Azer cel and all those negative commentsI guess its important to...

Azer cel and all those negative comments

I guess its important to do extensive research when considering an investment in a biotech stock, for reading snippets of posts from people on HC can sometimes result in misinformation. As an example I note someone on these threads suggested recently they suspect the only reason Allogeneic therapy isn't mentioned in the current FDA restrictions placed on autologous CAR T cell therapies is because they (i.e., allogeneic therapies) aren’t approved by the FDA …

This to me was a strange if not ill informed comment. For those in the know are well aware the issues facing autologous Car T’ s are far removed from allogeneic therapies. The latter, such as Imugene’s Azer Cel, are clearly showing significant advancements in the treatment of patients relapsing from autologous Car T therapy. It would appear that some on these threads are as usual endeavouring to cast aspersions on the Imugene science for their own ends, whatever they may be, rather than focusing on the facts at hand.

BACKGROUND

By way of background for those unfamiliar, CAR T cell based therapies are transforming the treatment of haematological malignancies and have the potential to do the same in solid tumors. However, despite showing some evidence of anti-tumor effect, CAR T cell therapies still need to prove their efficacy to become a viable and impactful therapeutic option in the solid tumour arena.

As the aforementioned poster correctly notes all of todays approved CAR-Ts to date are so-called autologous treatments. Autologous Car T’s are based on donations from a patient’s own cells. Whereas allogeneic, or "off-the-shelf," therapies, use engineered cells collected from a third party. This type of therapy is a new and up coming class set to rival autologous Car T therapy when treating blood cancers such as non Hodgkins lymphoma and other lymphomas. As such I tend to disagree with this posters comment that although both forms of treatment have their differences, the mechanism of action is the same. Yes, both autologous and allogeneic therapies are both re-engineering cells in one way shape or form, hence the same mechanism, but more often than not Allogeneic therapies use cells from healthy donors, as opposed to those suffering from cancer. Thats why industry pioneers such as David Chang, formerly Kite now the CEO of Allogene Therapies believe the best is yet to come with Allogeneic Therapies. And the results would support his view and the notion that Allogeneic, as opposed to Autologous therapies are actually, to use the posters phrase, something to keep an eye on.

RESULTS

An article in https://www.nature.com/articles/s41408-023-00822-w notes in recent studies the Complete Response rate of patients receiving allogeneic cells was 80% and that of patients with autologous products was 40%. During the follow-up period, the relapse rate showed more remarkable differences. One patient (25%) with allogeneic CAR-T cells suffered CD7− recurrence. One hundred percent of patients treated with autologous CAR-T cells relapsed whether in BM or in EMD. Patients experienced CD7+ recurrence, but CAR copies were not detectable in vivo. The less persistence of autologous CAR-T cells might contribute to the treatment failure. CAR-T cells could stably survive in 75% of patients with allogeneic cells but only 33% of patients receiving autologous cells at month 2.

Imugene as you are aware has their own (recently acquired) allogeneic therapy in Azer cel. Azer cel has achieved magnificent success to date. The allogeneic therapy has achieved an 83% overall response rate, a 61% complete response rate with 55% durable response greater than or equal to six months in this difficult to treat auto CAR T relapse setting. Whilst there is definitely no assurance Azer Cel or any Allogeneic Therapy can traverse the terrain from blood cancers to solid tumour treatment, either way Imugene’s Azer Cel exhibits significant promise for those having failed on autologous Car T therapies.

EXPERT OPINION

Perhaps unlike some posters on these threads industry pioneers and now leaders such as David Chang see huge differences between allogeneic and autologous Car T therapy.

As Chang noted recently when speaking of allogeneic Car T’s “As with the first CAR T revolution with autologous therapy, this milestone is also a cumulation of years of hard work and perseverance, which could only be accomplished in collaboration with our dedicated team, investigators, clinical trial sites coordinators, regulators and most importantly patients who have been devoted to the pursuit of bringing an allogeneic alternative to people in need.

An on-demand world. This next CAR T revolution has the potential to bring the power of cell therapy to every eligible patient – right when they need it.”

From where I sit autologous Car T’s and allogeneic ones are actually poles apart, due to the fact that unlike autologous Car T’s, allogeneic CAR-T manufacturing involves using peripheral blood mononuclear cells (PBMCs) from a random healthy donor, as opposed to an existing cancer patient.

There is the remote possibility allogeneic therapies may result in the toxicity at worst fatalities placing autologous Car T therapies under the scrutiny of the FDA. But if I may leave you with a parallel thought

Up to 85% of all engines that are rebuilt have been in some sort of accident.. Rebuilt engines typically cost less but the job might not use high-quality replacement parts..

DYOR Opinions only

Nb. David D. Chang is a co-founder and Chairman of the Board of Directors of IconOVir Bio. He is a co-founder and currently serves as the President and Chief Executive Officer of Allogene Therapeutics, Inc. (ALLO), a clinical stage biotechnology company focused on pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) therapies for cancer. David previously served as Executive Vice President, Research & Development, and Chief Medical Officer of Kite Pharma, Inc., prior to its acquisition by Gilead Sciences in October 2017. He has an industry-leading track record of innovation in the field of oncology drug development, including the development for Yescarta™ (axicabtagene ciloleucel), the first CAR T therapy approved for non-Hodgkin lymphoma. From 2002 to 2014, he held senior leadership roles at Amgen, including Vice President of Global Development and Head of Hematology-Oncology. During this time, David spearheaded personalized therapy strategies that underlie the success of Vectibix® (panitumumab). He also provided therapeutic area leadership to pivotal programs for Blincyto® (blinatumomab) a bispecific T cell engager antibody in acute lymphocytic leukemia and for IMLYGIC™ (talimogene laherparepvec), a first-of-its-kind oncolytic immunotherapy, in melanoma.