Full Year 2023 Molecular Partners AG Earnings Call

Operator: Good day and welcome to the Molecular Prtnrs fourth quarter and full year 2023 results conference call. All participants will be in a listen-only mode.

Good day and welcome the molecular partners fourth quarter and full year 2023 results conference call.

All participants will be in a listen only mode.

Operator: Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star and 1 on the touchtone phone.

Should you need assistance. Please signal a conference specialist by pressing the star key followed by zero.

After todays presentation, there will be an opportunity to ask questions.

To ask a question maybe for star and one on a touchtone phone.

Operator: To withdraw your question, please press the star then. Please note, this event is being recorded. I would now like to turn the conference over to Seth Lewis, Senior Vice President, Investor Relations. Please go ahead.

She was try your question. Please press Star then two.

Please note this event is being recorded.

I would now like to turn the conference over to Seth Lewis Senior Vice President Investor Relations. Please go ahead.

Seth D. Lewis: Thank you, Betsy. And welcome, everybody. This is the 2023 full year earnings call for Molecular Partners. My name is Seth Lewis, Senior Vice President of Investor Relations. I wanted to just go over a little bit of housekeeping before we began.

Thank you Betsy and.

And welcome everybody good morning, and good afternoon to.

To be a 2023 full year earnings call for molecular partners. My name is Dr. Lewis Senior Vice President of Investor Relations.

I wanted to just go over a little bit of housekeeping before we begin obviously, we are speaking today in reference to the press release, which was issued after the close of market yesterday as well as the full year annual results, which are in the annual reports, which can be found on our website molecular partners dot com and we will be making reference in prepared remarks.

Seth D. Lewis: Obviously, we are speaking today in reference to the press release, which was issued after the close of market yesterday, as well as the full year annual results, which are in the annual report, can be found on our website, molecularprtnrs.com. And we'll be making reference and prepared remarks today to the presentation, the slides of which are also available under the investors section of our website. Partners.com, If you are following along in the presentation, I will refer to you. We are going to make certain forward-looking statements today, and I would refer you to our latest filings, and most recent. For the sake of the replay today, we are.

So the presentation with slides are also available under the investors section of our website like apartments Dot com.

If you are following along on the presentation I will refer to you we are going to make certain forward looking statements today and I would refer you to our latest filings.

Most recent.

<unk> filings with the SEC and with the six four.

For the sake of the replay today, we are recording this on March 15th 2023.

If you were on slide three I just wanted to take you through the agenda briefly.

Seth D. Lewis: I just wanted to take you through the agenda briefly. We are joined today by multiple members of our management team and Patrick Amstutz, our CEO. Robert Hendricks, our Senior Vice President of Finance, who will go over... Philippe Lejeune, who is our Acting Chief Medical Officer, who will discuss our MTL533 program. Anne Goubier, our Senior Vice President.

We are joined today by multiple members of our management team, including Patrick <unk>, Our CEO, who will take you through both the highlights of 23 and the outlook for 2020 for.

Robert Hendricks, our senior Vice President of Finance, who will go over some of our financial numbers.

Numbers, Philippe Jett, who is our acting Chief Medical Officer, who will touch on our MTO $5 33 program in AML M D S.

And <unk>, our senior Vice President of research and early development, who will discuss the switch DARPA and technology as well as our secret program.

Seth D. Lewis: Research and Early Development, who will discuss the Switch Darken technology as well as our C-Kit program, and Danny Steiner, our Senior Vice President, Research and Technology, who will touch on the radio platform. LLC. With that, I turn it all over to Patrick.

And Danny Steiner, our senior Vice President Research and technology, who will touch on the radio Darden platform a M P.

D L three program.

With that I will pass the call over to Patrick. Please go ahead.

Patrick Amstutz: Please go ahead. Thank you, Seth, for the introduction and kicking off our full-year earnings call. And also, a warm welcome from my side to all the audience on this call. And it is a special pleasure today to be here not only with the usual suspects, Robert and Seth, who are usually on these calls, but also to have Philip, Anne, and Donny on the call with me, as they are the ones who are really driving the progress of our programs, and they will be speaking about that progress here today, and that's a special pleasure I'm now moving to slide number four, and I will. Let's start with a short recap of what we do and how we do it.

Thank you Seth for the introduction and kicking off our full year earnings call and also a warm welcome from my side to all the audience on this call.

It is a special pleasure today to be here not only with the usual suspects Robert and Seth who are usually joining these calls but also drive affiliate and Donnie on the call with me as they are the ones who are really driving the progress of our programs and they will be speaking about that progress.

Here today, that's the special pleasure to see the team coming together and move molecular partners Fort worth.

Now moving to slide number four and I will.

Start with a short recap of what we do and how we deal with.

Patrick Amstutz: The DARPIN is a novel therapeutic modality, a novel class that we have validated in more than two and a half thousand patients with seven clinical compounds. And the DARPINs are different from other modalities, so not antibodies, not small molecules. They are the size, maybe a tenth of an antibody, and they're really well applicable for multi-specific.

But our opinion is a novel therapeutic modality a novel class that we have validated in more than 5000 patients in seven clinical with seven clinical compounds and the dart bins are different to other modalities do not antibodies not small molecules there or the size maybe it tends to.

And anti body and there really well applicable for multi specifics and our quest is to use the GARP indifferent to turn that into differentiate trucks. So what we do is we create unique dark pin solution two clinically validated problems that are up high medical.

Patrick Amstutz: And our quest is to use the DARP indifference to turn that into differentiated drugs. So what we do is we create unique dark pin solutions to clinically validated problems that are of high medical need. So true patient value means high medical need.

Neat so true patient value means high medical need and we termed the early clinical readouts that you can translate into single agent activity as why do we move the drug into development. We also will want to know if it works or not fast.

Patrick Amstutz: And we termed the early clinical readout that you can translate into similar agent activity as when we move a drug into development. We also will want to know if it works or not fast. And as we are working in many different fields, we love to work with partners so we don't have to reinvent the wheel.

And as we are working in many different fields, we love to work with partners that we don't have to reinvent the wheel and that is why that are named molecular partners and our strategy.

Patrick Amstutz: And that is why the named molecular partners and our strategy of partnering with those or collaborating with world-class partners is part of the strategy. I'm moving to slide number five. The 23 was an exceptionally productive year with progress on literally all of our programs, and those who are working in our field know that that's usually not the case. Often, there is a setback in one or the other program, but this year, every single one was moving forward at speed and producing the results we were looking for.

Partnering waste those are collaborating with the world class part for US is part of the strategy.

I'm moving to slide number five.

That 23 was that an exceptionally productive year with progress on literally all of our programs and those who are working in our fields no that that's usually not the case.

Often want have a setback in one or the other program, but this year every single one was moving forward at speed and producing the results we were looking for.

Patrick Amstutz: First and foremost is MPO533, our tetraspecific T-cell engager. A year ago, roughly, we dosed the first patient. At ASH, we reported good safety and efficacy of the first four cohorts, and today, we are recruiting, or we have fully recruited, those cohorts. On the switch platform, we were able to nominate the first target, and we're working towards a candidate, and we'll talk about that. We are absolutely excited as the switch concept is something that is very dark and unique, and you will see we will be able to target targets that are not easily accessible in other ways.

First and foremost, it's MTO 533 hour Tetra specific T cell engage her a.

A year ago, roughly we dosed the first patient at Ash, we reported.

Good safety and efficacy of the first four cohorts and today, we are recruiting or we are fully recruited dose cohort six.

On the switch platform, we were able to nominate the first.

<unk> and.

We're working towards the candidate and we will talk to that and we are absolutely excited as the switch concept is something that is very dark and unique and you will see we will be able to target targets that are not easily accessible other ways.

Patrick Amstutz: On the radiotherapy side, this is a whole field Molecular Prtnrs is heavily investing in; there are two key breakthroughs of the last. One is the reduction in kidney retention or accumulation, and we were able to now increase tumor uptake by engineering half. We were able to strike a collaboration with Oranomet, providing lead for our lead asset DLL3, and we have progressed with Novartis on the targets and programs we are working on with them. Those are two distinct targets that are exclusive to Novartis. 317 We have advanced through phase one. We have those several patients and could see a favorable and strong safety profile, and we have biological proof of concept showing activation of antigen presenting cells and remodeling of the tumor microenvironment. And we end the year with $187 million, and this brings us well into 2026, meaning we are capitalized to reach key value inflections.

On the radiotherapy side. This is a whole field molecular partners is heavily investing in there is two key breakthrough after last year. One is the reduction in kidney retention, our accumulation and we were able to now increase tumor uptake by engineering to half life.

We were able to strike a collaboration with Iran. Omit providing led also for our lead asset <unk> three and we have progressed with novartis on the targets and programs. We're working with them. Those are two distinct targets that are exclusive to novartis.

317, we have advanced through phase one we have several patients and could see a favorable and strong safety profile and we have biological proof of concept showing activation of antigen presenting cells and remodeling of the tumor microenvironment.

We ended the year with 187 million and this brings us well into 'twenty six meaning we are capitalized to reach key value inflection.

Moving to slide number six this is the pipeline chart, then sort of as my agenda for the next protocol 317, I did speak about that the antigen presenting cell activator based molecule has little single agent activity is ideally combine.

Patrick Amstutz: Moving to slide number six, this is the pipeline chart and sort of is my agenda for the next call. 317, I did speak about, that's the antigen-presenting cell activator. This molecule has little single agent activity.

Robert Hendriks: It is ideally combined with other IO drugs. That's why this is on the partnering track, and I will talk about that in the summary, but we will not cover it in the presentation itself. 533 Philip will talk about it, and we'll talk about the switch start pin and explain that, and Tonya will cover the radio. With that, before we go there, I will hand over to Robert to share the finances. Thank you, Patrick. With that, I'd like to run you briefly through the key figures of last year's financials and the guidance also for the year 24. My name is Robert Hendriks, and I'm the VP of SVP Finance at NP.

And with other Io drugs. That's why this is on the partnering trough track and I will talk to that in the summary, but we will not cover it in the presentation itself.

Three three Philip will talk about and we will talk about this late start pin and explained that Antonio will cover the radio piece.

With that before we go there I will hand over to Robert to share with that financial overview.

Thank you Patrick with that I'd like to run you briefly through the key figures of last year's financials and the guidance also a 40 year 'twenty for my.

My name is Henry I'm, the VP SVP finance at <unk>.

Pete.

Robert Hendriks: The numbers I present here are stated in million Swiss francs, and I'm on page 8 at the moment. Part of this number is the recharge of research FTE, and the other part is the recognition over time of the upfront of $20 million that we received under the December 21 agreement. Under that last element, we still have around $4 million to be recognized in 24. The revenue number in 22, as you may recall, is largely related to the funds we received from Lofartis in the early 22 upon their exercise of the option under the IMSOBED license agreement. The second number I'd like to point out would be the operating expenses, total of 68. The guidance that we provided during last year was 65 to 70. And the expenses ended right in the middle there. For a further breakdown, the R&D share of this number amounts to $49 million, and the SG&A number to $19 million. You can see that the overall costs have been reasonably stable over recent years.

The numbers I present here are stated in millions Swiss French and I'm on page eight at the moment.

The three numbers, it's a pool slides the three numbers in particular.

First one would be the revenue the revenue was $7 million. This.

This year is exclusively related to the agreement we have with Novartis on the radio leaving therapies as indicated.

Part of this number is a recharge of research FTE and the other part is the recognition overtime.

Front of $20 million that we received.

Under the December 21 agreement.

Under that last element, we still have around $4 million to be recognized in 'twenty four.

The revenue number in 'twenty two as you may recall largely related to the funds we received from Novartis in early 'twenty two.

The exercise of the option on the D and sobey the license agreement.

Second number I'd like to point out would be the operating expenses totaled 68.

The guidance that we provided during last year about 65 to 70.

And the expenses and it's right in the middle there Paul.

We're sort of breakdown the R&D share of this number amongst $49 million in SG&A number to $19 million.

You can see that the overall cost have been reasonably stable over recent years.

Robert Hendriks: It's fair to say that the reduction of just over $4.9 million last year related largely to a lower expense for the listing of the company in the U.S., as well as natural attrition. The third number, as already pointed out, would be the cash balance of $187 million. You can see that's down from the 249 at the end of last year, so an effective burn of 62 million. This amount will carry us well into 26, and we consider this continues to put us in a privileged position in the industry. Also, I would like to add and remind you here that the company remains without any debt. We feel that these three numbers tell the financial history of MPN 23 and the solid financial state of the company. If I didn't move on to slide nine on the guidance, I will. We will guide on operating expenses only, not on revenue or any other metric. We are guiding for a total of 70 to 80 million, of which around 8 million are non-cash.

It's fair to say that the reduction of just over $4 9 million last year.

Related largely to a lower expense for the listing of the company in the U S.

As well as a natural attrition in head counts.

Ah Stewart number has already pointed out could be the catch them $787 million.

You can see that's down from the $2 49 in the last year show, an effective burn of $62 million.

This amount will carry us well into 26 and we consider this continues to put us in a.

Privileged position in the industry.

Also I'd like to remind here that the company remains without any debt.

So we feel that these three number so the financial history.

Okay.

And 23, and the solid financial state of the company.

If I then move on to slide nine on the guidance.

I will we will guide on the operating expenses only not on revenue or any other metric.

We do guide for a total of 17 to 18 million, albeit shrunk 8 million on the cash.

Robert Hendriks: For clarity, this guidance is, as always, subject to the progress and changes in our pipeline and excludes any potential payments related to partnerships. To summarize and conclude, what I think is most relevant to recall from this overview is the continued solid financial base entering into year 24 that will allow us to continue to invest in our pipeline and bring drugs to patients. Thank you for your attention. I will be happy to take any questions during Q&A later. And with that,

For clarity this guidance is as always subject to the progress and changes of our pipeline and excludes any potential payments related to partnerships.

To summarize and conclude what I think is most relevant to recall from this overview is the.

Continued solid financial base entering into the year of 24.

Allow us to continue to invest in our pipeline and to bring drugs to patients.

Thank you for your attention happy to take any questions. During Q&A later.

It.

Philippe Lejeune: I will hand it to Philippe, who will provide an update on NPR-Pipe. Thank you very much, Robert. Good morning and afternoon to all.

I had two Phillips, who will provide an update on MTO price ratio.

Thank you very much Robert.

And good morning, and afternoon to AUM.

Philippe Lejeune: I am Philippe Lejeune, the Acting Chief Medical Officer at Molecular Prtnrs. I'm happy to share an update on our MP0533 program in EML, including some learnings from the dose escalation trial. Now, look at slide 11.

I am pretty pleased then the acting Chief Medical officer at molecular partners.

I'm happy to share an update on our M. P. Your phase three program in the email <unk>.

Including some learning from the dose escalation trial.

Looking now at slide 11.

Philippe Lejeune: I want to remind us that AML remains one of the most deadly cancers, where despite initial frequent responses and reductions in BLAST, the persistence of leukemic stem cells drives the frequent and quick relapses. A major challenge for the design of therapies in ML is that individual ML blasts and leukemic stem cells lack a single clean target. However, the opportunity is that AML cells can be differentiated from healthy cells like hematopoietic stem cells by their co-expression of specific agents or specific targets like CD33, CD123, or CD70. Moving to slide 12. We have designed MP0533-DARP in treatment as the first PETRA-specific T-cell engager binding to tumor antigens CD33, CD123, and CD70 on VML cells and to CD3 on the effector T cell. MP533 is designed to induce T-cell mediated killing preferentially when two or three target antigens, CD33, CD123, or CD70, are co-expressed.

I want to remind us that email remains one of the most deadly cancers, where despite the need for frequent responses and reductions in blast.

Since I'm leukemic stem cells.

How's the frequent and quick relapses.

A major challenge for design of therapy in the email is that individual email blasts and leukemic stem cells lack a single clean target.

How long is there.

The opportunity is that in their cells can be differentiated from healthy sounds like he might depleted stem cells, but they're quite expression of specific agents, especially targets like Cds or I'm, sorry did you want to three or C. D 17.

Moving to slide 12.

We have designed N P youre fighting between DARPA and treatment is the first Detroit specific T cell engaging <unk> binding to tumor antigens CD 33 C. D 123, MTB 70 M D M S N.

And to see these foods into CD three on the effector T cells.

And P. Five for Q3 is it designed to induce T cell mediated killing preferentially when two or three target antigen seeding certain threes do you want to see or should be 70 odd co expressed.

Philippe Lejeune: As such, NP0533 is hypothesized to preserve healthy cells, hence opening a broader therapeutic window that has been seen for other T cell engager therapies. MP533 has the potential to cure all AML cells, the BLAST and the leukemic stem cells, despite heterogeneity, translating into long-term disease control. Moving to slide 13, we can see that this scientific hypothesis of creating a therapeutic window is demonstrated in MOM-13 cells, describing on the graph the low potency of single antigen-expressing cells versus 100 times more potency when antigens are co-expressed on the cells. This data, alongside with additional preclinical experiments, Sorry, there is an ambulance just passing by. Just one second, please.

First such design.

Zero five centuries hypothesized to preserve the health himself.

Optimal border window that hasn't been seen for other so I gave her throat.

And you can find free thing has the potential to feel all AML cells.

The block on the leukemic stem cells, despite heterogeneity translating into long term disease control.

Moving to slide 13, we can see that this scientific hypothesis of creating a therapeutic window he's demonstrated on more frequent south.

Describing on the graph the low potency on single antigen expressing cells versus 100 times more potency when antigens are co expressed on b cells.

These data alongside with additional preclinical experiments sorry, David.

Just one second please.

Philippe Lejeune: Okay, so I was just saying that this data, alongside additional preclinical experiments, including AML patient samples, will be published in the next coming week. Focusing on Slide 14 now. The CP101 Dose Escalation Study in Patients with Relapsed Refractory EML and High-Risk NDS is ongoing and has now recruited the first six dose levels across... Can you hear me? I was just saying that the study, the Phase I, has now recruited the first six dose levels across nine sites in four countries. And preliminary data was reported at ASH 2023 from the first four cohorts, as Patrick mentioned earlier. Moving to slide 15, this slide refers to the safety profile of this population of elderly, heavily pre-treated patients with comorbidities, but this has been manageable. The most frequent treatment-related adverse events reported are infusion-related reactions and cytokine release syndrome, with no DLTs reported to date. This is important to mention. Slide 16.

Okay, so, but just saying that these data alongside with additional preclinical experiments, including AML patient samples.

Will you publish in the next coming weeks.

Focusing on that.

Slide 14 that now.

D C wonder one dose escalation study in patients with relapsed refractory AML and high risk Mds is ongoing and has now recruited the first six those levels are close.

Yeah.

Can you hear me.

Yeah, Hey, here, you're going to hear you yeah.

There's a turnaround coming up I think theres a big okay. So I was just saying that you know the this study the phase one that's not recruited the first dose level across nine sites and four countries.

And the preliminary data was reported at Ash 2023 from the first four cohorts as Patrick mentioned earlier on.

Moving to slide 15. This slide refers to the safety profile of this population of elderly heavily pretreated patients with comorbidities, but this had been manageable.

The most frequent treatment related adverse events reported or infusion related reactions and cytokine release syndrome with no D. O T reported to date. This is important to mention.

Slide 16.

Philippe Lejeune: The report's evidence of clinical activity, which was presented at the last ASH, and you can see that in each Cohort 3 of Dose Level 3 and Dose Level 4, a patient achieved an ELN response of MLFS and CR. Slide 17 summarizes the near future and some upcoming changes to our study design. Indeed, we are planning to initiate soon the last seventh dose level upon the dose escalation committee review. We are also submitting an amendment that would allow to increase the doses even higher as the safety profile has been so far manageable.

So reports evidence of clinical activity, which was presented at the last ash and you can see that in each cohort for each of those they're both free and do that before.

But cheap Yeah, then response all MLS at NCR.

Slide 17 summarizes the near future and some upcoming changes to our study design.

We are planning to initiate soon at the last seven dose level upon the dose escalation coming to review.

We have also submitted an amendment, allowing them to increase the dose is even higher.

Safety profile has been so far manageable.

Philippe Lejeune: And we want to evaluate how higher doses could impact target saturation and onset of response further. We also want to evaluate the impact of adding another dose at day 12, as you can see in the little square, to see if we can even increase the impact on the ML cells as early as possible. We look forward to sharing with you an update on the program at the end of H1 and more data later in 2024. I'm now passing this to my colleague, Anne, who will update you on Project 580, which is aiming at a complementary need in the treatment cycle of ML patients. Thanks, Philippe. And good morning or good afternoon, everyone.

And we want to evaluate how higher dose could impact target saturation and onset of response further.

Well its the ones, we built with the impact of adding another dose at the 12, you can see them Oh square.

To seek that if we can.

The increase impacts on the M S L I D.

It really is possible.

We look forward to sharing with you an update on the program are in at the end of each one of them and more Ddos leader coming up in 2024.

I'm now handing out to my colleague Ana who will update you on project 580, which is looking at a complementary meaning in the treatment cycle of AML patients.

Yeah.

Thanks, Pete and good morning, all.

And in every one of them in.

Anne Goubier: In the coming slide, I will show you how darpins can further change the game for AML by significantly enhancing the therapeutic outcome of hematopoietic stem cell therapy. So now we move to slide 19. As you know, HSCD is potentially curative for ML patients, but a lot of patients relapse, and conditioning regimens are highly toxic, encompassing GVHD, organ failure, sterility, or secondary malignancy. So one can apply reduced-intensity conditioning, but then the risk of relapse is higher. So our developing solution aims at delivering a safer and more potent conditioning regimen for HSCD with the potential to transform treatment for AML and other conditions. So in order to understand how this works, let's skip slide 20 and go directly to slide 21.

In the coming slides, we show you our adopting has confirmed that sounds again for AML by significantly enhancing the therapeutic outcome of hematopoietic stem cell transfer.

So let me move to slide 19.

You know it just puts and takes for anti inflammatory patients. That's a lot of patience and conditioning regimen up highly toxic encompassing gvhd organ say who's getting the keys are secondary malignancies. So one can fly had used in intensity conditioning, but then he's coffee that is higher.

So all that being said you shouldn't and so did you bring a safer and more potent conditioning regimen for intra C D.

Potential to close some tweaking and energy conditions.

So you know that's I understand that was he sweat, let's keep slide 20 and go directly to slide 21.

Anne Goubier: The key issue with current conditioning regimens is that they are not targeted, leading to bystander toxicity and ultimately lower potential. So our solution is to target sick kids, highly expressed on hematopoietic stem cells and leukemic stem cells. The challenge here is that, as we know, blocking CKIT binding to its ligands is not enough for hematopoietic stem cell depletion.

The key issue, we see unconvincing regimen is that they are not tied to get cheap needing to based on that toxicity and no way potentially.

So I always like to target.

Let me make a brief extension and leukemic stem cells. The challenge here is that as we know looking to keep banging tweaks like and he's not enough for the hematopoietic stem cell depletion, you'll need to induce killing others to keep what he says.

Anne Goubier: You need to induce killing of the CKIT-positive stem cell, and for this, we are leveraging our CD16-engager proprietary platform, which holds the potential to be safer than a CD3-engager or ADC and to be more potent than an RTBody by targeting the activating FC receptors and not the inhibitory receptors. One challenge that remains is that macrophages are limited in their activity by the don't hit me signal delivered by CD47.

And for this we are leveraging LCD 60, I'll get you a company, that's fun, which Oh has the potential to be say first in the city. So I'll get you owe a D C and to be more potent than somebody like targeting to activity.

And that seems to be doing well.

One challenge is that the Mcafee is limited as the activity that you don't eat me signals that he's on Bay City 47.

Anne Goubier: So the solution to that seems obvious, which is blocking CD47. But as you know, CD47 blocking therapy has been limited due to the high toxicity linked to the expression of CD47 on LDL. So our solution is conditional CD47 blocking, which will ensure that CD47 is blocked only in circuit positions.

So you shouldn't do that it seems like that's what she's broken with 47, but as you know people sit and go okay. That's the I've been limited due to the heightened activity linked to the expression of C. Difficile is an unnecessary.

So felicia, it's a condition that Sydney isn't looking which we ensure that city for seven each bill it's funny I'm thinking please keep safe and well at least we're leveraging our suites are adopting technology, which makes sure that city folks still remain to be such a in Brooklyn, Delphine Mendez when she can keep not expressed.

Anne Goubier: And for this, we are leveraging our switch doping technology, which makes sure that CD47 remains masked, CD47-blocking doping remains masked when it is not expressed, and that CD47 is blocked when cyclic is expressed. So I will not go into detail about the mechanism, and if you are curious about it, I invite you to go to our website. There is a very educational and very clear video that explains the depth of the mechanism. But now, let's move from the theory to real data. And in the next two slides, I will show you that the switch tapping is indeed safer and more. So on slide 22, I like the power of the switch that I've been using for conditional blocking of CD47. So what you are looking at here is the percentage of free CD47 on sale.

And that's important to say that he wants to keep these xpress. So let me not going did you say that wouldn't make any of them and just curious if that I think I invite you to go to our website.

Additionally, he has a video that.

That explains the depth of didn't make any sense.

But now let's move from the theory to react better.

And in the coming two Tonight I wish it was that just switched that being is it safer and more for instance.

So slide 22 highlights the power of the switched up in a condition that is looking actually switched it. So what you are looking at here is the what sounds like a P.

<unk> 47 onset so what it means is that the flying degrees when Sidney fortresses in each block.

Anne Goubier: So what it means is that this line decreases when CD47 is. So when you look at the light blue line, which is the secant negative cells, you can immediately see that there is no CD47 blockade until very high concentrations. So this tells us that at physiological concentrations, the molecule will be inactive.

So when you look at the light Blue line, which is sticky can they get you say you can immediately see that St. Louis C. D 47 blockade until very high concentrations. So as he said is that that figure does he got concentration and what it would be.

And it's safe.

Anne Goubier: The dark blue line illustrates CKIT-positive cells, and here you can see that CKIT-47 blockades start at very low concentrations. So when you compare the light blue and the dark blue, you see the depth of the therapeutic safety window, which is here more than three log in concentration between the CEQIP positive and CEQIP negative. So conditional blocking of CD37 ensures a high safety profile. Now, all about efficacy. Slide 23 shows the therapeutic potential of our CEQIT switch therapy, and I would like you to focus first on the dark green bar, which illustrates the phagocytosis induced by the IgG1 antibody. So, as expected, an anti-CEQIT IgG1 antibody does induce phagocytosis, but you can immediately see that this phagocytosis is limited in intensity, especially compared to the dark blue line, which represents switch therapy.

The dark Blue line.

Can you just play this tickets pledges. He says and here you can see that city council shouldn't look at that and then he knew concentration.

So when you called out the light blue and the data that you can see the depth of the safety.

Safety window, which is here more than three hnugginn concentration and between the ticket play to keep and take it make any sense. So the conditional looking at T cell. She said that ensure high 60 ports right now all about efficacy.

It's like 23 shows the potential for a sticky sweet shop, and I would like to just focus first on the dark Green bar and this illustrates the fact that she does these things is bad you went on to be so I was expecting.

Thank you and she went on somebody doesn't just fabulous.

But you can immediately see that he didn't eat me signal intensity, especially compared to the dark Blue line, which was based on this we stopped them.

Anne Goubier: And this tells us that we can expect a much deeper hematopoietic stem cell and leukemic stem cell depletion in patients with DARPIN as compared to an IVG1 or two. And, of course, you could combine this antibody with a CD47-blocking antibody like macrolimab. But as discussed earlier, you will face a high safety hurdle. And on top of this, as you can see here, comparing the light green to the dark blue, you are not as potent as what we see with the darpin, likely linked to the fact that in the darpin, both CD47 and CD6-T targeting are in the same molecule and then the same synapse, and both benefit from the CD6-T. So this data shows us that we have a molecule that is not only safer but also more potent than anything you can obtain even with a combination.

Just tell us that we can expect a much deeper and that's a pretty extensive and leukemic stem cell depletion in patients. We ended up being I suppose that's a nascent you why don't you Buddy. So of course you could go back just on somebody that's 84 to seven broke you want somebody that can I believe that but that's because we face a high pitch out there.

And then secondly, as you can see here comparing to the light green to the that you are not as important as what we see is adopting most likely linked to the fact that in adopting both C. D N.

And he keeps on getting I understand the molecule and then within sign ups and boosting its fun to actually $6.

So as these data so that's that's where the money because I don't think that's any safer, but also multiple times that any single thing even in the combination. So next up is a sign of ways to get these studies and the beauty of this study is that it is perfectly correlated to the human city once the dosing regimen to the safety and efficacy against interesting.

Anne Goubier: So next up is a cyanide efficacy study. And the beauty of this study is that it is perfectly translatable to the human setting, from the doping regimen to the safety and efficacy against HIV. We're expecting data from this study in the second half of this year and planning to be in the clinic in 2021. And with that, I'm very pleased to hand over to Danny, who will introduce you to another groundbreaking aspect of DARPing technology, the Radio DARP. Thank you very much, Anne, and welcome everyone from my side to this call.

We're expecting data from this facility in sticking with excellence each year, and so I need to be in the clinic in 2025.

And is this basically slammed investor day, what looks like another groundbreaking aspect of adopting technology to redo that thing.

Perfect. Thank you very much and welcome everyone from my side for this call. So it's a pleasure to on behalf of the team to give you an update on our radio therapy every platform on prospective pipeline assets. So.

Daniel Steiner: So it's a pleasure to, on behalf of the team, give you an update on our radio-dipping therapy platform and respective pipeline efforts. So, as you probably all know, the field of radiotherapeutics is experiencing a lot of excitement, and excitement is driven all by strong clinical efficacy and good tolerability data, and that first compound on the market or a new emerging compound delivery. What is limiting the expansion of this amazing promise to other cancer types is vectors that match targeted radiotherapeutic requirements and allow a broad target space to be covered. And that's exactly where we saw the benefit of the opportunity to engage in this dialogue.

So as you're probably all of you know what the field of radio therapeutic is experiencing a lot of excitement push driven all by strong clinical efficacy and good tolerability data and that's first compounds on the market or a new emerging compounds Geneva.

What is limiting the expansion of these amazing promise to other cancer types is vectors that are matching targeted radio therapeutics requirements.

Abroad target space to be cold and that's exactly what we saw the benefit of the unique opportunity to come in English diabetes.

Daniel Steiner: If you move to slide 25, so just for those of you who are not familiar with radiotherapeutics, the ideal properties of a radiotherapy product candidate are to deliver the radioisotope selectively to the tumor while sparing healthy tissue. And there's a special focus on kidneys and bone marrow, bone marrow being very tightly connected to blood levels, which are the most dose-limiting organs. If you move to slide 26, so on the left-hand side, if you had a target in mind with a cavity where a low molecular weight compound vector with high affinity and specificity can be identified, this is perfect; this is the ideal targeting moiety. The problem is that there is a very limited number of targets where this exists, where this possibility holds up. So to open up the target space, the most proven class are protein-protein binders where you can generate high affinity and specificity binding proteins that bind surfaces of a broad range of tumor targets. And to this class belong the monoclonal antibodies and antibody fragments and all other small proteins.

Would you move to slide 25, so just for those of you not familiar with radio Therapeutics, you ideal properties of our radio therapy product candidates are deliberate radios radio.

Selected me to the tumors, while sparing healthy tissue and Theres, a special focus on <unk> and bone marrow bone marrow being very tightly connected to blood levels, we talked most dose frequently those limiting Oregon.

If you move to slide 27, 26 apologies. So on the left hand side. If you. If you have a target in mind with a cavity, where a low molecular weight campau based group with high affinity and specificity can be identified does is perfect ideal targeting moiety.

These days there is limited target where does exist, but he's possibility holds up so to open up the target space. The most proven clause.

Clos are potent protein binders, but you can generate high affinity and specificity binding proteins, but I'm sorry. If this is a broad range of tumor targets into these clos belong belonged monoclonal antibodies.

Antibody fragments.

There are other small proteins.

Daniel Steiner: The problem here is that all of these protein-protein binders have key limitations for their effective and safe use as radiotherapeutic vectors. For antibodies, the high or long systemic half-life is leading to bone marrow toxicities, and the size is leading to limited tumor penetration. And for small proteins, they are limited by kidney accumulation and lower tumor uptake.

Series, but all of these protein protein binders have keen limitations for the effective and safe.

Use a radio therapeutic baxter's for antibodies the high.

But oh long systemic half life life is needing to bone marrow toxicity emphasize it leading to a limited tumor penetration and Ford to smooth proteins. They are limited by TD accumulation and global tumor uptake. So please remember those two elements high-keyed uptake and law.

Daniel Steiner: So please remember those two elements, high kidney accumulation and low tumor uptake. This is the dimension where we felt, looking into the molecular properties and biological mechanisms behind this, the team had the strong conviction that the DARPIN platform is ideally suited to building on the unique properties of DARPINs to overcome these challenges. So if you move to slide 27, this is just like showing you the engine that the team has built for building our radiodiping therapeutics candidate. Starting from the left-hand side, the starting point for all our projects is building a diverse set of high-affinity diaphragms against a specific target of wish, where you see, and this is always the lower graph, these diaphragms nicely accumulate in the tumor, but at the same time still have very high kidney levels.

So tumor.

Hi, T accumulation and low tumor uptake is is that I mentioned, where we felt looking symbolic cooler properties and biological mechanisms behind this with team had a strong conviction that the <unk> platform is ideally suited to exactly building on the new probe.

Eight properties of stipends to overcome these challenges.

So if you move to slide 27. So this is just like how we can use the engine that the team has build for building our radiotherapy therapeutics candidates.

From the left hand side, the starting point for all our project building a diverse set of high affinity diabetes against a specific target.

What do you see and that's always the lower graph piece the IP the Nike accumulating the tumor but at the same time, we still have very high keep me levels.

Daniel Steiner: So in the next step, we address the first limitation to kidney function. So what we've been building is what we call a stealth design, which I will show you a bit of data on the next two slides, where we reduce the kidney level down to below 25%. As a next step, we are addressing the second limitation, so we're increasing the tumor load by using our Half-Life toolbox specifically built for radiotherapy and therapeutics, increasing the tumor uptake by keeping the systemic exposure low. And, if needed, as a last step, we are increasing the affinity of the respective binders to ensure tumor retention. So the novel two aspects of the radio diopter therapeutics engine are the two middle ones, step number two and step number three.

So in the next step we addressed the first limitations.

So what we've been building is what we call stealth design, which I will show you more data through the.

Data on the next two slides, whether it be reduce the kidney level down to below 25%.

As a next step we are addressing the secondary mutations so we're bringing up the tumor load by using our horsefly toolbox, specifically built for radiotherapy therapeutics increasingly tumor uptake by keeping the systemic exposure low.

And if needed as it lost that we're building there.

Creasing affinity of the respective fine just to maintain to ensure retention.

So the novel two aspects of the radio Balcom Therapeutics engine to meet with one step number two and number three and I'm going to show you a bit more of a video stay tough to these two points. So if you move to slide 27. Please.

Daniel Steiner: And I'm going to show you a bit more of the data on these two. So if you move to slide 27, Please focus first on the upper right side cartoon, where you see this is what we call a normal or parenteral diaphragm. What happens is that it gets excreted by the kidney, it gets into the primary urine, there as all other proteins as well, it's reabsorbed, you get a lot of radioactivity into the kidney, and this is causing kidney damage.

Please focus first on the.

Upper right side cartoon, where do you see this is what we call a normal or prevent who die what happens is that the IP gets discrete into the ER.

Keep me he gets into the primary July the U S.

All other proteins as well, it's reabsorbed you get a lot of radio ex DVT into the kidney disease, causing kidney damage. What we've been building on is the extremely robust architecture of the <unk> scaffold healthily re engineered the whole backbone and be Colby <unk> therapy and this is now basically not recognized by this.

Daniel Steiner: What we've been building on is the extremely robust architecture of the diopine scaffold, heavily re-engineered the whole backbone, and we call this the stealth diopine, and this is now basically not recognized by these cells in the kidney anymore, and the diopine lipids radioactivity is directly excreted into the urine. If you move to slide 29, I'm showing you some in vivo data supporting the strong kidney- So if you look at the left-hand side first, this is an example of our front-runner program on DLL3. We successfully engineered three out of three diaphragms in three to four iterative engineering rounds, each of them taking three to four months, including all the production down to in vivo testing.

And cells in the kidney anymore.

The doctor can be fixed rate Jack DVT directed exclusively into the urine.

You move to slide 2029, I'm sure even some in vivo data supporting strong kicked me reducing effect off the shelf therapy. So if you look at the left hand side. First. This is the example of our front runner program on Yellow Street. So we successfully engineered three out of city diet pills.

In three to four introduce.

Engineering around each of them, taking three to four months, including all the production down to the in vivo testing now if you move over to the right hand side you see after integrating all these learnings from the first programs in monarch for new tumor antigens for out there for three.

Daniel Steiner: Now, if you move over to the right-hand side, you see after integrating all these learnings from the first programs, we managed to find new tumor antigens for three out of four diaphragms within a single round, and we managed to bring them down to low kidney levels. So what I wanted to take home from this is that we really established a robust, reliable engineering solution to bring kidney function down to low levels. So moving over to the second challenge, I'm showing you how we address the key limitation of tumor uptake. And this is where we use systemic half-life extension to increase tumor uptake. Focusing on the left-hand side, so you always see two examples here on ERR2 and DLL3.

Three out of four die within a single round, you manage them to bring them down to low kidney levels. So.

So what I want you to take home is that we really established a robust reliable engineering solutions group and keep them down too low levels.

So moving over to the second challenge.

Showing how we addressed the key limitations of tumor uptake and this is why we use systemic half life extension to increase tumor uptake.

Focusing on the left hand side. So you always see two examples here on her to a deal.

L. Three on the left hand side, you had like the naked cell therapy, which shows a tumor accumulation in the single digits.

Daniel Steiner: On the left-hand side, you have the naked stealth diaphragm, which shows a tumor accumulation in the single-digit percent range, very low blood level, or non-detectable blood level at these prime points. And then if you go over to the right-hand side, we applied different half-life extension leading to very low or low or medium and increasing systemic exposure, and this nicely drives the tumor uptake up to 30 percent on the And please keep in mind, all of these molecules have much lower systemic exposure compared to an antibody. So, quickly summarizing, so the stealth DARPing for reduced kidney accumulation and the half-life extension for increasing tumor uptake are the basis of our radiodarping therapeutic engine and basically the basis to build our pipeline.

Same range very low blood level of non detectable blood levels.

High points and then if you go over to the right hand side, we apply different half life extension royalties, leading to Bobby no or low or medium.

Increasing systemic exposure and fits nicely drives the tumor uptake up to 30%.

On the tumor and please keep in mind all of these molecules is much lower systemic exposure compare to an antibody.

So quickly summarizing quickly summarizing so the cell therapy produced T accumulation and the half life extension for increasing tumor uptake is the basis of our radio Balcom therapeutics and engine and basically the basis to build our pipeline in our pipeline we have two.

Daniel Steiner: In our pipeline, we had two targets with Novartis, then two targets with Oranomate, including DLR3, and quickly expanding on Oranomate, extremely happy with the collaboration that we had already started one and a half years ago, an amazing team, great capabilities, great expertise, and also there is very strong data emerging on LED212 as a radio client of choice in this specific case. And then we have additional targets that we are moving ourselves, which are not partnered at this current point. So we are looking very much forward to sharing more data at key upcoming conferences in the next month and months to come. And I'm finishing here.

Targets with Novartis to.

Two targets.

Or automate, including CLO, Sydney and quickly expanding on the Orlando made extremely happy with the collaborations that we've already started one under half years years ago Amazing team great capabilities, great expertise and also dear it's like very strong data emerging led to 212 as it relates.

Joe Klein of choice.

Okay.

And then we have additional targets, which we are moving ourselves which are not part but at this current point in time.

So we're looking very much forward sharing more data.

Key upcoming conferences in the next month month.

And I'm, finishing here happy to answer questions during the Q&A session and hand, it over to Patrick for the outlook.

Daniel Steiner: I'm happy to answer questions. Then, in the Q&A session, I'm handing over to Patrick for the outro. Thanks, Donny, for the exciting overview that we have on the radio space. And before opening up for questions, let's just look at the outlook. It's a really exciting year that we have ahead of us, and I will start with the first and foremost, most exciting one, which is 5.3.3, our AML drug. We're excited to look at the first data with you of dose codes 5, 6, and a taste of 7, still in the first half, give, obviously, the protocol amendment a push that we get that through, that we can then go to higher doses, and share with you what we And there is clear need in this indication, and we're starting to understand how we would also move forward beyond relapsed refractory. On the switch or seek it side, it's clear we are striving fast toward candidate selection. We will still talk about that in the first half of this year.

Thanks, Tony for the exciting overview that we have on the radio space and before opening for questions lets just look at the outlook. It's a really exciting year that we have ahead and I will start with the first and foremost most exciting one which is 533 R. A M L.

Drug we're excited to look into the first data with you of those cores five six and a taste of seven still in the first half give us obviously the protocol amendment.

Push that we get that through that we can then go to higher doses and share with you. What we are developing in very close collaboration with our Kols.

Our strategy that goes beyond relapsed refractory, but where would else would one applied this molecule and there is clear need in this indication and we're starting to understand how we would also move forward by armed relapse refractory.

Oh, the switch our CK side its clear we are ascribing fast towards candidate selection, we will talk about that.

First half of this year, then as Andy has pointed out it's all about the nonhuman Primate study and we will report the data second half of this year and I think this is maybe the most translatable daystar value we ever have ethanol excellent partner. So we are convinced that if we see strong data in nonhuman.

Patrick Amstutz: Then, as Anne has pointed out, it's all about the non-human primate study. We will report the data in the second half of this year, and I think this is maybe the most translatable data or value we ever had at Molecular Ptnrs. We are convinced that if we see strong data in non-human primates, the risk or the ability to translate that, the risk is low, and the ability is high to translate that into patient value next year, meaning in 2025 already. From Donny, we heard on the radio platform, it's all about the first candidate.

Primates.

The risk or the ability to translate that the risk is low the ability as high to translate that into patient value next year, meaning in 'twenty five already.

From Donnie we heard on the radio platform. It's all about the first candidate we want the DLL. Three also first half of this year that we can then move into IND, enabling studies.

Patrick Amstutz: We want DLL3, also in the first half of this year, so we can then move into IND-enabling studies and see the first human data next. We will add, as Tony said, the platform is ready, we're moving forward, and add new targets and additional candidates. And on that side, it's also a mandate for us to broaden the collaboration and move the ones we have forward. 317, I think we have recruited the last patients. We're still kind of in the trial, but we are expecting to close that, clean the data, open the data room for partners, and advance those. And just to remind you of our cash position, we are well financed with 187 million in cash that brings us into 26, capturing all those value inflection points that I... With this, I want to thank you for listening to the call. I want to thank the team here.

And the first in human data next year, we will add as he said the platform is ready, we're moving forwards add new targets and additional candidates.

And that side, it's also a mandate to us to broaden the collaborations and moved to the ones we have forward.

317, where we I think we have recruited the last patients where we're still kind of in the trial, but we are expecting to close that are clean.

Clean the data opened the data room for partnering and advance those and just to remind you on our cash position.

We are well financed weights 187 million in cash that brings us into 'twenty six capturing all of those value inflection points that I pointed out.

With this.

I want to thank you that's have been listening to the call I want to thank the team here I want to thank Seth Robert Phillips Dawn and Adam for presenting today I want to thank the entire molecular partners team. It has been an exceptional year at his hard work and also great team spirit.

Patrick Amstutz: I want to thank Seth, Robert, Philip, Donny, and Anne for presenting today. I want to thank the entire Molecular PRtnrs team. It has been an exceptional year. It has been hard work, but there is also great team spirit.

Patrick Amstutz: Working here is a pleasure, and the hard work comes easily if you work in a great team. I do want to thank all our partners and, especially, our KOLs running the trials and the patients in those. And with that, I would end the presentation part and open the floor to questions. We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speaker phone, please pick up your handset before pressing the key.

To work here is the pleasure and the hard work comes easily if you work and a great team.

I do want to thank all our partners and especially our kols running the trials and the patients in those trials.

And with that I would end the presentation part and open the floor for questions.

We will now begin the question and answer session.

To ask a question you May press Star then one on you touched on phone.

If you weren't music a speakerphone, please pick up your handset before pressing the keys.

Operator: If at any time your question has been addressed and you would like to withdraw your question, please press star then 2. At this time, we will pause momentarily to assemble our roster. The first question today comes from Richard Vosser of J.P. Morgan. Please go ahead. Hi, thanks for taking my questions. Two on MP 0533, please. Just whether you could give us any additional color, I suppose, the first question on, you know, what you're seeing and what has led to what is more important in leading to the further dose expansion, whether it's that the safety profile is clearly very benign, which is great, but, you know, is there a sense that efficacy needs higher doses? Just some context of that, if you can.

If at any time. Your question has been addressed and you would like to withdraw your question. Please press Star then two.

At this time, we will pause momentarily to assemble our roster.

Yeah.

Okay.

The first question today comes from Richard Foster with J P. Morgan. Please go ahead.

Hi, Thanks for taking my questions are two one a M. P O 533. Please.

Just whether you could give us any it additional color I suppose the first question is on on it.

What you're seeing and what has led to the what is more important than leading T. The the further expansion whether it's you know that the safety profile, clearly very but no I'm, which is great but.

Is there a sense that efficacy knee tie a day. She has just said just some context of that if you can second question eat.

Patrick Amstutz: Second question, maybe just sort of an idea of how much higher the doses are, if you can say something about that. And thirdly, when should we think about that phase three, phase two enabling decision? Is that more in 25 or is that more in the second half of 24? Just some color there would be helpful.

Maybe just sort of an idea of how much higher the diocese or if you're a if you can say about that in and thirdly. When should we think about a fact that phase three phase two enabling our decision is that more than 25 or is that more in in the second half of 'twenty for just.

Just some color that would be helpful. Thanks very much.

Patrick Amstutz: Thanks very much. No, thanks, Richard, for the fair and good question. So maybe just a bit of color on the doses. And when we started the trial, and obviously, Anne and Philip can then follow up on that, but the highest dose was calculated knowing that we would only reach around 80% receptor occupancy in the bone marrow. You have to know in the blood is one thing, but then you have to penetrate into the bone marrow, where you also expect leukemic stem cells and others.

No. Thanks Richard.

But a fair and good question, so maybe just a bit color on the doses and when we started the trial and obviously and then fill it can then follow up on that but the highest dose was calculated.

With that knowing that we would only reach around 80% receptor occupancy in the bone marrow you have to know in the blood is one thing, but then you have to penetrate into the bone marrow, where you expect also their leukemic stem cells and others.

Patrick Amstutz: And so we're just kind of looking at other T cell engagers that were held back by safety. We designed the trial, and the top dose was 80% receptor occupancy. So the news that we can go to higher doses is definitely helpful because you want to go beyond that. You want to go to 90 or above, which gives you, hopefully, an even more complete killing of these cancer cells, especially the leukemic stem cells.

So we're just kind of looking at other T cell engaged or that were held back by safety. We designed the trial at the top those was 80% receptor occupancy. So the news that we can go to higher doses is definitely helpful. Because you want to go by on that you want to go to 90 or a boss, which.

If you then hopefully an even more complete killing of cancer cells, especially the leukemic stem cells now if this is needed or not it's too early to say we're in dose range. Six we continue to see activity of the drug but to seek to understand if the dose responses, there and we get it better.

Patrick Amstutz: Now, if this is needed or not, it's too early to say. We're in dose range six. We continue to see activity of the drug, but to see, understand if the dose response is there and we get a better and deeper and prolonged killing of these cells, we cannot comment today. And we also said we would not piecemeal the data. So you'll have to be patient until we give that update.

And deeper and prolonged killing of T cells, we cannot comment today and we also said we would not piecemeal the data so you'll have to be patient until we give that update and that will be obviously, where we will be looking at.

Patrick Amstutz: And that will be obviously where we will be looking. And keep in mind, it's also about this MRD, so minimal residual disease. So we will be following the clones, so the clonality of the disease, and see if we can be killing the high-risk clones, as those are the ones which drive relapse fast. So it's more than just the response rates. It's really understanding what the drug is doing, also in the bone marrow. Maybe I'll quickly pause there on that one, that may be. And she's nodding her head.

And keep in mind, there's also about this edmar D. So minimal residual disease. So we will be following the close of the Clos Nallet tee off disease and see if we can be killing the high rates clones.

Those are the ones, which drive relapsed fast so it's more than just the response rates, it's really understanding what the drug is doing all seem to bone marrow.

Maybe I'll quickly called there on that one.

Maybe.

And she she's nodding her head I think I covered covered as well.

Patrick Amstutz: I think I covered well. So, and maybe I'll just, on top of that, add why Philip was pointing out that we want to dose escalate or some kind of dose escalate faster. So, you know, we have a step of dosing, and we are adding an additional step in there to reach the higher dose faster. And that is something in the first patients you saw; we had efficacy, and we saw deepening over time. Now, one point that has been pointed out by our KOLs, could you go in at an earlier line setting to kill remaining cells after you have a complete response, but you are still MRD positive, so you still have some leukemic cells, leukemic stem cells. Could we kill those fast?

Exactly right.

So and maybe I'll, just on top of that and why and.

Why Philipp was pointing out that we want to dose escalate or kind of those escalate into in faster. So you know we have a step up dosing and we are adding an additional step in there to reach the higher those faster and that is something in the eight and the first patient you saw we had the.

Efficacy and we saw deepening over time now one point that has been pointed out by our Kols could you go into earlier lines that thing to kill them remaining of cells. After you have a complete response, but you are still positive. So you still have some.

You can make cells leukemic stem cells could we kill goes fast and obviously this could even be before transplants in theory don't have three months, where you want to wait so you need to be fast. So this is already implementing some feedback we're getting from the kols for an earlier line.

Patrick Amstutz: And obviously, this could even be before transplant, and there you don't have three months where you want to wait, so you need to be fast. So, this is already implementing some feedback we're getting from the KOLs for an earlier line, where this would ideally be in two, three weeks. We have full efficacy. And that's why we are excited to be able to look into that for a steeper dose escalation. And that also goes back to your first question. I mean, we see good safety, so that's one, or the key driver, that we can do that.

This would ideally be in two or three weeks, we have to fool if he if he can.

And that's why we are.

Excited to be able to look into that too steep for dose escalation.

And that also goes back to your first question I mean, we see a good safety. So so that's one of the or the key driver that we can do that so we think the molecule allows us to explore kind of where the wells are on safety and we do see Crs I can also tell you we do see T cell activation. So we have to buy them all.

Patrick Amstutz: So we think that molecules allow us to explore kind of where the realms are of safety, and we do see CRS. I can also tell you we do see T cell activation, so we have the biomarkers there. So all of that is hinting that the molecule is doing its job, and we need to find out how we can tune it, how we use it to get the best patient benefit, and Patrick. Just one thought there, and then we can move on to the next question, but also to one last piece of Richard's question as far as dose. I think it's fair to say, and we have said before, that where we are now in dosing, we are either at or above where others have gotten with Bi-Specific Antibodies with T-Cell Engagers, but I don't know if there are additional comments there, but I wanted to just open it up.

Workers there. So all of that is hinting that the molecule is doing its job we need to find out how we can tune how we use it to get the best patient benefit.

And Patrick just one thought there and then we can alone and move on to the next question, but also tend to one last piece of Richard's question as far as dosing.

We haven't disclosed dosing I think it's fair to say and we have said before that.

Where we are now in dosing we are either at.

Or above where others have gotten too when it comes to bi specific antibodies with T cell engaged certainly but.

Additional down I'm sure, but I wanted to just open.

Seth D. Lewis: I often miss the obvious ones, so thanks for pointing that one out. All good. I just wanted to... I know.

I often missed the obvious one.

Thanks for pointing that somehow it's all good just wanted to I know the other.

Patrick Amstutz: The last point Richard made was what will be gating. And I think there are definitely two things. One is what is gating to go on in relapsed refractories. And we have clear cut-off criteria there. And I was talking about clonality and how we kill those clones, and that will likely be a gating mechanism, whether we move to earlier lines or not. We're working on that.

Thank you.

Last point of Richard was what will be gating and I think there. We there's definitely two things one is what is gating to go on in relapsed refractory <unk>.

And we have clear cutoff criteria out there and I was talking about the Clos Mallet T and how we kill those closed since that will be likely a gating mechanism do we move to earlier lines are not.

We're working on that this will be possible update later this year that we really share the strategy now heard the baked in which direction, we were thinking and I can tell you. It's a very good in close collaborations with the Kols.

Patrick Amstutz: This will be part of the update later this year that we really share the strategy. You have heard a bit about which direction we are thinking. I can tell you it's a very good and close collaboration with the KOL. Richard, I hope that was covering your point. I think we got it.

Richard I hope that was covering your point.

I think we got it.

Operator: As a reminder, if you would like to ask a question, please press star then 1 to be added to the question queue. In the interest of time, we ask that you limit yourself to one question and one follow-up. If you have additional questions, please reenter the queue. Your next question comes from Mike Nedelcovych with T.D. Cowan.

Operator, I think we have another question.

As a reminder, if he would like to ask a question. Please press Star then one to be joined into the question queue.

In the interest of time, we ask that you limit yourself to one question and one follow up.

If you have additional questions. Please reenter the queue.

Your next question comes from Mike Mcdonnell Kovich with TD Cowen. Please go ahead.

Operator: Please go ahead with the questions. I have one on MPO533 and then one on the SWITCH-DARPIN platform. So for MPO533, when we get the updated interim data from the Phase 1 trial in the first half of this year, what are you hoping to see? What level of efficacy in a given dose cohort would you consider a success? And on the expanded dose cohorts, is there a chance that we get those data by ASH at the end of this year, or is that more likely to be a 2025 event? And on the Switched ARPAN platform, can you describe the broader strategy for the platform? So the first targets would seem to be relatively de-risked, but perhaps a smaller indication. What are other good targets for this approach? In a blue sky scenario, what indications might you go after?

Thanks for the questions I have one on M. P. A phase III three and then one on the switch starting platform. So for N. P 0533, when we get the updated interim data from the phase one trial in the first half of this year. What are you hoping to see what what level of efficacy in a given dose cohort would you consider.

Success and on the expanded dose cohorts is there a chance that we get those data by ash at the end of this year or is that more likely to be at 25 events.

And on the switched arpin platform can you describe the broader strategy for the platform. So the first targets would seem to be relatively derisked, but perhaps a smaller indication what are other good targets for this approach in a blue sky scenario, what indications might you go after.

Yeah.

Patrick Amstutz: Thanks for the question. I think I'll just hit the first one and then hand it quickly over to Philippe, but I personally see two cutoffs. And if we, or where we will stand in the first half versus the second half of the dose escalation, we will see. But we always communicated that for relapsed refractory settings, so the patients we see today, that's where we're aiming for a roughly 30% response rate with well beyond three months of disease control. As I was pointing out, if you want to move to an earlier setting, it's really about this MRD conversion. Can we also kill the difficult-to-kill clones?

Hey, Thanks for the question I think I'll just hit the first one and then quickly over to Felipe, but I think we I personally see two cutoffs and if we or where we will stand in the first half versus second half in the dose escalation, we will see but we always communicated that for relapsed refractory setting so the patients we.

Seek today, that's where we are aiming for a roughly 30% response rate with wildfire.

Three months disease control as I was pointing out if you want to move to earlier setting. It's really about this edmar deep conversion can we also kill the difficult to kill Clos and so those are the in very short the elements we're looking for.

Patrick Amstutz: So those are, in very short, the elements we're looking for. And maybe, Philip, you're closer as you comment a bit more on safety and talk to these KOLs on a daily basis. Yes, thank you, Patrick, and thanks for the question. First of all, you know, I just want to reiterate that what is really a position of strength is that the agent seems to be very well manageable and tolerated so far. So it shows CRS, it shows IRRs, but enough to make us confident that it's doing something, but not enough to, but little enough that we are still within safe boundaries.

And maybe phillipe kind of Youre closer as you made the comment on more a bit more on safety. Our Q2. These kols on a daily basis, yes.

Yes, Thank you Patrick.

Thanks for the question.

First of all you know what I want just want to reiterate that what is really in a position of strength is that region seems to be very well manageable and tolerated. So far so it shows it shows your <expletive> he chose <unk>.

Yeah, I ours, but enough to make us confident that he's doing something but not enough to go but that's a little enough that we are still within safe boundary. So that's that's dispose position of strength and this is why we want to keep optimizing it you know we want to densify in the first cycle and.

Philippe Lejeune: So that's the position of strength, and this is why we want to keep optimizing it. You know, we want to densify in the first cycle, and we want to go higher to make sure that we give a chance to as many patients as possible to reply. So, because we, again, see activity, but we want to see a maximum of activity in most cohorts. In terms of numbers, I also want to say we are working on fairly large dose escalation cohorts, cohorts of, you know, six to nine patients so far. So, those can give us some good levels of learning.

And you're going to go higher to make sure that we give a chance to as many as many patients as possible two to reply. So because we again, we see activity, but people want to see maximum rate activity in most cohorts.

In terms of so I want to say, we are working on a fairly large, but we're just gonna shouldn't cohorts courtyard.

Six to nine nine patients so far so those can give us some some good development earnings.

Philippe Lejeune: And then, the question is when we are going to get the next important, relevant batch of data. And it still is a bit tricky to say because, in fact, we are hoping to go higher, as I have said already, and it will depend. You know, at some point, potentially, it will hit the DLT, so then we can expand immediately. Or, at some point, we will see that it's not worth going higher because, in fact, we have saturated all the targets, and we have maxed out what we think is a reasonable goal for activation. So, but all of that, as you know. It takes a few months before we get the final translational data that can really guide us for that. So it depends a bit on what we are going to see in core 7, potentially 8, 9, or even higher, but to really understand when we can trigger the expansion and also the movement into the earlier line, which is a goal.

And then and then the question is when are we going to get me to the next important.

You know relevant a batch of data and it's a it still is a bit tricky so to say because I'm. In fact, we are hoping to go how real it is as it was as I said already.

And and towards the problem you know at some point potentially it will hit the deal teams. So that we can expand immediately.

Or at some point, we will see that it's not worth going higher because in fact, we have saturated you know all the targets and we have maxed out what we think is a reasonable goal for activation, so but all of that as you know.

It takes a few months before we get the final.

Efficacy translational Buda that can really guide us for that so it depends a bit on what's going to sue them for several of them potentially eight nine you know or even Halle Barbara a mountain dew to really understand when we can figure the expansion and also the movement into earlier line.

Which is a go.

Anne Goubier: I think the last question was for much more Anne on the switch and the blue sky scenario. I think it's a wonderful question to ask somebody in early development, so I'm excited to hear, Yes, so thanks. As you rightly pointed out, SICK-IT, Diapince, which is just a starting point, and of course, there is a broad applicability for this platform.

Thankfully and I think and that's the last question I think was for much more in on the switch.

Switching blue Sky scenario I think that's a wonderful question to ask somebody in early development. So I'm excited to hear you and Scott.

Yes. Thanks, as you rightly pointed I would take it adopting switch is just a starting point and of course as a broad applicability for this platform and you can think of it from the point of view because here I'm just thinking to just it's a step that you can think that you're playing in smartphones and gates. So you need to do I get to be expressed are too.

Anne Goubier: You can think of it from a target point of view, because here on SICK-IT, it's just a first step. Now you can think that you apply this platform to N-gates, so you need two targets to be expressed on N-gates, initiating your therapeutic activity. So from a target point of view, you can revive well-known targets that have been stopped or have been limited due to their expression on LC cells. So, an example is, for example, EPCAM or this kind of target where they are beautiful, they are expressed on a large number of cells, they are very highly expressed, but they are limited by the fact that they are expressed on LC cells.

Yeah.

You can schedule a therapeutic activity.

So from the Italian rebate, well known targets that have been stopped all of that has been limited due to their expression on these systems. So I mean, we think somebody's thinking, but I was just kind of start to get to where.

Yeah, the beauty space on the lots and it says yeah very highly expressed that they are limited by the fact that takes place on AC. So think of that switch we can allow the gating and make sure that we can do the kitting and the Afghans distance. The second thing you can do it we need a platform is allow.

Anne Goubier: So thanks to the switch, we can allow gating and make sure that we will induce a killing outcome. The second thing you can do with this platform is allow..., and others. So, what we're trying to do is to look at different effector modalities and make them safe. Like seeing just about any CD3 engager, making sure that your T-cells are engaged only when your targets are expressed.

Different effect on the Daiichi and make them safe vaccine chest about CD three on gauge on making sure that your T cells Oh, it's funny when you I guess I expressed or he can also allows using co stimulation. If he thinks I hope I see 28, which galleons Bay high toxicity risk magazine.

Anne Goubier: Or it can also allow the use of co-stimulation, if we think, for example, CD28, which carries a very high toxicity risk. Now you think of CD28 and CD3, and you think that this will be activated only when a set of two targets are expressed. So you are opening a broad field of applications that honestly go even beyond what we can do only ourselves. So this is where we will also be looking for partners to completely exploit this switchback. Thanks, Anne. Good night. The next question comes from Kathleen Silberman with Lerank. Please go ahead. Hi team, thanks for the question. I am on for Daina today.

Do you see anything that these will be activated only when the states up to kind of guess I Express so youre opening both field of applications that honestly, but even beyond that he can do them all.

So these wells so we wouldn't be looking for partners to completely exploit as he switched platform.

Yes.

Thanks, Adam.

Yeah.

Your next question comes from Caffeine supplement with Leerink. Please go ahead.

Hi team. Thanks for the question I am onto a Dana today, a bit of a tag on to Michael's question from TD Cowen.

Operator: A bit of a tag on to Michael's question from TD Cowan. The scenarios for potential stock movement on the first half of 24 533 interim dose escalation data, if I break it into thinking at it as a layering and a floor, the layering being what's your conviction and potentially seeing as some other CD3 T cell engagers have seen a belt-shaped response, or some have called it a step up, or, And do you think there's a reason to maybe think about seeing that And then the last one, which I think you've pretty much nailed, is the floor scenario, which was Michael's question.

Scenarios for potential stock movement on the first half 'twenty 433 interim dose escalation data if I break it into thinking on and layering in a floor.

Hearing being what's your conviction and potentially seeing like some other C. D. Three T cell engaging athene adult shaped response or some have called it a desktop response.

And do you think there is a reason to maybe think about seeing that there's a desk or heart five level.

And then the last one which I think you've pretty much nailed it the floor scenario, which was Michael's question.

Patrick Amstutz: So in the relapsed refractory data, knowing that durability will be immature and you are targeting getting eventually into a larger trial over three months as a threshold in this current cut that we'll see in the first half, are you going to be sharing those directional signals like the MRD and the biomarkers of T cell engagement? Thanks so much. Yeah, happy to go on the first. I do think our molecule looks different than the other T cell engagers.

So in the relapsed refractory data.

Knowing that durability will be immature and you are targeting getting eventually in a larger trial over in three months as the threshold in this try and cut that we'll see in the first half are you gonna be sharing those directional signals like the M R&D and the Biomarkers of T cell engagement. Thanks, so much.

[laughter].

Yeah happy to go on the first I do think our molecule looks different than the other T cell engage her. So we also just on the safety side, we have really been able to dose to these doses that are off what competitors have been doing. So we also hope to have a bit of a different response profile.

Patrick Amstutz: So we also, just on the safety side, we have really been able to dose to these doses that are above what competitors have been doing. So we also hope to have a bit of a different response profile and to really be able to control the disease. And as you rightfully pointed out, we will not be, obviously, it's just a matter of time, sitting on data of several months of follow-up. And you also pointed out that the MRD level can be a good surrogate marker for the depth of effect that then directly links to duration. And yes, we will definitely want to update you on what we have. But keep in mind that clonality of the disease always takes time; you have to follow it over time.

And to really be able to control disease and as you rightfully pointed out we will not be obviously, it's just a matter of time be sitting on data of several months follow up and you also pointed out that MRV level can be a good surrogate marker.

The depth of effect that then direct links to duration and yes, we will definitely want to update on what we have but keep in mind, our kronos a commonality of the disease. It always takes time you have to follow it over time. So it will be a limited dataset, but we want to share what we have and how that lead.

Patrick Amstutz: So it will be a limited data set. But we want to share what we have and how that leads to the decision-making at Molecular PRtnrs to then further invest in the molecule, and it will be an interim update. Thanks. The next question comes from Flora Zinnerman with Octavian. Please go ahead. Yeah, hi, Jonas Zimmermann from Octavian.

To the decision, making up like with partners to further invest in the molecule.

And it will be an interim update.

Yeah.

Thanks.

The next question comes from Deforest Hinman with Octavian. Please go ahead.

Yeah, and you want us to a month from Octavian congratulations on all the progress impressive and thank you for taking the question one on the Rd deep platform and one on M. P. Peter increased 17.

Operator: Congratulations on all the progress, impressive, and thank you for taking the questions. One on the RDD platform and one on MP0317. On the RDT platform, you can have two partnerships, but you also have two internal assets or targets. Can you shed a bit more detail on your plans for following up with the two internal targets and any potential partners you see there? And then on MP0317.

On the Rd T platform, you've announced two partnerships, but also you have two internal estimates or targets can.

Can you shed a bit more detail.

On your plants that you will follow up with the two internal targets and any potential partner ratings you see there.

And then on M P zero mm 317.

Patrick Amstutz: Where do you stand there, and when can we expect the next update, and any potential partnership announcements? Thank you so much. Thank you. And I will quickly take 3.17 and then hand over to Donny to talk about the radio DARPIN and our internal targets and isotopes and everything. So 3.17, as I said, we are literally finalizing the trial. We are filling the data room with all the data, and that should be open, I guess, as of next month, allowing interested parties and partners to look at it. I do remind myself that at the moment, the I-O, and I-O combinations are not at their peak. We were joking that a few years ago, this would have been a multi-million or multi-hundred million dollar up front. Those times are not now.

Where do you stand there and when can we expect a next update any potential partnerships announcements.

Thank you so much.

Thank you and I'll quickly take $3 17, and then hand over to Donnie to talk about the radio dot opinion on our internal targets and isotopes and everything so $3 17 as I said, we are literally finalizing the trial, we are filling the data room with all the data.

And that should be open I guess as of next months, allowing interested parties and partners to look at that I do remind ourselves that at the moment.

Oh I O combinations are not at the peak.

We were joking that a few years ago this would be a multimillion.

Multi hundred million dollar upfront those times are not now so we are really looking for a partner that's committed to the program ran several combination trials and we're not going to try to optimize the selling price but more.

Patrick Amstutz: So we are really looking for a partner that commits to the program, runs several combination trials, and we're not going to try to optimize the selling price, but more that a partner can run these combination trials. And with that, I would hand over to Donny to talk about the kind of internal undisclosed targets and our thoughts on sourcing of isotopes and other partners. Thanks for the question. So, maybe I should start zooming in quickly on the target. So, our aim for peaking the target is, of course, driven first from the medical needs side, but also from there. We are zooming into targets where we feel like those are very difficult to address targets with certain, I say, biological or microbiological requirements that need to be met in terms of specificity, what part of the target do they address, and location of target expression.

That apartment can run these combination trials and it's always very difficult to two five to comment on timing.

With this I would hand over to Donnie to talked about kind of the internal undisclosed targets and our thoughts on sourcing of isotopes in other partnerships.

Yeah. Thanks for the question, so maybe I start zooming out quickly on the targets.

Our aim for peaking the target is of course, driven first from the the medical need side, but also then you're weird zooming into targets, where we feel like those are very difficult to address targets with certain I'd say biological a nightclub biology and requirements that need to be met.

In terms of safety TCT, what part of the target to digress location of target expression. So all the elements playing into this very.

Daniel Steiner: So, all the elements are playing into this, and we are very careful about nominating and peaking those targets. So, we have internal programs ongoing where we say like we love to move them to a point where we say we have this, I say, almost like proof of mechanism, proof of that we can really match those profiles well. And then afterwards, we would love to keep that element of freedom to decide ourselves which targets are ideally suited for a short half-life, short-range alpha emitter like lead, we really like lead from its profile, or would it be better to go into an extension, into other collaborations that are more built on long-lived alpha emitters or even beta emitters if indicated by the respective tumor indication by the respective tumor biology.

Very carefully both nominating and peaking those targets. So you have internal programs ongoing what do we say like we lost to move them to a point, where you said you had like I say almost like proof of mechanism proof of that we can really match those profiles as well and then afterwards.

We would love to keep that.

Element of freedom to decide ourselves are those targets, which are ideally suited for a short half life short range output me to like less really like led from its profile or would be back to go into an extension into other collaborations that would be more like on long list I'll frame it.

As or even better any truth is indicated by the respective tumor indication by the wayside respective tumor biology. So we keep it open for now, but we are definitely not only focused on legs.

Daniel Steiner: So, we keep it open for now, but we're definitely not only focused on lead. Thanks, Bernie. As a reminder, if you would like to ask a question, please press star, then 1 to enter the question queue. This concludes our question and answer session. I would like to turn the conference back over to Patrick Amstutz for any closing remarks. So, again, I would like to thank my team here for all the work and all the great Q&A and forshedding some light on the questions. I would like to thank you for your attention and all the good questions that we got. I think it's clear we're heading into a very data-rich period with a lot of strategic work on the background, linking data to decisions. We will be working internally and will be closely communicating with all of you to share what we have and how that forms the decision, and especially the investment potential that we see for the cash we have. We are truly excited to be bringing forward differentiated DARPIN therapeutics for patients that today have no good treatment options.

Thanks Bonnie.

As a reminder, if you would like to ask a question. Please press Star then one to enter the question queue.

Okay.

Okay.

Hmm.

Okay.

This concludes our question and answer session I would like to turn the conference back over to Patrick <unk> for any closing remarks.

So again I would like to thank my team here for all the work and all the great Q&A and shedding some light on the questions I would like to thank you for your attention all the good questions that we got.

It's clear we're heading into a very data rich period with a lot of also strategic work on the background linking that data to decisions, we will be working internally and be close to communicating with all of you to share what we have and how that informs the decision and especially the investment.

Potential that we see for the cash we have and are truly excited to be bringing forward a differentiated dark pain therapeutics for the patients that today have no good treatment options and with that I would like to enter call. Thanks again take care.

Patrick Amstutz: And with that, I would like to end the call. Thanks again. Take care and speak soon. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect. BF-WATCH TV 2021

Inc.

Yeah.

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

Okay.

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Yeah.

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