Coastar Therapeutics
Pioneering Intravenous Oncolytic Virus Delivery

As of 2018, cancer is the second leading cause of death globally, accounting for an estimated 9.6 million deaths. Surgical amputation, radiation therapy, and chemotherapy treat cancer with a brute, shotgun-like approach, blasting away healthy cells alongside the cancer cells. The human body can only take so much. A targeted and consistent treatment is imperative, and this is where oncolytic viruses (OVs)— such as the herpes simplex viruses (HSV)— hold immense potential, as they preferentially infect and kill cancer cells. Also, they not only cause the direct destruction of the tumor cells but also stimulate host anti-tumor immune system responses, resulting in the creation of a sort of cancer resistance within the patients’ bodies.

At the end of the day, however, OVs are still viruses, and by virtue of their design alone, they are immediately considered a threat by our immune systems and potentially eliminated. How can one introduce OVs then, without getting ‘detected’ by the immune system so that it can finish off its intended targets? In the past, the OV was introduced intratumorally, i.e., injecting the OV directly into the heart of the tumor to bypass most of the immune system. But this may not always be feasible, especially to target cancers at more difficult to administer regions such as the pancreas or liver. The need is imperative for more specific targeting mechanisms. Innovators, OV experts, and founders of Coastar Therapeutics, Han Liang Lim (CSO) and Eddie Chung (CEO), have cracked the code for introducing OVs intravenously, without immune systems detection.

When it comes to OV delivery, viruses have evolutionarily optimized themselves to have an affinity for cell membranes. Many researchers currently use the host cell as a carrier for the mesenchymal stem cell, which are immature cells capable of self-renewing and differentiating into many cell types. Due to their inherent tumor tropism, mesenchymal stem cells loaded with the oncolytic virus can improve the delivery of the therapeutic cargo to cancer sites. However, this presents several problems, especially when trying to put the virus into the stem cells at a larger scale. Furthermore, this treatment has only been available for personalized medicine. Alternatively, what had been long considered to be the gold standard in the field, liposomal technology ”where fats are utilized to help bring important vitamins, medicines, or OVs to certain parts of the body in little bubbles without impacting other parts of the body” is still rather behind in terms of what is being studied. Liposomal encapsulation is well-recognized to reduce immune elimination and enhance the stability of drugs in the bloodstream and relies on the potential of liposome-encapsulated plasmid DNA of telomerase specific oncolytic adenovirus (TelomeScan) expressing GFP (Lipo-pTS) as an oncolytic adenoviral agent suitable for systemic delivery. And while liposomal technology has had its successes, it is still plagued by limits on shelf life, toxicity when dosed, and its inability in some cases to generate immune neutralizing antibodies against itself, preventing its ability to be administered repeatedly.

What Coastar Therapeutics, on the other hand, is trying to use a membrane from the host body as the biomaterial surrounding the OV. Coastar’s ELCV coating platform uses human cell lipid that contains self-identifying motifs to protect the virus from being neutralized by neutralizing antibodies and immune cells. This helps the OV fit for long-term storage and enables it to be shipped worldwide. The OV can be a truly off-the-shelf product compared to the rest of the offerings in the market, where they have to preserve the living cells and use the cell to carry oncolytic viruses. “Our cell membrane is the material. It’s not a living cell. It’s a novel material that can largely improve the viral therapy efficacy, or clinical outcome,” Chung states.

Coastar has done several experiments with regard to coated viruses and various cancer models and maps xenografts. They found that if they administer intravenously, their solution shows a 70 fold increase in the blood-virus concentration and has the potential to improve the virus’ circulatory retention time when administered intravenously. At the same time, the biodistribution of the viruses remains largely unaltered (for intravenous administration) and will return to the original source. This is close to ideal because some of these viruses with the same biodistribution profile are already approved for intravenous use, and Coastar can improve on that. The Coastar solution thus follows the same profile and will ward off any potential off-target side effects that could be elicited with the original virus.

As Han states, “When we administer the viruses intratumorally into triple-negative breast cancer, we’ve seen a complete suppression of growth of the tumor. In an intravenous setting, we found that if we take the tumor out and do a PCR after the experiment, a five to six-fold increase in viral DNA within these tumors is observable, highlighting the fact that even intravenously in an immune competent mouse, we can see improved infection. I think the big problem in oncolytic virotherapy is that it’s marked by a lot of failure to demonstrate its efficacy or improve efficacy, especially in the phase three. And this is where I think we can come in to overcome that trend.” He also notes that once they coat the virus, there is complete suppression from the first dose through the study time. There is a five to six-fold increase in viral DNA within these tumors, highlighting that there is improved infection even intravenously in an immune-competent mouse. Coastar believes that in oncolytic virotherapy, there is a pre-existing failure to demonstrate efficacy or improve efficacy, especially in phase three, which they seek to overcome.

And while the company is currently focusing on oncolytic virus coating for cancer immunotherapy, they are also interested in adeno-associated virus (AAV) for gene therapy in the future. Coastar Therapeutics is also starting its series A very soon and is looking at closing that by the middle of next year. For the next two years, their goal is to have more strategic collaborations with companies that are already in a clinical stage, that want to co-develop a product or collaborate together to create more pipelines. “We want to get into clinical trials in three years from now,” Chung concludes