Whilst Imugene (IMU: $0.32) has historically been building a business based on multiple novel, immunotherapy platforms, the focus now is very much on its Azer-cel technology, which is yielding some exceptionally good results.
Imugene had a very important meeting with the FDA which sets the company on a path forward to a pivotal study with its Azer-cel technology, and to market for patients. A Phase II study will not be required.
The patients to be involved in the pivotal study will be those with DLBCL receiving third line therapy or those more advanced.
The Type C meeting outcomes were highly positive, reducing the potential complexity in getting this allogenic (off-the-shelf) therapy to market. Phase Ib studies have shown an 82% Overall Response Rate (ORR) in patients with DLBCL (a life threatening form of lymphoma) who had all failed CAR-T therapy, and an 83% ORR in patients who were CAR T naïve.
Imugene CEO Leslie Chong referred to DLBCL patients as a very sick population facing a deadly disease, where patients in its study had failed between three to six lines of previous therapies.
The benefit of this technology is that it does not take up to six weeks to collect and re-engineer the patients' own T-cells, which is required for CAR-T and is a very expensive process. One batch of Azer-cel cells can be used to treat multiple patients.
To bring this therapy to market, the FDA has agreed that only one, placebo controlled, pivotal study may be required. This comes with the potential for early 'accelerated approval' based on ORR and durability of effect. Full approval will take longer and will be based on the measure of Progression-Free Survival, which is also a less onerous measure than for instance, Overall Survival.
In a presentation to investors, Chong compared the 82% ORR to that achieved by CAR-T therapies for FDA approval, which were 74%, 73% and 52% for Yescarta, Breyanzi and Kymriah respectively in DLBCL. "We are seeing response rates of 82%. This is profound," said Chong.
The safety profile has been good, with no GvHD and no Grade 3 or worse Cytokine Release Syndrome cases, which is better than autologous CAR-T therapies, said Chong.
One of the first patients to receive Azer-cel with IL-2 had failed two different chemotherapies, failed CAR-T after seven months and failed prednisone, with Stage IV disease. Following treatment with Azer-cel and IL-2, that patient remains a complete responder after 590 days.
Imugene is preparing for its registrational study for Azer-cel in DLBCL to start next year. "The level of FDA endorsement we received is exceptionally rare in biotechnology," said Brad Glover, Imugene's COO. The manufacturing process was also cited as suitable by the regulator saving some minor refinements to analytic methods.
The next step for Imugene is to prepare its pivotal trial study protocol in line with the FDA directives. The control arm is likely to be the 'investigator choice'. The FDA generally considers six months as the durability window, although Chong stressed that patients entering the study will be receiving third line or later treatment (meaning they have failed at least two previous treatments). The durability window will require further discussion with the FDA.
The overall durability of the therapy will be an important aspect to measure. The size of the study will also need to be determined. Chong cited Cargo Therapeutics in DCBL which measured three month durability for its CAR-T therapy in a Phase II study in 51 patients.
However only achieving an 18% Complete Response rate at three months with significant side effects, that study was discontinued, even after achieving an initial ORR of 77% and a complete response rate of 43%. The patients in Cohort 3 of that study had to had failed at least two lines of therapy.
Imugene's current Complete Response rate sits 41% at 90 days (7/17). (This includes one patient who continues to have a complete response but received other therapies during the study period).
Imugene's Azer-cel therapy appears to be more durable than the Cargo Therapeutics treatment, has a better side effect profile, and has been trialed in patients who have failed more lines of therapy, including CAR-T. It has also reached agreement from with the FDA to proceed directly to a pivotal trial with no Phase II study.
Chong said that moving into the pivotal study, a partnership would be advantageous to the company. The FDA Type C meeting outcome provides significant derisking of the program, with appealing data and a validated manufacturing process. This will help in securing a commercial partner for the program.
Collaboration with JW Therapeutics
Imugene also recently announced a collaboration with JW Therapeutics in China. JW will explore Imugene's oncolytic virus, CF33-CD19, which induces CD19 expression on solid tumours, to be combined with JW's CAR-T therapy, Carteyva, which is approved for blood cancers (binding to CD-19). The collaboration will focus on applying the technologies to solid tumours. It is part of Imugene's revised strategy to focus on Azer-cel and seek external investment/involvement for other programs.
Imugene is capitalized at $101 million, with $32 million in cash at the end of September. It also has $20 million debt in Convertible Notes which have yet to be converted to equity. The minimum current conversion price is $0.65 per share.
Bioshares recommendation: Speculative Buy Class B
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