Theracryf (LSE:TCF) — Preliminary pharmacokinetic results from Phase 1b study of new SFX-01 tablet formulation

0:02 Good afternoon, and welcome to the FGen Pharma PLC Investor Presentation. Throughout this recorded presentation, investors will be in listen only mode. Questions are encouraged and can be submitted at any time using the Q and A tab situated on the right hand corner of your screen. Simply type in your questions and press send. The company may not be in a position to answer every question received during the meeting itself. However, the company will review all questions submitted today and publish responses where appropriate to do so. Before we begin, I would like to submit the following

0:32 poll. And I would now like to hand you over to CEO, Hugh Jones. Good afternoon. Thank you, Alice. Good afternoon, everybody, and thanks for joining us again for one of our investor meet webinars. With me here in London this afternoon is our chief medical officer, doctor Glenn Clark, who designed the clinical study that's gonna be partnered out of the q and a that we'll hold later. But to start with, we'll give you a short reminder between us of the company, of our recent history and and very recent news flow. As you know, we are an AIM listed company, the usual disclaimers apply. And to remind you about Evgen, we are clinical stage in drug development. We focus on breast cancer, glioma, other cancers with our lead asset, SFX-one.

1:24 For those of a technical bent, there are three molecular targets of interest and that's STAT3 and phospho STAT3, NRF2 and a phosphatase enzyme called SHIP2. We're developing a class of pharmaceuticals based on this very highly biological active agent called sulforaphane, which has a network effect. It's pleiotropic, we believe. There's a lot of third party historical, preclinical, and clinical data on sulforaphane, mainly preclinical in fairness. And we've got some very high unmet need diseases that we are focusing on. And the way we can make sulforaphane into a clinical drug suitable for use in cancer and other diseases is through our sulforadex stabilization platform. And it's a stabilized form of sulforaphane, fully synthetic drug that is now our lead compound, SFX-one.

2:16 And this is very strong, granted IP covering a whole bunch of aspects of the the molecule, s f x o one. As you can see from the number of gray hairs on this webinar, we're a pretty experienced management and board of directors. The business model is pretty standard, really, for biotech models that is established proof of concept, whether that's preclinical or clinical, and then partner. And we've exemplified that quite recently in the last quarter, which we'll tell you a little bit more about, but we did a webinar specifically on that subject in October of last year. We do believe we have got a lot of value inflection points with this lead asset. So two collaborations already done, some years ago, and it's still going on well. We are interacting frequently with Juvenescence, which uses our stabilization technology to develop a nutraceutical form of sulforaphane.

3:10 More recently, we out licensed the neurodevelopmental disorders and schizophrenia indications for SFX-one to a Swiss partner of ours called Stellickla. And that deal, as you know, has a 160,500,000 of milestones and double digit royalties in any scenario. As of the last interim, we've got a very strong cash position, and we maintain our cash runway, well into quarter four twenty twenty four. That's next year. So the the multiple targets that we mentioned are here in the pipeline chart. We're still working very closely with the University of Manchester and the Christie on our breast cancer collaboration, which is preclinical based on some phase 2a data we developed, in ladies with HER negative and hormone receptor positive breast cancer.

4:06 Stellixla now has the rights for neurodevelopmental disorders, while sulforaphane has quite strong evidence base. We are leading with glioblastoma. We gave guidance last year that this is now going to be an investigator sponsored study led by the Erasmus Medical Center in Rotterdam and a close collaborator of ours there. We have some interesting data in hematological malignancies, and we do have rights from a bunch of, Spanish institutions

4:36 to analogs of sulforaphane. So that's the pipeline. It's broad a number of interesting indications that we could go for with SFX one. So because biotech is a long term business, here's what we achieved in the latter part of last year. We got MHRA approval very quickly for our healthy volunteer study, which we announced had top line data yesterday. We've scaled up the active ingredient, and this active ingredient new manufacturing process has additional intellectual property protection. We've used that new IP API, as it's called, active pharmaceutical ingredient to make an enteric coated tablet, which was the subject of the Phase one study we reported on yesterday.

5:22 And that's suitable for scale up to commercial scale. We've made a lot of progress with our Manchester collaboration in metastatic breast cancer. We've started again in the middle part of last year two new academic collaborations, one with professor Marampon's group in Rome, which was published actually this week, the first part of that that collaboration, and a longer term collaboration with doctor Chen of the University of Michigan in The United States in colorectal cancer, somewhere we haven't looked at very deeply in the past. So more recently then, post our last interims and in the last quarter of last year to to date really, we did the out licensing transaction with Stellickler, as I said earlier.

6:09 We got very positive scientific advice from the Netherlands Regulatory Authority regarding our program in glioblastoma or brain cancer. And after Glenn's extensive, consultations, professor Margilaine is now going to lead our glioblastoma study as an investigator sponsored study. We, also published, as I said, this week, the effect of SFXO1 in enhancing the effect of radiation in cell lines through the Lassa Pienza Rome collaboration and coming right up to date,

6:46 the PKPD effects starting with the top line PK data of our new formulation, which we reported top line data on just yesterday. So over to Glen to talk a little bit about this rhabdomyosarcoma, and more importantly, the the radiosensitizing effect that we see to observe with SFX-one. Okay. So thank you very much. So rhabdomyosarcoma, although not a common tumor, is an important tumor, particularly in children. Where I believe the data are most important are the combination with radiotherapy because that is transferable to other tumor types. So what did we see? Well, we saw a direct effect on rhabdomyosarcoma cell growth, an effect on the tumor cells themselves.

7:35 And when we combined SFX-one with radiation, we saw a synergistic effect. And you can see the picture here, the two pictures on the left are radiation alone. And once we add in SFX one, you can see that those tumor cells

7:55 are pretty much gone at the fore gray to the bottom right hand box and significantly different to the top left hand box. So we are seeing a synergistic, not an additive, but a synergistic effect in with radiation in keeping with prior work that we had within GBM and as I said before this is transferable into other indications where radiation is used so particularly important for the, newly diagnosed glioblastoma patient population.

8:27 With regards to the, healthy volunteer study, the, phase 1b study, this is a new formulation of sulforaphane. We've moved to an enteric coated, tablet away from the simple capsule form and the idea behind this is that the drug is released beyond the stomach, beyond the acid in the stomach into the beginnings of the small intestine. And what we've seen is that we are able to measure sulforaphane and its active metabolites in the blood and that this is associated with an increase in the ability to be able to measure those with increasing dose.

9:01 They are in the range previously seen with preclinical experiments and clinical studies and in the range that we need to be with regards to hitting the targets required for breast cancer and glioblastoma. As far as the side effect profile is concerned, it's very much in the same ballpark as we've seen before with no serious adverse events. The adverse events being to the greater degree mild in

9:26 their intensity. Pharmacodynamics endpoints are now being explored currently at the moment. Those will take a little bit longer, but we're still on track to have full reporting for this study in the second quarter of this year. Thanks, Glenn. We'll take the rest by questions, of course. But that concludes for now the, formal part of the presentation. So we're on track. We're on schedule. We've got, confirmatory data on radio sensitization where SFX plus radiotherapy is better than either alone and one plus one equals a number greater than two, which is the definition of synergy rather than just additivity. We've got an enteric coated capsule. You saw the picture sorry, a tablet that replaces a prototype capsule, and you've seen that it, seems to release timing wise in the early part of the small intestine, as Glenn said, and it's producing levels of drug and metabolites, active metabolites, I should say, that's in the range we see in the test tube. That's very important. So there's plausibility then that getting those concentrations around the tumor is likely to be effective.

10:35 So, Alice, that concludes the formal bit, and I can see there are some questions coming in. Good to see. Glenn, that's great. Thank you very much indeed for your presentation this afternoon. Ladies and gentlemen, please continue to submit your questions using the q and a tab situated on the top right corner of your screen. While the company take a few moments to review those questions submitted today, I would like to remind you that a recording of this presentation along with a copy of the slides and the published q and a can be accessed via your investor dashboard. Hugh Glenn, as you can see, we have received several questions throughout today's presentation. If And I could just hand over to you and ask you to read out the questions and give responses where appropriate to do so, and I'll pick up from you both at the end. Thank you. Okay. Thanks. So we've got the first question at least in time terms. Good to see progress.

11:20 What's the next catalyst or catalysts, And is everything going to plan? Well, the next catalyst, I think, is the, progress internally for us on our glioblastoma program with the Erasmus in Rotterdam, and that's on track. And yes, everything is going to plan with Stellickla. You know, we've we're committed to deliver the full written up formal dataset of the PKPD study you just saw headlines of, by quarter two, and that's entirely on track. So, yes, things on plan as we like to have in in bi in biotech. Not always easy, but in Evgen, we do like to deliver what we say we're gonna deliver approximately at the time we deliver it. And so far, so good on that front. The next question, in the PKPD trial, published in one of the public domain, summaries, the plan was for four cohorts.

12:14 Well, I'll turn to Glenn in a second, but that was a maximum number of cohorts, and it's a modular study as we said at the beginning. So modular means we can pick and choose how far to go, and we believe with our top dose, which was six hundred milligrams once a day in one dose, that we've achieved as high as we need to go in the volunteers. So we didn't need effectively to dose the fourth cohort at an even higher dose even though we had the ability to dose so in the protocol and the drug to do so as well should we choose to. Glenn, any thoughts? Absolutely. So, we've been talking to the regulatory authorities, as part of this, and, the the collaboration with Stellixa would probably require us to look at doses lower than three hundred

12:58 milligrams once a day, which is the lowest dose we looked at in the healthy volunteer study. Likewise, we would like to push the dose, but having spoken to the regulatory authorities, for GBM, their view is that the data would be better generated in GBM patients. So following internal discussions with that feedback from the regulatory authorities, we felt that the three doses that we looked at were sufficient and that any further exploration of those doses would be better done in the patient groups in which we would be performing them. Great. Thanks, Glenn. A question here. It's a small sample, but any evidence that the nonserious adverse events are less frequent than with the old capsules? Most cases, very difficult. We didn't do a direct head to head comparison between the two because the old capsules are history for us. And the regulators, interestingly, did not need us, Either the FDA or the, the MHRA here in The UK did not need us to compare old with new.

13:52 So, it's very, very difficult to compare at the moment because the numbers are different. All we can tell you is, you know, mild is the lowest classification of adverse events that are out there. And, you know, the very vast vast majority of subjects in the study recorded mild adverse events. Nope. Nothing to add to that. Great. Thank you. When are we likely to hear more on time scales for the ISS and glioblastoma? As soon as we have everything is the answer. We have an engaged and enthusiastic investigator in Rotterdam, and we're working with them, on exactly how the lead in to this investigator sponsored study is gonna happen. So as soon as we hear anything concrete, we'll let you know. But as at the moment, it's work in progress.

14:43 Question here. We've got a significant proportion of institutional and high net worth investors. Any thoughts on why none of these appear to be adding at the current price? Well, that, as ever, is really a question for the investor. There is some liquidity in in our stock as you are all aware. The liquidity has dropped off of late, actually, but very slightly. But that's really a question for individual investors. Know, we have a hugely biologically active molecule. We have a very talented team to exploit the properties of that molecule. We've got for biotech in particular, a comfortably long cash runway with the plan executed. And I should add that the cash runway we've, given guidance on does not include any money in from our partnership with Stellickla or our partnership with Juvenescence.

15:35 So I think we're in good shape. The overall macro environment is, you know, not healthy at the moment, but, I think we're in one of the best positions to weather this particular storm. That's great. Thank you for that, Hugh Glenn. And I believe you have addressed all the questions that came over from investors today. And, of course, the company will review all questions submitted today, and we will publish those responses on the investor meet company platform. But perhaps before before we direct investors to provide you with their feedback, which I know is particularly important to you and the company, Hugh, could I please ask you for a few closing comments? Thank you. Of course, Alice. So so there we are, on track. We're seeing increasingly important radio sensitization, meaning that radiotherapy is more powerful, we hope, in the presence of SFXO one than it is in the absence of SFXO one. We've certainly proven that in the test tube, in whole animal models, in glioblastoma, and now in this rare childhood cancer of rhabdomyosarcoma through another Italian collaboration.

16:38 We're developing our commercial scale tablet, which is releasing in the right place and giving us drug into the bloodstream at total concentrations of drug and metabolites that are right and link very closely to the concentrations we see in the test tube or in our animal experiments. So I think SFXO one is in very good shape, and we are funded to execute the plan that we've outlined to everybody. Thanks again for attending, and, we wish everybody well. Thank you. That's great, Hugh and Glenn as well. Thank you once again for updating investors today. Could I please ask investors not to close this session as you will now be automatically redirected to provide a feedback in order that the management team can better understand your views and expectations. This will only take a few moments to complete, and I'm sure will be greatly valued by the company. On behalf of the management team of FGen Pharma PLC, we would like to thank you for attending today's presentation. That concludes today's meeting. Good afternoon to you.