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Oncolytic viral therapy - the road less travelled

Being an oncolytic virus there is much scepticism surrounding Vaxinia. As science.org recently noted, despite once being touted as the next big thing in cancer therapy, tumor-attacking viruses have been a letdown, failing in multiple clinical trials as far back as 1949. Is Vaxinia to prove successful? Are Vaxinia’s recent disease stabilisation results of early November 2023 to be replicated at higher doses, improved upon, or ultimately proved an anomaly?

If results released in another oncolytic virus trial late last year are anything to go by, Vaxinia may just have a chance. Preliminary results from a small Phase 3 study presented at a conference in late 2023 suggest these unconventional cancer treatments, known as oncolytic viruses, might work after all. The data illustrated that an oncolytic virus being investigated by Irvine, California–based CG Oncology eliminated tumors in 64% of 66 patients with bladder cancer, that didn’t respond to mainline treatment. At the time it was reported the follow-up period was only 6 months, and that much more research is necessary. But even a positive phase 3 result is enough to “shake the world of oncolytic viruses,” says surgical oncologist Omeed Moaven of the Louisiana State University Medical Center.

Oncolytic viruses prior to Vaxinia have proven effective in animal studies, but failed to deliver when it came to FDA approval and market participation. In fact up until now only T-Vec, has performed well enough to receive the approval nod from the FDA. That said outside of the US, it is with noting three other oncolytic viruses have received regulatory approval (I.e., in Japan).

The aforementioned GC oncology trial proved oncolytic viruses can perform well in combination with monoclonal antibodies, such as Keytruda. A Phase 2 study in 2022 showed that after a year of treatment, tumors still hadn’t returned in 68% of bladder cancer patients. Whereas Pembrolizumab (Keytruda) alone usually eliminates tumors in this indication in only about 20% of patients, as noted by urologic oncologist Roger Li of the Moffitt Cancer Center.

Irrespective of the recent CG Oncology success in treating bladder cancer patients, Vaxinia still has some high hurdles to jump over. Associate Professor Andrew Haydon, medical oncologist at the Alfred Hospital in Melbourne and adjunct senior lecturer at Monash University, told The Medical Republic, early in 2024 that despite hopes, T-VEC failed to beat standard immunotherapy in both regression rate and overall survival. “The biggest barrier to these treatments has been seeing positive effects away from where the virus has been injected. In the T-VEC trials for melanoma, we injected the virus directly into a tumour. The hope was that infecting that tumour would then stimulate the immune system to attack the melanoma more generally throughout the body. That didn’t happen,” he said.

Therefore interest surrounds Professor Yuman Fongs combination between Vaxinia and pembroluzimab (Keytruda). Added to which there is no doubt industry interest in results from the administration of the Vaxinia virus intravenously, in addition to intratumoural injections.

Where does this leave Vaxinia and the future of oncolytic viral treatment in Australia and beyond in 2024? Professor Haydon hopes a positive outcome from the GC Oncology phase III trial will reinvigorate Australia’s enthusiasm for oncolytic virus research. For isolated bladder tumours, such as in this trial, Professor Haydon said oncolytic viruses could very well be effective.

Obviously the FDA agrees with some of the assumptions put forward by Professor Haydon. Having recently afforded Imugene fast track designation and priority review status for Vaxinia in the bile duct cancer indication, oncolytic viruses may well be coming to the fore, when it comes to competing cancer treatment initiatives. Professor Haydon notes in no uncertain terms "What we are looking for is a virus you can get into the bloodstream, so it can go everywhere in the body rather than just where you can get a needle into, and to determine whether it is safe to do that.” If pre clinical study results are repeated within “in human” Vaxinia trials, Professor Fongs parental and potent strain of CF33 may indeed hold the key to success outside of intra tumour injections. Recent study results suggest CF33 can prove effective in reaching and treating tumours outside traditional so called “easy to access tumours”. Result show that CF33-OVs can deliver functional proteins and demonstrate effective anti tumour activity in GCPM models when delivered intraperitoneally. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083877/ for more.

In December the biotech world was alight with headings such as “Tumour-attacking virus has achieved elimination of tumours in 64% of patients with bladder cancer who were unresponsive to conventional treatment, according to interim findings presented at the 24th Annual Meeting of the Society of Urologic Oncology [SUO) in Washington in December.” Is Vaxinia to be the beneficiary of such accolades in April of this year at the AACR ANNUAL MEETING 2024 in San Diego? Time shall tell. Irrespective of the outcome of doses at the current 10 to the 8, I for one shall compliment Professor Fong on persisting with ardency in a class of treatment with limited success stories throughout the course of history. The infamous at times despised tyrannous leader Joseph Stalin is remembered for the atrocities he committed during WW2. But perhaps a quote he could be remembered for, if one were to acknowledge even the most disparaged among us are entitled a voice, would be “I believe in one thing only, the power of human will.” Without doubt Professor Fong, against the odds, could identify with “The power of human will.” From mice to humans “It’s not possible,”screamed the masses.

As cancer.org noted in late 2023, although these oncolytic viruses appear to be safe, and many have shown promising activity against cancer in clinical trials, a few logistical challenges have hindered their widespread use as cancer treatments. One challenge is the need to inject oncolytic viruses directly into tumors, so that the immune system doesn’t eliminate the virus before it can infect the cancer cells. In addition, specialized resources and training are needed to safely store and administer these viruses to people.

Although there are many challenges, if not obstacles facing scientists espousing the virtues of oncolytic viruses, such as Professor Yuman Fong, there is definite support for the development of this treatment arm. The recent decision by the FDA to support Vaxinia in the bile duct cancer indication is but one example of such support. As noted elsewhere on these threads, the majority of FDA approvals in recent years have stemmed from FDA Fast Track designations and Priority Review Status being granted to drugs. Irrespective of the challenges facing oncolytic viruses both in the past and present, this is one regulatory decision that auger’s well for both Yuman Fongs Vaxinia and Imugene alike.

DYOR Seek investment advice as and when required Opinions only