Molecular Partners H2 2024 Earnings Call Transcript

Quartr
Provided by Quartr
March 7, 2025

There are 11 speakers on the call.

Operator

Good morning and welcome to the Molecular Partners Fourth Quarter and Full Year twenty twenty four Results Call. All participants will be in listen only mode. Please note this event is being recorded. I would now like to turn the conference over to Seth Lewis, Senior Vice President, Investor Relations and Strategy. Please go ahead.

Speaker 1

Thanks Drew, and welcome everybody to the Molecular Partners' year end results and twenty twenty four highlights call. My name is Seth Lewis, and I'm joined today by members of our senior leadership team, including Patrick Amstrutz, Chief Executive Officer Robert Hendricks, SVP of Finance Philippe Lejane, Chief Medical Officer and Michael Stump, Executive Vice President of Projects and Head of the DLL3 radio program. The team will make some prepared remarks and then we will open the call for your questions. If you haven't had a chance to see the press release issued yesterday after market close, you can find it on our website, www.molecularpartners.com, where you can also access a copy of today's presentation. Today's call is being recorded and will be available for replay.

Speaker 1

Before we begin, I'd like to remind you that management will be making forward looking statements about the future development of certain programs. These statements reflect the current estimates in Molecular Partners and are subject to change. For For the most up to date information, please visit our website, www.molecularpartners.com. With that, I'll turn the call over to Patrick Amstruts. Patrick, please go ahead.

Speaker 2

Thanks Seth for the intro and kicking off the call. And please again go to our website and grab the presentation and we will be referring to a slide number that we're on and the slide number that I will kick off with is Slide number five. A warm welcome from my side. Great to have you all on this call. Before diving into the highlights '24, we did put on the twenty years Molecular Partners logo because it is our twenty years anniversary and it coincides with being ten years listed on the Swiss and then later on the U.

Speaker 2

S. Stock Exchange. And it has been twenty years of a quest to make certain drugs that matter for patients. And we have never gone away from that and this has really brought us where we are. And if we look back, it has not been a straight line.

Speaker 2

It is hard work for specific results. And twice we actually reached clinical POC with the wet AMD drug Avicipar and with the COVID drug EnsovyVet. And I think the call today is really to highlight where we are and how we're lining up our new programs to be in a position to have more of such readouts in the future. So let's look at the highlights 2024 and what we have done. It was a year of execution to get our programs closer to that clinical readout.

Speaker 2

Let me start with the radio dark pin franchise, where we have TLL3 targeting seven twelve that is our lead compound, passing all IND enabling studies and ready to go into the clinics and Michael will be talking about that. We also selected a new target. And I mean, if we say selected a target, it also means that we have data, we not just took a target and it is mesothelin and we will touch on that too. And maybe most importantly, the third bullet point is the expansion of our KoranaMed collaboration. And as you know, in the radio field, we bring the vector, but we still need access to an isotope and isotope supply is challenging.

Speaker 2

And with this collaboration, we have secured 10 slots of for products, real products, not just candidates, products for LES-two twelve, one of the most promising isotopes out there. So I think that is one of the possibly most important things of last year that we have secured that access to isotope. On the T cell engager side, it is five thirty three, where a year ago we had mediocre or underwhelming results and it was a year of understanding those, working with our investigators and putting that back on track. And Filip will talk about that, how we have tackled the target mediated drug disposition problem and are very curious and also to see what the future will bring. On On the switch side, there was a bit of a change.

Speaker 2

A year ago, we were moving six to one that was the NK engager and switch. We have called it upgraded that to the T cell switch and we will talk about that as we move. There's another program, three seventeen. It is less of strategic focus today, but still we finalized the Phase one. We had very good safety.

Speaker 2

We saw biological activity and we will be moving this one forward in combination with the PD-one in investigator initiated trial. We ourselves decide that we would not invest that much, but we still see a potential future for it and there is support from the investigators to move it forward. And last but not least, we did a small financing round late last year to bring in our friends from HVM, very strong reputable Swiss investor and the round was also backed by existing like BBS and SIBRETA, adding $20,000,000 to our treasure chest, which makes us well capitalized with the runway into '27 also well beyond those inflection points that I was pointing out before. So with that, let's move to the next slide. I'm now on Slide number six.

Speaker 3

Come again? Which is this one?

Speaker 2

Yes. The pipeline. It's not number five. Now it's five. So okay, thanks for that.

Speaker 2

So on slide number five, let me quickly start with what is missing on this slide and what is less important. The one line that is missing is the Novartis collaboration. So you remember three years ago, we entered into a collaboration with Novartis on two targets and we made darkens against those two targets and moved them into research. Over the years, they did not progress that fast. The results were there, but I think both Novartis and Molecular Partners, they did not see the strategic interest in the target.

Speaker 2

This happens and maybe an explanation is all those research targets now after three years, that was the research term, decided not to move now after three years, that was the research term decided not to move forward. We agree with that. We would also not move forward. So that line is missing. There was no technological setback.

Speaker 2

It was just not the right targets in the right time. They might come back. But as of now, this is not where we or Novartis would invest. The other one that we are not actively moving forward is 06/21, a nice molecule in HCT, so stem cell transplant, we said that is not our focus interest. The success of five 30 three and also the success of the radio franchise is much more relevant and important.

Speaker 2

So that is one that we can sort of put on hold and opt for partnering. Now that where are we focusing? This is five thirty three and the radio franchise. And I will hand over to Filip later, our Chief Medic to talk about May in AML and all the progress and Michael Stump will be walking you through the radio work on seven twelve and the latest from mesothelin and our collaboration with Oronomet. So before we go there, I'll hand over to Robert to give us the overview of the financial situations.

Speaker 2

Over to you, Robert.

Speaker 4

Thank you, Patrick. I hope you can all hear me well. Good morning, good afternoon to everyone on the call. I'd like to run you briefly through the key figures of last year and the guidance for the year 2025. My name is Robert Henriksen.

Speaker 4

I'm the SVP of Finance here at MP. The numbers that I will present are stated in CHF 1,000,000. More detail can be found in the press release as well as in the appendix to this presentation. Yesterday, we also published our full annual report in the twenty F. So plenty of opportunity to dive into more detail.

Speaker 4

The entire presentation is also available on the website. Moving now to Slide number seven on the key figures. There are a few numbers that I'd like to highlight here. First of all, the revenue number five and seven, as Patrick has just mentioned, this is exclusively coming in both of these years from the Novartis collaboration. In 2024, we recognized the last part of the upfronts that we had received back in 2022.

Speaker 4

And there is no more revenue to be coming from this collaboration. So that's on the revenue. Then the operating expenses at $66,000,000 well within the guidance that we gave, that was 65,000,000 to 70,000,000. Just a high level breakdown without too much detail around 74% of these costs are R and D related. So pushing the products through the pipeline there.

Speaker 4

The overall costs have been fairly stable over the years. The third number just to highlight if you look at the overview is the net financial results. Clearly, we benefited from high interest rates on our U. S. Dollar denominated deposits.

Speaker 4

This number is clearly volatile by design. And this year, I think we, as I said, benefited from the FX rate, the interest rates. And through the small raise we did in October, we gained another $20,000,000 So that added to the dollar pool that we have. With that and intro also to the cash balance at the end of the year, ending with $149,000,000 down from $187,000,000 at the end of last year. So resulting in a year on year cash investment of around $38,000,000 taken into account the receipts from the capital raise in October.

Speaker 4

The cash burn therefore for the year is around 54,000,000 This December 2024 balance of SEK 149,000,000 will carry us well into SEK 27,000,000, and we consider this continues to put us in a privileged position in the industry. And also I'd like to remind here that the company has been and remains without debt. All these numbers combined on this page, we feel these numbers tell the financial story of MPN twenty four and show the continued solid financial state of the company. Then moving on to the next slide, just a few words on the guidance for 2025. We will not guide on revenue or any other metric in terms of total operating expenses.

Speaker 4

We do guide for a total of 55,000,000 to 65,000,000 of which around 7,000,000 are expected to be non cash. And as always, this guidance is subject to the progress and changes in our pipeline and excludes any potential payments related to partnerships. So to summarize and conclude here, what is relevant to remember from these numbers, I would say, is the continued financial base, solid financial base entering into '25 that will allow us to continue to invest in our pipeline and to bring drugs to patients. Thank you for your attention. I will be happy to take any questions during the Q and A later.

Speaker 4

And with that, I'd like to hand over to Michael Stumpf, who will talk about our Radiodarpin programs.

Speaker 1

Over to you, Nicky.

Speaker 5

Thanks very much, Robert. Good morning, good afternoon, everyone. I hope you can also hear me well. I'm really very happy and proud about the progress and all the achievements the various teams have made in the year 2024. And let me, first of all, already acknowledge our collaboration partner, RANOMED, who is making all of this possible.

Speaker 5

I'll speak a bit more in detail later. And 2025 is really the year with the first clinical data from the radiotalpine and lead. And that's why I'm so excited to be here. Things are moving forward and let's quickly look back, but also then let's look a bit forward together. So moving on to Slide 10.

Speaker 5

I'm pretty sure you have heard about the darpenes before. So the big blue picture there, that's where we put a lot of effort into understanding what's the ideal properties of the radiopharmaceutical. It involves some protein engineering, but it also certainly involves the linker, chelator and of course, we also explore half life extenders. Most importantly, however, for the patient's benefit is the alpha emitting therapeutic isotopes. So that's the two twelve version of lead, which has proven clinical efficacy.

Speaker 5

Thanks to our collaborators from olanumet gives released a lot of high energy immediately within a very short time and cells then undergo double stranded DNA damage. And because it has a relatively short half life, it also seems to have an ideal waste management and the safety profile so far so good. Of course, we need to explore further in patients. So all in all, we think that the darpines are the ideal partner for lead and that's what we are going to establish in the future. So moving on to Slide 11, let's quickly have a closer look at why Oronomid is really one of the leaders in the targeted alpha therapy field.

Speaker 5

They are one of the pioneers. And I think the very, very big reason to mention here is they have the supply chain fully under control with virtually unlimited starting materials. You see a picture, these 22,000 drums of two Thorium, that's where it starts with. So there is really unlimited supply. Ranamet also recently validated their approach by an agreement with Sanofi, which is, of course, one of the pharmaceutical players in the field.

Speaker 5

And that included their meat asset, the AltaMedix program, which is showing very nice clinical data presented last year at ASCO. And of course, there are a couple of technical advantages that's how our teams chose to focus on that. Again, the short half life makes it relatively easy for patient administration. They don't have to stay very long until they are so called cleaned, waste management risk and asset and the very high energy release from the alpha emitter with a clean decay chain. So lots of reasons to believe that this is the ideal isotope for us.

Speaker 5

We didn't stop there. This partnership was greatly expanded and that's what really changed late last year and the beginning of the year we announced it around JPMorgan. So it's a global partnership expansion more and above and beyond what we had before. We're now basically together the owner of 10 products that are composed of lead and protein moiety. And the first one has been designated MPO-seven 12.

Speaker 5

I'll talk in more detail. That's our DLL3 program. And we have also announced the mesothelin, our second dalpine program together with the one hundred and fifty fifth cost share and split. Beyond that, we have two MPO programs, number five and six here, where there is an opt in, and then we have another four MPO programs. So we have a very rich supply chain, so to say now for lead based programs.

Speaker 5

So let's go one step closer. That's Slide 13, our first program that we are really very, very actively involved in development Most patients initially, we will be treating our small cell lung cancer patients. They have a very high unmet medical need, relatively low five year overall survival. And most importantly, the target was validated last year by the approval of HEMTEN's tarlatanab in Deltra. So we believe there is room to do to get results above and beyond tarlatanab, but it's also a proven pathway for approval.

Speaker 5

If you look again at the right picture, seven twelve, that's the darpine that we added some albumin binding half life extension to. So it's composed of three essential parts, the darpine binding TLL3, the albumin binding royalty and the LAD212 radioisotope. Moving on to the preclinical results, just to be very brief here, please feel free to ask questions. This was presented late last year, a very potent molecule. And the potency is very important because the target is actually expressed at a relatively low level.

Speaker 5

You see the brownish stain at the left, so there are different tumors, but the small cell lung cancer tumors we are staying in with a relatively faint brown color, which means in the molecule that is very, very potent. Cetus A in the middle, that the biodistribution, we get exceptionally high values at the tumor, thanks to the design of the molecule and much above the kidney. So we also feel we have a good safety window and very nice to see in this xenograft study on the right that we saw complete and durable regression in that very relevant model at a dose that is probably the right dose clinically. So with that, I think we can look at what the clinical program will be like. So there are many parts to the program.

Speaker 5

And as you can see, there is a green box that's the Phase zero component focused on imaging. And from the imaging, you can calculate then the doses for the various organ. And this together should build the confidence that we reach relevant therapeutic levels in the tumor lesion called dosimetry, probably about 10 patients in the use should be enough. And we anticipate these studies to start in the second half of the year. The initial Phase II, Phase zero imaging will be complemented by a therapeutic part, Phase IIa study in patients.

Speaker 5

The first part, dose escalation with the main objective to establish the safety and the recommended Phase II dose thinking of about 15 to 20 patients. Of course, we need to get the buy in from the FDA. And then the Part II will be the dose expansion where we hopefully can also go a bit beyond the small cell lung cancer patients, so including neuroendocrine carcinoma and of course, looking then for responses and response rate, which will lead then and we don't know exactly when in the future to a registration study. And of course, there could be more than one registration study depending on the integration and the line and maybe other factors. Moving on to now something completely different, our second program just in a nutshell.

Speaker 5

I'm very excited about this one because it has a true darpine differentiation. We have found darpines that are very specific for the membrane proximal epitope shown here in pink and therefore not disturbed by a lot of very high levels of SHAP mesothelin that has hampered previous approaches. So that's the unique power of adalpine that can discriminate very small differences. And again, it's adalpine with a half life extension and led to trough. This will take some time to finish the preclinical development and the manufacturing, but hopefully, we can also report on that progress during the year.

Speaker 5

Note that there will be a poster at AACR, which is, I believe, late April with more preclinical data. And just to conclude my part, there is one important biochemical distinction. You see here a graph in the middle on Slide 17, where we have added SHET mesothelin in high concentrations. And the distal darpine, which binds an epitope we don't like so much, so it's also then inhibited by shap mesothelin, very different profile in the curve from the proximal darpine that's binding the membrane epitope and that's totally maintained by ensures total maintained binding throughout the whole activity race tested. And again, this will be shown at AACR twenty twenty five in late April.

Speaker 5

So again, very excited what the teams are doing together with Olinumet, fantastic collaboration partner and very excited to look both back, but especially forward throughout this year to have first patient result from these programs. Thank you very much. And with that, I hand over to my good colleague, Philip, who is running the whole from the medical side and will talk today about the $5.63 program. Thank you all.

Speaker 3

Progress of our $5.33 DARPAIN. Can you hear me?

Speaker 1

Yes, we can hear you now. You're good. Go.

Speaker 3

Okay. So I restart. So again, thanks, Nishi, first. And I am very happy to share an update on the progress of our five thirty three DARPAIM, which we are developing in AML. On Slide 19, basically, let's remember, it's important to remember that AML is a very challenging disease because of the heterogeneity of the cell population as well as the difficulty to kill the leukinix stem cells, which tend to persist despite treatments and they drive the recurrence.

Speaker 3

So we have DESIGN five thirty three as the first tetra specific T cell engager that recognizes the ML blast and the LSCs, leukine stem cells, through their co expression of either CD33, CD123 or CD70 and kills them when they express at least two of the three TAA simultaneously. By doing that, this multi specific approach has the potential to open the therapeutic index and particularly kills the endocrine stem cells more effectively than a single simple targeting single targeting agent would do. Moving to Slide 20. So this slide describes the clinical journey that we have studied two years ago. When I reported last year, we were still in the blue left part of the schematic.

Speaker 3

We are now reporting on the orange middle one and we will be initiating soon a new amendment corresponding to the green. In the initial dose escalation cohorts on the left, the blue, we were able to understand the manageable safety profile of the drug up to CORT7 and obtain signals of efficacy, however, too low and not durable enough. Then what we did is we identified with a group of international experts that we had in fact too much loss of exposure, likely due to the multi target antigen sync. Let's remember, we are targeting three antigens two to three. And so at that time, we initiated a First Amendment to accelerate the step up dosing and densify the regimen by adding an additional dose during the first fifteen days at day 12.

Speaker 3

And I'll show you the results of that and basically that we have now significantly increased the efficacy and we are now very encouraged to further accelerate that step up dosing and have a more frequent administration, particularly during the first cycle. This new amendment corresponds to the green schematic and has been submitted to regulators. Moving to Slide 21. You can see on the left swimmer plot corresponding to the blue part of the dose escalation, during which we saw some initial responses, however, not enough and not durable enough, as I already said. On the right part, you can see that the outcome after the initial amendment and the initial step of dosing and one level of densification.

Speaker 3

And you can see that this now appears to be very promising with three CRs out of eight patients that were treated past day 12. Moving to the next slide, which is a waterfall. That slide in a way that visual adds one level of granularity to the document, to document the blast reduction on top of the full ELN criteria. And we can see here that the drug had effect with approximately half of the patients having reduction in blast even during the dose escalation. However, the new amended cohort certainly has more.

Speaker 3

And also this helps understand that most of the patients that have blast reduction had a lower disease burden at baseline as is frequently seen for effect for T cell engagers. Moving to the next slide, Slide 23, it's a key slide. Because when we discussed the blue curve representing Court six with our experts, they were even surprised that we had even responders and blast reduction because as you can see, there were only very few concentration peaks in the effective dose range on day eight, day 15 and day 20. So very little stimulation or effective stimulation to generate that blast reduction or initial responses. And this is what is very interesting is that in the recent amendment, so corresponding to the orange curve, we see that there that in those orange curve, the concentration achieved effective ranges at the eight, twelve and fifteen for significantly more time.

Speaker 3

And we hypothesize that this component supports the higher activity that we see in this new cohort. So based on that learnings on those learnings, we have now built on this finding and are further densifying the dose and also introduce a B cell depletion pre medication to also reduce the proportion of patients who were developing ADAs at the end of the first cycle. So we basically, it's a two pronged approach, more densification to generate deeper response, more responses and a B cell division to make sure that we have a maximum of patients that have long exposure beyond the first cycles. So Slide 24, describe the further amendments, which is currently in review. And we anticipate to initiate it soon and communicate outcome of those new cohorts in by the end of the year coming.

Speaker 3

Okay? So I'd like to expand a bit on this now, meaning that the first experience regarding T cell engager has driven us to develop further the platform. And we have initiated programs in solid tumors, where it is key to manage the on target of tumor risk of toxicity. And you may know that there has been some good level of excitement recently on that topic with development from companies like Genux. So Slide 26 is an example of how we are integrating the concept of masking the CD3 binders in absence of TAA as well as the concept of coactivation to mitigate the risk of T cell adorption.

Speaker 3

So it's two scientific concepts integrated. And more precisely, you can see on the left schematic that the Dardpen has the CD3 masks in circulation. And on the right that when engaged with the first TAA like here mesothelin and similarly with a second TAA like EpCAM, this will free the CD3 binding to the T cell. And the CD2 co activation does potentially de immune mobilization. So this is a very sophisticated approach, highly relevant, we think.

Speaker 3

And again, some others are analogy others analogy to what all of us doing, but we think that we are doing it in a very sophisticated manner. And I will share further detail

Speaker 2

of this interesting approach at the upcoming AACR. So on this, I want to thank you. And I will pass again the phone to Patrick. Thanks, Filip, for these very nice explanations and also showing us how we have worked through some challenging settings and findings to give especially five thirty three the best chance to succeed and help these patients. Let's have a look at what we can expect in B25.

Speaker 2

I will start on the radio side. And I think there, as Michael pointed out, we are really excited by the perspective to share that the first clinical data of 07/12, the radio DLL3 program. We do start with imaging, as he explained, that it's a Phase zero approach, and then we can do dosimetry and have then clinical results in efficacy and safety in 2026. And let me just take a minute here because in most instances, your Phase zero imaging is maybe not that relevant. This is different here.

Speaker 2

We will have the understanding of how much of the drug will be in the tumor and how much will be on the healthy organs. And for those who are less familiar in the story, the one organ we're really zooming into and excited to then see results is the kidney, because most of these approaches have high kidney absorption. So we'll be first and foremost looking for a tumor to kidney ratio. And should that be positive in the dosimetry, that is an exciting moment to move the program forward. So the imaging holds real value for molecular partners and the whole radiodar pin pipeline.

Speaker 2

Meza will go forward, we will update that at AACR and we will definitely not stand still, but add additional programs that are some fully owned by us, others likely also moved forward by OraNomed. Moving to five thirty three, as we just heard from Philip, we are now at this moment where we can test maybe the optimized or even optimal dosing for this compound in a deadly disease. So that is a highly exciting moment for us. That's the reason we go to work to test our drug in the setting where it helps patients and we will be able to update with more data from cohort one in H1 and for sure in H2, this new amendment that Philip was talking about will be in place and be delivering results, guiding us on response rate and especially also on duration of response. On the switch side, as I said, we are there moving forward, hopefully a first candidate can well be the mesothelin or maybe another one.

Speaker 2

We're still looking at a few. We're also opening for partnering, be it six to one or also on the T cells because we will not have the bandwidth to move all options that this new platform gives alone. Cash situation strong, almost boring for us, but I think boring in this market is a good thing as many biotechs are struggling for funding and we are in a position that we can execute our plans, move forward, bring value to patients that will then also move into value for shareholders. Now before opening for questions, this is a moment to also thank you for dialing in, thank the presenters that I had on the call and they obviously just present the tip of the iceberg of the Molecular Partners team and that team really makes all this work. All those hours, all those troubleshooting, all those coordination meetings, moving things forward, big thanks to everyone at Molecular Partners, highly and full of gratitude to be able to be part of that team.

Speaker 2

We don't do this alone. We do this with partners. I think the name Oronomet was said many times, big thanks there. Also to Novartis, without Novartis, we would not be in this call, we would have not moved forward in radiotherapy. And it is maybe more on a personal side said that we're not continuing that one, but I'm sure there will be opportunities also with Novartis to move things forward in the future.

Speaker 2

The troubleshooting not only happens in our four walls, we are very closely with our investigators, KOLs, experts that know our drugs, big thanks to them. And I do think the last and possibly most important thanks goes to the patients that are in our trial that are part of them and allow us actually to test these drugs early on to see if they actually do what we want them to do. With that, thanks for everyone diving in, especially also the analysts that cover us for these many years for those ten years. Some of them have been doing it for ten years. Big thanks for that and looking forward to your questions.

Operator

We will now begin the question and answer session. The first question comes from Jonathan Chang with Leerink Partners. Please go ahead.

Speaker 6

Hi guys. Thanks for taking my questions. First question on MP-seven 12, can you provide more color on where you are in the IND submission process and preparations for study initiation? And how should we be thinking about the initial clinical data by year end? And then second question, can you discuss why you think mesothelin is a good target for radiodarpans?

Speaker 6

Thank you.

Speaker 2

Mickey, are you on? Because I think that is goes directly to your area of expertise.

Speaker 5

Yes, I can start and then please continue. So thanks, Jonathan, for the question. I'd love to sit down with you in more detail and go over, but just give you the top line. So as I said, late last year, we started 2025 with the GMP manufacturing that has moved forward really nicely. Of course, there are a lot of technical challenges to be overcome, including logistics.

Speaker 5

Q2, so next quarter will be the submission, maybe there are several ones to the FDA. And that's where hopefully then in Q3, we can open the first part of the program, the imaging part. And in the latter part of the year, so I'm not exactly sure where we will be. We will then have the first therapeutic doses. If FDA agrees to our proposals to start close to therapeutic dose rates, we should see something maybe in the first two dose cohorts.

Speaker 5

And as you know, probably tumor shrinkage and then also the duration of it will probably take a bit of time. So early twenty six will be then the clinical data from the therapeutic part, submission in Q2 anticipated. Your, I believe, third question, mesothelin, why is it a good target? Excellent question. Of course, we are hoping it will be a good target.

Speaker 5

There is certainly a high medical need in the ovarian cancer patients and mesotheli expression is very high there. Whether it will be perfect for alpha emitter molecule, we need to establish. It looks good pre clinically, but whether it will then work, that depends to the future data. There are a number of programs also using other modalities. But I hope with the alpha radiation of lead, we can tackle these tumor cells.

Speaker 5

Maybe over to you, Patrick, anything to add from your side?

Speaker 2

Yes. No. And we often get the question on mesothelin because it's, let's say, in public, it's a bad target because others have failed on it and are not moving. I think as what we do is we go back and we triangulate the data and it's also a phrase we use internally, we like to work on clinically validated problems. And in this case, as you said, Michael, ovarian is immune more silent.

Speaker 2

So you don't have that much effect. You often have chemo resistance, so and also not the highest response rate for ADCs. And meso was in principle a good target, but the shedding and the high level of free target made it a very difficult approach for radiotherapy because you don't want to be binding shared target being in the body everywhere and having an on target of tumor effect. So this is the hypothesis that ovarian will be radio sensitive when delivering an alpha via mesothelin. The target very difficult for peptides to do.

Speaker 2

So we don't expect anyone from the peptide field to be able to crack that one. So it is DARPA unique and differentiated. And that's the thesis that we will have to prove. If it works, the good thing is I do think we are very differentiated versus other radio approaches.

Speaker 6

Understood. Thanks for taking the questions.

Speaker 7

Thanks, John.

Operator

The next question comes from Richard Vosser with JPMorgan. Please go ahead.

Speaker 8

Hi. Thanks for taking my questions. I wondered if you could just explore learnings taken from the Novartis programs before they were discontinued. What you could take there? And also whether there were any issues with the DAPN hitting the target?

Speaker 8

Or was this, as you said, just the targets don't work or they've been deemphasized? And then a second question just on you mentioned the key for seven twelve is the kidney ratio to target ratio. So what could be if you could help us with a good level on that ratio that we should be looking for when we see the data and you'll be looking for? Thanks very much.

Speaker 2

Thanks, Richard. I'll start off with Novartis one and then I'll hand over to Michael. I think when and we started this three years ago and that was really our first steps into radio. And we learned a lot by sharing and learning what profile makes a good radio therapeutic. So tumor to kidney and Michael will come to that, half life.

Speaker 2

And this is all also gauge to which isotope you need and you apply. And der Novartis is obviously Lutetium and more recently Actinium, while we are going towards lead for different reasons. The learnings, I mean, I can't be too detail oriented here, but the one thing we all agree in this field is you have to test many candidates, meaning many different sequences to find the optimal tumor to kidney ratio and you need to have the right models up and running and different models will give you different insights. And it was very helpful to compare notes on the models, how to run the models, how to use the models, and at the same time, find what can you learn and what can you not learn from these models. And I think you have to understand this field is still in the early days.

Speaker 2

And for the DLL3 molecule, I think we were in iteration seven or eight. So that's the seventh generation that we have. With Novartis, just given the broad pipeline to have and the way they operate, we think never made it by on level three. So it was maybe not that fast cycling. I do think that I'm fair to say, I've said that on stage that that was also learning for Novartis and that was one reason they acquired Mariana to have hot labs faster, to be able to cycle faster, to test more in shorter time.

Speaker 2

At the same time, the targets they picked, which were very reasonable three years ago, did not like half the data or the excitement building. Like DLL3, when we started was also not present. And then with tarlatanov and all the excitement, it validated itself. These targets are still as unknown, I would say, as they were three years ago and nothing has built around them. So when you come to this moment, say, should we now invest another three, four cycles, maybe it will yield, maybe not.

Speaker 2

On a target that today neither Novartis and us puts to that top of the list, We sort of together said, let's end it here, see how this goes on, and then rather reengage when we actually have a candidate. I mean, this is a research phase. But the learning was really good. Collaboration was good. Scientifically speaking, I think both teams really liked that and we'll see where it goes.

Speaker 2

I think I can also say that Novartis wants to see clinical data on lead. Now we're talking about the isotope. They have obviously seen Oranomed, but for Novartis to add a third isotope to their ward chest that would need clinical data or definitely what they're saying publicly. Maybe Mihi, could you be a bit, or could you take seven twelve tumor kidney?

Speaker 5

Yes. Thanks, Richard. And also here next time we'll meet, let's take the time and sit together, say, look at the piece of paper or the laptop screen. I think the challenge is in animals, it's relatively perfect. So you can control everything, you can give a number and pre clinically, you've probably seen this before, we like to go above one.

Speaker 5

So ideally two to one tumor to kidney. And then of course, sometimes there is a question which time point do you integrate over many time points. So animal model is relatively easy. In patients, we need to learn clinically whether there is exactly the same translation. In the end, it boils down to the therapeutic dose we can deliver.

Speaker 5

So ideally, we have, as Patrick said, more of the uptake in the tumors, but I'm pretty sure it depends on the tumor size, the blood perfusion, whereas the kidney will be probably relatively similar from patient to patient. So if we can deliver a therapeutically relevant dose to the tumors and we're speaking in the order of one hundred megaaccarat per dose and the kidney stay below the safety limit that is at the moment accepted, so several grades. But it's exactly one of the questions we don't know for sure whether the kidneys for alpha metoliglad have the same limit. So we will have the discussion with the FDA who will propose our dose escalation rationale. And I'm pretty sure it will be similar to preclinical data, but I would not look for a specific number because tumors in patients are very different.

Speaker 5

So on average, I hope it's above the kidney value, but maybe in the end it's about therapeutic link dose.

Speaker 8

Excellent. Thank you.

Speaker 5

Thank you, Jeff.

Operator

Thanks, Richard. The next question comes from Mike Pszczolkovich with TD Cowen. Please go ahead.

Speaker 9

Hi. Thanks so much for the questions. I have two. When it comes to DLL3 and radiotherapy, do we know you mentioned the kidneys, which I believe is nonspecific off tumor uptake. Do we know are there any on target off tumor DLL3 expressing organs we should be concerned about when we see the first imaging or dosimetry data?

Speaker 9

That's my first question. And then my second question is on the switch DARPAIN platform. This is very unique and very promising. How do you think about partnering in terms of the scope and scale? Would you be pursuing a partner for an individual molecule or more kind of platform wide?

Speaker 9

Thank you.

Speaker 2

Maybe Filip takes the first question on DLF3 and I'll be happy to talk a bit on the platform or candidate partnering. Yes. So thanks, Mike.

Speaker 3

DLL3 is a clean target. That's why there is so much excitement about it, I would want to say. And experts are very excited, in fact, based on the recent accumulation of experience, which has a conveyed on the antibody on the ADCs or on the radiopharma approaches. So there is a body of experience, which is still early, but rapidly shaping. And I think what we know from the programs is that pituitary gland is the only place, which is has some level or a mini level of DNF expression.

Speaker 3

All the rest is clean. And when we looked at the tadalatanab experience, for example, they did not have any specific safety profile. And of course, we checked on the pituitary gland and there hasn't been any adverse event that makes think that would be an issue. But of course, technically, if I could say there is little expression there outside of the tumor. So that will be the one that will watch.

Speaker 3

Although again, we are not very worried because if there hadn't been a problem, we would have seen it already. So that's so very clean target and we are confident, obviously, and as we're preparing our protocol, obviously, what are the adverse events of special interest and that this is short for us, but also for the others.

Speaker 2

And maybe just to add, because there is a big hype on DLL3. So I think on the target, people totally agree that that is, call it validated and a very good target to go after. And we just had dinner with a PI that is in many trials. And for me, what was reassuring to hear is that the different modalities and we're talking T cell engagers, ADCs and radiotherapy that he also said there is a need for all of them. None of them will cure as of now and the sequence and how we can actually develop them, it was very exciting for him.

Speaker 2

And he actually sees a big place for the radiotherapy there, even a bit in an earlier line to help the others move forward. But thanks for the question. I'll take also the partnering one. And the question is great. I mean, some partners like to work on a candidate.

Speaker 2

These are either companies that have a specific need. Let's say you're just take this as an example, you are in breast cancer and then you want a breast cancer target and candidate for the pipeline and ideally then we have a candidate there. You sort of are the missing piece in the puzzle. As you don't know and kind of in which puzzle you fit well, that is sort of an opportunistic one. You obviously look who's what do we have, which candidates do we have and where would they fit.

Speaker 2

That is one part of the partnering versus the other. The big pharmas obviously take long shots. They see that they want to fill their pipeline over time And often they say, okay, your targets are a nice showcase, but can you do these? And both discussions are valuable. Obviously, if you have to start from scratch, that's been eighteen months, thirty, yeah, two to four years of research and development as we just saw with the Novartis collaboration.

Speaker 2

Usually they come with a good upfront because there is high risk. So you have to also commit something there versus a candidate that is ready to be in the clinics within the next eighteen months. That is exciting. At the same time, it has that puzzle piece has to fit and we don't know sometimes where it fits. So both we're looking at, we're looking into both, discussions are ongoing and we will see how they develop from here.

Speaker 9

Thank you so much.

Operator

The next question comes from Kiara Monterone with Kempen. Please go ahead.

Speaker 10

Hello, Tim. This is Kiara from Kempen. Thanks a lot for taking my question and congratulations with the update. On 07/12, I was wondering, the Phase zero and one will not run-in parallel, right? So did I understood correctly that the Phase one start is contingent upon good imaging data or am I wrong?

Speaker 10

Thank you.

Speaker 3

I can take yes, go ahead, Nikit.

Speaker 5

Sorry, Philip. Thanks a lot for the question. It's a really good one because we are proposing to the FDA that it should not depend on each other. We want to do them in parallel. We have the required animal data to argue for the parallel start.

Speaker 5

But in the end, of course, we will listen and have to live with what FDA decides. So stay a bit with us, ideally in parallel, but it's a regulatory question. So and if that is, I think we'll probably keep them together just a few months apart because patients like to be treated and not just image stores for the patient. We keep them closely staggered.

Speaker 10

Yes, of course. Thanks a lot. Really helpful. Welcome.

Speaker 2

Thank you.

Operator

And the last question today will come from Juris Zimmerman with Octavian. Please go ahead.

Speaker 7

Yes. Hi, Patrick and team. Thanks for the presentation and for the opportunity to ask questions. I have a short one, I guess, on just on the structure of your deal with Autonomy. If you could elaborate a little bit on how those different programs are split between the two companies?

Speaker 7

I mean, you've nicely depicted that on Slide 12, I guess. Just to understand, so the later programs will be fully owned by you and then there is two with opt ins, but who will take the commercial lead for those and then also for three and four, is it correct that this will be mainly led by Oronomid?

Speaker 2

Yes, no, thanks for the question. And this is a good opportunity to quickly explain how the deal works. And I'll do a short recap of how this all came about. So we started the collaboration on NTA with Oronomid on the DLS redarpin. And, so that was sort of call it the honeymoon.

Speaker 2

And we had made very good progress on it. And then we said, okay, let's move forward. At that point in time, we did a deal with actually three targets or three products of these were both fiftyfifty. We got the first, the idea was they would take the second and then the third, we would see how that develops. And I think we have underestimated the speed and productivity of what we were doing.

Speaker 2

And so what had happened is that we took the first, but then mesotheli came about and we had to approach them and say, actually we have a second. And then there was an imbalance. So we said, okay, then let's add a fourth that we get one and two and they can have three and four in the fiftyfifty, but commercial lead for one and two are with us. In the meantime, they were successful in their Phase two and did a massive deal with Sanofi bringing in $400,000,000 for late stage development and commercial supply. So they have a clear mandate now to put that money to work, build the manufacturing sites, build the last mile, build the logistics.

Speaker 2

So Sanofi is not doing that, that will be with Oronomid. And it's sort of, I would say it is clear where their focus is. And so we were like, okay, we have one and two, you have three and four, and your focus is late stage, let's sit together because we cannot wait until you move to your programs, we want to do more. And then where this win win situation happened where we said, okay, let's add six. Molecular partners can move them forward and add early clinical phase zero ish data, Oronomib can opt in into two, while four will remain with us.

Speaker 2

So I'm not going to go into all the details, but you see, we are helping each other. They have time, focus, money to build the late stage. We are working a bit more on the early stage and they also get done with the opt in what they need to build their pipeline. So for me, it's a beautiful example of a win win situation. And I do think on value, this has gone very much under the radar that we have 10 products worth of lead supplies with the most advanced and credible partner you can have.

Speaker 2

So big thanks to them. Indirectly also big thanks to Sanofi for putting all that money to work and we're ready. One point also, these are commercial products. So if number eight would fail in Phase three, even then we can go back and replace it. So these slots are up to commercial stage.

Speaker 2

So if you want, this is a thirty-forty target setting you can do. We don't have to, we can also do other isotopes, but I would say for lead, we have access to whatever we need.

Speaker 7

Thanks very much. That makes a lot of sense. Maybe a very quick follow-up, you mentioned the high productivity. So how should we think of timelines and frequency of you and Oronomid disclosing the additional programs?

Speaker 2

Yes, that's a good question. And that's sort of like, you never communicate too much what you're doing in research because it is so risky. And if I will give you an update on our pipeline today in research and a year later, a lot has changed. That's why it's always that we're careful. But I think it's fair to say that my guess is we'll have two new targets that we will be talking about this year and also new, call them, technologies that we're testing.

Speaker 2

So it's not that we are waiting in radio and sitting there, but we're also evolving our platform for next generation as we go. So I think in all fairness, roughly two targets per year is likely a productivity that is fair. Pending the results of seven twelve,

Speaker 3

obviously we

Speaker 5

can ramp up more.

Speaker 2

There clinical data will be key. If that looks as we hope for, then let's move forward and do more.

Speaker 7

Thank you so much.

Speaker 2

Thanks.

Operator

This concludes our question and answer session. I would like to turn the conference back over to Patrick Amstruts, CEO for any closing remarks.

Speaker 2

Yes, thanks again. Twenty years Molecular Partners, twenty years innovating and bringing DROPs forward. I'm also proud on the timing. This is almost with timing. We're right on the hour as we had planned.

Speaker 2

So also thanks and thanks for all the great questions. We're off to an exciting year. We'll keep you updated as we collect the data. We'll also work closely with you to give you the what you need to understand the data as we're doing that. And also I'll end with a big thanks to my team, treating physicians and especially the patients.

Speaker 2

See you all soon. We're at many conferences going forward, so reach out and we'll be in contact.

Operator

The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

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Earnings Conference Call
Molecular Partners H2 2024
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