STEP ONE -Imugene licenses powerful oncolytic viruses shown to...

STEP ONE -Imugene licenses powerful oncolytic viruses shown to eradicate all cancer lines against the NC1 60 (This is a list of the 60 human cancer cell lines used in the screen and maintained at NCI-Frederick).

STEP TWO - They administer the viruses in both IT and IV format to late stage cancer patients in the USA and Australia. The viruses are proven to be safe and signs of efficacy are visualised at exceptionally low doses.

STEP THREE - Imugene works alongside these clinical in human trials to ensure the viruses are accessible off the shelf to potentially hundreds of pharmaceutical, CAR T and allogenic therapy providers through their licensed platform known as Oncarlytics.

This thread was designed to discuss a prospective commercial deal with respect to Imugene’s CF33, Vaxinia and Oncarlytics platform(s). Whilst Imugene’s CF33 and Vaxinia are now in human patients, Oncarlytics is not yet in humans. Though recent results in human xenograft models point to outstanding success in reducing solid tumour presence and size within cancer patients across a multitude of cancer indications. In fact “significant tumour killing” was the result of collaborations with some of Big Pharma’s leading CAR T and allogenic therapy products in 2022. The management at Imugene has stated their Oncarlytics platform is now seeking FDA approval for a clinical trial soon to be announced.

In the beginning of 2021 Imugene made the decision to license the platform known as Oncarlytics from the City of Hope Cancer Research Facility in California.The science focuses on being able to target difficult to treat solid tumours in cancer patients. Pre Clinical studies with a number of collaborators has strengthened the view of the City of Hope research scientists, together with the team at IMU, that the science is capable of significant tumour killing in patients. Whilst at the core of the science is the presence of Imugene’s oncolytic virus CF33, the mark, target, hunt and kill approach of Imugene’s CF33 CD19 science is bolstered by the presence of CAR T cells. These re engineered human cells work in concert with Imugene’s science to enhance the patients immune system, once their solid tumours have been destroyed by the CF33 virus. By infusing CD19 as a biomarker into Imugene’s Oncarlytics mix, CAR T cells effectively have a bulls eye or target to identify cancerous solid tumour cells. This is important for up until now CAR T cell therapy has been most effective in the treatment of blood cancers, as opposed to solid tumours in patients. Keep in mind whilst most B cells express CD19, not all cancerous cells do. As noted by frontiersin.org “the first major difference between solid tumors and haematological tumors is that it is more difficult to find an ideal target antigen. Unlike cancers such as ALL or CLL in which the tumor cells universally express the B-cell marker CD19, solid tumors rarely express one tumor specific antigen.”

Both videos courtesy of Imugene.com sourced from the link https://www.imugene.com/oncarlytics-cf33-cd19

Let’s Review ALL Imugene ANNOUNCEMENTS herein as can found on the IMUGENE.COM Website

IMUGENE LICENSES CD19 ONCOLYTIC VIRUS FROM CITY OF HOPE TO TURN CAR T THERAPY AGAINST SOLID TUMOURS - Sydney, Australia, 18 May 2021

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Imugene enhances portfolio with novel CD19 expressing oncolytic virus from City of Hope, a Comprehensive Cancer Center in Los Angeles, California, to be developed in combination

with CD19 CAR T cell therapy Worldwide exclusive licence to combine the oncolytic virus and cell therapy technology

City of Hope scientists led by Saul Priceman, Ph.D., have combined two potent immunotherapies. Imugene’s CD19 oncolytic virus and CD19 CAR T cell therapy — with the goal of targeting and eradicating solid tumours that are otherwise difficult to treat with CAR T cell therapy alone.

“Our research demonstrates that oncolytic viruses are a powerful and promising approach that can be combined strategically with CAR T cell therapy to effectively target solid tumours in patients,”said Priceman, assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation.” This therapeutic platform addresses two major challenges that make solid tumours so difficult to treat with immunotherapy. There are limited solid tumour targets that T cells can be redirected against with CARs. Solid tumours are surrounded by a brick wall -- a so-called immunosuppressive tumour microenvironment. When a CAR T cell attempts to enter the tumour, survive, and kill cancer cells, it can’t effectively because of this barrier.”

Imugene’s MD & CEO, Ms Leslie Chong said “This platform opens up the entire field of use to cellular therapy for the CF33 OV. Supercharging CF33 with CD19 is a revolutionary new paradigm in combination therapy with any CD19 binding therapies to include bi-specifics, antibody drug conjugates and CAR T, cell therapy for solid tumours. The CAR T cell field currently only treats ~10% of all cancers such as blood or liquid tumours, whereas this technology has the potential to open up the solid tumour market.”

City of Hope scientists genetically engineered an oncolytic virus to enter tumour cells and force the expression of CD19 on the cell surface. The scientists were then able to use CD19 directed CAR T cells to recognise and attack these solid tumours. The preclinical research was published recently and featured on the front cover of the prestigious journal Science Translational Medicine

SEE “summarised” Announcements from Imugene pertaining to Oncarlytics collaborations

Imugene Oncarlytics and Arovella Therapeutics 26 September 2022

NEW PRECLINICAL TRIAL OF AROVELLA’S iNKT CELL THERAPY AND IMUGENE’S onCARlytics (CF33-CD19) PLATFORM TO EXPLORE POTENTIAL IN SOLID TUMOURS

HIGHLIGHTS:

• Arovella's CAR19-iNKT cell therapy will be combined with Imugene's onCARlytics (CF33- CD19) platform to target solid cancers in a pre-clinical trial.

• This trial will explore the potential of expanding the use of ALA-101 in solid tumours, which pose significant unmet need and account for more than 90% of all diagnosed cancers.

• onCARlytics is a CD19-expressing oncolytic virus that enters tumour cells and forces them to express the CD19 protein on the cell surface, presenting a target for CD19 targeting therapies.

Imugene Oncarlytics and Celularity Announcement 8-12 November 2022

Dr Anthony Park from Dr Saul Priceman’s lab at City of Hope presented the poster, “CF33-CD19t oncolytic virus (onCARlytics) in combination with off-the-shelf allogeneic CYCART-19 T-cells targeting de novo CD19t expressing tumors.”

• CYCART-19 treatment 7 days post onCARlytics infection showed significant tumor regression

compared to onCARlytics or T cells alone in a mouse xenograft model of triple-negative breast cancer.

Imugene Oncarlytics and Estrella Biopharma 8-12 November 2022

Dr Anthony Park from Dr Saul Priceman’s lab at City of Hope presented the poster titled, “CF33-CD19t oncolytic virus (onCARlytics) targets hepatocellular carcinoma (HCC) and in combination with CD19- Redirected ARTEMIS® T cells results in significant tumor killing.”

Imugene Oncarlytics and Amgen’s Blinatumomab 8-12 November 2022 USA

Dr. Anthony Park, from Dr. Saul Priceman’s Lab at City of Hope, presented “Combination immunotherapy using a novel chimeric oncolytic virus to redirect CD19 bispecific T cell engagers to target solid tumors”.

Further in the announcement Imugene CEO/MD Leslie Chong said “Blinatumomab, sold under the brand name Blincyto, is a bispecific T cell engager antibody that targets CD19 and is used to treat a particularly acute form of leukemia. Now combining this with our novel CD19-expressing onCARlytics, we are pleased to see an ability to deliver an outstanding impact including tumor killing and higher tumor regression, which will ideally lead to improved outcomes for cancer sufferers. The results certainly support further development of the combination and program.”

Imugene Oncarlytics and Arovella Therapeutics November 7, 2022

Arovella has partnered with Imugene (ASX:IMU) to combine ALA-101 with Imugene’s onCARlytics platform, which opens up the possibility of using ALA-101 to tackle solid tumours.

Arovella’s ALA-101 has been shown in pre-clinical studies to outperform conventional T cells against cancers that express CD19 and CD1d. A key feature of iNKT cells is that they can be used off the shelf and collected from a healthy donor, re-engineered to target cancer cells and given to patients when required.

Imugene Oncarlytics Eureka Therapeutics and 3 May 2023

The abstract presented at ASGCT noted that the combination of onCARlytics and Artemis® CD19 T cells demonstrated impressive in vivo anti-tumour responses in a human xenograft HepG2 model. It also stated that the combination strategy can be applied to otherwise target-less tumours such as HCC, and this shows the potential this could be applicable to a wide array of solid cancers as an effective immunotherapy approach.

Leading CAR T Providers

Leading Car T providers can clearly benefit from collaborations with Imugene’s City Of Hope licensed platforms. As CF33 the oncolytic virus (OV) plays an integral role in the platforms effectiveness to treat solid tumours all eyes are now clearly on Imugene’s current in human OV trials with Check Vacc and Vaxinia. If as inventor Professor Yuman Fong has eluded to the trials are successful in reducing tumour size within patients, the Oncarlytics platform shall increase in value immeasurably. According to Professor Fong the results of the said OV trials are now being independently verified with biopsies from existing patients being assessed for both size, composition and so forth. Any signs of necrosis and tumour regression at relatively low doses is set to propel IMU into another trading zone.

It is worth noting that Imugene has been successful in receiving FDA Approval for their existing B cell and OV platform trials, hence FDA Approval for their Oncarlytics arm trial would appear a certainty, given the wealth of pre clinical data now on hand (see above). What is more of a leading question for shareholders is for which Oncolytic Virus treatment shall they be seeking Full FDA Approval for, under the current FDA Fast Track Approval designation for “breakthrough therapy”? And if so when? One would have to surmise it would be for the powerful parental viral strain of CF33, Vaxinia, given the breadth of the current clinical trial (i.e, up to 100 patients) and the broad based nature of the Vaxinia MAST Trial into a range of solid tumours. With this in mind this trial is sure to be be the one most closely watched by Big Pharma, who are said to be excited by Imugene’s OV therapies. Big Pharma do not like to take risk, as technologies have failed in the past, but now more than ever, with theImugene OV’s in humans, and those OV’s being said to exhibit “unequivocal signs of cancer killing in humans”, they would surely be poised to make some commercial decisions. Imugene need a partner to take these oncolytic viruses to market. With a strong safety profile and positive signals of efficacy, as eluded to in previous IMU ASX Announcements, they are destined to reach the market. The question now becomes who is going to take them there? Imugene have the technology waiting to meet the huge unmet need, that being to treat solid tumours in cancer patients. The technology is patented. They have a manufacturer in ABL positioned to produce the products. They have the ability to harness their offering by selling it “off the shelf” through a myriad of CAR T and allogenic therapy providers. They have world leading scientists in place to ensure the technology is delivered safely to the increasing number of individuals diagnosed with solid tumours each year. This should surely provide Big Pharma with the comfort of knowing that ongoing approval safety milestones can be met. All they need now is the marketing force visa vie Big Pharma to take them there.

In the coming weeks investors shall no doubt have an update on the current IT and IV Vaxinia combination trial with Merck’s Keytruda. This could be accompanied by data or information already amassed by Professor Fong, on existing patients within the existing OV trials. Day by day as more patients are dosed with Imugene’s oncolytic viruses in hospitals both here and in the US, the company moves one step closer toward achieving their mission, to develop transformative cancer medicines to improve patients' lives and to establish value and trust with their stakeholders. Don’t be blinded by the background noise, be blinded by the science set to be announced in the coming weeks and months. In my opinion Professor Fong’s lifes work is about to take centre stage, and we are all set to benefit. Sit back and relax, whilst opening your mind to the immense opportunities awaiting us.

DYOR Seek investment advice as and when required Opinions Only