Heidelberg Pharma AG (HPHA) Earnings Call Transcript & Summary

Hello, everyone. Thank you for standing by. Thank you for joining Heidelberg Pharma's conference call to discuss 2023 Fiscal Year Results and provide a business update. [Operator Instructions] Please note that today's call is being recorded. [Operator Instructions] I would now like to turn the call over to Dr. Andreas Pahl, CEO of Heidelberg Pharma. Please go ahead, Andreas.

Good afternoon, everyone, and welcome to the Heidelberg Pharma conference call to discuss our 2023 Fiscal Year Results and to provide a business update. My name is Andreas Pahl, and I'm the CEO of the company. Joining me on the call today is CFO, Walter Miller. Please note that this presentation is available for download on the Heidelberg Pharma website. This conference call is being recorded, and the replay will be available on our website after the live event. Before I begin, let me remind you that we'll be making forward-looking statements on this call as well as during the question-and-answer session. Please see our safe harbor statement here. For a more detailed discussion of the risks and uncertainties affecting our business, please see the 2023 Management Report published today on our website. On the call today, we will give you a brief corporate overview and outline key achievements. We also will provide an update on our programs. This will be followed by a review of our financials and an outlook for the year ahead. Following our prepared remarks, we will have a question-and-answer session. Slide 3 gives you a snapshot of our company and highlights in general, and in particular, over the last few months. We have a proprietary innovative ADC technology for manufacturing novel Antibody Targeted amanitin Conjugates or ATACs. Our technology has now matured and it moved to the Plug & Play mode, which means we will be able to go from target to IND in only 2 years. While the technology enables the use of different payloads, we have until recently been solely focused on Amanitin and natural toxin found in the death cap mushroom, which has a unique biological mode of action, the inhibition of RNA-Polymerase II. This makes Amanitin a very differentiated payload compared to existing and approved payloads. We have developed a fully synthetic process for manufacturing Amanitin, and have completed 5 GMP grade batches. Over the past year, we have been expanding our ADC toolbox to include other ingredients such as the Topoisomerase Inhibitor Exatecan and agonist for the immune stimulating Toll-like receptor 7 or TLR7. More on this exciting development a bit later. We have one ATAC, HDP-101 in the clinic, which is showing good activity in patients with multiple myeloma. We are preparing IND applications for 2 additional product candidates. We will provide more information on these programs during today's presentation. We have several IP with several patent families, including a very strong protection for Amanitin as a payload for ADCs. And we have 2 great partnerships, who are done for the development and commercialization of several products in the Greater China region, then ATAC technology partnership with Takeda. Importantly, we have a team in place here at Heidelberg Pharma and sufficient cash to advance our groundbreaking work. What motivates all of us is our mission, mainly to develop novel drugs based on our ADC technologies for the targeted and highly effective treatment of cancer. In a nutshell, it's all about the patients we have the potential to help with the important work we are doing. Turning to corporate activities. The Executive Management Board was strengthened last spring with the addition of Chief Financial Officer Walter Miller. Walter comes to us with many years of experience in the biopharma industry and corporate finance, M&A, strategic controlling as well as accounting and corporate development. I have now had the pleasure of working with him for many months, and he has been a powerful addition to the team. At the end of the reporting period, we announced that long-serving Chief Executive Officer, Dr. Jan Schmidt-Brand, would resign effective February 1, 2024. I'm truly honored to have been appointed by the Supervisory Board to take over from Jan, and look forward to continuing to work with the Board, the entire Heidelberg Pharma team, in my new role to move our company forward. I would also like to take the opportunity to warmly thank Jan for his many years of service to the company and for bringing Heidelberg Pharma to the clinical development stage. Last summer, Heidelberg Pharma sold its minority interest in Emergence Therapeutics, after Eli Lilly and Company acquired all outstanding shares of Emergence. We received EUR 6.8 million in cash because of the sale. There remains a potential upside of an additional EUR 4 million, based on the achievement of certain defined long-term non-financial milestones by Emergence. And recently, we announced the successful closing of the royalty purchase agreement of HealthCare Royalty. Under the terms of the agreement, Heidelberg Pharma is eligible to receive up to USD 115 million from the partial sale of its future royalties on the worldwide sales of Zircaix, the legacy assets that we out-licensed to Telix Pharmaceuticals several years ago. Walter will walk through this agreement in more detail during the financial part of the presentation. Importantly, we received a patent for site-specific ATAC conjugates from the European Patent Office, which also covers a method for synthesizing such conjugates and the use in the treatment of diseases. Last but not least, we are making particular good progress with our combined Phase I/IIa clinical trial with HDP-101, and we have seen first objective responses and partner missions in Cohort 5. We will discuss our clinical program in the detail a bit later. Taking a look now at our R&D work. In the past year, we expanded our ADC technologies. We are developing an ADC toolbox and clinical product pipeline to overcome tumor resistance across cancer types. Starting with our proprietary Antibody Targeted Amanitin Conjugates or ATAC technology. Heidelberg Pharma has extensive experience with the compound, Amanitin, and to the best of our knowledge, we are the first company to use it to develop new cancer treatments, which has another mechanism of action, inhibition of RNA-Polymerase II, which results in programmed cell death or apoptosis. It also offers the potential of breaking through drug resistance and destroying dormant tumor cells, which could result in significant clinical advances. During 2023, we made a major step forward in advancing our technology to an ADC toolbox, by developing a Link Health platform or other compounds beyond Amanitin. By broadening the scope of our ADC capabilities, we have the potential to both expand our own portfolio to other targets and indications, as well as provide more option for potential partners. First, we have developed a new ADC platform technology that uses Exatecan, a Topoisomerase or TOPO I inhibitor as payload. Exatecan is a proven compound for cancer therapy, which is closely related to the payload used in an already approved ADC trastuzumab deruxtecan brand named Enhertu, which is FDA approved for the treatment of HER2-positive metastatic mammarian carcinoma. The scientific team is currently working to select a lead candidate for this platform, which will be developed as HDP-201. We are also developing an immunostimulatory technology platform from our collaboration with Binghamton University in the U.S. The platform uses potent novel immunostimulatory compounds Toll-like receptor 7 or TLR 7 agonist and the ADC technology for the specific delivery of these compounds to tumor tissue. The resulting immunostimulatory ADCs have the potential to harness the patient's own immune system by making the tumor visible to the immune system to thus attack and eliminate malignancies. These immunostimulatory agents could be synergistic with cytotoxic agents, including ADCs generated by Heidelberg Pharma's ATAC technology. These ADC platforms, including different payloads and antibodies, will lead to multiple development candidates with different modes of actions. This slide provides you an overview of our pipeline, including our proprietary portfolio of candidates, our partner programs and our legacy assets. Let me here just mention a couple of things. The first 3 assets from our pipeline are on track, and I will provide more details shortly. We have made the decision to prioritize HDP-201 to generate more data on our new payload Exatecan. HDP-201 addresses the same target as HDP-104, Guanylyl cyclase C or GCC, the surface protein that is overexpressed in the variety of gastrointestinal cancers. Let me also update you on our long-standing partnership with Takeda Oncology. In 2017, we signed an exclusive research agreement with Takeda, related to several targets for joint development of ADCs using Amanitin. Under the terms of the agreement, Heidelberg Pharma produced several ATACs using antibodies from Takeda's proprietary portfolio. As a result of this work, Takeda acquired an exclusive license in September 2022, to commercially develop an ATAC with a selected target. Takeda is responsible for further preclinical and clinical development as well as potential commercialization of the licensed product candidate. In August 2023, Takeda reached the development milestone by starting a Good Laboratory Practice toxicological study for an ATAC, which triggered a payment to Heidelberg Pharma. We are pleased that Takeda continues to make progress with this program. Looking at our legacy assets. As a reminder, a few years ago, we out-licensed several clinical product candidates that were no longer part of our core business of ADCs. These are being developed solely by licensing partners, and Heidelberg Pharma is eligible to receive development milestone payments as well as royalties on sales for any of the programs that make it to the market. Indeed, following positive Phase III results, our licensing partner, Telix, began a rolling Biologics License Application submission for TLX250-CDx or Zircaix, for the identification of clear cell, clear renal cell carcinoma, which is essentially the basis for the royalty purchase agreement with HealthCare Royalty. We now come to the R&D update, starting with our ATAC technology and proprietary projects. Let me now provide an update on our lead product candidate, the ATAC HDP-101. As a brief reminder, HDP-101 consists of an anti-BCMA antibody, a specific linker and the toxin Amanitin. BCMA is a surface protein highly expressed on multiple myeloma cells and to which a BCMA antibody specifically bind. Just a few words on the indication, multiple myeloma is a type of blood cancer that develops from plasma cells in the bone marrow, and can affect more than one part of the body. Plasma cells are a type of blood cell that makes antibodies to fight infection created by bone marrow. In myeloma, the bone marrow makes lots of abnormal cancerous plasma cells. The worldwide incidence of multiple myeloma is current 160,000, with a mortality of 106,000. A Phase I/IIa clinical trial for the treatment of relapsed or refractory multiple myeloma is ongoing in the U.S. and Europe. The study is designed to assess the safety, tolerability, pharmacokinetics and efficacy of HDP-101 in patients with multiple myeloma, when treated with an intravenous infusion every 3 weeks at decreased dose levels in the target patients. The first part of this trial is a Phase I dose escalation study to determine a safe and optimal dose for HDP-101 for the Phase IIa part of the study. At the end of the 2023 fiscal year, 5 patient cohorts, a total of 18 patients, have been treated with doses of up to 100-microgram per kilogram. In the first 4 patient cohorts, treatment was shown to be safe and well tolerated. We would like to share with you an exciting case from this ongoing study. One trial participant who was part of the third cohort at 60-microgram per kilogram, has been treated with HDP-101 now for more than a year and has a stable disease. As of mid-February 2024, he had received 17 doses. He was given a 60-microgram per kilogram dose until the end of the fourth cohort. Upon confirmed completion of the fourth cohort, he was offered this cohort's higher dose of 80-microgram per kilogram, to which he consented. We are excited about this patient's story, which gives us a first snapshot of the potential of this exciting compound. Since September 2023, patients in the fifth cohort have been treated with a dose of 100-microgram per kilogram HDP-101. Encouragingly, clinical efficacy was observed after multiple doses of HDP-101 in cohort 5, including 3 objective responses and partial remissions out of 5 patients continuously treated with 100-microgram per kilogram. Please note that the dose level, 100-microgram per kilogram, and after the initial administration of HDP-101, a temporary drop in thrombocyte count occurred in all patients. However, that's normalized within a few days without any clinical observations, with counts returning to pre-dose levels. In order to mitigate the effect of the initial administration and adjustment and optimization of the medication, regimen was developed based on the recommendation of the Safety Review Committee. The corresponding protocol adjustments were implemented and recruitment of the sixth cohort was started. As I mentioned, we submitted a protocol amendment through the -- via U.S. FDA related to a plan modification and optimization of the dosing regimen, to lessen the initial transient and reversible reduction of thrombocyte. The dose escalation continues with an amended dose scheme. Cohort 6 will have 3 arms, but each arm enrolling at least 3 patients. Patients in Arm A will be treated with a single dose of HDP-101 on day 1 of each 21-day cycle after a pre-medication. Arm B will receive a weekly dosing of HDP-101, with patients treated on days 1, 8 and 15 of each cycle. Arm C will receive a dose of HDP-101 on days 1 and 8 of the first cycle and then a single dose on day 1 of each of the following 21-day cycles. If additional cohorts are warranted, only promising regimens from cohort 6 will be carried over. Let me now briefly discuss our next 2 product candidates. HDP-101 is an ATAC targeting CD37 that is overexpressed on B-cell lymphoma cells. Heidelberg Pharma is planning to develop HDP-102 for non-Hodgkin lymphoma. In preclinical trials, this development candidate was found to have a very large therapeutic window. Production of clinical trial supply according to Good Manufacturing Practice, GMP standards is proceeding according to plan, and mostly has been completed. In addition, further preclinical and toxicological studies have been completed, and the data package required before initiating first in human testing expected to be completed the first half of this year, and will be submitted to regulatory authorities in several countries. We will present preclinical data on HDP-101 at the AACR Annual Meeting in April. Our other product candidate coming along is HDP-103, which we plan to develop for the treatment of metastatic castration-resistant prostate cancer. The antibody used to bind to PSMA, a surface antigen that is overexpressed on prostate cancer cells. This is a promising target for ATAC technology, because PSMA shows only a very limited expression in normal tissue. In vitro and in vivo efficacy, tolerability and pharmacokinetic studies have shown that HDP-103 has a promising therapeutic window. There's also a very high prevalence, 60% of the 17p deletion in metastatic CRPC. Increased sensitivity to prostate cancer cells, with a 17p deletion has already been preclinically validated. As we have previously reported, tumor cells with the 17p deletion are particularly sensitive to Amanitin. Cell PSMA-ATACs might be particularly suitable for the treatment of metastatic castration-resistant prostate cancer. Please note that we presented the preclinical results at the AACR Annual Meeting in April 2023, demonstrating for HDP-103 that a subcutaneous administration resulted in an improved therapeutic window compared to intravenous administration, i.e., better tolerability while maintaining antitumor efficacy. Over the past few months, production of HDP-103 and the GMP condition was completed as planned. Preclinical and toxicological studies with HDP-103 are now mostly completed. A clinical trial to investigate the tolerability and efficacy is currently being planned. We plan to be able to submit an IND application of [indiscernible] to regulatory authorities for HDP-103 in 2025. Please turn to the next slide, where I will tell you a bit more about our exciting new project, HDP-201. In 2023, we introduced a new platform that uses the compound Exatecan, a Topoisomerase I inhibitor in connection with the new linker technology. This was an important step in diversifying our proprietary pipeline, as well as being able to offer additional options to our partners. Exatecan, as I mentioned earlier, is a proof compound for cancer therapy that is also being used in an approved ADC. Following extensive work, including a number of in vitro and in vivo studies, we are excited to unveil our first project using this platform [indiscernible]. HDP-201 targets guanylyl cyclase-C or the GCC, a receptor that is expressed on the surface of intestinal cells and cancer cells in various gastrointestinal tumors. The GCC antibody has already been produced for our HDP-104 program, and there are sufficient quantities of the antibody available to supply to ADC projects. Since the GCC antibody was already available, we were able to complete our research quickly and start the development process for HDP-201. Preclinical results to date show the tolerability and efficacy of HDP-201, to be at least comparable to approved Exatecan medicine. HDP-201 is our first pipeline project to utilize both a new drug payload and a new linker technology. As mentioned before, this payload has a different mode of action than Amanitin, and expands our toolbox of available payloads. Turning to our out-licensed clinically legacy assets. In 2017, we out-licensed the diagnostic antibody girentuximab or TLX250-CDx, which now has the brand name Zircaix, to the Australian firm, Telix Pharmaceuticals. The license agreement also covered the development of a therapeutic radioimmunoconjugate program. Telix conducted a Phase III trial evaluating the use of Zircaix and positron emission tomography, PET imaging to reliably detect clear cell kidney cancer compared to so-called standard of proof. The histology of surgical samples. Positive top line results from this study were reported in November 2022. As a product candidate with breakthrough designation, TLX250-CDx has been granted a rolling review process, which enables a progressive submission and review of required modules in the timetable pre-agreed with the FDA. Telix also requested a Priority Review. Granted Priority Review, the FDA's goal would be to take action on the application within 6 months, compared to 10 months under standard review. In December, Telix began the submission of a rolling BLA to the U.S. FDA. Telix also has opened an Expanded Access Program to provide patients with access to Zircaix ahead of approval. Patients have been -- have already been on road in this program in both the Netherlands and the U.S. Telix is planning for potential market approval and launch in the U.S. in the second half of this year. Telix is conducting further clinical trials with the TLX250-CDx to expand the indication. We're excited by the progress and the commitment of Telix in advancing these programs and bringing them to the market to help patients. As mentioned earlier, we have recently sold part of our future royalties from worldwide sales of TLX250-CDx to HealthCare Royalty. Let me now turn the call over to Walter, who will discuss our financial results. Walter?

Thank you, Andreas. Let's start with our profit and loss statement for fiscal year 2023. As a reminder, our fiscal year ends on November 30. Starting with sales revenue and other income. Heidelberg Pharma generated sales revenue and other income totaling EUR 16.8 million in fiscal year '23 compared to EUR 19.9 million in 2022. [indiscernible] we generated sales revenues of EUR 9.9 million compared to EUR 18.5 million in 2022. This mainly included revenues from collaboration agreements for the ATAC technology of EUR 9.8 million in '23 and EUR 17.5 million in '22. Sales revenue in '22 was extraordinarily high, due to the licensing payment received from Huadong, as part of an exclusive license. We invited them to develop and commercialize HDP-101 and HDP-103 in parts of Asia. Sales revenue also included revenue from our service business of EUR 2.1 million compared to EUR 1.5 million in the year before. Other income amounted to EUR 6.9 million compared to EUR 1.4 million in the previous year, and was primarily attributable to the unexpected sale of Emergence shares of EUR 5.9 million. In '22, there were primarily foreign exchange gains of EUR 1.0 million. Other income also including government grants to support projects by Heidelberg Pharma research, income from [indiscernible] of unused accrued liabilities and other items. Turning to operating expenses. Operating expenses, including depreciation and amortization, increased slightly to EUR 38 million in '23 compared to EUR 37 million in the previous year. Cost of sales includes costs directly related to sales revenue. These costs were mainly related to expenses for customer-specific research and for the supply of Amanitin linkers to licensing partners. At EUR 3.3 million, they were down compared to the prior year, which was EUR 4.7 million and accounted for 8% of operating expenses. Research and development costs were slightly higher year-over-year at EUR 28.1 million versus EUR 26.4 million. The slight increase was due to the cost-intensive production of antibodies for successor candidates. At 74% of operating expenses, R&D remained the largest cost item. Administrative costs were EUR 5.2 million, an increase compared to the prior year figure of EUR 4.8 million and accounted for 14% of operating expenses. This included staff costs of EUR 3 million, of which EUR 2.3 million [indiscernible]. These figures for '22 were EUR 2.6 million and EUR 0.2 million, respectively. Administrative costs also included legal and consulting costs in the amount of EUR 0.8 million compared to EUR 1.1 million for '22, and expenses related to the Annual General Meeting, Supervisory Board remuneration and the stock market listing, which was EUR 2.7 million in '23 and EUR 0.6 million in '22. Other items amounted to EUR 0.7 million compared to EUR 0.5 million for the previous year. Other expenses for business development, marketing and commercial market supply activities, which mainly comprised staff and travel costs, increased to EUR 1.4 million year-over-year compared to EUR 1.1 million in '22, and made up 4% of operating expenses. All these resulted in a net loss for the year of EUR 20.3 million compared to net loss of EUR 19.7 million in '22. Basic loss per share improved from EUR 0.53 in the previous year to EUR 0.44. Turning to cash flow and balance sheet. Looking first at cash flow. Total cash flow and cash inflow from investing activities came to EUR 4.3 million previous year, minus EUR 0.6 million, and was mainly due to the sale of the shares in Emergence in the amount of EUR 6.8 million. We used cash for a partial repayment of the shareholder loan to dievini in the amount of EUR 10 million. The remaining loan outstanding is currently EUR 5 million. Let's now have a look on the balance sheet. Noncurrent assets were EUR 13.7 million as of end of September '23 compared to EUR 12.7 million in '22. Current assets decreased from EUR 87.9 million in the previous year, to EUR 56.6 million this year. Cash and cash equivalents included in this item amounted to EUR 43.4 million and were down on a prior year figure of EUR 81.3 million [indiscernible]. Other current assets increased to EUR 13.3 million compared to the previous figure of EUR 6.6 million. Inventory included in this figure rose from EUR 4.6 million to EUR 10.5 million, while other receivables grew from EUR 0.4 million to EUR 1.3 million. Total assets at the end of the fiscal year amounted to EUR 70.4 million, previous year EUR 100.6 million. This decrease was mainly due to the outflow of cash and the increase in inventory. Turning now to liabilities. [indiscernible] contract liabilities decreased from EUR 6 million in the previous year to EUR 1.3 million. This reduction was due to [indiscernible]. Current liabilities fell to EUR 19.8 million at the close of the reporting period compared to EUR 28 million at the close of the prior year period. Equity at the end of the reporting period was EUR 49.3 million compared to EUR 66.6 million as of November 30, '22. The equity ratio was 70.1% at year-end '23 compared to 66.3% at year-end '22. Let me now walk through the royalty purchase agreement we recently entered with HealthCare Royalty. On March 4 this year, Heidelberg Pharma announced that we had signed a royalty purchase agreement with HealthCare Royalty. The agreement was closed on March 19. Under the [indiscernible] agreement, Heidelberg Pharma is eligible to receive up to USD 115 million for a partial sale of its future royalties from worldwide sales of Zircaix. HealthCare Royalty paid us USD 25 million upon closing. Heidelberg Pharma is also eligible to receive USD 75 million upon FDA approval of Zircaix as well as a further USD 50 million tranche, if calendar year '25 worldwide net product sales of Zircaix exceed a certain level. Once HealthCare Royalty receives a certain maximum cumulated amount, royalty payments will revert to Heidelberg Pharma, and HealthCare Royalty will receive a low single-digit royalty percentage thereafter. This is a highly attractive year for us, providing Heidelberg Pharma a substantial [indiscernible] funding now, while risk shifting as upfront payment is nonrefundable in addition to significant long-term upside potential, as Zircaix hopefully advances to approval [indiscernible] market. The approval payment will reduce the risk of market uptake for us and the capital royalty stream secures participation in mid- and long-term upside for us. We will utilize this funding to further advance clinical development of our lead [indiscernible], HDP-101, and progress preclinical [indiscernible]. We like this deal, as Heidelberg Pharma will benefit now and later from global product sales of Zircaix. I would now like to conclude my part with the outlook for the figures for '24. For fiscal year '24, we expect sales revenue and other operating income to be between EUR 11 million and EUR 15 million. This does not include revenue from any potential additional license agreements. Total operating expenses in '24 are expected to be between EUR 36 million and EUR 40 million, if business proceeds as planned, not remaining at a level of similar to '23. The company expects expenses to continue to exceed income over the next few years. The operational result is expected to be between minus EUR 23.5 million and minus EUR 27.5 million. If income and expenses developed as anticipated, financing requirements for fiscal year '24 are expected to be between EUR 28 million to EUR 32 million. This corresponds to an average monthly use of cash of EUR 2.3 million up to EUR 2.7 million. Our cash reach is secured until mid-'25, based on current planning, but will be expanded with the expected additional payments from HCRx. Please note that given how recently we entered into the agreement with HCRx, proceeds from the royalty purchase agreement are not yet reflected in our guidance. We will update the guidance in due course according to updated R&D plans. Let me now turn the call back to Andreas for the operational outlook for the year ahead. Andreas, please.

Thank you, Walter. I'm pleased with the strong progress we made in 2023. Let me now wrap up with a look at what we expect in the year ahead. Looking at our proprietary pipeline. For HDP-101, dose escalation is ongoing in the Phase I part, with an enrollment in cohort 6 started. If all goes as planned, we expect to be able to identify the recommended Phase II dose in Q4 of this year, which will enable us to initiate the Phase IIa part of the study in early '25. In the meantime, we will present first efficacy data at AACR 2024 in April in San Diego. For HDP-102, we expect to soon complete the necessary data package and are on track to submit the CTA application in the second quarter of '24. With HDP-103, we expect to complete preclinical and toxicological studies to be able to submit IND and our CTA application in 2025. We have placed HDP-104 on hold, and made the decision to focus on our new program, HDP-201. Both programs address the same target and use the same antibody. Data regarding HDP-201, our latest candidate, will be presented at AACR next month. Preclinical work with this program is in preparation, and IND and our CTA applications are planned for submission at the end of 2025 at the earliest. We're also looking forward to present new preclinical data for HDP-201 at the upcoming AACR in April. We are excited about what the future holds for us, and are driven by our vision of developing new options to address major challenges in cancer therapy and becoming an important global ADC player. We have potentially disruptive technology and our excitement for our work [indiscernible] by our partnerships. We are pleased with our partnerships [indiscernible] clinical development of HDP-101 in China and Takeda conducts IND-enabling studies. We believe we are very well positioned to reach our goals and bring new hope to patients. This slide summarizes multiple value inflection points mentioned in today's presentation over the upcoming years to increase company [indiscernible] significantly. With this, I would like to thank everybody for attending, and I would like to now open the call to questions.

[Operator Instructions] Our first question is from Marietta Miemietz with Pareto.

The first one is on HDP-101 and the protocol amendments. So you're trying to see approaches to prevent the drop in thrombocyte count upon first dosing. So I'm just wondering, how confident are you that one of these 3 approaches or more will actually do the trick? Or what would you do if you're unable to address this issue? Do you think that you would be able to go into Phase IIa and just introduce some additional monitoring around the first dose? Or do you think that you would then have to go with a lower dose than the 100 mcg? That's the first question. And then just quickly on the IP around the topoisomerase inhibitor of payloads, if you could just please give us a brief summary.

All right. Thanks, Marietta, for your question. I'll try to answer as much as possible as of today. I mean we will present more data at AACR, and we will have an R&D day later in April, where we give more details. We are highly confident that one of these 3 arms will work. There are precedents for this one. So briefly, I recall the first arm, the [indiscernible] arm, the second is the dose fractionation arm, and the third, the step-up doing. So all of these 3 methods have been demonstrated for other programs, for example, for the [indiscernible] dose fractionation was the way forward for them to be approved, step-up dosing is a validated approach for the bispecifics. And the reason for this one is that we have seen this reduction in thrombocyte count only on the first cycle. So after from the second dose on the thrombocyte drop was insignificant or very mild. So that makes us highly confident that one of these 3 options will work, and we will work this out to enter into the Phase IIa part. For the 201 program, there we have filed IP around the platform of our Exatecan platform and of the [indiscernible] 201. The Exatecan is free of protection because it's an old compound. So the IP around the platform is the combination of the linker and a specific solubilizer on that linker, which makes these highly hydrophobic payloads available [indiscernible] so that's the combination where we have [indiscernible] and significant novelty [indiscernible] families around the -- one for the 201 and one for [indiscernible].

We have several questions coming in, in writing. The first one is what will be the dose in Cohort 6? 100 mg per kg or 120?

So we do not disclose, but we do not elevate the dose for cohort 6. So the Safety Regulatory Committee was not fine with this one. So we first want to find out what of the 3 arms works best to reduce this to, let's say, minimize the reduction of the thrombocyte counts. And from cohort 7 on, we will escalate the dose further, with the idea to enhance the response rate and the deepness of responses.

Another question related to HDP-101 is if these patients are -- have a 17p deletion?

Of course, in 18 patients, some of them have a 17p deletion, but it's too early to make a correlation between 17p deletion and the responses. So here, we will wait for more patients to look into this one, to see whether a significant number of 17p-deleted patients [indiscernible] responses for the HDP-101.

We have a financial question. Is Heidelberg Pharma in negotiations for new license agreements? And this is related to the remark in the press release about possible additional revenue for potential additional license agreements has not been included in the 2024 revenue plan?

I take this question very, very easy because it's ongoing efforts. We are talking to several interested parties. There is always a good time for doing this. We believe that with the upcoming clinical data, that's also the reason why we are going very much public with this one, which will intensify discussions around potential partnering of the HDP-101 assets and the other assets as well.

And we have one final question, and this is related to what does maximum mean for the 75 million payment in 2024? And can you give us an approximate number about what's your tax revenues when the earnings would return to Heidelberg Pharma?

Delicate question, which I'll leave over to Walter.

Okay. So the [indiscernible] is related to the second tranche. So the approval payment of 75 million. There is a possibility for the purchaser to reduce that [indiscernible] but substantially. So we are confident that we will get the 75 million in full, and all other would be not only unexpected, would be more a surprise to us. When it comes to the multiple [indiscernible] of repayment, [indiscernible] confidentiality with the purchaser and can give you any [indiscernible]. If you search in the market, what would be something realistic, you will identify depending on the approval, whether it's [indiscernible] or not in the market update, whether it's a diagnostic or [indiscernible], that you have a multiple, you will see between 2 and 4.5. We can only say, we have a very attractive deal and very favorable for the company, that's why we decided to take it. Otherwise, [indiscernible] sorry for that.

Okay. We've had actually several other questions come in. Regarding HDP-101, do the 3 patients from Cohort 5 that showed partial response continued treatment?

Yes, indeed. So all 3 patients are still on the trial. We are monitoring them. They go for the 3-week cycle of the HDP-101. As long as the disease does not progress, they will continue to be on treatment.

And can you confirm that HDP-101 has received orphan drug designation? And if so, what are the benefits that come with this?

Yes, this was without any further, let's say, lead time for us coming in this last week. So we will issue a press release around this one, I can confirm that it will receive better orphan drug status, main benefit is the extension of the IP protection.

And another question coming in is, what are the next concrete steps with Huadong?

We cannot disclose so much, but what I can tell you here is that there is planning for an IND. So we are, let's say, we are working together with Huadong on a pre-IND meeting and both for an IND in China, that's actively ongoing work. We are also preparing a clinical trial supply for them. So there's active work preparing for starting the trial in China.

And then we have a question related to employee development. For fiscal year '23, R&D employees went down despite increasing R&D work. Why is that? And then what is the planning for fiscal year '24?

Yes. As you can imagine and you're aware of -- and as I say, I think -- there is an obvious reason for that. We had over the last 2 years already a [indiscernible] between research [indiscernible] activities and more clinical activities that were performed by external service providers. So we had indeed, an increase in R&D expenses. We would also expect that they will further increase in particular when we are done with the second trial into [indiscernible]. So that's the reason. So internally, we reduced slightly that the research efforts [indiscernible] externally, we have high expenses to fully ongoing studies.

And we have one final question on asking about the future of your segment service business?

Segment service means CRO, I assume. The segment service -- and this is, let's say, becoming less and less important. We haven't made a final decision yet, but this will go substantially down because it contributes little to our business, so that we are not promoting this anymore. And this will, let's say, needs to be discussed in the company, whether we will continue this at all.

That was our last question. This now concludes the Q&A session, and I will hand the call back to Andreas for closing remarks.

Yes. Thanks, everybody, and for a number of very good questions. There's one coming in. Laurie?

Yes, there was. One more. And this is about your impairment on Page 118 of the annual report. You expect a cash flow of 0.4 million for 2024 to 2026. This implies significant revenue to compensate research costs, is this correct?

Now I need to really [indiscernible].

The cash flow of 0.4, is it?

I need to come back on that. So it's really -- I don't get any moment. So let me come back. [indiscernible] direct contact, so I can provide that or we can share with all the participants.

All right. Again, thanks, everybody, for attending our conference today, a lot of questions. We see a lot of interest in our company. We have seen a lot of progress in the last year, especially in our clinical trial and with this purchase agreement. And let's say definitely, let's say, giving more details at the AACR [indiscernible]. So I hope you to stay tuned for the next news and looking forward for the next development of Heidelberg Pharma. Thanks, everybody.