Welcome To ASX Briefs

Andrew Musgrave 0:04

Welcome again to ASX Briefs, and joining me today is Ebru Davidson, the interim CEO and Managing Director of Q Biotics Limited. QBiotics is an Australian unlisted life sciences company developing small molecules from its platform and reporting compelling data from its oncology trials, including a 78% response rate in a phase two head and neck cancer trial and dose escalation progress in its EBC 1013 wound healing program. Ebru, great to have you with me today and welcome to the ASX Briefs podcast.

Ebru Davidson 0:38

Thank you so much, Andrew. It's a pleasure to be here.

QBiotics Platform And CEO Priorities

Andrew Musgrave 0:41

Ebru, before we discuss QBiotics in more detail, can you give a brief overview of the company and also as interim CEO and Manager Director, what's been your main focus since stepping into the role?

Ebru Davidson 0:51

Thanks, Andrew. So QBiotics is an unlisted public company headquartered in Brisbane. We're a clinical stage biotechnology company developing first-in-class small molecules for major markets from our epoxy tiglianes platform. Currently developing three distinct programs from the platform, spanning oncology, wound healing, and antibiotics. Our oncology and wound healing programs are in clinical development. Our lead asset is our oncology asset, Tiglonoltiglate, which is currently in phase two clinical development. Our second clinical asset is EBC 1013, which is a wound-healing hydrogel, has broad application against wounds and burns. It's currently in a phase one clinical trial for venous leg ulcers. So I stepped into the interim role about nine months ago now, and what has been my main focus is really on execution and positioning cubiotics for its next stage of development. Scientifically, the company has built a very strong foundation over many years. The company's been around for about 25 years in different forms, essentially as a discovery company in the first 10 years and then going into a development company for the last 15 years. So my job, and of course, that of my management team, is really to ensure that we translate the science into disciplined clinical, regulatory, and commercial strategy. So that means being really clear about which studies create the greatest value and allocating capital carefully and building the partnerships required to take our programs further. I've also focused on strengthening the way we operate as a company, so clear priorities, accountability, and good communication across the company. More immediately, we've been focused on delivering the current prospectus offering and ensuring that the company is appropriately funded to advance its clinical programs. You know, ultimately, our focus, as you know, my focus and the board's focus is really turning the scientific potential we have into meaningful outcomes for patients and long-term value for shareholders.

Discovery Story Behind Tigilanol Tiglate

Andrew Musgrave 2:56

Okay, and can you walk us through how tiglanol tiglate was originally discovered and what was the starting point and how did that process lead to identifying it as a promising cancer therapy?

Ebru Davidson 3:07

So Cubiotics was um actually founded by Dr. Victoria Gordon and Dr. Paul Ridell, both former CSRO research scientists, and it was founded around uh year 2000. The company was actually called Ecobiotics back then, and the basis of ecobiotics was the discovery technology called ecologic. So the founders saw an opportunity to really refine the search for biologically active molecules from nature, and they were looking at things like plant-animal interactions. For example, uh, plants produce particular chemicals to repel or attract and to access nutrients. So this was of great interest to them, and they um having that understanding of how the natural system works, because as you can appreciate, Andrew, nature runs on chemistry, um, they really put together targeted strategies for you know identifying particular biological activity. And it was really the way TT came about is a really amazing Australian story. It was um certain interactions that were happening between the musky rat kangaroo, which is the smallest kangaroo, and the blushwood plant that really led them to discover to led them to TT. Um, essentially what was happening was the musky rat kangaroo would grab the fruit of the blushwood tree, which looks much like a peach, run off with it, um, eat it up, and then spit it out and you know, make a funny phase. And it was very unpalatable. The seed of the tree was uh the fruit was quite unpalatable to the musky rat kangaroo, which signals that anti-herbivory activity that really gave the first clue to our founders that they were onto

How Funding Focus Is Set

Speaker 1 4:58

something.

Andrew Musgrave 4:58

And you're running the two distinct clinical programs, Tiglontiglate in oncology and EBC 1013 in wound healing. So, how do you prioritize investment and management attention across the two?

Ebru Davidson 5:10

So they actually both, as I mentioned, epoxy tiglianes platform, so they come from the same platform, so there are some returns on investment there. Um, but they are they're very different to answer your question, they're at different stages of development and require different level and types of investment. So our focus, uh TT is our lead program, and it is certainly our focus. It's already in phase two development and has produced encouraging clinical data across a number of solid tumour types. Um, so it's really the focus is for us there, and we're really under the capital raise. We're currently undertaking most of the funding's focused on on tigel and all siglade and really augmenting our oncology program. EBC 1013, our wound healing program, as I mentioned, is an earlier development, but chronic wounds represent a very substantial unmet need, and the program has the potential to create significant value. So although our focus is on tiglonaltiglate and our oncology program, um we will we're looking to fund our wound healing program through other means. So through non-dilutive funding, through government grants. Uh so yes, majority of the funding and focus is on our oncology

Head And Neck Phase Two Context

Speaker 1 6:30

program.

Andrew Musgrave 6:30

Turning now to the phase two results, the QB46C H08 trial achieved a 78% objective response rate in injected tumours in patients who are refractory to the standard of care. How significant is that number in the context of what's currently available to these patients?

Ebru Davidson 6:48

Uh yes, look, uh treatment of head and neck cancer is still a relatively high unmet need, and our subset of patients that came into this trial were either refractory, which means they have not responded to standard of care or the current standard of care, or for whatever reason, the standard of care is not appropriate for them. So uh you're right, 78% for this subset of patients is very, very encouraging. The um in in recurrent and metastatic head and neck cancers, the first line of treatment, first line is usually Pembrolizomap-based therapy, which produces around 20% that's with just Pembro alone, and it goes up to about 36% when combined with chemotherapy. So once patients progress through treatments, response rates to available options are generally much lower. So against that backdrop of 78% response rate in injected tumours, that is highly encouraging, particularly in a refractory population. Look, although I have to say we recognize that this was a small early stage study and that injected tumour response is not directly interchangeable with conventional sort of patient-level response rates. But to answer your question, um, how significant is that number in the context of what's currently available? So, current leading treatments again is uh CETAx SIMAP, which is around 30%, sitting around 32% ORR.

Andrew Musgrave 8:19

And six tumours achieved complete ablation and none recurred during the time patients were on study.

Durability Signals And Mechanism Of Action

Speaker 8:26

What does that durability signal tell you about TT's mechanism and how confident are you that it will hold up over a longer period?

Ebru Davidson 8:35

Uh so look, the absence of recurrence in all six completely ablated tumours during the period patients remained on study, which is up to five months, is again very encouraging. It's consistent with how TT, you know, TT is a multifactorial mode of action, really. The drug is designed to cause rapid destruction of injected tumour, including through tumor cell death, disruption of the blood supply through vascular disruption. It also produces a local inflammatory response and has been shown to stimulate immune activity as well. So, together, when you take all those things together, those effects may help produce a more complete local ablation and reduce the potential for recurrence than rather than simply slowing tumor growth. Um, we saw similar, I'll just add in in addition to head and neck, we saw similar low recurrence rates in the soft tissue sarcoma trial. And I mentioned that um that's a two-stage trial at memorial slow and kettering. We've uh reported on the first stage, which was out to six months. So we so similar thing in that, which is which is always encouraging when you when it's consistent, sort of the results are consistent. Um, but I'll take you to our veterinary studies as well. So in our registrational veterinary study, we had a longer-term follow-up with recurrence, and we saw that 90 per 96% of evaluable patients in that registrational trial remained free of tumour recurrence at 12 months. So this clearly sort of illustrates the durability of the response to treatment with TT, in our view.

Andrew Musgrave 10:17

Okay, and just touching on the soft tissue sarcoma and the positive results, how does the head and neck data change the case for TT as a treatment across multiple solid tumour types rather than a single indication drug?

Ebru Davidson 10:30

Yeah, so I don't think it's it changes it at all. Rather, it it really strengthens the case considerably because we're now seeing encouraging activity in more than one indication. Uh, so it really supports that early observations from our phase one clinical trial where we saw responses or indications of efficacy in nine different tumour types. Um, so as I mentioned earlier in our head and neck, we were, you know, that was a sort of very heterogeneous patient population, with I think it was up to nine different histologies tested. So similarly, soft tissue sarcoma is a heterogeneous patient population. There are over over 80 different subtypes of soft tissue sarcoma, and we reported 82% objective response rate from stage one of that trial, which is currently recruiting patients at MSKCC. Um, so that consistent response rates are important because TT is administered directly into the tumor. So its mechanism is not dependent on a single tumor-specific mutation. It acts sort of locally through several complementary effects, including, as I mentioned earlier, tumor destruction, vascular disruption, inflammation, and immune activation. Um, again, I mean, this is early data, but what we're trying to demonstrate is the tumor agnostic potential of the drug. And different, you know, different tumor types, anatomical locations, different settings will require their own clinical evidence. But the head and neck results make the broader opportunity much more credible and really help us identify where the drug may provide the greatest clinical benefit.

Where TT Fits In Treatment

Andrew Musgrave 12:12

And now looking at the broader oncology opportunity, head and neck cancer is a large market, roughly 940,000 new cases and 480,000 deaths globally each year. So, where does TT fit alongside existing treatments like surgery, radiation, and immunotherapy?

Ebru Davidson 12:29

Uh look, we certainly see potential for TT to be used as a monotherapy for selected patients, but really complementary to existing treatments. Um, we think that it really has the potential to be a nice fit alongside existing treatments. So surgery and radiation, for example, can be highly effective, but in some patients they are no longer feasible for a number of reasons, because they may cause substantial, you know, functional or cosmetic morbidity, or the disease may reoccur following treatment, or patients have become refractory to standard of care. Um and immunotherapy, relatively sort of newer sort of treatment, has somewhat changed the landscape, but only a proportion of patients really achieve a durable response, and it's only effective in about 20 to 30% of patients. So we do see potential for TT to be used in combination with standard therapies, including immunotherapy, to really um, in in the case of immunotherapy, really to lift that efficacy rate for those drugs.

Andrew Musgrave 13:37

And 64% of response evaluable patients met the primary efficacy endpoint. What does cubiotics need to demonstrate next to advance TT towards registration in this indication?

Ebru Davidson 13:50

So um, yeah, we would, I mean, to register TT in that indication, we would require a much, much larger phase two trial uh with a randomized control group. You would want the FDA or the EMA buy-in, any sort of trial design and also the endpoints. Um, but having said that, our business model, I think I mentioned earlier, is really to partner at phase two proof of concept. Um, we're a small biotech company without really the financial resources to roll out a large study like that. So we've been undertaking, uh what we've been undertaking really is to demonstrate the safety, tolerability, as well as the as well as efficacy of TT to de-risk it prior to, so to really de-risk it prior to partnering. So our business model is to partner uh with large pharma to de-risk the opportunity and to continue development.

EBC-1013 For Chronic Wounds

Andrew Musgrave 14:46

Looking now at the wound healing pipeline, you touched on EBC 1013 and its phase one trial. What has the safety data shown you so far about the drug's therapeutic window?

Ebru Davidson 14:58

So uh what the data's shown so far is that we've been able to escalate through the first three cohorts without the safety review and dose escalation committee identifying dose limiting toxicity or another safety signal that would prevent progression. So that's encouraging. And it really allows us to continue exploring the dose range, which is important, in accordance with the study protocol. It's it's probably still too early to say that we have uh we have fully defined the therapeutic window from this phase one safety trial. Um, but that is precisely what this phase one dose escalation study is designed to help establish. So what um but progressive, you know, as you say, progression to the fourth cohort without a dose limiting toxicity gives us, you know, growing confidence in the safety profile of this of this drug.

Andrew Musgrave 15:48

And around 20% of venous leg ulcers fail to heal despite standard of care. How does EBC 1013's mechanism differ from existing wound care treatments and what would success look like for those hard-to-heal wounds?

Ebru Davidson 16:02

Yeah, so absolutely. So much of current wound care is really focused on managing the conditions around sort of wound compression, dressings, infection control, deprivement, and just managing the underlying vascular disease. And you know, these measures are essential, but they don't always restart the biological healing process in a chronic wound. Um, EBC-1013 is intended to act really directly on the biology. It's a topically applied uh hydrogel, small molecule, designed to stimulate an acute, controlled inflammatory response, uh remove damage or non-viable tissue, and help move the wound out of its stalled chronic state and into a more sort of active healing phase. Um what it really does is it disrupts the biofilm that you that forms on um on top of wounds, which makes it really difficult for them to um get back into that um that uh get out of that stalled chronic state and into an active healing phase. So the preclinical and veterinary work that we've done also indicates wound infill. Um you really have to see the photos to believe it, seeing is really believing with the drug. And um, what we're seeing is that wound infill, closure activity, limited scarring, and um, and also local antimicrobial effects. So um success uh would ultimately mean more difficult wounds moving into a sustained healing phase, uh faster and more complete closure, you know, fewer reoccurrence complications, better quality of life for these patients who are suffering with these horrible wounds, and potentially less reliance on prolonged and expensive wound care, which is costing our governments millions and millions of dollars a year.

Milestones Partnerships And Prospectus Raise

Andrew Musgrave 17:55

Looking ahead, with positive data now in hand across both oncology and wound healing, what are the near-term milestones investors and partners should be watching for?

Ebru Davidson 18:03

Yeah, so for TT, our oncology drugs, so we're continuing stage two of our phase two soft tissue sarcoma trial, following the encouraging stage one results. That's as I mentioned at Memorial Sloan Kettering. We're also um progressing a phase two breast cancer collaboration with Unicancer in France. So that, as I mentioned earlier, came about through um the work that we've been doing with Gustave Russie, where they were using tiglanol tiglate uh as um under compassionate use on uh breast cancer patients. And that sort of the results from that really encouraged Unicancer to reach out to us to undertake this trial, which we're very excited about. We're looking to kick that off later this year, early next year. And also, of course, we're continuing to work, um continuing the work directed at extending the opportunity into visceral, um, which is sort of internal tumours, and we're doing that in liver, liver cancers at the moment. For EBC, I guess the immediate milestone is to continue the dose escalation and complete phase one study.

Andrew Musgrave 19:13

And finally, Ebru, as an unlisted company progressing two clinical programs simultaneously, how are you thinking about the funding and partnership pathway required to take these molecules through registration?

Ebru Davidson 19:25

So we currently have a prospectus offering open and we're looking to raise up to $40 million. Uh, the funding is really to augment our oncology program to, you know, uh as I mentioned, we are looking to partner and we believe we're partner ready, but it's really about augmenting that program and just um funding our breast cancer trial with Unicancer, although Unicancer is sponsoring that trial and they are largely funding that we will still have to contribute some funding towards that trial, as well as our liver liver trials that we're looking to kick off as part of that funding. But on funding discipline, the funding will uh will primarily go towards oncology and our wound healing will be wound healing trials will going forward will be predominantly funded via non-dilutive funding and uh grant funding.

Andrew Musgrave 20:19

Okay, Iru, well it's been great to chat today to get an update on where the company is at. So thanks for your time. We wish you all the best and we look forward to further updates in the upcoming months.

Ebru Davidson 20:28

Thank you so much, Andrew. Thank you for having me on your podcast.

Closing And Subscribe

Andrew Musgrave 20:31

That concludes this episode of ASX Briefs. Don't forget to subscribe, and we look forward to catching you on our next episode.