to as therapeutic cancer vaccinations in the scientific literature—lyse them and activate a robust anti-tumour immune response.

CanVirex’s oncolytic viruses are genetically engineered to encode immunomodulatory payloads (transgenes) that activate the patient’s immune system specifically. The measles vector is highly flexible and can be considered a versatile platform to deliver all kinds of immune modulating transgenes. After application, these transgenes are produced by the infected tumour cells and trigger powerful T cell responses that can be capable of tumour clearance and prevention of tumour relapse. “We give patients ‘armed’ oncolytic viruses and the patient’s body produces the encoded immunotherapeutics at the tumour site, making them potentially less susceptible to systemic side effects,” informs Dr Ungerechts. By delivering immunotherapeutics only to tumour cells, CanVirex’s oncolytic viruses not only minimise adverse effects but also maximise local concentrations at the tumour site.

Another significant aspect of CanVirex’s oncolytic virus platform is its safety profile. The vector backbone of CanVirex’s technology is identical to a commonly used measles vaccine strain which has been administered to billions of people across the globe over the last 50 years. Contrary to the standard chemotherapy or radiotherapy procedures that have severe adverse effects such as fatigue, loss of appetite, nausea, bowel issues, hair loss, mouth sores, skin and nail problems, and memory loss, the oncolytic measles viruses have very few adverse effects on the patient. “While traditional procedures can kill the motivation of patients to continue the therapy, our technology can significantly improve the quality of care and the patient’s quality of life during treatment,” says Dr Tobias Speck, VP of Product Development at CanVirex. Besides, the multiplexed platform can also increase the response rates by rational and patient-specific selection of the appropriate immune modulating vectors from the platform. Notably, the production of these viruses is less expensive as compared to other cancer immunotherapies.

Vaccination against infectious diseases

The same technology of vector engineering can also be used for vaccination against infectious diseases. When the COVID-19 pandemic wreaked havoc and forced governments across the world to impose many social distancing measures, including closing borders, suspending international flights, followed by restrictions on domestic mobility, CanVirex added a vaccine for the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) to its pipeline.

The company collaborates with the German Center for Infection Research (DZIF) to develop a measles-vectored vaccine for protection against COVID-19. CanVirex’s vaccine induces a multifunctional immune response. The measles-based COVID-19 vaccine encodes a SARS-CoV-2 antigen that has been shown to induce significant cellular and humoral immune responses, making it an ideal candidate for the fight against the virus. “We are encoding the full-length surface protein of the SARS-CoV-2 virus on our measles vector that induces very balanced Th1 and Th2 responses for an effective vaccination against COVID-19,” informs Dr Ungerechts.

Unique Translational Capabilities, Strategic Collaborations and Distinctive Manufacturing Process

The company has formed a strategic collaboration with the Heidelberg University Hospital for the research and clinical development of measlesvectored therapeutics. The Heidelberg University Hospital is connected to Europe’s largest cancer research institute, the German Cancer Research Center (DKFZ), Heidelberg. The collaboration with the Heidelberg University Hospital allows CanVirex to access laboratories and staff for their research, keeping its management structure lean. “Our collaboration gives us unique clinical translation capabilities and know-how that provides us an enormous competitive advantage regarding the clinical development of our vectors,” states Dr Ungerechts.

To use the measles vector in cancer therapy, where the doses are up to a million times higher than a traditional vaccine dose, CanVirex had to develop a unique and highly sophisticated manufacturing process to achieve high yields at viable prices. This know-how has become particularly relevant regarding the development of CanVirex’s COVID-19 vaccine candidate, where orders will quickly amount to hundreds of millions of doses upon successful completion of clinical trials.

The work culture at the company is exceptionally cooperative, which helps foster innovation and productivity. “We believe in complementarities at our company. So, we look at people with high personal and professional integrity to keep a very amicable and collegial situation inside the company,” asserts Dr Tschollar.

Established in 2017, the company is making a mark for itself in the treatment of cancer and infectious diseases. Led by Dr Ungerechts, the proficient and highly experienced team at CanVirex consists of leading experts in the field of molecular immunology, clinical oncology, and drug development. The whole team is dedicated to developing safe, effective, and commercially scalable virus vectors. The company’s lead candidates for the oncology program and the COVID-19 vaccine project are pre-clinically fully developed, and are targeted for clinical testing in 2021. CanVirex is now on the look-out for an effective collaboration with a large pharmaceutical company to expand its geographical reach and enhance distribution infrastructure for a global rollout of its products. “We have complete in-house competencies, with regards to preclinical formulation, pre-GMP manufacturing, toxicology, quality assurance, clinical and business development, licensing, legal, and other aspects to develop our products. We are now in talks with some of the big pharmaceutical companies for the marketing, sales, and distribution of our products,” concludes Dr Ungerechts.