Good morning to everyone. I'd like to welcome all of you to our third quarter 2021 results conference call. On the call with me today are Luis Mora, Managing Director of PharmaMar, and María Luisa de Francia, Chief Financial Officer of PharmaMar. As we usually do, following with no prepared remarks, today we'll 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 might vary from those projected. We disclaim any obligation to update any information provided herein.
We refer you to a Safe Harbor statement on our corporate presentation, which is available on our website together with the press release of the results we released yesterday. As a headline of the results released yesterday, we show a profit of EUR 54.7 million, which María Luisa will explain with more detail in a minute. Let me also highlight that out of the total revenue of EUR 144 million for the group during the last first months, our recurring business grew by 31% up to EUR 92 million. Like in previous quarters, this growth has been mainly driven by the oncology business.
Our royalties of Zepzelca coming from U.S. sales in the U.S., and as we did in the previous quarter, the information provided in our quarterly report is an estimate, since information about the amount of U.S. sales of Zepzelca was not available at the end of the publication of our results. Jazz had its earnings call on November 9th, and we will know then the actual sales of lurbinectedin in the U.S. in Q3. Talking about Zepzelca, we're very happy about how things are going. In this regard, during the last September, we saw the approval for commercialization of our drug for the treatment of small cell lung cancer in countries like Emirates, Singapore, Australia and Canada. To go over more details, I'll now leave you with María Luisa de Francia. María Luisa, please.
Thank you, José Luis. Good morning, and thank you all for joining this earnings conference call. I will briefly refer to the three main aspects of the group's financial statement as of September 13th. These are revenues, investment in R&D, and net cash position, including cash flow generation. The group's recurring revenues, comprising sales plus royalties received from our partners, increased 31% year-on-year to EUR 119 million. Most of these recurring revenues was due to net sales of Yondelis, 4% lower than in the same period of the previous year, despite gross sales being 2.5% higher. This was due to price pressure in several European countries. It is remarkable that Yondelis's gross sales continue to grow after more than 14 years on the market.
Yondelis's active ingredient sales to our new partners in the newly licensed countries also continue to rise. Sales of lurbinectedin in Europe under the Temporary Authorization for Use program increased 78% this period to EUR 23 million, stabilizing in the last three quarters. Royalties received from our partners amounted to EUR 27.2 million, including 25.2 million from Jazz Pharmaceuticals. However, please note that the first quarter 2021 amount is an internal estimate. Non-recurring revenues are those resulting from agreements with our partners, upfront and milestone. Whereas as of September 2020, we recorded EUR 131 million of these non-recurring revenues, at September 2021, we have recorded EUR 24.6 million, in both cases from Jazz Pharmaceuticals agreement.
R&D, which is the group's largest expenditure, has increased by 21%, reflecting the phase III clinical trials currently underway in COVID-19 and in dry eye, specifically in patients affected by the congenital disease under RNA interference technology. In oncology activities, a new phase III trial has been designed with lurbinectedin in both small cell lung cancer and other indications, and progress has also been made in the preparation of new candidates for clinical development. Other operating expenses remained a slight increase of 1.4%.
All of the above led to a net profit for the period of EUR 54.7 million compared to EUR 121 million for the same period of the previous year. If we were to eliminate the impact of non-recurring revenues, mainly Jazz Pharmaceuticals upfront and milestones, the results as of September 2021 would be significantly higher than the results as of September 2020. Regarding cash position, I would like to highlight that we have improved the net cash position we had at the beginning of the year by almost EUR 8 million. A point to be valued if we consider that we have allocated more than EUR 47 million to R&D expenses. So that at September 13th, we had a net cash position of EUR 171 million and cash of EUR 222 million.
Finally, it is important to note that the group generated nearly EUR 25 million of cash flow from operations. To summarize, recurring revenues keep their growing trend. R&D investment increases along with trial activity. Compared to 2020, after eliminating non-recurring revenues, the group's net result is much higher in 2021. We have generated operating cash flows, so we maintain a net cash position that allow us to address all ongoing projects without any stress. Now I pass the microphone to Luis Mora.
Thank you, María Luisa. Good morning, everybody. Well, my colleagues have commented on many important items of these third quarter results. Regarding Yondelis, the Yondelis sales in Europe increased in the volume setting, and we slightly increased our market share in soft tissue sarcoma and second-line treatment, and Yondelis is considered reference standard of care for this treatment. Unfortunately, in some countries, in South European countries, increased the pressure in the pricing and the discounts, then for this reason, the net sales are slightly different than the last year. Regarding the rest of the world, from end of 2019, we recovered the rights from Johnson & Johnson for Yondelis in many countries in the rest of the world.
We signed eight new deals for eight new partners, and these new partners start to promote and sell the drug in these areas. We are so happy with the evolution, and we expect that these sales continue increasing in next months. The second one was the results of phase III trial, SaLuDo trial in leiomyosarcoma front line in combination with doxorubicin against doxorubicin alone, was the best results shown for any clinical trial in the history to treat this disease. Now we expect that this exceptional results, the doctors start to use this combination for the patients. Regarding Zepzelca, the very important item for us was that we achieved the agreement with the FDA regarding the phase III trial in the small cell lung cancer, a mandatory trial for U.S. market.
This will be the trial we will submit, if it's positive, obviously, for the European authorities to commercialize the drug in our territory in Europe. The trial is well designed, the trial is agreed, and the trial we expected to start in a few months, end of the year, the beginning of the next year. Other indications, important indications for us are plitidepsin, and we will announce probably in the next quarter results. Regarding regulatory process in different countries around the world, part of the countries was approved in the third quarter, like Australia, Canada, Singapore or Emirates. Many countries was submitted the dossier for small cell lung cancer. The regulatory process is ongoing and we are expected to announce new approvals in a few months in other countries.
Regarding this special expanded access program in Europe for Zepzelca in small cell lung cancer, we are so happy and it's encouraging for us because in two years we treated more than 1,700 patients in Europe. In some countries, it's for free, in some countries, it's reimbursed, and these figures are reflected in the quarter results. What is very interesting is that the treatment of the patients, the Zepzelca is well received for the doctors and more and more patients are treated now. For us this is very important. The drug today is available for the patient when it's needed. Our partnering with Jazz is very good, we are so happy.
Even the level of royalties is an estimation for the company, but reflected the well position today the drug in U.S. The other drug, important drug for us is ecubectedin, PM14. Now this drug finally they have a name. ecubectedin is the INN name. They started this quarter the phase II trial in solid tumor. The trial is ongoing and we expect the trial continues very, very well in different tumor types. For the virus area, the pivotal trial, NEPTUNO trial is ongoing. The trial is going, is enrolled in different countries. You can imagine that the level of enrollment depend on the level of the pandemic in different countries.
As we expected, this enrollment will increase in few weeks because in some countries where the trial is open, unfortunately for the population, the incidence of the COVID-19 is increasing. Finally, sorry, our activity in licensing. We are working very hard. We are working in that. We contact with selected several drugs from several companies, and then when we will achieve any agreement, we will announce appropriately. I pass to José Luis.
Thank you, Luis. These are the, you know, remarks for today from our side. We'll open now the time for questions. Simona?
Thank you. If you would like to ask a question, please press star followed by one on your telephone keypad. When preparing to ask your question, please ensure that your phone is unmuted locally. Our first question today comes from Joseph Hedden of Rx Securities. Joseph, your line is open. Please go ahead.
Good afternoon, everyone. Thanks for taking my questions. Just firstly on the NEPTUNO trial, appreciate what you were saying there about the incidence increasing and likely to speed up enrollment. At this time, what's your best estimate of when we might see top line results? Is that Q1 scenario?
We can't disclose that today because the trial is ongoing. You can imagine when you achieve the number of patients we need to include in this trial is 609. We need some period of time in order to close the database, clean the database, and finally to see the top line results. It's very difficult today to answer this question.
Okay. Then in your release, when talking about your program, you spoke of it's essential to start another trial in COVID-19 patients with a different profile. Could you go into that a little bit more? What kind of profile are we looking at, i n terms of the opportunity ?
Yeah, the pivotal trial is ongoing. It's for the hospitalized patients, moderate hospitalized patients that need oxygen, pneumonia, etc. This new small trial is for severe patients, okay? If the patient have progressed and they are in worse situation than the moderate hospitalized patients, then this is the most important new target population. The population at high risk hospitalized, the cancer patients, immunosuppressed patients , etc. For this target population, we will start this new trial. Probably the dose will be different. We will see. This one, phase I/II. We expect it to start in a few months.
Okay. Lastly, just on Zepzelca, and the trials that are ongoing in small cell lung cancer with combinations with Opdivo and pembro. I think we were hopeful to see results from those at some point this year. Is there any update on when we might see results from those trials?
The trial is. We have two trials in combination with immunotherapy. One is with pembrolizumab and the other one is with atezolizumab. I want to remember this trial have a management sponsor. There is an IAS trial. Then, depend on the investigator or PI of this trial, they will, finalize and we will present this data in any congress in the near future.
Okay, thanks very much.
Thank you, Joe.
Thank you, Joseph. Our next question comes from Alvaro Lenze of Alantra Equities. Please go ahead, Alvaro.
Hi, good morning. Thanks for taking my questions. Regarding the performance of Zepzelca, I understand that you do not have the full information from the U.S. I don't know if you can provide us some information on, because the ramp up of the royalty seems to be rather slow. Whether this is due to changes in the stocking of clients or whether you're not seeing a very fast penetration of the product in second line. Also in Europe, I understand that Europe is only compassionate use. You do not have, like, normalized demand. Whether this EUR 7 million-EUR 8 million of revenues from Zepzelca in Europe is what we should expect going forward until the product is eventually approved, or whether it could also increase even under a compassionate use setting.
Thanks.
Well, regarding the first question, our estimation is to increase the royalties about 14%-15%, something like that. This is our estimation, okay? It's not just numbers. It's an estimation, quarter- by- quarter. In my opinion, if in one quarter is increased 14%-15%, it's very, very important growth, not only the sales, the penetration, etc. This is an opinion. The fact is we increased our estimation 14%-15%. Regarding the second question, I don't know if you are aware the conditions for expanded access program. For your knowledge, when any company launch this type of programs in Europe is when the available therapy, the therapies are exhausted.
What it mean? Today, Zepzelca in Europe is used in expanded access in third or fourth line treatment without any activity, commercial, medical affairs, nothing. If the drug is approved in the future, first of all, they move to the second line, not third or fourth line. Second one, we will perform the activity regarding medical affairs and commercial setting. Number three, the reimbursement is only in one country, not in 28 countries around Europe. Okay?
Okay, thanks. A follow-up, if I may. Looking at drug prices, you mentioned that you have had some pricing pressure in Southern Europe, in Yondelis. Whether this is a one-off or do you expect further pressure going forward or could this be reversed, I don't know if you can provide us more color on that.
In any country is one-off. Then they increase the discount from one figure to the other figure, and this maintain in the time. I don't know if in two years or in three years they modify, increase or not. This is the decision of the governments of the different states, of the rules, etc. This reflect the last decision for these ministers of health in different countries, and this is in place until the new one or not, depend. It's country- by- country.
Okay, thank you very much.
Okay.
Thanks, Alvaro.
Thanks, Alvaro. We currently have no further questions, so I will hand back to José Luis Moreno for any closing remarks.
Thank you, Simona, and thank you very much for your help today. Thank you to all participants for joining us in our conference call today. For those who would like to meet with the management, we'll be participating in the JMP Capital Iberian Conference and the Piper Sandler Healthcare Conference both in November. Thanks again for joining the call and have a nice weekend.