Imugene Ltd (ASX:IMU, OTC:IUGNF, FRA:ILA) earlier this week reported the first complete response in the concurrent Bruton Tyrosine Kinase inhibitor, or BTKi, cohort of its ongoing Phase 1b azer-cel trial, marking an early clinical signal in a patient population with limited remaining treatment options.
Managing director and CEO Leslie Chong told Proactive the first patient in the cohort, who had follicular lymphoma and had previously failed BTKi therapy, achieved a complete response at the Day 28 assessment. Chong said the result was meaningful because patients who had failed several lines of therapy often faced a significant impact on both themselves and their families.
Chong said a complete response meant the patient’s cancer was “completely gone”, adding that patients who relapsed on or became refractory to BTK inhibitors did not have many alternatives. She said BTK inhibitors were widely used in blood cancers and were held by major pharmaceutical companies, but resistance over time could leave patients with few options.
The potential catalyst for Imugene is whether azer-cel can restore or enhance the activity of BTKi therapy when used concurrently. Chong said the company was seeking not only to help patients regain a response but potentially allow them to continue on a BTKi therapy that was already familiar to them.
She said azer-cel could stop cancer from escaping through alternative pathways, using the analogy of limiting or blocking traffic across a bridge. Chong said this may allow BTKi therapy to continue working in a setting where the patient had previously failed treatment.
Commercially, Chong pointed to BTKi therapy as a market worth about US$12 billion, suggesting that a successful combination approach could have relevance beyond the initial trial population. She also said Imugene was in discussions and that the company’s business development activity had “greatly increased” because of the strategy.
Another potential catalyst is the allogeneic, off-the-shelf nature of azer-cel. Chong said traditional autologous CAR-T therapies could require patients to wait four to six weeks while their own T cells were re-engineered. By contrast, she said azer-cel was “frozen, shipped and ready when the patients are”.
Chong said this availability could be important for patients away from major treatment centres, describing on-demand and off-the-shelf access as part of the next generation of CAR-T therapies.
Looking ahead, Chong said Imugene would continue enrolment in the concurrent BTKi combination cohort and provide more mature data to shareholders and the wider audience as the dataset develops.
Interview highlights
- Imugene reported the first complete response in the concurrent BTKi cohort of its ongoing Phase 1b azer-cel trial.
- The first patient in the cohort had follicular lymphoma, had previously failed BTKi therapy, and achieved a complete response at the Day 28 assessment.
- Leslie Chong said a complete response meant the patient’s cancer was “completely gone”.
- Chong said patients who relapse on or become refractory to BTK inhibitors often have limited remaining treatment options.
- Imugene is evaluating whether azer-cel can be used concurrently with BTKi therapy to restore or enhance treatment activity.
- Chong said azer-cel may help stop cancer from escaping through alternative pathways, potentially allowing BTKi therapy to work again.
- BTKi therapy was described as a US$12 billion market, highlighting the commercial relevance of the combination approach.
- Chong said Imugene’s business development activity had “greatly increased” as a result of the concurrent BTKi strategy.
- The interview also highlighted azer-cel’s off-the-shelf allogeneic CAR-T profile, which could provide an availability advantage over autologous CAR-T therapies.
- Chong said Imugene would continue enrolment and provide more mature data to shareholders and the wider audience as the dataset develops.
Proactive: Imugene has reported the first complete response in the concurrent BTKi cohort of its Phase 1b trial. Here with me to discuss this milestone is Managing Director and CEO Leslie Chong. Leslie, it’s good to see you.
Leslie Chong: Hi, Jonathan. How are you?
Proactive: I’m very good. I hope you’re well too. This is a significant milestone. Talk me through the result and why it matters for patients who had already failed BTKi therapy.
Leslie Chong: For any cancer patients who have failed several different lines of therapy, you could imagine the devastating impact that it has not only on themselves, but on family and friends.
I am delighted that these patients have come on to azer-cel. These are not only BTKi failures, but patients who have failed other treatments, and they have responded in such a major way where the cancer is completely gone.
A complete response, by definition, means no tumour markers. In this case, with a Bruton Tyrosine Kinase inhibitor, these small molecules are mainstays in blood cancer. All the big pharmaceutical companies, even the biggest one in the world, own these. When patients fall off these BTK inhibitors, they do not have a lot of options.
What we are trying to do is not only have patients get the same level of response as they did when they first started their BTKi, we are actually fixing them genetically so they can take another BTK inhibitor or the same one to continue that level of response. They can enjoy a response, a complete response or a partial response for a number of years before they fail.
We then fix it with azer-cel in that concurrent setting and allow the BTKi to work. These patients get to continue on the same medicine they have been on before, and they understand the side effects. Azer-cel is a major allogeneic CAR-T that can help them regain their life again.
I am delighted that these concurrent BTKi patients are able to continue, and we are seeing the cancer doctors on our study become so excited. They are literally lining up patients to get on the study.
Proactive: You are evaluating azer-cel alongside the BTKi, and you have just discussed the rationale for combining the two. How could this approach restore or enhance treatment activity?
Leslie Chong: If you think about it in the simplest sense, let’s think about a major bridge, say Sydney Harbour Bridge, and that is the only way you can get out of Sydney. When the cars find a different route, the cancer escapes.
What azer-cel does is stop other cancer from escaping, thus allowing that BTKi to work. So that bridge again has limited, or completely stopped, the traffic from going forward to create more cancer.
This is the beauty of BTKi, because it really stops cancer from growing anymore or having those cellular signals to leave. It is a US$12 billion market. It is a huge market because when it works, it works well. When it fails, this is where we can combine with several different pharmaceutical BTK inhibitors.
I do not mind telling you that we are in discussions, and it looks to be a route where our business development activity has greatly increased because of it.
Proactive: Taking it back to that first patient, the patient had follicular lymphoma and achieved a complete response at the Day 28 assessment mark. What does that tell you about azer-cel’s potential in difficult-to-treat B-cell malignancies?
Leslie Chong: What that tells me, and what the evidence has shown not only in our cohort one and our DLBCL, the diffuse large B-cell lymphoma, but also in our naïve cohort where we saw follicular lymphoma, CLL, marginal zone and those diseases, is that at Day 28, Day 60 and Day 90, patients started having partial responses to complete responses.
What it tells me is that azer-cel is stopping the disease and allowing the immune system to come to the rescue and really fight off the disease.
Proactive: One of the other significant aspects of this is that azer-cel is positioned as an off-the-shelf allogeneic therapy. How important is that speed-to-treatment advantage compared with traditional autologous CAR-T products?
Leslie Chong: It speaks to availability. Autologous products have very limited access. Big institutions can dose with autologous CAR-T, where patients can wait four to six weeks for their own T cells to be re-engineered.
However, we are frozen, shipped and ready when the patients are. They can be very far from major centres or major cities and still be able to get this life-treating, life-giving formula.
This is the importance and the next generation of CAR-Ts to come — the ability or means of being on demand and off the shelf.
Proactive: Exciting things to come and it looks like it is all going very well at the moment. What can we expect next from Imugene?
Leslie Chong: I am really excited about the concurrent combination. Our haematology oncologists seem quite excited to offer this to patients who do not have a lot of options.
I am excited to continue enrolment. I am excited to provide more mature data to our shareholders and to the audience.
I am pleased, actually pretty thrilled, that this patient gets to have another line of therapy where the cancer is completely gone and the patient has a complete response.
I love it when these things happen to every single patient. We have seen it 81% of the time, or 83% of the time in naïve patients, and now I hope to get a response every time these patients come on.
Proactive: Given the problem of cancer around the world and the numbers, this is really exciting stuff.
Leslie Chong: I am very excited.
Proactive: Leslie, thanks for your time. It has been great to speak with you again.
Leslie Chong: Thank you so much, Jonathan.