Medivir AB (publ) (MVIR) Earnings Call Transcript & Summary

My name is Jens Lindberg, I'm the CEO of Medivir and it's my pleasure to give you an overview of where we are on our journey as a company. For those of you who are not as familiar with Medivir, we are a Swedish biotech focused on the development of innovative treatments for cancer. And we have a focused strategy, so we spend most of our time on our in-house compound, which we are developing for liver cancer, which is what you see on the left hand on the screen here. It's a first-in-class orphan drug in development for liver cancer. We are also spending time on a focused partnering strategy, i.e., we do have a number of assets that we have either already out-licensed or that we are looking for partners, where we spend about 20% of our time. So today, I will focus most of my presentation on fostrox, our lead asset, where we are in the development and what we are looking to see in 2023 and 2024. But if we just look back a little bit in terms of where we are from a highlights perspective, the development for fostrox is picking up speed quite rapidly. We have set the recommended Phase II dose recently for one of the combination arms, the combination with LENVIMA. It's now been established at 30 milligram, and we have also already started dosing the first patients in the expansion phase, i.e., the Phase IIa. We have had patients on drug now for quite some time, and the longest-running patient in that combination has actually now reached 9 months treatment without disease progression. We are rapidly recruiting into the Phase IIa part. Importantly, there is a high level of interest from both physicians and from the patients in terms of one thing to be included in the study. So we dosed 7 patients already, with additional 6 patients in screening. Just recently, we also presented our first data in a triple combination, nonclinical data, at the AACR conference. Quite encouraging data, and I will come back to that in a little bit. On the other portfolio, we continue to see very nice progress as well on 3 of our compounds. So 2 of our compounds that we have out-licensed, which you see on the bottom, the Tango compound or TNG348, as it's actually called, and the MET-X compound that INFEX has licensed. Both of them are entering the clinic in 2023. So quite encouraging, and we're also seeing progress with birinapant. But I will come back to that in a little bit. So let me then move to our lead compound, which is fostroxacitabine bralpamide. Whew, long name, difficult to say. So we shortened or abbreviated that, and we reference it as fostrox. So that's how I will be talking about it in the presentation. And fostrox basically a combination of 2 proven mechanisms. On the right-hand side, is a chemotherapy. The active substance is troxacitabine and that induces tumor-selective DNA damage and cell death. So that it has proven antitumor efficacy. Problem with chemotherapy in liver cancer is that when you give it intravenously, it gives a lot of systemic side effects. So it's sort of chemotherapy aren't used today in liver cancer. But we have combined that with a prodrug tail. And the prodrug tail is a technology that has been -- and a mechanism that has been used quite a lot in hepatitis C. So it's a way of in sort of directing the treatment to the liver. So by attaching the prodrug tail to the active substance of troxacitabine, we're able to give it orally rather than intravenously. And where all -- it sort of -- it goes through the gastrointestinal tract without being absorbed, and then it's absorbed and metabolized in the liver. So we are able to achieve a hundred-fold higher concentration when administering troxacitabine with the prodrug tail. So a very unique different approach, enabling patients in liver cancer to sort of have the benefit of a chemotherapy as well. And as I mentioned, the traditional chemotherapy has had problems in liver cancer and aren't being used today. So -- and partially as the exposure in the liver is difficult to achieve -- appropriate exposure in relation to the systemic side effect. So the prodrug approach that I mentioned, that enables a liver-targeted approach and that liver-targeted exposure, so we minimize systemic side effects. We've also chosen a chemotherapy that has sort of a high cell-killing selectivity. So it's a strong link between the DNA replication and DNA damage. That means that we only kill tumor cells and not healthy liver cells. And it has an L-nucleoside approach, and that means it kind of goes around or avoids certain resistance mechanisms for improved benefits. So we truly believe that we found a way to solve for the shortcomings of traditional chemotherapy and enable patients to reap the benefits of this type of treatment. In terms then of where we are, this is our program in full. On the left-hand side is the Phase I monotherapy studies, which we have concluded. They've shown benefit. We're now in the middle phase here, with Phase Ib combo and Phase IIa combo. And we have 2 arms: 1 arm with lenvatinib and 1 arm with pembrolizumab. The lenvatinib arm is recruiting faster, and we have been able to set the dose at 30 milligram for that combination. So we're now in the expansion phase where we are including more patients. And I will speak -- talk a little bit more about that combination today. And then as we look to the future, the aim is then to select the best possible arm for Phase IIb, which we're then looking to initiate in 2024. And I will come back to some of the elements around selecting that -- which arm is the best. But encouragingly then, sort of as I mentioned, the combination arm of a fostrox and LENVIMA has been generating quite strong interest from clinicians and patients. So we've sort of dose escalated, we found -- and set the dose at 30 milligram. We have now had the Phase IIa part open for sort of around 8 weeks. And we have dosed 7 patients already, and we have an additional 6 patients in screening. So we're including patients rapidly, and there's quite a strong interest. I also wanted to share a bit information on what we are seeing. We'll share much more detail later in the year. But 2 examples of patients. First patient is a female Caucasian patient, 56 years of age, which has a hepatitis-driven HCC. She, as a first-line therapy, had a combination of TECENTRIQ plus Avastin, which she progressed on after 5 months. She was initiated on fostrox 20 milligram plus lenvatinib, and she has now actually been on treatment for 9 months without disease progression and are sort of encouraging clinical science, et cetera. So she's are clearly benefiting from a treatment at this point in time, and encouragingly sort of being able to stay on treatment for that long period of time with our progression. And I will come back to that as well on the next slide. The other patient is a slightly different patient. It's a male patient, an Asian, and it's a nonviral-driven hepatitis. This patient progressed on the same first-line treatment already after 1.5 months. He initiated treatment with lenvatinib, but had some side effects with lenvatinib. So they continued with fostrox as a monotherapy. So this patient is an outlier. So he is not part of the combination study, but he is still on treatment, so we're, of course, still following him. And he has now been on treatment for 6 months and continue to do well, again, without disease progression, and he is on the slightly higher dose cohort of 30 milligrams. So encouraging to see patients, quite different patients, one mono patient and one combination patient, sort of enjoying the benefit, sort of as shown by being able to stay on treatment for this long period of time without disease progression, sort of 6, 7 months. And I'm saying that because when we look at this patient population in previous studies, this is 4 studies highlighted, there is a lot of information on this one. But what I want to sort of direct your attention to is the red circles, and that is progression-free survival in each of these studies, i.e., how long have they been able to stay on treatment without progressing. And as you can see, around 3-plus months is what you see across most studies in terms of progression-free survival. So then having patients in the second-line cohort that are able to sort of stay and enjoy a benefit without progressing for 6 to 9 months is very encouraging in comparison to what we have seen in other studies. So what we see then is that sort of there are low response rates, short time to progression across second lines. So that indicates there is a very high unmet medical need, and it doesn't matter whether you are looking at sort of immune therapies or kinase inhibitors, it shows the same in terms of response rates. So it does highlight the need for different modes of action. And fostrox, again, is a very unique liver-targeted compound. So it's different from what's on the market today. So as we look forward, the next step for us is then to select the best combination arm, because we're sort of -- in terms of moving into IIb. And then factors influencing that selection is, of course, safety, tolerability for each arm and clinical benefit. But the other third element that is important is what's the strategic fit in the treatment algorithm today, sort of what makes sense to move forward for Phase IIb. And this is where the 2 arms are a bit different. This is a simple overview of how patients are treated today -- and see if I can get the laser pointer. We are in this advanced stage, that's the patient population that we are talking about. They will receive a first-line systemic therapy, and this is where the majority of the patients will receive a combination of TECENTRIQ plus Avastin. We see that in our study as well, almost all of the patients have had TECENTRIQ-Avastin before moving into the second line where we are today with our study. And in the clinic today, this is where LENVIMA or lenvatinib is the preferred option. So that makes, strategically, the combination of fostrox plus LENVIMA probably the most relevant one strategically. So that's clearly a factor to take into account. And this is probably also one of the reasons why this combination arm in our study is recruiting faster than the other. So as we then look ahead, with the fact that the LENVIMA arm is recruiting with speed, is encouraging, as there are a number of factors sort of pointing in the direction of this being then potentially the best arm to take forward for IIb. We're able to increase the fostrox dose to 30 milligram in the combination, that's encouraging, without disease limiting toxicities or dose-limiting toxicities. Patients are being able to stay on treatment, as I show in sort of patients here and that I exemplify with 6 to 9 months, in a very difficult-to-treat population. And as I mentioned, it is perfectly aligned with the treatment guidelines moving forward. So it points to it, but that's a -- it's a decision we need to take as we see more data, but it points in that direction. Then there will be an arm that will not be selected for second line moving forward, and then sort of happens with that arm. And the interesting bit is that there could be alternative opportunities here for this combination. There is an overall trend towards sort of triple combinations, earlier treatment. So what we do see is that the fostrox plus KEYTRUDA arm could inform a combination sort of with potentially other PD-1s. It could potentially point in direction of combining with more than one other drug, i.e., triple combination. And this is relevant because, as I mentioned previously, in this first-line setting, most of the patients, about 90% of the patients, will receive TECENTRIQ plus Avastin. Other combinations have sort of tried to show improvement, but none has done it better. So all combinations, so far in this sort of first-line setting, has shown same efficacy. So our belief is that you will need a different mode of action or you will need a sort of additional treatments to improve the benefit. And this is where we believe that kind of our sort of local liver-targeted chemotherapy could be approved in mechanism to add on top of other combinations already being used. And we recently showed our first triple combination data at the AACR conference in the U.S. There's a lot of information on this slide, but I think that there are 2 things to take away. On the left-hand side, it shows that fostrox induces increased expression of PD-L1, LAG-3, i.e., it increases the immune-mediated antitumor activity and then subsequently helps the immune therapy, the PD-1, to do a better job. And what we see on the right-hand side is exactly that. So when we add fostrox to the combination of PD-1 plus lenvatinib, we see a significantly improved sort of efficacy. So clearly, synergistic efficacy with regards to triple combination versus the standard combination of PD-1 plus lenvatinib. So encouraging triple combination data. We'll continue to sort of explore this and look to see what opportunities there might be for a first-line strategy from a triple combination perspective. So in summary, we do have a unique first-in-class potential treatment in an area of significant unmet need. Our mode of action is unique as it sort of targets the cancer in the liver to minimize side effects, and we have a very strong potential for attractive combinations across lines of treatment. To help us shape our future development for fostrox, we have formalized a scientific council. So 5 highly renowned KOLs across the world will be working with us to design and shape the development and make strategic decisions going into 2024. 3 of the KOLs are investigators in our current study and then 2 additional investigators coming on board. And we're very encouraged by the enthusiasm and then the willingness to engage with us to shape our path going forward. Because as we look forward, we do see the early sort of the kind of combination approach in liver cancer as a first step, we believe that with our unique mechanism of action, being the first liver targeted, that we could potentially be a backbone for combination across liver cancer. And then looking forward, liver metastases sort of from colorectal cancer could definitely be an area to explore going forward. Something that we will discuss with the scientific council. So with that, I'll just sort of say a few things about the pipeline overview and some of the programs that we have partnered already, and those are the ones that are highlighted in green here. And three, to make specific comments on. Birinapant, which we out-licensed to IGM Biosciences from the U.S. They have seen very nice progress in 2022. They've completed the fourth dose escalation cohort in the combination of birinapant and their own DR5 agonist. They are now dosing patients in the fifth cohort. They've actually been able to go up a cohort or a higher dose than they originally anticipated because they haven't seen any dose-limiting toxicities. So that's encouraging. And preclinical models across a whole range of tumors, exemplified with breast cancer here on the right-hand side, show very strong synergistic antitumor activity. So we're looking forward to seeing more data, clinical data later in the year. One other program is a preclinical program that we out-licensed to Tango Therapeutics called USP-1. They recently, on the right-hand side here, presented additional nonclinical data at the AACR conference, showing strong synergy with PARP inhibitor and then showing ability to overcoming PARP inhibitor resistance, which is quite important. They have reiterated that they're moving into the clinic, and they are filing an IND mid-2023. So one additional Medivir research compound moving into the clinic just as this one, the last one, MET-X, which is a potential best-in-class metallo-beta-lactamase inhibitor for -- so kind of targeting the threats of antimicrobial resistance. They received an FDA QIDP designation early in the year, and they've also said -- communicated that they are moving into the clinic in 2023. So another preclinical Medivir research compound moving to the clinic. So very nice progress in 2022. Just a few words on the financials. And I think that the key take-home message from here from a Medivir point of view is that our cash position is that we do have a cash runway into Q2 of 2024, as communicated in our latest quarterly report. So with that, I'll just sort of sum up. And the 2 highlights are, as you can see on the left-hand side, the fostrox development in liver cancer is picking up speed rapidly, with a number of patients dosed in the Phase IIa part and encouraging signs with patients still on treatment, quite long, after initiation without disease progression; and encouraging process -- or progress across the out-license progress. So we're very much looking forward to sort of additional data, additional information in 2023 and planning for the next phase of fostrox development to initiate in 2024. So with that, thank you.