Imugene - where to now?
Those searching for divine inspiration as the IMU SP plumbs new lows need look no further than Imugene’s Oncarlytics treatment arm, and the promise this therapy brings to the field of oncology. As noted by Saul Priceman Ph.D,. When speaking of Imugene’s Oncarlytics platform in https://www.eurekalert.org/news-releases/881797 "Our research demonstrates that oncolytic viruses are a powerful and promising approach that can be combined strategically with CAR T cell therapy to more effectively target solid tumors" said Saul Priceman, Ph.D., the study's senior author and an assistant professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation.
The same article, as noted in a recent post by @Ibraz4me reads ”In addition, this therapeutic platform addresses two major challenges that make solid tumors so difficult to treat with immunotherapy. There are limited, established solid tumor targets that T cells can be redirected against with CARs," Priceman added. "Furthermore, solid tumors are surrounded by a brick wall -- a so-called immunosuppressive tumor microenvironment. When a CAR T cell attempts to enter the tumor, survive, and kill cancer cells, it can't effectively because of this barrier.”
In short such a novel approach to marking solid tumours, malignancies that do not express CD19, opens the door for them to be targeted by CAR T therapies, which have traditionally only been successful in treating blood cancers, such as lymphoma’s. If investors were looking for confirmation of this analysis they need look no further than the same article, wherein the City of Hope’s Professor Yuman Fong and Anthony Park express their considered opinions. "We designed this oncolytic virus to do what it does so well," Fong said. "It entered the cancer cell and used the cell's own machinery to replicate itself, and engineer the cancer cells to express a truncated form of the well-known CAR T cell target, CD19.”
"When we infected tumor cells with the virus, we observed the first signal that this may work. CD19t was being expressed by tumor cells much sooner than the virus was able to kill them, giving us a window of opportunity to be targeted by CD19-CAR T cells," said Anthony Park, Ph.D., the study’s lead author and a postdoctoral fellow in Priceman's lab. "The combination of the two had a powerful, synergistic effect.”
But its not simply about marking, infecting, exploding and killing solid tumours when it comes to the City of Hope designed Oncarlytics, its about ensuring they don’t come back. "The immune system built a memory response to the tumor," Park added. "Once it eradicated tumors, following the initial combination treatment, the mice were shielded against tumor recurrences.”
And that’s another issue facing Car T’s. Aside from being ineffective in treating solid tumours, they are prone to relapse in patients. As noted in the article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913679/ patients who relapsed following CAR-T therapy fall into two main groups: antigen-positive relapse and antigen-negative relapse . An antigen-positive relapse occurs when the response to CAR-T therapy is not sufficient, with a minimal effect for CAR-T cells and only transient B-cell aplasia. With flow cytometry, CD19 can be detected on the surface of the cells . This type of relapse is associated with poor CAR-T cell persistence and proliferation in the human body. An antigen-negative relapse is caused by antigen escape, which may be caused by a gene mutation. For instance, the CD19-negative relapses represent up to 20% of the relapsed CAR-T cell-treated patients. With a CD19-negative relapse, CD19 is not detected on the surface of the cells.
But alas, Imugene even has a solution for those who relapse after Car T therapy. Its called Azer Cel. Azer Cel is an allogeneic therapy they licensed last year from Precision Biosciences. Around the time the licensing deal was struck, Alan List , M.D., Chief Medical Officer at Precision BioSciences noted “Azer-cel continues to demonstrate promising results in DLBCL patients who relapsed following CAR T, and we are encouraged by the high overall response rates with molecular remissions in this patient setting,” he said.
Oncarlytics and the value proposition
A few years ago Imugene released pre clinical data for their Oncarlytics arm following a number of strategic collaborations with Celularity and Eureka Therapeutics, in addition to a combination between Oncarlytics and Amgens Blincyto. Suffice to say the pre clinical studies were viewed by some as heralding a “new dawn” in the treatment of solid tumours, with “significant tumour killing” being observed in the process. Such a therapeutic strategy presents Imugene with a distinct value proposition for the six CAR T therapies currently approved by the FDA, not to mention those seeking approval, many of whom are feeling the FDA’s heat due to recent adverse outcomes for patients at the hands of autologous Car T providers. In addition to these players it creates an opportunity for Imugene themselves to combine their Oncarlytics therapy with their very own Azer Cel therapy, to treat patients who have relapsed from Car T therapy in the past.
So what does this mean for Imugene investors? And is this value proposition something Big Pharma would consider? In short most definitely would be the answer to the latter question, IMO. As Saul Priceman suggested to me in person back in late 2022 on a visit to Sydney with the esteemed Professor Yuman Fong, “All eyes shall be on Oncarlytics when it enters the clinic,” he said. To me I read his assertions as I think many players shall be looking to see how they can capitalise on this opportunity.
So where to now, for Imugene in 2024/5? Well, clearly Oncarlytics following a rapid fire FDA Ind, is in the clinic now. A handful of patients have been dosed, with many more to be administered in the near term. Is Imugene planning on licensing the drug to CAR T owners to alleviate their medium term cash flow requirements? Are they planning on out licensing the treatment arm altogether, with upfront capital followed by royalty payments down the track? Are they planning on selling off a large tract of shares to an interested third party, in return for monies to further develop this innovative technology? Or are they simply going to await the trial results and align with a Big Pharma to manufacture and market this potentially game changing therapy?
Your guess is as good as mine. But from where I sit if they choose the last solution to this interesting equation, I’d be adding a few more zeros to the dollars outlined in their most recent Corporate Presentation. Affording outsiders a look see and the chance to get their hands on the keys to the holy grail that is solid tumour treatment should come at a hefty cost I would have thought. All going to plan there are plenty of patients standing to benefit from this diverse approach to oncology. For last time I checked the figure of solid tumour diagnosis, being close 90% of all individuals with cancer, represents a large proportion of the those requiring treatment. Even if Imugene’s Vaxinia, Oncarlytics and Azer cel prove successful in treating one or two of the indications present in this collective, its going to represent significant dollars and cents for the ultimate owners of this unique approach to medicine.
DYOR
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