Scientists have long been studying how to turn viruses into cancer-fighting tools, prompting the rise of a form of immunotherapy involving oncolytic viruses. These viruses are specially engineered to infect and replicate inside tumor cells, leaving normal, healthy cells uninfected. Once inside a tumor cell, the viruses cause the cell to die. By killing a tumor cell, the viruses then help the body’s immune system recognize tumor cells as foreign because it also sees the virus as foreign, stimulating immune cells to attack and kill them.
This technique is now being employed in the development of several drug candidates currently in clinical trials. In this article, we take a look at seven of the top oncolytic virus companies advancing their therapies.
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Akamis Bio
Formerly known as PsiOxus Therapeutics before changing its name in early 2023, oncology company Akamis Bio’s mission is to leverage its Tumor-Specific Immuno-Gene Therapy (T-SIGn) platform to deliver novel immunotherapeutic proteins, biomolecules, and transgene combinations to treat solid tumors. The company’s portfolio is made up of solid tumor-targeted T-SIGn therapeutics that aim to enable a patient’s own immune system to recognize, attack, and clear their cancer.
Delivered intravenously, these therapies target both primary and metastatic epithelial-derived solid tumor tissue. Once at the tumor site, the therapies essentially turn solid tumor cells into “drug factories” while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. The company says that T-SIGn therapeutics have the potential to be used either as a monotherapy or in combination with other immuno-oncology agents, such as CAR-T cell therapy.
As well as changing its name in January 2023, Akamis announced a $30 million financing, which helped to fund development activities for its clinical-stage programs, NG-350A and NG-641.
Calidi Biotherapeutics
Calidi Biotherapeutics wants to revolutionize the effective delivery and potentiation of oncolytic viruses for targeted therapy against difficult-to-treat cancers. Its off-the-shelf, universal cell-based delivery platforms are made to deliver cancer-killing viruses by loading them into stem cells, which protects the therapeutic virus from the immune system until it can reach the tumor cells and destroy them. In addition to directly killing the cancer cells, the company’s platforms also prompt a second phase of attack, making tumors that can usually hide from the immune system become noticeable so that the immune system then recognizes them and kills them; this even includes cancer cells that may have already traveled away from the primary tumor.
Calidi’s lead candidate is called NeuroNova 1 (NNV1). It is composed of immortalized neural stem cells loaded with oncolytic adenovirus, for the treatment of patients with glioblastoma. A phase 1 clinical trial in patients with newly diagnosed high-grade gliomas has already been completed, establishing NNV’s safety and signals of efficacy. In a press release from December 2023, Calidi said it now plans to commence a phase 1b/2 clinical trial for NNV1 in collaboration with Northwestern University during the first half of 2024.
In June last year, the oncolytic virus company announced the commitment of $25 million in series B funding, which would enable it to continue the advancement of its pipeline.
CG Oncology
Focused on developing and commercializing a potential bladder-sparing therapeutic for patients afflicted with bladder cancer, CG oncology has one primary product candidate called cretostimogene grenadenorepvec, which is an engineered oncolytic immunotherapy that has been designed to preferentially replicate in retinoblastoma gene pathway-defective cells present in the majority of urothelial carcinomas and trigger an anti-tumor immune response.
Cretostimogene is currently being evaluated as a monotherapy in two phase 3 clinical trials for the treatment of Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) and intermediate-risk NMIBC, as well as in a phase 2 trial in combination with pembrolizumab in BCG-unresponsive NMIBC. It is also being studied in an investigator-sponsored clinical trial in combination with nivolumab for the treatment of muscle-invasive bladder cancer.
In December 2023, the oncolytic virus company announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track Designation and Breakthrough Therapy Designation for cretostimogene in BCG-unresponsive NMIBC with carcinoma in situ with or without Ta or T1 (papillary) tumors. Furthermore, in January 2024, CG Oncology announced the closing of an upsized $437 million initial public offering (IPO).
Genelux
Focused on developing a pipeline of next-generation oncolytic immunotherapies for patients suffering from aggressive or difficult-to-treat solid tumor types, Genelux’s discovery and development efforts revolve around the company’s proprietary CHOICE platform, from which it has developed an extensive library of isolated and engineered oncolytic vaccinia virus (a poxvirus similar to smallpox) immunotherapeutic product candidates.
The oncolytic virus company’s most advanced candidate, Olvi-Vec (olvimulogene nanivacirepvec), selectively targets malignant cells and is currently being tested in a phase 3 trial evaluating its efficacy and safety when used in combination with platinum-based chemotherapy in patients with platinum-resistant/refractory ovarian cancer. Genelux is also planning to initiate a phase 2 clinical trial of Olvi-Vec in combination with chemotherapy in patients with recurrent non-small cell lung cancer (NSCLC).
In November 2023, the company received FDA Fast Track Designation for Olvi-Vec in platinum-resistant/refractory ovarian cancer.
IconOVir Bio
IconOVir Bio’s discovery pipeline consists of multiple differentiated oncolytic virus candidates that have the potential to be potent, tumor-selective, administered intravenously, and broadly infect tumor cells.
In 2021, IconOVir managed to raise $77 million in series A financing. This funding allowed the company to advance its lead candidate, IOV-1042, which is derived from the common cold virus and has been rationally designed with genomic modifications to confer tumor-selective replication, broad tropism (the ability of a virus to infect different cellular types ultimately to produce a successful infection), and enhanced tumor cell killing, as well as allow for either IV or intratumoral delivery. Preclinical research has shown that it is able to infect and kill a broad range of tumor cells, including head and neck, bladder, lung, and breast, suggesting that it could have potential utility in a wide range of solid tumor indications.
Most recently, in July 2023, IconOVir announced that the first patient had been dosed in a phase 1 clinical trial of IOV-1042 in patients with relapsed or refractory solid tumors.
KaliVir Immunotherapeutics
Oncolytic virus company KaliVir Immunotherapeutics has developed a vaccinia virus-based platform – called the Vaccinia Enhanced Template (VET) Platform – that can generate potent novel oncolytic vaccinia viruses with modifications to maximize viral replication and enhance intravenous delivery. The platform utilizes the large transgene capacity of the vaccinia virus to deliver therapies that match tumor immunophenotypes (immunophenotyping identifies cells based on the types of antigens or markers on the surface of the cells) to stimulate patients’ immune systems and modify the tumor microenvironment. KaliVir’s oncolytic virus candidates are designed to be safe, potent, and systemically deliverable to treat cancer patients across multiple tumor types.
Discovered and developed by KaliVir and licensed to Astellas in December 2020, ASP1012 was the first candidate to be built from the VET platform and KaliVir recently announced FDA clearance of an Investigational New Drug application to initiate a phase 1 trial for the drug in patients with locally advanced or metastatic solid tumors.
As well as the aforementioned licensing agreement with Astellas, KaliVir has another significant collaboration with Roche to design and generate novel oncolytic vaccinia viruses derived from its VET platform. Furthermore, in January, the company unveiled its new state-of-the-art GMP cleanroom facility to manufacture its pipeline of oncolytic viruses and, said that it has already successfully executed the inaugural manufacturing run for its current lead clinical candidate, VET3-TGI.
TILT Biotherapeutics
TILT Biotherapeutics is developing cancer therapies based on oncolytic adenoviruses armed with molecules including cytokines that activate T cells and destroy cancer cells. The company’s TILT technology eliminates cancer’s ability to evade immune responses, which also enhances the efficacy of T-cell therapies, such as immune checkpoint inhibitors, tumor infiltrating lymphocyte (TIL) therapy, and CAR-T cell therapies.
TILT’s lead candidate, TILT-123, is an adenovirus armed with two human cytokines: an inflammatory cytokine called TNF alpha and a signaling molecule called IL-2. It uses the cancer cell’s own machinery to replicate and produce both these cytokines in increased quantities. When the cancer cell lyses or ruptures, these cytokines are released into the tumor microenvironment, providing powerful alert signals for the immune system. TILT-123 is now in phase 1 clinical trials in combination with tumor infiltrating lymphocytes (TIL) therapy in Europe. About fifty patients have been treated in four international trials sponsored by the company, with promising initial efficacy responses observed in some of the patients.
In 2019, TITL initiated a collaboration with Merck KGaA and Pfizer to evaluate TITL-123 with avelumab – a human anti-programmed death ligand-1 (PD-L1) antibody – in patients with solid tumors. Furthermore, in 2022, TILT also signed a second clinical trial collaboration and supply agreement with MSD (a trade name of Merck & Co) for a new clinical trial evaluating TILT-123 in combination with KEYTRUDA, MSD’s anti-PD-1 therapy. And, just last month, the oncolytic virus company was awarded a $2 million grant from the U.S. Department of Defence for ovarian cancer immunotherapy research.
Oncolytic viruses: a growing market
According to Emergen Research, the global oncolytic virus therapies market size is expected to reach $609.7 million in 2028, registering a compound annual growth rate (CAGR) of 26.2% during the forecast period. The primary factors driving the growth of the market are a rise in the prevalence of cancer, an increase in the number of clinical trials, and investment in research and development (R&D) for cancer therapies.