Imugene Ltd (ASX:IMU, OTC:IUGNF) earlier this week reported a second complete response in the concurrent Bruton Tyrosine Kinase inhibitor, or BTKi, cohort of its ongoing Phase 1b azer-cel trial, adding momentum to an early clinical signal in patients with limited remaining treatment options.
The latest response was recorded in the first mantle cell lymphoma, or MCL, patient treated in the azer-cel Phase 1b study. The patient had previously received and failed BTKi therapy before achieving a complete response at the Day 28 assessment.
MD and CEO Leslie Chong told Proactive the result was especially meaningful because MCL tended to be an aggressive disease. She said BTKi therapies could work very well for patients over extended periods, but that patients who progressed or stopped responding could face a steep decline.
Chong said she had initially expected tumour shrinkage to become clear later, potentially at Day 60. Instead, she said clinicians confirmed a complete response at Day 28. Chong described the response as involving “no tumour markers” and “complete shrinkage of tumours”, calling it “incredible for this aggressive disease”.
The milestone follows Imugene Ltd’s first complete response in the concurrent BTKi cohort, highlighting a second early response in a patient group that has relapsed on or is refractory to BTKi therapy. A potential catalyst for the company is further enrolment into the cohort, with Chong saying the result could encourage additional participation in the study.
Another focus for investors is the potential for business development. Chong said BTKi therapies represented a major drug class and that azer-cel was designed to help address why those therapies stopped working in certain patients. She said the aim was to allow patients to continue using an existing therapy, with azer-cel helping make that treatment effective again.
Chong said business development activity had increased “quite a lot” and that Imugene Ltd was in conversations with pharmaceutical companies, with some discussions more advanced than others.
Looking ahead, Chong said Imugene Ltd was concurrently dosing and combining azer-cel with an existing approved drug, which could potentially support a shorter path toward a registration strategy. However, she said the immediate priority was to continue pharmaceutical company discussions, with collaboration and partnering described as the “organic next stage” of development.
Interview highlights
- Imugene reported a second complete response in the concurrent BTKi cohort of its ongoing Phase 1b azer-cel trial.
- The latest response was recorded in the first mantle cell lymphoma, or MCL, patient treated in the azer-cel Phase 1b study.
- The patient had previously received and failed BTKi therapy before achieving a complete response at the Day 28 assessment.
- The result follows closely after Imugene reported its first complete response in the concurrent BTKi cohort.
- Leslie Chong said MCL can be an aggressive disease and that patients can decline steeply after progressing on BTKi therapy.
- Chong said azer-cel is designed to help address why BTKi therapy stops working and to help make the treatment effective again.
- Chong described azer-cel as a one-time dose.
- She said the second response could encourage further enrolment into the cohort.
- Chong said business development activity and conversations with pharmaceutical companies had increased, with some discussions more advanced than others.
- She said collaboration and partnering represented the organic next stage of development.
Proactive: Welcome back to Proactive Investors. Ladies and gentlemen, I’m your host, Kerry Stevenson. Leslie Chong, MD and CEO of Imugene Ltd, ASX code IMU, is with us. Just a day after reporting the first complete response in the concurrent Bruton Tyrosine Kinase inhibitor, or BTKi, cohort of the ongoing Phase 1b azer-cel trial, Imugene Ltd has reported a second complete response. Leslie, welcome back. Lots of news is coming out of Imugene Ltd at the moment, and the market seems to be getting pretty excited as well. Let’s talk about it.
Leslie Chong: I love the science, and I love talking about it. I think it is thrilling for these patients who have progressed off other lines of therapy, especially these Bruton Tyrosine Kinase inhibitors. These BTK inhibitors are a huge drug market. It is $12 billion a year. It is one of those drug classes that is a little short of a miracle for a lot of these blood cancer patients, especially in the diseases that we are studying.
When patients fall off a BTKi, it is catastrophic. The reason I am over the moon thrilled about the mantle cell lymphoma result is that mantle cell lymphoma tends to be a really aggressive disease. When a BTKi works, it works incredibly well. Patients can respond for an extended amount of time, but when they progress or fall off those products, it is a steep decline. It is an aggressive disease.
To be honest, I thought it would take at least Day 60 scans to show tumour shrinkage. I knew azer-cel would do the work, and I knew that it would open up and desensitise the BTKi to work again. At Day 28, for the oncologist, the hematology oncologist and the radiologist to confirm that this is a complete response, meaning no tumour markers and complete shrinkage of tumours, is incredible for this aggressive disease.
Also, our follicular lymphoma patient also got a complete response at Day 28. Can you imagine these patients being able to go home and tell family and friends: “Look, I had cancer, and at Day 28 my doctor tells me I don’t have cancer. The drug that I was originally on is starting to work again.” azer-cel has done it again. We are improving patients’ lives, and that is exactly what we are here to do.
Proactive: That is what I love about what you are doing, because you care so much about getting patients’ lives back into a full recovery. Leslie, this is patient number two with a full response. What is next? Why should people start to really sit up and take notice?
Leslie Chong: Beyond patients, I think this is also going to encourage more enrolment into this particular cohort. Bruton Tyrosine Kinase inhibitors, the BTK inhibitors, are a huge drug class. Roughly, the top ten biggest pharmaceutical companies in the world own those drugs and help in those cells.
azer-cel basically desensitises or fixes why the BTKi does not work anymore in these patients. azer-cel is a one-time dose. It is one time and done, and it fixes the issue on a genetic level. It makes the BTK inhibitors work again.
For these pharmaceutical companies that own them, I am very happy that patients and the pharmaceutical companies can keep the BTK inhibitors, the drugs that patients are used to taking, and continue on them, with azer-cel providing another way of making existing drugs work.
This is great for patients and great for pharmaceutical companies. I dare say the activity has increased quite a lot. The business development activity and our conversations with pharmaceutical companies have increased, and some are in more advanced stages than others.
I am happy that we can make an existing product work even better, perhaps even the second time around. azer-cel is in a place where it can help so many patients continue to have the quality of life that they have been enjoying with previous lines of therapy.
Proactive: Is anyone else out there doing something similar, or is this absolutely an Imugene Ltd product that nobody else can emulate?
Leslie Chong: That is a perfect question. There were some studies that were run, but not to get it approved. We took that scientific hypothesis and actually placed it in a clinical trial with a very active azer-cel and a very active BTKi. We are combining two incredibly active drugs. This is an innovative approach to how we can make two products work in one.
Proactive: Final question for you, Leslie. This is the second patient with a full response. How long will it take before this becomes available for patients around the world who want to use azer-cel along with this drug?
Leslie Chong: We are concurrently dosing and combining the two drugs together with an existing, already approved drug. It could be less time for a registration strategy. But for right now, Kerry, I think the most important thing for me is to continue that conversation with pharmaceutical companies so that we can do a collaboration and partnering, because I think that is the organic next stage of our development.
Proactive: Leslie, you are going along in leaps and bounds. Congratulations. I know how excited you are, but I also know how busy you are at the moment, so I really appreciate your time here on Proactive today. Keep up the fantastic work. Ladies and gentlemen, this is groundbreaking work and it is changing people’s lives. Thanks so much, Leslie.
Leslie Chong: Thank you so much.