Welcome to Oncopeptides Investor Update October 2026. For the first part of the conference call, the participants will be in listen-only mode. During the questions- and- answers session, participants are able to ask questions by dialing pound key five on their telephone keypad. Now I will hand the conference over to CEO Sofia Heigis and CFO Henrik Bergentoft. Please go ahead.
Welcome everyone to today's conference call regarding Oncopeptides and our clinical brain cancer program. Please take note of the disclaimer regarding forward-looking statements. Today's presentation is led by me, Sofia Heigis, and I am joined by our CFO, Henrik Bergentoft, who will be available during our Q&A session at the end of the call. We have announced an important clinical milestone from our ongoing OP-701 INSULA Window of Opportunity study in glioblastoma.
An interim analysis of data from three out of five patients in the first cohort confirms that our proprietary peptide drug conjugate platform successfully crosses the human blood-brain barrier. The finding is in line with our preclinical models. Biopsies taken from resected tumor tissue showed consistent presence of the active metabolites in pharmacological relevant concentrations. Furthermore, the treatment was well-tolerated in the evaluated patients with safety findings consistent with our prior clinical experience and without unexpected surgical complications.
Limited penetration across the blood-brain barrier is a fundamental reason why more than 90% of oncology drugs fail to address the high unmet need of glioblastoma patients. By confirming meaningful blood-brain barrier penetration, we have proven that the PDCs do overcome one of the greatest challenges in drug development for CNS tumors. With this finding, we are one step closer to support patients with a very high unmet need. We are also one step closer to unlock value for our shareholders, as the addressable global glioblastoma market is assumed to grow into an $8 billion market by 2035.
The Window of Opportunity study will include 10 patients with recurrent glioblastoma, meaning patients with a very poor prognosis. This study is divided into two parts. Cohort I consists of five patients and aims to demonstrate penetration across the blood-brain barrier in line with our preclinical models. The second cohort is exploratory and aims to gain insights on the pharmacodynamic profile of PDCs. The full study will inform the safety profile of the drug in the severely ill patient population. The second part of the study is an open label extension.
This part is added for ethical reasons, as patients with no other options must be offered to continue the study drug, a decision solely made by the physician and the patient. While the primary intent of offering continued treatment is ethical, this extension also provides valuable observations of how the patients are doing under continuous PDC therapy. We have today, with an interim analysis, confirmed that the primary objective of the study is reached. That is, we do demonstrate blood-brain barrier penetration in line with our preclinical data.
We have so far three patients analyzed in Cohort I, and the fourth patient is enrolled but has not yet received study medication. We have two patients in the open label extension arm, one that recently got its second cycle, and the very first patient in the study, which has now received five cycles of treatment, equaling five months of treatment. We should note that this patient has an aggressive disease with poor response to previous therapies. The patient has received standard of care alkylation, had a poor response, and was progressing in approximately three months.
The patient then got an off-label option and progressed within two months. The patient was enrolled in the Window of Opportunity study just before the third surgery. It is only 25%-30% that gets a second surgery, so a third one is uncommon. As of now, there are no specific safety concerns and no new tumor-related neurological symptoms observed. Post-operative paresis related to the surgical procedure was observed and is improving under ongoing treatment. We, of course, cannot draw any efficacy conclusions based on one patient.
Given that this patient has such an aggressive disease, it is rewarding for all of us to know that the patient is still on drug, doing relatively well. Looking at the road ahead for this study, our priorities are focused and well-defined. We will work to complete enrollment of Cohort I to be able to initiate Cohort II during this year. Second, we aim to complete the full study, including analysis of pharmacokinetic profiles, tissue distribution, and pharmacodynamics. Third, we will utilize this human mechanistic proof of concept to inform the further clinical development and regulatory strategy for the PDC pipeline in neuro-oncology.
Finally, we continue to support and observe the open label extension cohort. To fully understand why this is a scientific breakthrough, it helps to look at how our PDC platform works at the cellular level. PDCs enter cancer cells freely due to high lipophilicity without requiring transporter proteins. Once inside, tumor overexpressed peptidases and esterases rapidly hydrolyze the molecule, releasing hydrophilic alkylating agents. This rapid cleavage creates an intracellular concentration gradient that continuously drives more drug into the cancer cell.
Crucially, as outlined on this slide, the releasing alkylating payload causes double-stranded damage to both nuclear DNA and mitochondrial DNA. This dual targeting allows our platform to overcome conventional resistance mechanisms such as upregulation of DNA repair, which we have already demonstrated in clinic in multiple myeloma patients, where Pepaxti overcomes p53 deficiency-mediated resistance seen with conventional alkylators.
It is important to note that this platform is not an unproven laboratory concept. It is already commercially and clinically validated. With Pepaxti, we have treated over 1,000 patients across Europe, including patients with CNS myeloma, demonstrating blood-brain barrier penetration. We are now taking this validated mechanism and directing it toward high unmet need solid tumors like glioblastoma. This transforms Oncopeptides from a specialized hematology company into an innovative player across difficult-to-treat cancers.
Let us turn to the disease itself. Glioblastoma is the most common and aggressive brain tumor. It grows rapidly, relapses universally, and currently has no cure. It affects approximately three to four people per 100,000 each year, typically patients over the age of 60. Even with surgery, radiation, and chemotherapy, median survival is only 12- 15 months. The medical community has seen virtually no new medicines to the market in decades.
New brain-penetrating treatments that can overcome the resistance are desperately needed. Why have other therapies failed? As we have entered this field, we have discussed with different experts, both pharma industry professionals who have tried to develop drugs for glioblastoma, and key opinion leaders in the field. They all conclude that there are four major barriers that need to be addressed. Glioblastoma is a sturdy tumor.
Most agents exhibit no antitumor activity at pharmacological concentrations. The blood-brain barrier limits drug bioavailability from plasma, preventing systemic treatments from entering the brain. Resistant pathways, particular DNA repair upregulation by MGMT, limits the treatment effect. It is a cold tumor, which means that it is difficult to get immunotherapy to work. The current standard of care, temozolomide, was approved back in 2005. While alkylating agents remain the cornerstone of treatment, temozolomide comes with several limitations.
It achieves only around 30% CNS bioavailability. It demonstrates relatively low intrinsic cancer-killing potency, and this is most likely due to that it is a monofunctional alkylator. It is highly vulnerable to DNA repair mechanisms like MGMT mutations, meaning up to 60% of patients get no or very limited response. Several attempts have been made, but there has been no major therapeutic breakthrough since temozolomide over two decades ago.
Despite these limitations, temozolomide is still the standard of care, and alkylation is the only mode of action proven to work so far. This is why it is logic to give the peptide drug conjugate drug class a go. The peptide drug conjugates belong to a novel drug class, providing improved alkylation through a dual mode of action and very clever distribution that support to overcome resistance. Our journey into glioblastoma originated with compelling external science.
There was an article published in Nature Communications in 2022 by Professor Lene Uhrbom 's team at Uppsala University. The researchers have screened dozens of oncology agents across 29 patient-derived glioblastoma cell cultures. Lower cell viability on the vertical axis represents stronger tumor cell death, and melflufen consistently demonstrated potent killing. As highlighted on the chart, melflufen emerged as one of the most efficacious compounds in the entire screen, with higher cytotoxicity than today's standard of care.
Even if there are some drugs on this screen, like melflufen in viability, it is known that they cannot penetrate the blood-brain barrier. This external finding put our core hypothesis in place. If our PDCs can reach brain tissue in pharmacological concentrations, we should have the cytotoxic activity needed to kill aggressive glioblastoma cells. Building on those initial findings, we, through a collaborative consortium, moved in to generate more preclinical data.
Through these efforts, our PDCs have demonstrated very promising data with strong activity at pharmacological concentrations. Crucially, it confirmed efficient blood-brain barrier penetration alongside significant tumor reduction in preclinical models. Furthermore, our translational studies with Crown Bioscience using patient tumor tissue confirmed that our PDC compounds maintain potent cytotoxicity across heterogeneous patient profiles, including tumors that are resistant to temozolomide.
Together, these preclinical results established a scientific rationale and confidence to take our platform into the clinic in our ongoing Window of Opportunity study. Just last month, part of this research was showcased at EANO in Rome, Europe's premier neuro-oncology congress. We presented three scientific preclinical abstracts demonstrating blood-brain barrier penetration, our dual mode of action with mitochondrial and nuclear DNA damage, and activity in treatment-resistant models. The last abstract was shortlisted for the prestigious EANO Poster Award, giving us strong third-party recognition from the international clinical community.
I will soon tell you more about how we, based on this science, believe we can address all of the most common barriers that I previously outlined for drug development in this field. Important is, however, to understand why we can address the barriers. So let me start with our scientific rationale behind our belief. As outlined by these articles, mitochondria are essential for CNS tumors like gliomas and glioblastoma. Mitochondria act as a power plant for the tumor cells, supplying them with energy.
One mitochondrion can in fact supply several tumor cells, and if you manage to damage the DNA in the mitochondria, you can shut off the power and put the cells into apoptosis, meaning cell death. As already explained, our PDCs come with a dual mode of action, damaging both the DNA in the nucleus and in the mitochondria, giving us a strong scientific rationale for why we see the activity we do in preclinical models. Furthermore, the brain is an organ rich of blood vessels with high perfusion, which makes it a solid tumor suitable for a lipophilic drug like a PDC.
Based on the dual mode of action and the lipophilicity of the PDCs, we believe we can address the limitations with today's standard of care. When comparing our PDC platform side by side with temozolomide, the differentiation is clear. While temozolomide achieves only 30% CNS penetration, our PDCs demonstrate 100% bioavailability across the blood-brain barrier in preclinical models. And we have now confirmed the blood-brain barrier penetration in humans. Temozolomide has modest cell killing, whereas PDCs provide high targeted glioblastoma cytotoxicity.
Temozolomide is vulnerable to single-strand repair via unmethylated MGMT, and our bifunctional alkylator cause double-strand DNA damage in the nucleus and mitochondria, and in preclinical models, remains active regardless of MGMT status. In summary, we on Friday announced a major scientific breakthrough at Oncopeptides. We have, together with the study team in Oslo, demonstrated that our PDC platform is confirmed to successfully cross the human blood-brain barrier in line with preclinical data, which means that we achieve pharmacological concentrations in patient tissue.
Treatment has been well-tolerated in the evaluated patients and with safety findings consistent with prior clinical experience. These findings mark a critical clinical proof of concept for PDCs to be developed for patients with CNS tumors. Looking ahead, we will finish recruitment of the first cohort, including five patients, to open the second cohort this year, followed by full data readout next year.
We will observe the patients in the study and analyze the data on a continuous basis to inform the next steps, including the regulatory pathway and clinical development for PDCs in neuro-oncology. The journey of our CNS tumor program is built by high engagement, deep expertise, and close collaborations, and I do wish to recognize all the people that has contributed to the journey of reaching this milestone. And by that, I wish to take the opportunity to thank you all for your interest and continued support. And we are now ready to open the floor to questions.
If you wish to ask a question, please dial pound key five on your telephone keypad to enter the queue. If you wish to withdraw your question, please dial pound key six on your telephone keypad. The next question comes from Georg Tigalonov- Bjerke from ABG Sundal Collier. Please go ahead.
Good morning. This is Georg from ABG Sundal Collier. Congratulations on the great findings, and thank you for taking my questions. I have two, if I may. First, I am wondering how you can distinguish penetration of the intact blood-brain barrier from drug accumulation in regions where the barrier is potentially already disrupted by the tumor or prior surgery. Have you also measured concentrations in non-enhancing or infiltrative tumor regions? Then secondly, given the initial data, what do you think would be a realistic timeline for bringing melflufen to the market for glioblastoma? How do you assess the potential and accelerated regulatory pathway given the significant unmet medical need? Thank you.
Thank you so much, Georg, and good morning. If we take them one by one. You are right that we are studying now recurrent glioblastoma, and obviously there can be disruption of the blood-brain barrier. Given the lipophilicity of our PDCs, we are quite certain with the method that we are using that we see a real blood-brain barrier penetration. As I have stated, what we do see is that inside of the tumor cells, we have a pharmacological concentration. We know from the pre-clinic that we then do see pharmacological concentrations inside of the glioblastoma cell. We see cell killing. When it comes to the second question, can you please repeat that one? I did not really get what you were after.
Yeah. That was regarding timeline. Both what is, of course, it is still early days, but the timeline that could be realistic and also linked to that, to what degree you assess the potential here for accelerated approval, or at least an accelerated pathway at some point, given the significant unmet medical need.
Yeah. Thank you for clarifying. When it comes to the timelines, it is, to your point, difficult to comment on because we need to have regulatory discussions with both FDA and EMA obviously. You are right that when you have a very high unmet need, you commonly can get accelerated approval and orphan drug designation, et c. That will, of course, then shorten the timeline versus a regular development path.
But I would like to refrain from commenting on exact timings to market, given that we still have those discussions to take, and we will base those discussions on the initial data that we get from the Window of Opportunity study and, of course, aim to find a path that is as fast as possible to the market, as we do believe we can really make a difference for patients here.
Great. Thank you.
The next question comes from Richard Ramanius from Redeye. Please go ahead.
Good morning. I have a few questions. One of them is kind of a follow-up to the last one. Is Pepaxti melflufen the intended candidate for further development? If that is the case, how do you intend to, so to say, fix the IP situation for that asset?
Thank you, Richard. What we have communicated is that we have several PDCs where we have been studying OPD5, the sister molecule of melflufen in glioblastoma and pre-clinic. We also have some data, as I referred to during the call, on melflufen. The reason why we are now using melflufen in the Window of Opportunity study was because it was on the shelf, and we could move fast into this type of study to clear that we can address the greatest challenge, the blood-brain barrier penetration.
We wanted to do that before we invest further in any other PDCs. As we have been discussing and communicating, we have OPD5 with a longer IP, and we are looking to formulate OPD5 for a CNS tumor program. With that said, we do wish to discuss with regulators to understand for the different geographies how we should work with the different PDCs.
Okay. So far, have you used the same dosing with the Pepaxti as in multiple myeloma?
Yes. In the Window of Opportunity study, this is a phase zero, meaning we have no dose-finding study for a glioblastoma. We have been referring to the multiple myeloma SmPC, and then it has been a judgment call for the physician on which dose to use.
I was wondering, how do you intend to fund the next step? Could you say something about what kind of study the next step would be?
We have been clear on that we do not have financing for the clinical development program for the PDCs. In general, you do formulation and a phase I study. But as I just said, we would like to take the initial data to the regulators and discuss with them, because this is a tumor with very high unmet need, and that is why we collaboratively want to conclude exactly what the next step would be. But in general, you commonly don't even do phase zero as we have done, but you start with a phase I.
Okay. That's all for me for now. Thank you.
There are no more phone questions at this time. I hand the conference back to the speakers for any written questions and closing comments.
There's quite a few written questions. We'll start from the top. Has the positive INSULA data changed management assessment on Oncopeptides' ability to create shareholder value from the PDC platform without requiring substantial additional shareholder funding?
What I just said was that, and what we have communicated all the time, is that we do not have financing for the clinical development program of CNS tumors. We will obviously secure financing in a way that we believe is best for our shareholders, meaning in the sense that we can move as fast as possible to hopefully be able to develop and get a PDC to the market in a timely manner, because that's the highest value we can generate for all of you. Then choose financing paths that are supporting that. I would argue that this is how we have been looking at this all the time and how we have been communicating previously as well.
Yes, Sofia, and this is Henrik Bergentoft, CFO. I can only echo what you're saying, that the latest rights issue that was clearly directed towards taking the company to positive cash flow based on the commercialization of the Pepaxti in Europe and including the Window-of-Opportunity study for glioblastoma. Any additional financing for moving into clinic would be on top of that. Just echoing what Sofia said, this is very consistent with our previous communication.
Next question. In the 2015 study of melflufen in advanced solid tumors, clinical anti-tumor activity appeared limited despite evidence of tumor exposure. What is fundamentally different about the current glioblastoma program that makes you believe the blood-brain barrier penetration could be translated into meaningful clinical efficacy at this time?
So the study back in 2015 was a study on different types of solid tumors. What is important, and I actually mentioned this, but I want to emphasize this, what is important when you look at solid tumors and the likelihood of success for a PDC is that you have a tumor rich of blood vessels with high perfusion, because then you will get a lot of drug into the tumor. Then we have designed a Window-of-Opportunity study to confirm that we can cross the blood-brain barrier, just as we have been showing in pre-clinic.
Today, we have a much greater understanding from the pre-clinic, both on our mode of action, where we know we have a strong scientific rationale to be able to kill the glioblastoma cells. We have shown that we can kill glioblastoma cells in pre-clinic and in animal models, regardless of the different mutations, so we can overcome resistance. When it comes to our belief that we can also show this in humans, the first step was now to prove the blood-brain barrier penetration in humans, which we have now done.
Then, of course, the next step will be to find a dose and prove the efficacy. But given that this is a solid tumor that ticks all the boxes for the PDCs, that is, we know that we get active drug into the cell in high concentrations and pharmacological concentrations that has shown in pre-clinic that we can get cell killing. We get that because it's a tumor rich of blood vessels and high perfusion, and it's kind of hidden behind the lipophilic barrier. We have a very lipophilic compound. So we have all the belief and the confidence and the understanding today that was not there in 2015.
Next question. Have you observed measurable pharmacodynamic effects in the human tumor samples, such as DNA damage or apoptosis? Were those effects consistent across the three patients?
So, as I said, the study consists of two different cohorts. The first cohort is only targeting pharmacokinetics, that is to prove the blood-brain barrier penetration. We are not looking at pharmacodynamics in the first cohort, and that is because we are dosing the patients just before the surgery. To look at pharmacodynamics, you need to have the PDC inside of the tumor, so you need to dose it a bit earlier, and that is what will happen in Cohort II.
I want to point out that these patients are recurrent. The tumor is not that easy to analyze because it is a very heterogeneous tumor. So we have added this more as an exploratory objective to look at this, to understand if we can gain any insights. But that is for the cohort number two. As I said, we aim to start that during 2026.
Great. Moving on. Given the encouraging initial results, is Oncopeptides considering external partnerships to fund further development of the PDC platform rather than financing expansion internally?
Yeah. To build on my previous answer, we have all the time said that we do not have financing for this program, and we are exploring different ways, where partnering is, of course, one. At the end of the day, we will conclude financing over time that we believe generates the most value for the shareholders.
Will this change the timeline for Oncopeptides to become cash flow positive?
Yes. Thank you for that question. Clarifying that, no, it will not change our statement as it was formulated, meaning for our core business being commercializing Pepaxti in Europe, inclusive of advancing with the Window of Opportunity study. Now, when and if glioblastoma is moved into further clinical studies, as Sofia said, that would require additional financing, and that filing, of course, has an impact on cost. If that happens, which of course I hope it will, that will have an impact on the company's cash flow positive statement.
Just to add to what you just said, Henrik, I think it's really important to look at different boxes of value here, where the commercialization is current and present. Obviously, we still aim to become cash flow positive in 2027. It's also important to note that if you are going to advance a clinical program and generate with the opportunity to generate much higher value in the future, as this would then potentially be a global market that we address, then we would have to invest.
Next question. To what extent can the INSULA findings be extrapolated to other PDC compounds? What additional validation would be needed before the platform could be considered commercially licensable beyond melflufen?
We have a library of hundreds of PDCs, and they are obviously different, and our team has been playing around with different PDCs to see in pre-clinic which PDCs are penetrating the blood-brain barrier the most. We have a couple, and one of them is OPD5 that we have mentioned before. OPD5 is a sister molecule of melflufen. We would argue, and this of course needs to be discussed with regulators, et c, but that you can draw the same conclusions from OPD5 and melflufen as it has to do with the lipophilicity of the compound, and that is exactly the same.
It should also be said that regulators are not requiring a Window of Opportunity study. They are not requiring that we are proving blood-brain barrier penetration. We are doing this study to know that we are not investing and financing a case that is not viable because we do not get enough drug into the brain. I think that's important to remember. But to your question, the short answer is yes.
Great. Next question. Why are normal, healthy cells not affected? Or are they?
Yeah. This comes down to our very clever distribution, and our mode of action, because our PDCs are a very rapid, and as said, passive diffusion across the lipophilic membranes. So when you get a PDC into the cell and you have a tumor cell, that tumor cell has an overexpression of peptidases and esterases. You can think of these as small scissors. So when you get into a sick cell, these scissors start to cut the PDC compound, and the active metabolites that are alkylating agents, they are hydrophilic, that is water loving, because you have water inside of the cell, so they can't easily get out of the cell.
Given that this is happening, you get a concentration gradient where you get more of the PDC outside of the cell into the tumor cells. Because obviously, with this rapid hydrolyzation, you don't have a lot of melflufen or the full PDC inside of the cell. This is sparing the healthy cells where you have much lower expression. So of course, the PDCs can be hydrolyzed in healthy cells, but to a much, much lower degree than in the sick cells.
So it is the distribution of the PDC and how it is going from being lipophilic to hydrophilic inside of the cell that is making the PDCs targeted to tumor cells. We of course know this from multiple myeloma. We see in the clinic that the major side effect of the PDCs, that cytopenias, and you get actually some efflux. That is, you get some transportation of the active metabolites out of the cells where you get the cleavage, and that is probably what is causing the cytopenias to the major extent.
As many of you know, the cytopenias are manageable. We have not seen in multiple myeloma that it is a great barrier because the doctors, hematologists can manage it in multiple myeloma patients. Of course, we need much, much more data. But the initial findings from a safety perspective is that the safety profile is very consistent, and there has been no major concerns.
Thank you. The next question, I think, is going to be our last. Will this now make you open up the U.S. market again with the FDA?
When it comes to the CNS tumor program, we are looking at this as a global opportunity where we will definitely discuss with the FDA.
Fantastic. That is all the questions that we have. Back to you, Sofia, for a closing remark.
Thank you so much, and thank you for all of your questions. I wish you a nice day.