Roquefort Therapeutics plc (0AG.F) Earnings Call Transcript & Summary

Good afternoon, and welcome to the Roquefort Therapeutics acquisition of Coiled Therapeutics presentation. Today, we are joined by Stephen West, Executive Chairman; Edward Painter, Chairman and CEO of A2A Pharma; and Sridhar Vempati, Chief Strategy Officer and Executive VP of R&D of A2A Pharma. [Operator Instructions] I'll now hand over to Stephen to begin the presentation. Thank you.

Great. Thanks, Harry. Welcome, everyone. Thanks for joining us today. As Harry outlined, we're here to talk about the acquisition of Coiled Therapeutics, which is a transformational acquisition for us. My name is Stephen West. I'm Executive Chairman of Roquefort. So I'll be giving a bit of an introduction to the transaction outlining the reasons behind why we're doing it, why we think it's very exciting for us and also very exciting for A2A. And I'm pleased to advise that I am joined here by Ed Painter and Sridhar Vempati from A2A today as well. And they can go into a lot more detail about the science and the massive potential of the therapy that they have within Coiled Therapeutics. Next slide. So just a few sort of bites on why we're doing this presentation and why it's so exciting. So back in March this year, we did signal to the market that we were pivoting away from being a preclinical stage company into being a clinical stage company. And by acquiring Coiled Therapeutics, we're achieving this new strategic shift for the company. We are looking at acquiring Coiled Therapeutics for GBP 30 million. It's going to be payable in Roquefort shares. So it is a reverse takeover transaction. And as part of the transaction, we'll be looking to move on to the high-end market. We're currently on the standard market. We will be renaming the company called Therapeutics plc once we complete as well. And we're very pleased to say that Coiled is interested in progressing our STAT-6 program that we hold as well, which was one of our preclinical programs. There are other preclinical programs in the company, but they're subject to a sale at the moment. And we are looking at largely protecting the value of those for current shareholders as well. So just a sort of a bit of a background to Coiled Therapeutics. It is being spun out from a company called A2A Pharma. And Ed and Sridhar will give you a bit more detail on that a bit later But Coiled has exclusive worldwide rights to a therapy called AO-252. What's very interesting for us, I'm sure it will be for investors as well is A2A Pharma have done a spin out previously, and this was Biomea Fusion. That was spun out and listed on the NASDAQ. It hit a market cap of over $1 billion, now that has come back a little bit since then, but I think it does show the potential of the assets that A2A Pharma are developing. And also with this transaction that we're doing, this is a bit different to Biomea Fusion transaction in as much that A2A Pharma are bringing over their management team as well. So we'll be using the expertise of the A2A Pharma, Coiled team to progress the therapy through the clinical stages. And what's also very encouraging for us is A2A Pharma and its investors have committed to providing GBP 6 million towards the funding of the program for the next 2 years as well. So we just -- we think it's a fantastic deal. So AO-252, I'm not going to go in too much detail because Ed and Sridhar would do this shortly. But it's a novel first-in-class, first-in-human drug, targets a protein called TACC3 and we're doing that for the treatment of cancer. There's a Phase I trial, which is currently underway in the U.S. right now, and it's getting very good results, good efficacy and clinical benefit and a benign safety profile. Now the team is very focused on taking it through the clinic very quickly. So actively looking at expanding the studies later this year and enrolling patients in 2026 for a Phase III registrational and trial. So very, very fast moving. Now the interesting thing with AO-252 is it has quite a large therapeutic index. So it's not just limited to 1 or 2 indications, there's lots of indications. So ovarian, endometrial and triple-negative breast cancer is what they're currently doing Phase I trials for. That's about to be expanded into quite a few other indications as well. Now all in all, we're probably looking at potential cancer patients of about 350,000 through the U.S. and the EU. So if you work that through, that's a potential multibillion-dollar market where Coiled will be a first mover. So huge, huge potential. So after that introduction, I'll hand it over to Ed Painter to take it through the next few slides. Thanks, Ed.

Thanks very much, Stephen. Thanks, everyone, for joining us this afternoon. A brief background on A2A. We started around 10 years ago, focused on the use of computational tools to design new drug candidates for unique targets rather than me to targets to be similar to everyone else. We've used generative AI and other tools along the process. And as Steve said, our first program we put into a spin-out company Biomea Fusion, which continues to do very well. Their burn rate is a bit higher than we would like, and that's one of the things we also look to differentiate ourselves with Coiled and have with A2A, keeping the spend at a reasonable level as possible in advancing the program through the clinic. So I'll turn it over to Sridhar to talk about TACC3 as a target specifically. Similar to menin, when we started Biomea, TACC3 is a very unique target. We're the first in the market to go after this target. And it's differentiated as being not required for healthy cells, but very dependent for cancer cells. And that's really what we look for specifically with the targets that we engage in. Sridhar, go ahead.

Good afternoon, everyone. I'm very excited to present our story of AO-252, and I think this will be a game changer in multiple different indications given its potential and also not required in normal cells. AO-252 is a small molecule given as tablets or capsules to the patients. And it's given daily -- once daily or twice daily, depending on the indication right now. It's a brain penetrant molecule, which is extremely rare for a lot of small molecules because there is a blood-brain barrier and the drug doesn't go into the brain. In our case, we have a very, very strong indication that our molecule goes into the brain. And we are also targeting patients right now that will go -- that will have brain metastasis. Because right now, this is one of the huge unmet need where a lot of patients have brain mets and they become ineligible for the current drugs. And we provide the potential there for a lot of these patients. And we have spoken to some of our PIs, investigators were looking at it and they are very excited about it. Preclinically, we have shown very, very strong efficacy in multiple different tumor indications where we have seen that some of the mices have become -- some of the mice have become completely cancer-free. Even after stopping the treatment, cancer doesn't recur in some of these indications. So we are very, very excited about it. It's in Phase I right now. And right now when we started it, we started with endometrial, ovarian and triple negative. But we have completed the amendment. And I think everyone should be able to see this. We update it in our clinical trial site that now we are going to enroll all solid tumors with our potential being hugely in gastric, prostate sarcomas and lung beyond the current 3 indications that we are going after. We haven't tested in some of the other indications, but that is a plan going forward, then we will be testing other indication that if we see a signal, we will enroll more patients into it. As Steve mentioned, we currently are only seeing that it's 350,000 patients for second-line and third-line patient depending on the indication, but that would expand even higher if we move into patients who are newly diagnosed for metastatic disease. TACC3 is a very, very selective target, and I'll go about in the next slide after discussing about the team. Next slide, please. As we've mentioned that Coiled being spun off as a separate entity from A2A and the AO-252 program that will come into this company, and I will be taking over as the Chief Executive Officer. And we have a very, very experienced team where more than 50 to 20 years of experience in the industry. Robbin Frnka, who's our Chief Clinical Operations heads are all the clinical operations right now along with the assistance from our CEO of A2A and also another Co-Founder, Sotirios Stergiopoulos. He is going to be our Chief Medical Officer, but he will be continuing as CEO of A2A. Chaemin Lim, who is our lead chemist and who helped develop the AO-252, is going to lead the chemistry and also the CMC aspects of our AO-252 program, and she will be also assisting in developing this STAT-6 program and taking it to the next stage. Next slide, please. So coming to what is TACC3. TACC3 is a multifunctional protein. It just -- it basically acts like the way we describe is that -- it's like an intersection. Some part of that intersection is just required for normal cells and some part of that intersection is required for cancer cells. And the way we do it is that TACC3s -- we are only blocking the TACC3s intersection, which is responsible for the cancer cells to grow. And the way it works, TACC3 binds to multiple proteins that are involved in different process. And the process that we have identified is mitosis, DNA damage repair, immunity and also in the replication stress. And then -- and these are very really crucial for cancer cells. And the reason why we are excited is a lot of the targets out there in clinic or that are approved, they only go after a certain process. And that's why resistance develops. And we think that when we block multiple process involved in cancer cells, it doesn't allow the cancer cell to have resistance. And if there is resistance, it will take a long time to overcome our drug and develop resistance. Previously, when you go into Broad Institute, DepMap which is like encyclopedia for cancer people is that you go and type your target, and you see that whether target is a good target for cancer or not. If you go now and you see TACC3, you will see that it's a very, very selective target, and it is been said to be a good target to go after in cancer. And we have worked with some of the people at Broad Institute on that, and they have verified this data that TACC3 would be a very, very good target for cancer cells. TACC3 is not required in normal cells based on the mouse data. So if you knock out TACC3 in adult mice, the normal cells have no effect. And that's why we think that when you select targets like this, which are very, very important embryonically but not required in normal cells in adults, it gives us a very, very strong therapeutic index or strong safety signal because we do not limit the potential of this drug. And that's what we are seeing in the clinic. We have a very, very encouraging or a very, very strong safety profile so far. Next slide, please. So how do we achieve this strong safety and strong efficacy in our -- with our drug. So what we have done is that if you divide TACC3 into 2 halves, so one half is responsible for the -- need to be called N-terminus and C-terminus. The N-terminus, there are interactions, which are involved in normal cells too, and we don't block them. We are only blocking the other half, which is very, very crucial for the cancer cells. And there are a lot of interactions that happen on that side. And when we block that side, all these interactions are so crucial for cancer cells that the cancer cells go into panic mode, and they cannot avoid it and eventually they die. And I'll talk about it in the next slide. We have seen very, very strong efficacy in multiple cancers, ovarian, endometrial, breast, prostate, gastric, sarcoma, bladder and lung. Here, we have seen several of the indications showing tumor regression. Tumor regression is basically the tumor is going down from when you started. It's not -- the aim is to [ mark even ] keep static. The aim is to completely get the mice get rid of the cancer, and we have seen that with our product. And the indications mentioned here are the indications where we have seen extreme strong efficacy where we have seen tumor with that. But we are still testing other indications based on our other preclinical models and that data we will present as [indiscernible]. In the clinical trial, we have seen very, very strong safety with minimal and the best maybe grade 1s or very, very little of grade 2s, but no grade 3s or grade 4 that would derail a lot of those programs. And especially the programs that get derailed, you basically see the issues in bone marrow tox or the liver tox. And in both the cases, we are not seeing it, and we haven't touched any of the bone marrow related toxicity so far. Next slide, please. So how does AO-252 work. So AO-252 is working by blocking the centrosomes. Centrosomes are like -- they are like -- they held cancer cell, I mean, like any cell divide and there are 2 centrosomes in the cell. But in cancer cells, you will see more than 2 centrosomes, and that helps the cancer cells survive or, I would say, give advantage, and we are blocking that. And when we block that, the cells in an ideal way should undergo a lot of DNA damage and then die. That is when the cells are like divided. But what when the cells are not dividing? We also [indiscernible] multiple different interactions that are involved in DNA replication, DNA damage repair or cell cycle. Like cells have multiple phases, and they have to transition from one phase to the other to go into the next phase. And whichever stage they are in, AO-252 has a function in each phase, and we are blocking those cells in each phase. And when that happens, there is a lot of DNA damage happening and when that DNA damage is too extensive, it comes out from nucleus into a cytoplasm. And when that happens, immune activity happens. And this is -- this also happens with a lot of the viruses that happen -- viruses that come into our system. So this is also about viral mimic like if there is an external DNA coming in, the cell senses that it's a danger to that, and it would stimulate immune actuation and kill that cell. So similarly, we are activating. We are causing a lot of DNA damage, which actuates the immunity and then causes the cancer cell death. And we have shown that in multiple different experiments, that how this happens. And that's why we are very, very excited because we are blocking cells in multiple different stages to cause this damage and we cell death. Next slide. So our strategy right now for this program is that because we have seen some responses and clinical benefit in multiple different patients, very, very strong safety in some efficacious cohorts because the dose that we have seen efficacy in the mouse, we have not reached that dose in like humans yet. So the next couple of cohorts, we think is where we would be in that efficacious cohorts. And given that we are already seeing efficacy in sub-efficacious cohort, we are very, very excited for our next cohorts, where we expect strong efficacy in -- without drug. We expect to complete the next doses by end of this year. But this is not like a fixed timing because as we see signal in particular indication, we will expand into those indications and keep enrolling those more patients into those indications. So even though we say Q1 2026 or those expansion, it could be earlier also because if we are -- right now, we are seeing very, very strong efficacy in signal in ovarian and endometrial triple-negative, we have very few patients enrolled, which we are trying to enroll more now. But we are seeing efficacy signal in both these indications. So we plan to enroll more patients of the upcoming doses. Also to go into earlier lines of therapy and not stuck in the third line, fourth line, we want to initiate combination trials with some of the known drugs. In our preclinical trials, we have shown combination synergy with TROP2 ADCs, HER2 ADCs, multiple chemotherapies and also with immune therapies. So that's why we believe that this drug could be a game changer in multiple different indications. And based on that data that we generate of dose expansion in the next year, and we keep generating more data, and we have discussion with the FDA on how many number of patients they would like to see, especially in the unmet need populations for us to go into a registrational trial. So we will continue discussing with the FDA next year and the following year to decide on the Phase II registrational strategy, which we call Phase II, Phase III registration strategy for that in 2027. Next slide, please.

Great. Okay. Well, thanks, Sridhar and thanks, Ed. So back to why we think this is transformational for us. I mean there's lots of reasons. We've narrowed it down to 6. It's a fantastic opportunity to create a company not just in 1 clinical stage asset, but we'll have 2 because we have the AO-252, which is an exciting therapy, which you just heard about. And then we also have our internal STAT-6 therapy, which we're looking at developing as well. but actually AO-252, I mean, you've heard already, it's in Phase I trials already, so we're getting news flow coming out of that already, and we expect lots of news flow coming out from those trials and investing into other trials during the course of next year. So looking at lots of news flow coming out from that program. It is -- for a layman like myself, it is an alternative chemotherapy. So it's not attacking good cells and bad cells at the same time. It's just attacking bad cells. So it's less toxic to patients. So a lot better outcome for patients. In terms of the addressable market, you heard from Sridhar, we're talking about 350,000, but that could be expanded upwards if we go into sort of first line of treatment for some of these cancers. So multibillion-dollar market here. And to be a first mover in that is significant. And there's a clear road map here. There's lots of inflection points, lots of news points. So in terms of becoming a listed company, this is a great example of why -- and why should become a listed company, access to extra capital, but also lots of news flow, lots of publicity around it. So yes, I was just thinking it's such a great story. And then in terms of A2A, we haven't really gone into that too much, but A2A has AI generative platform called SCULPT. This is where the TACC3 target came from. So we'll have the benefit of a strategic partnership with A2A as well. That would be very beneficial for us going forward as well. So that concludes our presentation. I believe we're going to move over into the Q&A now, Harry.

We've had a number of questions pre-submitted and submitted live. The first one being what strategic advantages to Roquefort anticipate from acquiring coiled therapeutics? And how does this align with the company's long-term goals?

Good question. So I mentioned earlier, we announced in March this year that we're pivoting away from preclinical assets into clinical stage assets. I'm sure you agree after saying what you've seen today, this is a fantastic opportunity to do that. It transforms us from a preclinical company into a clinical stage company, which is our long-term goal. So it ticks all those boxes.

Thank you. The next question is, how many new shares will be issued for the GBP 30 million consideration and what will be the pro-forma share ownership split post-deal. Can you clarify the dilution effect?

So unfortunately, I can't answer that because we haven't publicly announced that yet, and we're still negotiating the final details around that. And so that won't be known as we sign a binding agreement. But I mean, all I can say is that it will be a fair -- it will be based on a fair price for Roquefort shareholders and for Coiled shareholders. And so I don't think there's going to be any surprises for that. Yes. Unfortunately, I can't really go into much more detail.

The next question is, what is the rationale from moving from main market to AIM.

So yes, we looked at this long and hard. So there are several reasons why we've chosen AIM. I mean, one is it opens up additional pools of capital over and above what you get on the standard list. The standard list, it's gone through a few changes recently. So you need to keep track of the changes constantly evolving. It's a lot more expensive because of that, it's a lot more regimented. And bigger name, you get -- there's a lot more tax benefits for being on AIM. But I think overall, I think AIM is a lot better platform for growth companies. And the Coiled team certainly has very ambitious growth plans. And I think this is a lot better platform for that.

The next question is the GBP 6 million funding from A2A Pharmaceuticals, how exactly will that money be used for AO-252 development?

So yes, you're right. So A2A and its investors will be providing GBP 6 million. That will be the majority of the funding that the large company will need for the next 2 years. In terms of the specific development milestones for AO-252, I might hand that over to maybe Sridhar to answer that.

Yes. The idea basically is to do expansion studies. So the [ $6 ] million (sic) [ GBP 6 million ] will give us enough to do the expansion. We plan to enroll 50 to 60 patients at least, and it could go higher depending on how much money we want to spend more on it. But that 50 to 60 patient data is what we are being asked for by multiple formats for strategic reasons. And that data would give us a signal and the dose that we will be taking forward further into our registrational studies too. So that is also a requirement for FDA. So we think that the [ $6 ] million would give us enough to do the dose expansion and the remaining amount that we are going to that -- Roquefort is going to bring into the company. That amount will robustly into the preclinical -- some of that will go into clinical and some of that will go into the preclinical developing the STAT-6 program. The STAT-6 program, I forgot to clarify, we are not looking into oncology for STAT-6 program because STAT-6 is a very, very drastic target that is getting a lot of attention lately in the immune space, and we are trying to -- we are going to develop that program for the space. So that would be a high level what the amount of money that we are [ using ] to go into. A majority would go into to develop some [indiscernible].

Thanks, Sridhar. And just to finish that off. So listing on AIM, you obviously need to demonstrate you have 12 months of capital. We're going to have well over 2 years' worth of capital when we relist. So it's going to be a very healthy company with lots of news flow.

Thank you. The next question is, how do you balance early-stage discovery programs with later-stage clinical development?

I mentioned earlier -- sorry, you want to take it, Steve?

No, I was actually going to -- about to say that's one for you, Sridhar.

It's a very interesting question. So -- and we have done that with our current programs at A2A, we have multiple programs we start with, whichever is generating more better data, we have advanced that. And given that AO-252 is now our priority, a significant portion of our money will go into that program to generate enough data for strategic reasons. We don't think we will be taking this program into commercialization. We are definitely looking for partnership or I mean, if -- or an M&A, but that's our aim. But our aim to generate enough data for a partnership or strategic acquisition at some point of time. And then once that happens, then the preclinical programs that we go into clinical becomes a priority.

Thank you. What are the projected time lines for the dose expansion studies and the initiation of Phase III registration trials of AO-252?

Right now, it's a revolving door. It's because it depends on the indications, we will be prioritizing the dose expansion. Right now, we think that given our current efficacy cohorts, ovarian endometrial would be a priority. But we are very, very strongly believe in prostate, gastric and some of the lung indications. And given our now amendment is approved, we think that we will be enrolling these patients. And the next year, we will be going into prostate and some of these other indications and expansion cohorts. And based on that efficacy, we will decide at least 1 or 2 indications that will have severe unmet need and will fulfill the FDA requirements for a registrational study that we think that initiated in 2027.

Thank you. What lock-ins will Coiled shareholders be under?

So I'm a bit restricted to give on what I can say because we're still negotiating this. But needless to say, I think it's a fair comment that both parties are quite keen to have lock-ins. We see this as a long-term value-building transaction. So we're all very committed to getting this -- not only getting this transaction done, but we're very committed to growing the company and making -- advancing the program and making everyone money, I guess, is where we're trying to get to with this.

Thank you. The next question is, are CPS Capital still actively involved with CoiledTX?

So yes, they are. And just for the benefit of people who don't know CPS Capital, they're an Australian-based broker, very -- a boutique broker, very successful broker, who are brokers to A2A Pharma and by virtue of that to Coiled as well. So they're very supportive and actively involved in this transaction.

Thank you. The next question is, given this is a reverse takeover, what are the regulatory, legal and shareholder approval processes required? And what are the major risks those processes pose?

Yes. So it is a process. And I think in terms of what we need to achieve during the process is high level, we need to do legal DD on ourselves and the target. There's certain accounting reports that need to be done. There's an admission document that needs to be approved by AIM. And then we also have to have shareholders approve for the issue of the shares that are needed in order to complete the transaction. I've said earlier, and I'll say again, both parties are very committed to this. So I can't see any risks around it in terms of anything other than it's just a process that we're going through now. So we are pulling all the stops out to try and get this done as soon as we can.

Following on from that, how long do you expect to be suspended for the RTI?

So again, we don't know. We're still in discussions with the regulators around this. So we're not sure when a suspension will occur, if at all. This has not been confirmed to us yet.

Thank you. The next question is, how is the Board strengthening itself to support the transition from preclinical to clinical stages?

So the exact composition of the Board is still being finalized. However -- and we'll announce it very shortly. But I think it's fair to say that the intention of the parties is to bring the core expertise from Board over to Roquefort. They certainly have the expertise to drive the program forward, and we welcome that. So yes, there's going to be some very experienced individuals in the Board. And I think you probably saw some of them in the presentation today.

Thank you. What are your expectations for burn rate over the next 12 to 18 months?

Sorry, I can't go into specifics, obviously, but I think what is a good indication for people is that, we've said this a couple of times that [indiscernible] and its investors are committed to investing GBP 6 million into the company, into the large company, and that's the majority of the funding over the next 2 years. So you should probably get a pretty good picture of burn rate off the back of that.

Thank you. What is the status of Lyramid SPA transaction?

So as we announced recently, so that is still in place. There's a long stop date, which is the end of October. And for the benefit of those who don't know what we're talking about. So we did sign an SPA to sell our subsidiary, Lyramid, which holds some preclinical assets to a private company called Pleiades Pharma. And Pleiades Pharma raising some capital at the moment, and they have until the end of October to raise that capital. And when they've raised that capital, we'll complete and the sale will go through.

There was a similar question with what is happening with Oncogeni as well?

So Oncogeni was our other subsidiary, and that held 2 assets in it, the STAT-6 and NK Cell programs. We were in discussions with the group in the Middle East. That was announced through a term sheet earlier this year. We are now progressing this trend, have expressed interest in STAT-6. So we're keeping STAT-6 in the company. So we're no longer looking at selling Oncogeni.

Thank you. The next question is, what is the status of your relationship with A2A Pharmaceuticals beyond Coiled? Is there scope for more collaboration?

We would certainly like to think so. I -- maybe something you can comment on Ed, if that's okay.

Sure. So A2A, as Steve talked about a little bit, we have a computational program using generational AI to develop new drug candidates for a variety of different targets, including KRAS, TEAD and other cancer-focused programs as well as for the autoimmune space. So we will continue to look for opportunities to introduce new programs to Coiled over the next few years and hopefully enhance shareholder value as continuing shareholders of Coiled. That's really what our business model is like. And we're very excited about the TACC3 program as well as potential opportunities in other programs, including the STAT-6 program, which we can no doubt help with as well.

Thank you very much. We currently have no further questions. So I'll hand back over to the management team for any closing remarks.

Great. Thank you, Harry. I'd just like to thank everyone for your time today. I really appreciate it. As you can see, this is truly a transformational transaction for Roquefort that elevates us into a clinical stage company. It not only benefits Roquefort shareholders, it also benefits A2A, Coiled shareholders. It provides them with a growth platform while they develop the AO-252 therapy and also provides another clinical target, which is STAT-6. Both parties, Roquefort, A2A and Coiled are all very much committed to getting this transaction done, and we look forward to providing further details in due course. So thank you, everyone.

Just to -- yes, to add to that, the team at A2A and Coiled, we're very excited about going forward with this as well. Our focus is really on the patients. And as we see efficacy in patients at much lower dose than we originally expected and expect to see further efficacy in the next few months as we escalate the dose, this gets more and more interesting to both us as well as potential partners in larger pharmaceutical companies. So thanks very much, Steve, for bringing this to us.

Thanks, Ed. Thanks, Sridhar.

Thank you. Thanks, everyone.

Thank you to everybody for joining us today. That concludes the Roquefort Therapeutics acquisition of Coiled Therapeutics presentation. Please take a moment to complete a short survey following this event. The recording of this presentation will be made available on Engage Investor. I hope you enjoyed today's webinar.