Fundamentally Imugene continues to move from strength to...

Fundamentally Imugene continues to move from strength to strength. With this in mind let's take a look at their B cell platform in light of recent developments.

HER-Vaxx

Recent news surrounding Imugene (IMU) has only served to strengthen the company from a fundamental analysis perspective. Ursula Wiederman’s notification of HER-Vaxx’s success in preclinical trials in combination with Herceptin and Perjeta were a standout. (see Science Direct for further details). The ability to reduce tumour size and mitigate further cancer progression is once again testamany to the fact HER-Vaxx has succeeded not only as a standalone treatment in Phase 2, but as a combination option with leading market participants. Either way the ability to reduce the frequency of vaccinations saves patients money, and the subsequent reduction in toxicity and therein side effects reduces their pain. HER-Vaxx, the drug for all seasons.

By way of background Leslie Chong Imugene CEO notes “HER-Vaxx is not a T cell vaccine, it is a B cell vaccine using peptide epitopes from a cancer receptor to induce the immunße system to mount an antibody response against cancer cells over-expressing a marker (HER-2),” she said. In other words, HER-Vaxx is an immunotherapy drug designed to treat tumours that over-express the HER-2/neu receptor, including gastric, breast, ovarian, lung and pancreatic cancers.

In Imugene’s current Phase 2 trial for the Wiederman designed HER-Vaxx, patients received SOC chemotherapy for a maximum of 6 cycles with the HER-Vaxx group also receiving 50ug dose of IMU-131 at Baseline/Day 0, Day 14, Day 35, Day 77 and then every 63 days until disease progression. The per protocol pre-planned first interim analysis (OS, PFS and safety) in a total of 27 patients after 15 progression events was reviewed by the independent data monitoring committee (IDMC). The results illustrated that 8 of 27 patients died on the control arm and 4 on the HER-Vaxx plus SOC chemotherapy arm with an overall survival HR of 0.418 (2 sided 80% CI: 0.186, 0.942) and a 1-sided p-value of 0.083. Out of 27 patients, 9 patients progressed on the control arm while 6 patients progressed on the HER-Vaxx plus SOC chemotherapy arm with a HR of 0.532 (2 sided 80% CI: 0.267, 1.060) and a 1-sided p-value of 0.086. A robust HER2 specific antibody response developed in the HER-Vaxx arm compared to the control arm whereas there was no difference in safety between the two treatment arms.

We are but weeks if not days away from receiving the Overall Survival Data on the aforementioned HER-Vaxx Phase 2 trial. Data that is eagerly awaited by both the medical and investment community. Suffice to say that when it comes to HER-Vaxx all roads are leading to Rome for Imugene, given the company’s recent desire to secure worldwide patents for the drug, in addition to announcing combination trials with market heavyweights Merck and Pfizer. Keep in mind Roche’s Her 2 drug Herceptin annualised $6.09 billion dollars in sales in 2019. If the HER-Vaxx results are in any way comparable to Herceptin that would place a value for HER-Vaxx (given its low toxicity and potential for biosims) at approximately 30 billion dollars US. This would add a few extra dollars to the IMU share price if anything close to the current 5 times peak sales figure was paid by Big Pharma to secure the services of the drug to 2038.

Nb. A fact the current share price does not appear to be reflecting.

PD1 VAXX

What about the the PD1 Vaxx Science Series featuring Professor Kaumaya? He all but insinuated during the podcast that Imugene in conjuction with his lab have developed a PD1-PDL-1 combination capable of tackling a plethora of cancer types head on, with great succees. He as much said that in a few years time Imugene would possess the keys to the castle when it comee to mitigating, reducing and in certain instances eliminating a cross section of cancer types in human beings.

Lets recap, sciencedaily.com noted that preclinical results for Imuegene’s PD1 Vaxx conducted at The Ohio University by Professer Kaumaya’s team published in the journal Oncoimmunology, on October 1, 2020, the showed that the peptide called PD1-Vaxx, a first checkpoint inhibitor vaccine, was safe and effective in a colon cancer syngeneic animal model. Science Daily went on to note the study found that PD1-Vaxxwas effective in inhibiting tumor growth. It was even more effective when used in combination with a second therapeutic peptide vaccine, one that targets two sites on the HER-2 receptor on colon cancer cells. The combination treatment produced complete responses in nine of 10 animals. That vaccine, called B-Vaxx, was developed earlier by the same research team.

"Our study is important for two key reasons," says first author and vaccine developer Pravin T. P. Kaumaya, PhD, a member of the OSUCCC -- James Translational Therapeutics Research Program and professor of medicine at The Ohio State College of Medicine. "First, PD1-Vaxx activates both B- and T-cell functions to promote tumor clearance. Second, the treatment is targeted to block signaling pathways that are crucial for tumor growth and maintenance. By giving this vaccine in combination with an immunotherapy drug, we are essentially super-charging and specifically directing the immune system to target and kill cancer cells.”

Then following the recent in human Phase 1 trial of PD1 Vaxx in Australia and subsequent US locations in 2020-2021, wherein one patient is notably still cancer free after 14 months, PD1 Vaxx is now set to enter a strategic combination with the Roche manufactured Tecentriq. By way of background the PD-L1 inhibitor Tecentriq represents another key growth engine for Roche, with 2020 sales at CHF 2.74 billion after an increase of 55% at unchanged exchange rates. The drug achieved several milestones last year, including U.S. approvals in newly diagnosed non-small cell lung cancer and for use in combination with Avastin for previously untreated liver cancer. In 2021with sales of 1.9 Billion Tecentriq continued to strengthen the Roche war chest. Whilst on a subgroup analysis of patients with tumors with high PD-L1 expression, Tecentriq had the highest probability of ranking as the best treatment as measured by overall survival, while the Keytruda plus platinum-based chemotherapy combination was best as measured by progression free survival.

What’s on the Horizon

Speaking of Keytruda, that is yet another combination Imugene has in the wings as it looks to combine HER-Vaxx with the KEYTRUDA drug in its forthcoming Phase 2 trial for the combination drug to be known as nextHorizon. The open-label, signal-generating phase two study — in combination with anti-cancer drugs like pembrolizumab or chemotherapy —will take place in patients with metastatic HER2/neu over-expressing gastric or gastroesophageal junction adenocarcinomas who have previously received a monoclonal antibody, known as trastuzumab, and progressed on this treatment.

Further to which Imugene hopes to evaluate HER-Vaxx's performance in combination with the anti-PD-L1 immune checkpoint inhibitor BAVENCIO, co-commercialised by Merck KGaA and Pfizer, and standard chemotherapy. Merck KGaA and Pfizer will supply free BAVENCIO to IMU and could potentially take a greater interest in HER-Vaxx if the trial results demonstrate a clear HER-Vaxx benefit in a HER2+ gastric and gastroesophageal adenocarcinoma disease setting.

Recent share price movement

So why the down draft? Is it all macro? Covid, war and inflation related? Perhaps not. Following a few “Please Explain” letters from regulators in 2021 Imugene’s CEO Chong and Chairman Hopper have clearly taken their foot off the pedal when it comes to market communication and announcements. In fact in a recent CEO outing Chong went as far to avoid partnership discussions by referring to her babies (i.e., Imugene’s immunotherapy drugs) as being university students, unable to partner with anyone until such time as they have graduated from Uni with flying colours. Which I guess places Chong at odds with the investment market, a market constantly in search of commercial outcomes, as opposed to Research and Development collaborations. I personally believe Imugene, having lost Axel Hoos as a director, is in need of a director with a strong commercial background. Bob Harari’s Celularity (CELU.Nasdaq), with whom Imugene (IMU) has a strategic alliance, have wisely taken that approach, in bringing John Sculley Former CEO of Apple Inc and Former President of Pepsi-Cola to thier board. I am in full agreement that following the science is a noble strategy that ultimately shall bring riches to all IMU LTH’s. However from where I sit there is an inherent need to focus front and centre on commercial outcomes at all times, to ensure the company take full advantage of financial opportunities as and when they present themselves. Whilst Imugene have 11 if not 12 products either in, or heading into the clinic in 2022, Big Pharma collaborations or even a Big Pharma partnership could fast track product development and FDA Approvals, enabling Imugene products to find their way into patients much faster than would be the case if Imugene continues to fly solo. The ability to bring Kaumaya’s aforementioned PD1-PDL1 combination, in addition to his other B cell peptides and peptide combinations into the clinic now, rather than later, is of the essence in my opinion. The competition in the immunotherapy field of cancer research is hotting up now as US regulators and patients alike are screaming out for cheaper cancer drugs with reduced side effects.

Either way Imugenes jewel in the crown may well not be found on the B cell side of their equation. The oncolytic virus brainchild of Yuman Fong, CF33, in combination with Saul Priceman’s CD19 - Oncarlytics platform, stands to put a rocket up the solid tumour market when combined with Celularity and Eureka’s products later this year. For as you are aware the solid tumour market is the holy grail of cancer therapy as it were. Noone as yet has come close to penetrating that space. And now that Imuegene is in active communication with the likes of Merck, Roche, Pfizer and even Celularity themselves, there are sure to be many suitors waiting at the gate to embrace Imugene as she makes her way to the hilltop. I only hope she takes time out from following the science to value the keys to the gate.

DYO Research