Allogenic therapies - An off the shelf revolution for allDavid...

Allogenic therapies - An off the shelf revolution for all

David Chang speaks of four waves in cancer treatment history, the first producing chemotherapy to treat cancer, the second being monoclonal antibodies, the third being the employment of targeted therapies and proteins to prohibit cell growth, the fourth wave of treatment being to unlock CAR T treatment for all patients, through what are known as allogenic therapies. Previously, as EVP, Research 7 Development and Chief Medical Officer at Kite Therapeutics, David helped pioneer the development of the first CAR T therapy to receive FDA approval for non-Hodgkin lymphoma.

Chang speaks glowingly of that time when he notes

“By the 2016 American Society of Hematology (ASH) Annual Meeting, we presented initial data from the Phase 2 trial which had treated 101 patients, 76% of whom achieved objective response and 47% of whom received complete response.(1) Just a few short months later, we were able to share durability data that was groundbreaking. It was literally life-changing for many patients, and these milestone moments will forever be emblazoned in our collective memory - mine, my fellow Kite colleagues and our study investigators. It created an unbreakable bond and built a broad community whose aspirations rise above competition.”

Now, as the President, Chief Executive Officer and Co-Founder of Allogene, he is working to revolutionise how cancer is treated by developing allogeneic CAR T (AlloCAR T™) therapies, the next-generation of CAR T therapies. When Changs original employer Kite sold to Gilead a few years back in 2018 for close to 12 billion USD, Chang and some colleagues raised hundreds of millions of dollars in a heartbeat and with the support of Pfizer went for an ALLO IPO on the Nasdaq. Before long they were quickly worth 3 billion USD, before taking a breather in 2022, along with many others in the biotech sphere. But alas, of late Chang is on record as saying he aims to have the first allogenic therapy approved by the FDA in the US. Allogene's mission is to create and lead the next revolution in cancer treatment by delivering to patients the first allogeneic CAR T cell (AlloCAR T™) products for blood cancers and solid tumors. In October 2022 Allogene Therapeutics, Inc (Nasdaq: ALLO), announced the initiation of a potentially pivotal Phase 2 clinical trial of ALLO-501A (ALPHA2 trial) in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). This was the Industry’s First Allogeneic CAR T Phase 2 Trial.

The primary difference between allogeneic and autologous therapies are the source of the cells for the therapy. Allogeneic therapies are manufactured in large batches from unrelated donor tissues (such as bone marrow) whereas autologous therapies are manufactured as a single lot from the patient being treated. In other words Autologous CAR T-cell therapy uses a patient's own immune cells while allogeneic, or off-the-shelf, CAR T-cell therapy uses T cells from donor blood or sometimes umbilical cord blood. CAR Ts are an ex vivo form of gene therapy, in which T cells are removed from cancer patients, genetically modified to express cancer-cell seeking receptors, and re-infused into patients. The FDA gave the green light to Novartis's tisagenlecleucel for the treatment of acute lymphoblastic leukaemia (ALL), marking a historic approval for a first-in-modality chimeric antigen receptor (CAR) T cell therapy back in 2017. What made Gilead’s purchase of Kites CAR T in August 2017 even more astounding than the 12 billion USD price tag paid, was the fact that it was not even approved by the FDA at the time of acquisition. It shows what money is floating around in this sector for pre revenue products that have scope in the oncology treatment arena.

Yet David Chang, and one assumes Imugene (IMU ASX) M.D and CEO Leslie Chong, believe allogenic therapies have even more scope than autologous CAR T’s, given their desire to utilise them in not only the treatment of blood cancers, but in the treatment of the much larger solid tumour patient population. Chong was recently behind Imugene’s acquisition of the allogenic therapy Azer Cel, from Precision Biosciences in the USA. A few weeks ago Imugene announced a Phase 1b trial for azer cel, serving as a precursor for a potential Phase 2 registrational study in 2024, pending FDA agreement. The successful outcome of this trial could pave the way for a groundbreaking achievement, potentially making azer-cel the first approved allogeneic CAR T cell therapy for cancer. From all accounts it looks as if Chang and now Chong are in a race to the finish when it comes to allogenic therapy reaching cancer patients in the US.

Chang did race out and sell a terms sheet to Pfizer in 2018, something Imugene’s business representatives have not chosen (or been able) to do. But that said, either way one market is valuing one allogenic therapy treatment at far less than another. Guess which? Oh you guessed it, the good old ASX. David Changs allogenic therapies in the US are valued at around $766 million AUD, whereas Imugene’s total Market capitalisation is currently over 100 million dollars less than that. Effectively if we are to compare apples for apples, Vaxinia, CF33, PD1 Vaxx and Her Vaxx, not to mention Oncarlytics, are valued at nothing by the ASX, if Azer Cel is to be compared with Allo’s allogenic therapies value. It’s not for me to explore in depth the pros and cons of both allogenic therapies candidates running for FDA approval, (as Novartis and Kite had done 6 years earlier with respect to CAR T therapies), suffice to say Chong told Proactiv Investors in early November Azer Cel could be “first in class, best in class”, meanwhile Chang believes his allogenic therapy candidate is one step closer to making a difference for patients, marking another ground breaking milestone for this modality.

Chang notes : 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.

If allogenic therapies are to be responsible for the fourth wave in cancer treatment as Chang predicts, with the development for an off the shelf treatment for all, should they be suffering from blood cancers or solid tumours, the money received for his first CAR T sale, (i.e., that being the 12 billion USD paid for Gilead for Kite), could be something of a side show. If allogenic therapies are the real deal and Azer Cel is acquired for anything close to 12 billion USD prior to FDA Approval, if not after, now many years later, that would equate to about $2.60 per IMU share for an Azer Cel sale. The ASX market may not be so keen to value CF33, Vaxinia, Her Vaxx and PD1 Vaxx at zero, if such a result were to arise. That is if imugene management continue to subject Imugene investors to the ignominy that is the ASX, when it comes to progressive biotech stocks.

DYOR Seek investment advice as and when required Opinions only