Imugene’s Vaxinia, oncolytic viruses, MRNA’s and OncarlyticsAt...

Imugene’s Vaxinia, oncolytic viruses, MRNA’s and Oncarlytics

At least 18 months ago now Saul Priceman M.D noted across the table at lunch there was certain to be much interest from Big Pharma when the platform he co founded, that being Oncarlytics, hit the clinic. Nothing appears to have changed from his analogy when one takes into consideration statements from Leslie Chong of Imugene in recent weeks. Oncarlytics has the ability to effectively target solid tumours utilising a CD19, CF33 concoction to mark and kill these dastardly malignant growths, so commonly found in cancer patients today. Professor Yuman Fong, the founder of CF33, has long identified the need to effectively target solid tumours. Once this abnormal mass of tissue is infected with the potent and parental version of his CF33 virus, known as Vaxinia, he believes it can be successful in eradicating solid tumours within a myriad of cancer indications. But given the fact the majority if not all the patients in his trials are well advanced in the late stages of cancer, is he setting the bar too high? A pre-requisite of entry to the trial(s) is that participants must have failed on all previous lines of therapy, now surely that doesn’t help. That said, Vaxinia killed all cancer lines within mouse and xenograft models. But is CF33 Vaxinia going to prove effective in treating much larger species, such as humans? Moreover does Fong’s virus need to be combined with a CAR T or allogeneic therapy to produce the best results? In other words can Vaxinia stand alone, or does Saul Priceman's Oncarlytics therapy need to work in concert with CF33 Vaxinia to produce the best outcomes for solid tumour patients?

Clearly answers to some of these questions may be found in the wash up from Imugene’s ongoing Phase 1 dose escalation trial for Vaxinia. Results thus far have not been overwhelmingly conclusive either way, but what they have provided is a definite window of opportunity for up to half those being treated with Vaxinia. Now thats a promising outcome given cancer is more likely to spread than stabilise during the latter, advanced stages of its existence.

The CF33 Vaxinia (MAST) Trial

Progress in the Vaxinia (MAST) Trial is at the epicentre of the Imugene (IMU - ASX) universe given a number of factors. Firstly many investors hopped on board the IMU train having heard Professor Fongs oncolytic virus killed all cancers against the NC1 60 pre-clinically in xenograft models. Secondly the company purchased what they term as an Oncarlytics platform wherein CF33 Vaxinia provides the nucleus for treating patients with solid tumours. Thirdly, they purchased their own allogeneic or “off-the-shelf” therapy made from donor-derived T cells, modified using a proprietary gene editing, which they aim to trial in conjunction with CF33 Vaxinia and Oncarlytics in the treatment of solid tumor patients. Then finally company management took the step of prioritising the aforementioned Vaxinia (MAST) Trial over and above their other immunotherapies, late in 2023.

When it comes to the Vaxinia (MAST) Trial, biotech analysts in the US Roth Capital note the following in their most recent analysis:

MAST trial. IMU provided an update on all of its clinical programs, in addition to several other business items. Most notable was an update on its MAST trial in solid tumors, which is evaluating IMU's oncolytic virus VAXINIA given intratumorally or intravenously, with or without pembrolizumab. As of a data cutoff of 04-24-24, 40 of 47 dosed patients are efficacy evaluable, and ORR was 8% (3/40; 1 CR and 2 PRs), with 43% (17/40) achieving SD, thus indicating a 50% overall DCR. There were no additional objective tumor responses from the last update, and we look forward to initial data from the recently opened bile tract cancer expansion cohort (n=10) in 2H24. The new MAST trial data compares to the prior MAST update at AACR (data cutoff of 12-19-23), in which 31 of 38 dosed patients were efficacy evaluable, yielding a 21% (3/14) ORR in the 14 intratumoral patients, and a 53% (9/17) DCR (all SD) in the 17 intravenous patients.

The results are based on patients in a Phase 1 dose escalation trial for Imugene's oncolytic virus Vaxinia, and represent patient outcomes for those dosed at relatively low doses of the drug, with longer term outcomes for those dosed at higher levels yet to come. The fact these late stage solid tumour patients from a variety of solid tumours have realised disease stabilisation is impressive. With a disease control rate of 50% (i.e., 20 out of 40 evaluable patients) there is the hope that some advanced patients may move from a state of pseudo-progression to one in which the drug produces an immune response, be that partial or complete, at some time in the future.

The results haven’t been enough to move the IMU share price, despite the FDA having granted Imugene the right to pursue the fast track designation pathway for the drug in the indication of bile duct cancer, in which they attained a complete response. The reason being many are sitting on the sidelines waiting either for clinical trial results for those dosed at a higher level, alternatively awaiting results for those dosed in the trial expansion into the bile duct cancer indication. Is one complete response an anomaly, some may ask? Or is CF33 Vaxinia truly capable of eradicating bile duct cancer, a deadly form of this insidious disease?

In a recent interview CEO and Managing Director Leslie Chong highlighted investor interest in the US for oncolytic viruses, whilst touching on the point there was supposed interest from US investors in the company's Oncarlytics OASIS Trial, being conducted in conjunction with the Amgen blockbuster BLINCYTO. Clearly none of this activity is reflected in the volumes being traded on the ASX for Imugene (IMU - ASX), which are meagre to say the least in dollar terms when compared to their Nasdaq competitors. What is it going to take to convert some of these US investors to actually move from the sidelines to hop on the IMU train? Obviously a lot more data is required, if history is anything to go by, when it comes to Imugene's flagship candidate CF33 Vaxinia. Vaxinia’s November 2023 data cut illustrated positive immune response for 6 out of 7 gastrointestinal cancer patients. Yet the recent data cut as at April 24 failed to specifically outline the ongoing development of these patients. Once again one assumes they are in a state of disease stabilisation, with their solid tumours neither decreasing nor increasing to any large extent.

The future of oncolytic viruses

One day ago nature.com published an article wherein they discussed the rise of MRNA vaccines and their potential for use in the creation of cancer vaccines, when used in combination with immunotherapies. As you may be aware on 2nd Oct 2023, the Nobel Prize in Physiology or Medicine was awarded to two developers of mRNA vaccines. nature.com notes the accelerated availability of mRNA coronavirus disease 2019 (COVID-19) vaccines has provided valuable health protection, but it only scratches the surface of the vast potential of mRNA vaccines. When speaking with regard to oncolytic viruses nature.com highlights a few salient points which correlate to the application of Professor Fongs Vaxinia virus. Firstly that as we know oncolytic virotherapy is another promising treatment for solid tumors due to its selective nature, optimal immunogenicity, and ability to deliver transgenes directly to the tumor site in a targeted manner, But secondly, and perhaps more importantly that In current clinical trials, intratumoral injection is considered the most effective and safe route of administration for OVs, particularly for surface or localised tumors. However, systemic administration, such as intravenous injection, holds greater clinical application prospects and commercial value, especially for the treatment of metastatic tumors. Hence when assessing the results from Imugene’s aforementioned Vaxinia (MAST) Trial of significant importance is the breakdown of patient outcomes, whether they be from intratumoral or intravenous administration.

It goes without saying, given the lack of approved oncolytic viruses, that this form of therapy has to date shown limited success as a standalone therapy. Though from all accounts oncolytic viruses do have the potential to act synergistically with other immunotherapies, such as adoptive cellular therapy. Given the high cost and challenges associated with personalised CAR T or TCR-T treatment, the induction of specific T cells through mRNA vaccines holds the potential to establish a more transformative therapeutic strategy. Imugene investors shall be hoping that just as the administration of mRNA vaccines in combination with OVs holds promise as an effective therapeutic strategy for solid tumors, their Oncarlytics platform can garner similar opportunities for those inflicted with solid tumours.

Like the Vaxinia trial before it, Imugene's Oncarlytics OASIS Trial aims to evaluate the safety and efficacy of both intratumoural injection and intravenous (IV) infusion — either alone or in combination with blinatumomab, (i.e., marketed as BLINCYTO).

Oncarlytics and the OASIS Trial

As recently as March 2024 Chong noted the company had successfully completed the first monotherapy intratumoural cohort in the OASIS trial, paving the way to move onto an important combination dosing stage with Blincyto. One thing working in Oncarlytics favour could be thatrecent Vaxinia results highlight the fact that patients with a higher level of T cell diversity in peripheral blood (pre-treatment) respond better to VAXINIA therapy, consistent with the known mechanism of action of oncolytic virotherapies and their ability to promote an anti-tumour T cell response. Moreover that both IT- and IV-treated patients treated with Vaxinia have displayed promising immunological changes in on-treatment tumour biopsies (including increases in cancer fighting CD8 T cells and PD-L1 expression), indicating that VAXINIA can transform the tumour microenvironment.

If these results are replicated in the OASIS Trial, the addition of BLINCYTO could well be the trigger required to not only eradicate solid tumours within cancer patients, but to propel the IMU share price at the same time. Maybe then, as Imugene’s CEO AND Managing Director Leslie Chong notes, funds may well find Imugene, without her having to go looking for them.

Imugene, Vaxinia, PD1 Vaxx, the IMU share price and capital raises

Many may have anticipated CF33 Vaxinia would, could or should have already delivered the knockout punch for Imugene. Its frustrating sitting on the sidelines awaiting more and more data to come to the fore. And yet when it does come it is from such a small sample size there may be little to be gleaned from the figures. Hence my recent requests for the company to pursue a much broader brush of their existing product suite through either US capital from large investment participants or perhaps a Nasdaq listing themselves. Leslie Chong noted in her recent interview the cluster of data to be released from the clinic in late 2024, 2025. Much of this may provide the tipping point required to take IMU to the next level.

Yet once again communication from Imugene management needs to be much clearer than it has been in the past. As an example correspondence pertaining to Imugene’s B cell platform, including but not limited to their Her Vaxx and PD1 Vaxx vaccines, leaves a lot to be desired. From the outside looking in Her Vaxx appears to have gone missing in action. Whilst PD1 Vaxx, once considered by some as the great white of hope of Imugene following a successful Phase 1 trial with Non Small Lung Cancer participants, has not produced any data since entering a combination trial with Roche’s Tercetriq back in June 1, 2023. At the time Leslie Chong lifted investor hopes when the first patient was dosed in the trial by using such phrases as “outstanding achievement” and “we are looking forward to evaluating patients with PD1 Vaxx’. Since then investors have barely heard anything from the PD1 Vaxx Imprinter Trial.

Of perhaps more concern for investors were Chongs comments in the same interview she had no idea why IMU was languishing around 8 cents, other than to suggest other like minded stocks were performing well in the US, and that IMU has been the subject of much volatility in the past. Either way its fair to say IMU is underperforming when compared to other stocks in the Aussie biotech sector such as Clarity and Neuren, who whilst being somewhat more mature than Imugene, are nonetheless alternate targets for investor funds within the biotech market segment.

The fact Imugene management persist in raising funds on the Australian market alone at a significant discount to the prevailing company share price of the day clearly hasn’t helped. If Leslie Chong and her Chairman are still assuming roles on the Imugene Board in 2025 and a further capital raise is required to fund existing and future programs, then surely a long hard look at how, where and from whom funds are raised, needs to occur. From where I sit running down another rabbit warren with their much fancied Bell Potter brokers would be akin to adding another dose of Myxomatosis to an already bleeding share price. Unlike capital raises in the past let's hope Imugene’s shareholders have a bit more say next time around, for the sake of their own investment holdings. Maybe, just maybe, the results in the ongoing Vaxinia and Oncarlytics trials may negate the need for such a dilemma.

DYOR Seek investment advice as and when required Opinions only