Telix Pharmaceuticals Limited (TLX) Earnings Call Transcript & Summary

Well, good morning, good evening, everybody, and thank you for joining us at short notice. Just over an hour ago, we launched an announcement on the ASX with an update on the regulatory progress for TLX101-CDx, our brain cancer imaging agent. Although the announcement says what there is to say, we did want to take this opportunity to explain the situation and provide the opportunity to ask questions. We have about 30 minutes scheduled for the call. We'll get through as many as we can during that time. And for those that we can't get to, we will answer your questions separately. With that, I'd like to hand over to Dr. Chris Behrenbruch, our Group CEO and Managing Director.

Good morning, colleagues and shareholders. I'll get straight to the purpose of the call today. So per the disclosure just released, as mentioned by Ky, I'm here to inform you that Telix has received a complete response letter, or CRL, from the U.S. Food and Drug Administration for TLX101-CDx or FET-PET, Telix's glioma imaging drug candidate also branded provisionally as Pixclara. This is obviously a disappointing outcome and not what was expected by the company. As you'll be aware, TLX101-CDx has been granted FDA orphan drug and Fast Track status, reflective of its potential clinical importance to the management of rare brain cancers. FET-PET is also written into the standard of care practice guidelines in most international neuro-oncology guidelines and is widely practiced in many parts of the world. Telix undertook an FDA submission for TLX101-CDx based on the 505(b)(2) pathway that was reflective of the intention to attain approval based on a multitude of data sources, including third-party data, given the extensive clinical experience with the product in thousands of patients. Unfortunately, when we approached the labeling phase of the approval process, this was towards the end of the NDA review. We had difficulty in convincing the FDA that there was quantitative consistency across the different data sets used by Telix in the submission. This is obviously not the viewpoint of the company, but it has ultimately led to the CRL. During the review process, there's been no material CMC or manufacturing site inspection issues raised that would prevent a drug product approval as is often the case for CRL. The rate-limiting aspect of the submission at this time is clinical. No safety issues have been raised by the agency whatsoever. I wish to make it clear, Telix had a well-defined strategy for the clinical package for TLX101-CDx. The various data sets used as part of the submission were presented to the FDA in advance. The entire submission strategy was discussed with the FDA and endorsed as part of a pre-NDA submission at the outset of the process. While the outcome isn't as we expected, we believe that the agency remains highly supportive of TLX101-CDx attaining approval and that submission remediation has a high chance of success. We, of course, remain committed to the success of the product, and I think it's also important to affirm that the company will be keeping the Expanded Access Program, or EAP, running for TLX101-CDx in the U.S. due to the unmet medical need for the product. This is part of the company's continued commitment to serving American patients with brain cancer. Preemptively, I do want to state that we are disappointed with the FDA's decision, and I believe it reflects a change in the culture of the FDA over the last few months. We don't think it's a decision that reflects the scientific merit or the patient risk benefit of the data that was included in the submission, including clinical data sets that were muted with the FDA in advance and that we clearly indicated were going to be used as the basis for approval. At this stage, we don't know exactly what the remediation will need to be. It could be a reanalysis of the current data or it could involve augmenting the package with additional confirmatory data as indicated by the FDA in the CRL. We do have additional confirmatory data available to us. And as part of the post-CRL process, we will be requesting both a hearing to understand the detailed basis of the FDA's decision as well as in parallel, progress further consultation around providing additional data if needed, some of which, as I've already said, is in hand. Generally, we have also been collecting further data, for example, through the EAP that may be useful as we progress the submission further. Finally, although this is a disappointing outcome, we are absolutely in a position to progress this new drug application and are 100% committed to doing so. As soon as we have clear time lines and scope for remediation, we will inform the market accordingly. This is a priority program for us, and it's still our mission to address the unmet need in this patient population and complete this regulatory review process in 2025. I will now take any questions or comments from the floor.

[Operator Instructions] Your first question comes from David Stanton from Jefferies.

Can you hear me okay?

Yes, crystal clear.

Great. So I guess I'm interested whether you think this has implications and sorry to change the topic immediately to something like Zircaix, can you potentially explain the sensitivity and specificity of Pixclara versus Illuccix and give us specific percentages on sensitivity and specificity for that? And if you're able to follow that up with the same question on Zircaix, sensitivities and specificities?

So David, I think your question is a really good one. And I can't straightforwardly answer it quite the way you've postulated, but I'll try and answer your question in a different way. And the reason is, is that the data sets that we used in the 505(b)(2) submission for Pixclara, we haven't fully disclosed the scope of that data. And therefore, we haven't disclosed publicly the sensitivity, specificity range. I'm going to be happy to point you to some publications that sort of range that. But as to what we were specifically claiming in the label, we haven't yet put that out into the public domain, and we probably won't until we are in a position to kind of get further feedback from the FDA. But the big difference between Zircaix and Pixclara, and the 2 should not be conflated or confused with each other, is that we did not rely on a definitive pivotal trial for Pixclara. FET-PET has been widely used globally. It's a standard of care. It's just not available in the United States, and we elected to commercialize Pixclara because it targets the same target as our therapeutic drugs. There was a natural rationale for developing this product. And so we chose to use the 505(b)(2) pathway, which, as I think everybody knows that's listening, allows you to take a more flexible approach to data. And in fact, we've used the 505(b)(2) pathway before with Illuccix. So we have a pretty good understanding of the risks and benefits of that approach. Zircaix is a completely separate beast. And Zircaix was run on the -- Zircaix was filed on the basis of 2 Phase III clinical trials, including a confirmatory clinical trial that was accepted and designed in consultation with the FDA. And the trial far exceeded all of its 14 primary and secondary endpoints. So we're just dealing with a completely different submission process. The clinical submission of Pixclara was a lot more creative, I would say. The Zircaix clinical submission is a very vanilla primary and confirmatory Phase III trial. And so I think that the 2 sort of submission processes shouldn't really be conflated with each other. Does that make sense?

It does. I guess the question that I'm going to get asked in about 10 seconds at the end -- after the end of this call, though is why not disclose the sensitivity and specificity around this -- the Pixclara trial, please?

Well, because the range of data that we've used in a 505(b)(2) submission is commercially sensitive. So you can certainly have a look at the public domain and you can pull out papers and you can see a range of meta-analysis that will give you -- and I'd be more than happy to point you in the direction of that if need be. So again, we're -- the Pixclara NDA submission is not -- hasn't had a speed bump because it doesn't warrant clinical -- doesn't warrant approval based on its clinical data. We've hit a speed bump because in the clinical review process, we've been unable to convince the regulator that we've got quantitative consistency between those data sets. So it's not about the merit, it's not actually about whether the clinical utility of the product is there or not, it's about the company's approach to quantitatively tying the data sets together that we used in the submission, and that's been found inadequate by the agency. Now I'm bound to tell you, again, per the disclosure we've put out and my comments just before, we did discuss the entirety of our submission process and approach with the FDA in advance. Now the FDA, as you know, will not preapprove an application based on a pre-NDA consultation. There will be a number of matters that will be left to review, right? Otherwise, we wouldn't have drug approval processes. But this was the sticking point at the end of the day. So the take-home message should be that there's plenty of established and widely published merit in the clinical utility of the product. But what we haven't managed to do as a company is convince the FDA that the data sets that we chose for submission have quantitative alignment sufficient to meet our label claims. And that's frankly why a lot of the issues have arisen late in the process. It really wasn't until we approached the labeling phase of the submission, which, as you know, is right at the end of the process that we really started to experience some information requests that were challenging. So I'll leave it at that. I think it's a lot of detail, and I think we are providing transparently a lot of detail precisely because we want investors to understand a little bit the uniqueness of the situation. It's a little bit of an unusual outcome in some respects.

Your next question comes from Tara Bancroft from TD Cowen.

This is Nick on for Tara. For me, what additional clinical trials are underway or what additional data do you guys have in hand that could be submitted to the FDA? And if there are additional trials that are underway for the confirmatory aspect of the CRL, how long do you think that could take to potentially read out and support a refiling?

Yes, it's a great question. So I'm not going to provide completely detailed guidance around this topic today because there are a number of things that are in progress within the company that haven't been disclosed publicly yet. What I can tell you, what I'm comfortable telling you is that we have had a pre-IND meeting with the FDA for the brain met study that we have talked about publicly. We haven't had agreement with the FDA that an additional indication could form the basis of a confirmatory trial, but that's one possibility to consider. Of course, that would be a longer-term solution, and that's not something that's immediately appealing. We have been running over the last 12 months, I'm going to say 12 months roughly. I don't know the exact start and end date. But in the past year, we've been running an expanded access program with Pixclara that was there to essentially service some of the medical need for the product in advance of approval. It was something that was agreed with the FDA. That's obviously an active IND, and you can find the IND number in our public disclosure. We have collected a good amount of data in that EAP. It's possible that, that may be an additional source of data. And then we have a number of clinical collaborations because this is an anticipated approval. We have a number of clinical collaborations with luminary academic centers where there may be additional data sets that we can call upon. The one thing I want to point out, and again, repeat, this was a 505(b)(2) pathway. So it wasn't based on the expected need for a confirmatory trial. So the FDA's expression that confirmatory data may be required, that confirmatory data can come from a number of different places in the submission process, including existing published data. It's just we haven't had consultation yet with the FDA to agree what might be a suitable scope of data. But clearly, in pursuing a 505(b)(2) pathway based on a variety of data sources, including company data and third-party data, the FDA was anticipating that there'd be a fairly hybrid data set involved in the submission. Does that make sense and hopefully go some way to answering your question?

Yes, it does.

Your next question comes from Silvia Luo from JPMorgan.

Just maybe asking the last question in a different way. When assessing the possible pathways ahead, what's the probability or likelihood of needing to execute a new pivotal trial for Pixclara and also perhaps pursuing a different type of pathway that's not the 505(b)(2) that you're talking about?

I think that I'd love to spitball some ideas around that with you, but I think that it's more appropriate for us to get some feedback from the FDA first. We are scrambling to get a package together so that we can have a hearing. As you know, that once you have your submission in place, that's a 30-day scheduled time line, I mean, at least theoretically a 30-day scheduled time line. So we're moving as fast as we can, and we've already started that work over the weekend, which is obviously when we receive this notification. So I think we'll keep you informed. I just want to point out, it's very odd for a company to go down to 505(b)(2) with a pre-NDA consultation that pre-agreed the scope of the data submission on an orphan drug with a Fast Track designation and for which the company has an expanded access program that was approved by the FDA running in the background. But when you add up that multitude of parameters, just a really unusual situation to be in, right? So the reason why I'm being cautious about what I think the scope of confirmatory data might need to be. We are obviously committed to the 505(b)(2). If we are going to further this submission, it will have to be as a 505(b)(2). We agreed with the FDA that a 505(b)(2) was appropriate for this asset. So I think it's really about augmenting the data set that we already have. But I don't expect -- I mean, it wouldn't be typical for us to pursue a different pathway at this time. Does that answer your question, I think, at least to some extent?

Yes, that was helpful.

Yes. I mean this is all a little bit hot off the press, right? So over -- I expect in the next few weeks as we get a package together and have a hearing with the FDA, I mean, I'm certainly interested to understand really fully what the basis of this is. And again, I want to reiterate, I think the company has a bunch of remediation options at its disposal. We just don't know what the FDA is going to accept at this point in time, and we'll keep you informed as that evolves.

Your next question comes from Dennis Hulme from Taylor Collison.

Chris, can you give us a little more color on your expected time line for FDA consultations? You mentioned 30 days. Is that 30 days to put in your request? Or is that the time until you have the meeting? Just a little color around that, please.

Yes. So to set up the hearing process and to have the appropriate type meeting with the FDA, it's going to take, obviously, the company a bit of time to prepare because we do need to come prepared, obviously, to have a conversation around what the options will be. So essentially, we've got a bit of preparation work to do. And then typically, the meeting is granted within 30 days of receiving that submission. So I mean, obviously, we're highly motivated to get that meeting in place ASAP. I think based on the information requests that came through at the end of the process, I think we have a good structure and approach to set up those meetings. So I don't expect that the meeting request should take us very long. And then once it's in, it's a 30-day turnaround.

Your next question comes from David Stanton from Jefferies.

Sorry, I just thought I'd sneak another one in. I'm interested in your comments in your prepared remarks around it reflects changes at the FDA. Could you give us your views on those changes and some color around that, please?

Look, I think we're all supportive of the challenges that are going through the Department of Health at the moment and the FDA specifically. I think that we had a pretty well-defined understanding with the FDA from the outset around the scope of the submission. And I think that where we've landed isn't entirely reflective of that. I don't want to imply that the agency hasn't somehow become -- has changed or become less scientifically led. But I think that there was less flexibility than what we had seen previously towards the back end of the process. And I don't think that the process was the best process as we got towards the end. So that will be one of the discussion points, I think, with the hearing. I'm not implying that there was a failure in the administrative process, but really the outcome that we expected is just not aligned with the consultation process that we went through with the FDA. I hope that gives you kind of sort of sufficient indication.

[Operator Instructions] Your next question comes from John Hester from Bell Potter.

You talked about the quantitative consistency between data sets. Normally, with these diagnostic agents, we refer to the signal to background ratio. Is that what you're referring to there and the lack of consistency or perhaps diversity of results that you saw across the patient group involved in the trial?

I mean we haven't given more color than what we've obviously disclosed and we're not going to do a deep dive yet into the basis of the nitty-gritty of the CRL. I think it's sufficient for the company to indicate the area of -- or the basis for the CRL because I think that informs shareholders and investors of where the potential difficulties lie with the package. I think it is important to reiterate that CMC and manufacturing are not the basis of the CRL. So it's about focusing the scope of the CRL on clinical. And I think that, in turn, gives us a nice straightforward platform to engage further as we learn more about the FDA's expectations going forward. But I think, again, you'll appreciate when you do a 505(b)(2) and you're relying on a number of different data sets, including third-party data, that's the whole point of the 505(b)(2) pathway. A big part of that clinical exercise is to reconcile different data sets. And obviously, that's the -- both the challenge and the opportunity of that particular pathway. So I think I'll leave it at that.

I have a follow-up, if I may. At the start of the process, you obviously were dealing with some individuals at the FDA. Did that team change towards the end of the process?

Look, I don't think it's appropriate for me to comment on staffing and resourcing at the FDA. But clearly, there's a lot of pressures on the organization right now. And I would imagine we're not the only company encountering them.

And finally, you said that you hope to complete the regulatory process in 2025. That sort of seems a little ambitious given what you talked about and potentially in April additional data. Sort of can you elaborate on that time frame?

Well, you're entitled to your viewpoint. It's April...

No, no, no, that was your comment.

Well, a de novo submission with an orphan drug and a Fast Track would take 6 months. So I think that given that we don't have manufacturing or CMC related, we've had a complete review of the rest of the dossier. I mean, I think that there's a perception somehow that a CRL is like an end of process. It's not an end of process, it's a stop in a process. So the next step, I mean, obviously, I don't want to get too speculative about it, but the next step is to do exactly what we said we're going to do, which is to, first of all, have a hearing to decide whether or not there's a basis for appeal of the decision. And that's just a due process that comes at the back end of this. In parallel, we'll be engaging with the agency around their expectations around the data, whether it's just further data analysis or additional confirmatory data. And again, to point out that the FDA accepted that a 505(b)(2) pathway was appropriate for this, and the FDA has given the asset an orphan drug and a breakthrough and a Fast Track designation. So that certainly means that there's a good audience there with the agency to come up with appropriate measures to remediate the package. The point of a Fast Track designation is that the company has demonstrated that there's clinical utility and clinical benefit to the asset. And that just means that everybody has got a vested interest in making sure that the asset progresses. And certainly, again, I'll also reiterate, it's very unusual to be in a situation where you've agreed on a regulatory pathway, you've agreed on a scope of data submission and you've got an approved expanded access program running and you don't get to the end of the process. So we've got to understand that first before we provide further guidance on what we think is the likely remediation. Okay. We're really getting close to the end of the allotted session. There are a couple of online questions that have come through. I'll hand over to Ky to read them out.

Thanks, Chris. The first one is, [ Eric, UBS]. Did the FDA indicate that they were uncomfortable with positioning Pixclara as an agent to MRI without further U.S.-based data? Was the FDA concerned that the label claims for differentiating true progression versus pseudoprogression needed a higher level of evidentiary support?

It's a bit of a detailed question, but to put your mind at rest, we included -- the submission was largely based on -- or the clinical data we submitted was largely based on U.S. patients. So that wasn't a consideration. And then in fact, from a pseudoprogression label perspective, I think there's clear clinical evidence, including in our submission to support the fact that the inter-reader variability between TLX101-CDx and MRI is vastly different and vastly superior in the case of the PET tracer. So I don't see the fundamentals of the clinical utility of the asset as being the basis for the CRL. The clinical utility of the asset is established in thousands of patients. I think the challenge that we have encountered is achieving and demonstrating and convincing the agency that we have quantitative consistency across the data sets that we've used, and that's going to be the first goal of the remediation process on the clinical package. I think, Ky, maybe there's one more question that's come through.

We have one last question, and we're just coming to time. So this question is from Shane Storey at Wilsons. Would I be correct in thinking that the EAP for Pixclara would cover its anticipated use in any planned clinical trial activity with TLX101 in the U.S.A.?

Well, the expanded access program was put in place. It's kind of an implied agreement when you get a Fast Track designation because it's all about the product being available to patients as soon as possible. So we opened an expanded access program as part of the readiness for making the product more widely available. I think it's just good corporate behavior and good patient relations to do so. And clearly, the FDA has to agree that an expanded access program is appropriate for the asset and for the patient population under investigation. So we have plenty of clinical activity ongoing around this asset. That has not been paused in any way by the CRL. We are continuing the EAP in parallel to progressing the conversations. The EAP is a valuable source of data gathering for the company. I mean it is an IND. So there is data collection happening. So I think certainly, it's important for us to signal to patients and to their physicians that we remain committed to taking this product through to its endpoint. And I think keeping the EAP going is a very important part of that commitment. All right. Well, look, we're at the end of the hour. And there are a few other questions that have come through, and I don't want to be dismissive of them. Some of them are either not straightforwardly answerable at this point in time or probably a rehash of some of the topics that we've already put out there. Obviously, I invite reach out to our Investor Relations team if you feel that there's topics we didn't adequately cover off. I think it's typical for companies. Well, it's necessary for companies to disclose the CRL, I think it's typical for companies to explain the basis of the CRL. I think that hopefully, we've provided you with enough clarity and imparted that we have a number of options going forward. We aren't taking our pedal off the gas with this asset. The asset absolutely warrants regulatory approval. It does address an unmet clinical need, and we'll be progressing the dialogue with the FDA as rapidly as we can, and we will keep you closely informed of our progress. And on that note, I'll wrap up and say thank you for your time this morning and this evening.