Good morning to everyone. I'd like to welcome all of you to our first quarter results conference call. On the call with me today are Mr. Luis Mora, Managing Director of PharmaMar, María Luisa de Francia Caballero, Chief Financial Officer of PharmaMar, and Pascal Besman, our Chief Operating Officer of PharmaMar U.S. Following our prepared remarks today, we will open the line for questions. I'd like to remind you that today's conference call might include forward-looking statements regarding future events or the future financial and operating performance of the company. Such forward-looking statements are only predictions based on our current expectations, and actual results may vary from those projected. We disclaim any obligation to update any information provided herein. We refer you to our safe harbor statement on our corporate presentation, which is available on the website together with the press release of the results we released yesterday.
We started this year as we left last year, which is with the business growing, again, showing very robust financial results and balanced position. This is due to the continuous growth of our recurrent business, which are revenues plus royalties, and this growth is basically coming from our oncology business. In relation to our cash, the group generated EUR 36 million in operating cash flow in the first quarter of this year, which leaves us with a total net cash position of EUR 206 million, which is an increase of 23% since December last year. To give you more details about all these financials, I might turn over now to María Luisa. María Luisa, please.
Thank you, José Luis. Good morning, and thank you all for joining this first quarter results call. In the first three months of the year, financial data has evolved in line with our expectations and consistently with what we have seen in previous quarters, confirming the strength of recurring revenues that have increased 7% compared to March 2021. Oncology sales, which include commercial sales of YONDELIS, revenues from ZEPZELCA under early access program, and sales of active ingredient to our partners, increased 1% compared to March 2021. YONDELIS sales and ZEPZELCA revenues remain at similar levels to previous quarters, with raw material sales increasing the most. Royalties received from our partners also increased compared to the first quarter of 2021 by 27% from EUR 8.7 million in March 2021 up to EUR 11 million.
Please note that this amount is an internal estimate. Nevertheless, there is an upward trend in the sales made by our partners every quarter. Regarding R&D expenses, this quarter has increased 29% to EUR 19 million. Of which EUR 11 million were spent on oncology activities, EUR 5 million on virology activities, and EUR 2.5 million on RNA activities. The data in the first three months of 2022 increased 6% year-over-year to EUR 20.6 million. This quarter, we have generated cash from operating activities of EUR 35.8 million, mainly due to the collection of commercial milestone from the JAVELIN agreement in the amount of EUR 22 million. The group continued to reduce its financial debt by a total of 4% since December 2021.
As a result, we end the first quarter with net cash flow of EUR 2,005.7 million, 23% higher than net cash at December 2021. I end my presentation, as I began it, by highlighting the consistency of the figures that we have presented to you today and pointing out that financially we are ready to address all the clinical development sourcing in our R&D plan and to place new molecules in clinical development. Now I pass on to Luis Mora.
Thank you, María Luisa. Thank you very much. In oncology area, as María Luisa mentioned before, YONDELIS sales in Europe have been slightly lower compared with the first quarter last year. YONDELIS is under net price pressure in some Southern European countries. Volumes have been a little lower, and so we are seeing in April that they are recovering. Regarding YONDELIS in the rest of the world, the sales are better than 2021. Our partners do a good job, and we can say YONDELIS today in soft tissue sarcoma is a standard of care in the second line. We maintain the market share like last quarter. Regarding lurbinectedin, the LAGOON trial, remember, is a pivotal trial phase III, is progressing as planned. For lurbinectedin, the new registration dossiers are being prepared in different countries. There were meetings with our partners.
Those meetings have been held with different regulatory authorities, and we will keep progress in this regard through this year. We expect the regulatory decision in some countries within this year.
The good behavior for the early access program in some European countries is important. We receive more drug requests day by day, which show the great interest in lurbinectedin, the need for treatments in small cell lung cancer and the confidence in our product. Work is also being done in the new phase II trial in mesothelioma. We are working on that, which we hope will start in the second half of the year. Regarding ZEPZELCA in the USA, I can only say we are very satisfied with both our partner Jazz and the evolution of ZEPZELCA in that country. As you can see, as we anticipated in the last conference call, phase II and its development is continuously supported in evident tumor types in the basket trial.
We can say also we are working on two new compounds. We plan to enter into phase I clinical trials this year, 2022. Regarding the area of biologics, the phase III trial, the NEPTUNO trial continues to recruit, but at a slower rate than we would like due to the changes in incidence and hospitalizations of the pandemic in the different countries. I can advance that we are preparing a new study with a different population than NEPTUNO, where there are no therapeutic solutions for these patients. They will be immunosuppressed patients with COVID-19. Finally, regarding Sylentis, we have only announced that it has started a new phase III with the drug tivanisiran with the objective to show its safety in dry eye syndrome.
In addition, the phase III of efficacy continues to recruit satisfactorily, and we hope that recruitment will end within the year. Thank you, and Pascal, please.
Thank you, Luis. Good morning or afternoon to all of you. I'll start off with a recap of a few key events from Q1, and then I'll highlight some coming attractions for Q2. In Q1, we had a very nice KOL event with Dr. Besse from Gustave Roussy in France and Dr. Jacobson from Dana-Farber/Harvard, discussing second-line small cell lung cancer today and tomorrow. Now, it's clear that small cell has been an underserved unmet medical need and that lurbinectedin is filling that void and that it is well-tolerated. Dr. Besse presented an interesting case study of a patient who had a partial response lasting 36 cycles. That would be about 26 months, which is wonderful. Of course, an anecdote of one patient.
We also can share another anecdote of one patient, an American lady from Alabama who's been on lurbinectedin for over four years from a clinical trial to extended access. Certainly, we don't mean to make anyone extrapolate out to any goods. However, it's nice that there is this hope of a lasting response. At the ELCC virtual meeting in March, we had an abstract presented on lurbinectedin real-world safety and associated costs from Switzerland real-world setting. It showed that lurbinectedin costs were EUR 1,200 in comparison to topotecan of the order of EUR 8,000 and CAV of EUR 4,500. This is mainly due to reduced myelosuppression and the use of primary prophylactic G-CSF in topotecan and CAV case. An interesting abstract that was presented that we hope will further the case for lurbinectedin in Europe at the appropriate time.
Moving on to things to look for this quarter at abstracts for ASCO, we've had four accepted. I can only share with you at this point the titles. One is the BRCA cohort of the basket trial in breast cancer, the phase II. The second is number of patients from the ATLANTIS study that continued onto monotherapy lurbinectedin after the completion of nine cycles of doxorubicin. A third is the LUPER study, which is a combination of lurbinectedin and pembrolizumab in the relapsed small cell lung cancer setting. Fourth, which is an e-poster only, but I would guide you to have a look at it's an interesting study, is lurbinectedin efficacy from our basket trial compared to standard of care from real-world setting, external control arm, and the author of that is Dr. Ettinger, who is the chairman of the NCCN panel for small cell.
Lastly, a comment on ZEPZELCA. With ASCO around the corner and this year being in-person and virtual, and from what we can tell, will be well-attended and the opening up of the U.S. post-pandemic, we may see accelerating progress with ZEPZELCA, especially in the community physicians who have been harder to reach because they stayed in their offices for the last two years. Small cell does have a large proportion in the community setting, so this could be a benefit going forward. Just a thought going forward, and we hope to see that. Lastly, a comment on business development. We continue to pursue our goals there and are in active negotiations. Certainly, the impact of the public markets is being felt. People seem to be more motivated with fewer options for equity raises being there.
We're being opportunistic and reconnecting with many counterparties and hoping to meet many at ASCO. As I always end, I say, we'll let you know as soon as we have something to let you know. With that, let me pass the microphone back to José Luis.
Thank you. Thank you, Pascal. This will be the end of our prepared remarks today. Victoria, if you would like to open the line for questions.
Perfect. If you'd like to ask a question, please press star one on your telephone keypad. If you have joined us online, please press the red flag icon. Please, ask your question, please ensure that your line is on mute locally. Our first question comes from Christian Deleny from Citadel Institutional. Please go ahead. Your line is open.
Hi, guys. I've got some questions. Can you hear me okay?
Yes, we do.
Hi, Christian.
Hi. Just wanted to tease out or clarify something you said around, I think, Luis may have said around sort of market share at ZEPZELCA. I think in terms of you sort of maintaining that market share. Is that sort of right? I mean, when I look at sales or the implied potential sales, obviously reading, you know, between the leaves and the tea leaves around royalty, whatever royalty, right? Looks like Q1, the estimated sales around sort of flattish versus Q4 last year. Is that the right way to think about it?
No, I used to go on about market share, not ZEPZELCA. Regarding ZEPZELCA, we can say nothing. This is just really we can't say more than we said before. I speak about market share in Europe and in the rest of the world, standard of care and not specific.
In regard to the ZEPZELCA, Christian in the U.S. has just said in the third quarter results call, they had, you know, 37% market share, and they haven't updated that ever since.
Yeah. Yeah. No, fair enough. Okay. Just wondering, unless I missed it, just an update on the ZEPZELCA trials.
We are still working on that. I announced in the last conference that we are very close to a deal agreement with the immunotherapy licensor from a big company. Rest of the protocol or the infrastructure, we are still working on that, and our objective is to start this trial in the second half of this year. We have already all the panel of principal investigators, hospitals, contracts and et cetera. The trial will be done in Europe and in USA, mainly.
Okay, thank you. A bit more on, you know, asset that is interesting, maybe we don't spend enough attention on, is obviously the Sylentis asset now that it's starting the phase III. Just a bit more on the cost of that trial, the timings there to data and the, you know, the commercial strategy, you know, partnering and the commercial strategy for the asset.
At this stage, we are on the stage where we already announced it. For the NDA, we needed three clinical trials, two for efficacy, one for safety. The first for efficacy was already started, and we expect to finalize recruitment this year. The safety phase III trial is already ongoing. We announced it a week ago. Number three, the third clinical trial phase III we will announce when we will start. Usually, the second efficacy trial is started when the first one is finished. Okay. Usually.
The timing on completing the first phase III?
We've analyzed recruitment for Sylentis, the efficacy trial this year. Probably in the first half of next year, we'll give a readout of the results. The safety has just started. Again, this model is one year when you're in a trial. Phase III, we will start when the first one is finished. Okay?
in terms of the potential commercial strategy, I mean, is this something you already tried to license and now decided to platform yourself or?
I cannot announce today what is the strategy. Okay?
Okay. Okay, thank you. I mean, Pascal, I mean, you know, there's obviously, you know, the searches ongoing for new assets. You know, anything else you can sort of share in terms of, you know, what, how many might be in the hopper, sort of late stage? I know you can't be drawn on timings, but, you know, the concept, the same sort of concept around it's, you know, an asset that licensing to Europe or European commercial infrastructure makes it from a, you know, it's a $50 million-$150 million product or something like that. Anything to say around this and what you previously said on that as well?
Well, I'm gonna be really boring, Christian. I'm sorry, but I'm gonna just end up repeating what I said previously, which is we're involved in multiple potential discussions regarding oncology assets for the European theater. Some are commercial, some are late stage, and we've got a lot of capacity to do
Small to medium-sized deals and access capital if we need it. Really beyond that, being so cool.
Okay, thank you. Fair enough.
Thank you, Christian.
Okay, thank you so much, Christian, for your question. Our next question comes from Ervan Alente from Alantra Equities. Please go ahead. Your line is open.
Hi. Thanks for taking my question. The first one would actually be a follow-up on the question from Christian on the evolution of your royalties personally from during this quarter. We see a quarter-to-quarter decline. What my question would be is whether this reflects some sort of seasonality or just an effect of inventory management by your client or through the distribution network, or whether this is just an adjustment because this is just an estimate because you do not have the final number, whether this is an adjustment from the estimate that you made last quarter, just to make sense of the quarter-on-quarter evolution.
Regarding your question, remember the first quarter 2022 royalties perspective from Jazz is an estimation. Then we will see the final figure. The second one, I don't see what you say the decline of the royalties. Sorry, but I don't observe that. The explanation was that six months ago, eight months ago, an adjustment was a public statement by us, an adjustment in the difference between gross and net sales regarding the rate or the returns estimations. That's why some we even is growing quarterly basis, the volumes. Okay.
Okay. Understood. Another question on the tax side, you reported a tax gain, this quarter, just as last year. If you could provide us what your normalized tax rate would be, and when do you expect run rate tax rate level to be achieved?
We have the tax benefit because we monetize the deductions due to R&D activity. That's why we have positive figures in income tax benefit. We expect to continue doing it as long as legislation allow us.
Yeah. I understand. Just wanted to know for how long will this last? I mean, I understand that this is where you can imbalance some previously off-balance-sheet type assets that were not quite nice before. I understand that's what happened.
Yes. Yeah, this is not due to our off-balance tax shield. This is because of monetization of R&D investment. Yeah.
Okay. This could continue for the whole year, maybe into 2023.
Yeah. It will continue, but it depends on the quarter, on the profits of every quarter, the amount that will compensate this monetization. Yeah.
Okay. Perfect. A question on the pipeline. You mentioned two new compounds coming in. Whether you could provide some detail of how related are these new compounds to trabectedin and to lurbinectedin, or whether these are completely different compounds and whether you expect them to be mostly used in solid tumors or maybe to other parts of oncology in blood and in blood cancer or something like that.
I can advance because when we will start it, we will announce that. I can advance to you two new compounds coming from our R&D platform. Those compounds in principle will be focused in solid tumors. These compounds are different mechanism of action. Okay? Most compounds are code. One is the PM184, and the other one is PM534, is internal code. Okay? We expected to start these trials, phase I in the second half. We are already in contact with the hospitals, with the doctors, tonight. We were in charge of these trials. In principle, these trials will be conducted in four or five different countries, like, European countries and US. Okay.
Perfect. Yeah.
No, go ahead, please.
Okay. My last question would be on YONDELIS. The performance has been remarkable in terms of market share despite the age of the product. As we approach patent expiration, do you have any insight that you can share with us on competitors, generic drug manufacturers researching for a potential generic version of trabectedin? When do you expect to see either price or volume competition from generics? Thank you very much.
Well, as you know, UBRELVY is about 15 years in the market, the mature product. Obviously, I mean, then we know in different countries in Europe that the generic companies are actively filing different dossiers. This is, in this sector, as far as we know, not all the dossiers submitted are linked to the sales of the product in the end. Okay. We will see. On the other hand, what I think is that we maintain the market share. In April, we recover more than the volumes from the first quarter, the difference between first quarter of the last year. We are working on that. The generics will surely, not only for all the products will come out early or later. It is not in our hands.
This is in the generic company's hand. We will see. We expected that some generics will be coming next year, in 2024, at the end of 2022. We don't know. The dossiers are submitted, not only, it's more than 20 products, oncology products. At the end of the day, the decisions, they are in these generic companies' hands. Depending on this, the impact is secure, but the impact is not global impact because it's different country by country. In some countries it's different region by region or in autonomy by autonomy. It's not linear in all the countries it is secure. You have the other examples for the other products, other companies, and this is the trend today. For generics, you know, the commercialization trends is by tenders. There is no need commercial.
This is a purely commercial support. It's more tender than not. In any case, good.
Okay. Thank you very much.
Perfect. Thank you, Alvaro, for your question. As a reminder, if you would like to ask a question, please press star one on your telephone keypad. Now our next question comes from Joseph Hedden from Rx Securities. Please go ahead.
Good afternoon. Thanks for taking the question. First one on ZEPZELCA, and the combination trial with pembrolizumab. I'm just wondering what your thoughts on how important that trial is now, considering that there's a first-line study ongoing with atezolizumab.
Thanks, Joe. That is an IST run by Dr. Kayes. I think your point is well taken. The pembro, since this trial has started, lost its third-line label and is still in the NCCN guidelines for second-line. However, it's an interesting trial insofar as the combination of pembro and lurbinectedin may be suitable in other indications.
Okay. Just talking about the atezo, ZEPZELCA combination, and I appreciate it's Roche's and Jazz's study. I seem to remember there may be an interim analysis there at some point. I'm just wondering if you can refresh our memory as to when that might occur.
Your memory is correct, Joe. There may be.
Right. Okay. It's not, I think it's not a 2022 event. It might be a 2023 event.
It hasn't been announced that there is an interim, first of all, and therefore it's an effect. If it hasn't been announced, there may be an interim. They haven't given the timing.
Sure. Okay. If I could, you made an announcement last week or a few days ago about the oligonucleotide plant. I just wanted a few more details on that. There was talk about need in the Spanish market, because you're going to outside players at the moment. Is this designed to serve just Spanish customers or will it be open for the kind of RNA players across Europe?
Thank you very much. This is a pilot plant. The capacity is not a lot, and we will use these products for our trials and our needs. We have newer plants we will announce appropriately. This is the first defined plant inside of the Sylentis facility. Okay. Within this capacity they will produce, we don't need to move to the third-party production in this stage, under development of the products.
Okay.
It's a GMP.
Okay.
It's a GMP. They are perfectly prepared for this task.
Okay, thanks for that. Have you had much interest so far from people wanting to use the plant?
Yes. Yes, because there are not a lot of facilities for oligonucleotide production. Some third parties approach us and they want to have some if we have products to sell to them. Our priority is to produce for our needs, but if we have the space.
Okay. I'm just thinking about the finances of that. From you know, a cost perspective, how much investment are you putting into that? I noticed in Q1 there's not really any significant CapEx, you know, in investment. When is that coming through and how much is that likely to be? Or is this replacing a facility that you already had and it shouldn't expect anything significant?
No. The Sylentis plant we announced the investment is not different material. It was already done. The main investment was done in 2021. Okay? In this quarter, we finalized the quality assurance works in order to be ready. Was not with less than EUR 1 million. Okay? Not small.
Okay. Great. Thank you so much.
Thank you, Joe.
Perfect. Thank you, Joseph, for your question. Well, the next question comes from Isabel Carballo from Oddo BHF. Please go ahead.
Hello. Good morning. It's just a quick question on your level of cash. You ended the quarter with a high level. I was wondering if you want to maintain some level of cash beyond your corporate movements, beyond your acquisitions, potential acquisitions. Thank you.
Isabelle, you don't have a very clear line. Could you repeat the last part? If we want to maintain some cash beyond?
Yeah. Which level of net cash do you feel comfortable to maintain after the M&A?
After the M&A.
Are you talking about the possibility of acquiring some product to incorporate, to include in our commercial sales force or structure?
Exactly. Exactly.
Yeah.
You are right now making different options from as you mentioned. I was wondering that you also have some R&D projects, new R&D projects coming and also some investments. The level of the cash you would need for all of that.
No. What we have mentioned always is that this amount is the one that will allow us to carry out all the clinical trials that we have currently on our current plan from now to five years plan, and also to introduce or include new products in our pipeline. This amount is devoted to our current development.
Isabelle. This is to ensure, as María Luisa said, our R&D investment. As for in case we, you know, we find a deal and we need to finance, well, we can use some of that cash and, if not, you know, you've seen, from our balance sheet as well, we've reduced net more than half in the last three years. You know, we've already increased our capacity for having strength in case we need to finance, you know, potential deals if we need it.
Okay. Thank you.
Thank you.
Perfect. Thank you, Isabelle, for your question. At this time, there are no further questions. I would like to pass back over to José for any final remarks.
Thank you. Thank you, Victoria. Thank you very much for your help today. I would like to finish by saying that once again, we're very happy with these robust results, which of course allow us to concentrate in all our development plans, in order to follow our pathway to continue growing. I would like to thank all participants for joining us in our conference call today. For those who would like to meet with the management, we plan to be on the road in London and Paris during May. We'll also be participating at the BME Investor Conference in Madrid the last week of May. Thank you again for joining the call and have a nice weekend.