Hi everyone and welcome. My name is Francesca Bijo and I will serve as your moderator today. Thanks for joining us for today's webinar Navigating the Regulatory Landscape for mRNA Based Therapeutics. As your moderator, it is my role to ensure that we make the most of your time with us. I'm here today with our speakers Doctor Oliver, Daniel Schweig and Maliki Uzun. Oliver is a regulatory expert for mRNA drug substance offering located at our mRNA Center of Excellence in Hamburg, Germany is responsible for surveillance of mRNA related guidance, assuring face appropriate application and supporting customers regarding drug substance CMC sections. Menike or Mel is a regulatory expert within pharma registration at our company. Her responsibilities include CMC, in particular module 3 quality for established APIs excipients, as well as manufacturing authority and GMP certificate activities for mRNA based drug substances with the respective competent authority. But before I turn things over to our speakers, I'd like to cover a few housekeeping items. At the bottom of your screen you can find several application widgets you can use. All the widgets are resizable and movable, so feel free to move them around. To get the most out of your desktop space. You can expand your slide area or maximize it to full screen by clicking on the arrows in the top right corner. If you have any questions during the webinar, you can submit them using the QA widgets. We will try to address all the questions during the webinar, but if we don't have enough time or a more detailed answer is needed, we will answer later via e-mail. Please note that we do capture all your questions during the session. You will also have the opportunity to participate in some quick poll questions. I encourage you to take part and if you're watching this webinar on demand, you can still submit your responses. You can also find your Our Reaction button which is indicated by the thumbs up emoji and this one allows you to give immediate feedback on the presentations or any topics that stand out. An on demand version of this webinar will be available and you can access it using the same link that was sent to you earlier, but that's it from my side. I'm now happy to turn things over to our speakers, starting with Oliver. Oliver, over to you. Thank you very much for the kind introduction and good morning, good day, good evening to wherever you are joining from Live Today or wherever you are watching the capture of this webinar on demand. I'm very happy to be with my colleague Mel to navigate you through the regulatory landscape of mRNA based therapeutics in this webinar. And to begin with, we will start with a small poll to get to know you better. So please let us know what is your relation to mRNA based therapeutics. If you are coming from academic research, if you are manufacturing starting materials, drug substance and or drug products, if you are coming from an CRO, if you are with regulatory authorities, if you are coming from Pharmaceutical industry in general or anything, other answers are flowing in perfectly and already nearly half of you have submitted their answers. So let's have a look and yeah we have quite a big audience joining us from academic research today. That's very nice. And then the second biggest parts are Pharmaceutical industry in general as well as drug substance starting materials and drug products manufacturers. Good to have you on board. So brief agenda on what we are going to cover today with this webinar. We will begin with a small introduction to the mRNA as a therapeutic model, a molecule before we will guide you through the mRNA drug substance and products regulatory framework before translating those frameworks into practice and finally closing out with what we can do for you with our mRNA integrated offering. So to start I will give you a brief introduction to the mRNA as a therapeutic molecule in general and we will begin with a brief history on approved RNA based medicines, in this case representative small interfering so SIRNAS and mRNA based therapies. In 2018 on petrol was the first siRNA based therapeutic which was approved in rapid procedure by Alinlam Pharmaceuticals. This also was quite important as it used lipids so lipid nanoparticles as a delivery agent. Then in 2020, two 1020 when the COVID pandemic hit the first mRNA based therapeutic komenati by Pfizer Biontech was approved with exemption regulations using a rolling review procedure. Just a year later Spike Vex by Moderna also was approved showcasing the power and effectiveness of mRNA based therapeutics. Since then in 2023, Acturos and CSL Therapeutics got their approval for the first self amplifying mRNA therapeutic also covering COVID-19 showcasing that there's also a quick development within the mRNA therapeutics field going from small interfering RNAs which are very short over to mRNA up to self amplifying mRNA therapy. But basically, how does the mRNA work? So in this scheme, on the left side you can see a cell with the mRNA in the center of everything, basically in the DNA of the genetic information our cells require stored. Whenever required, a certain gene is transcribed into mRNA in the nucleus, transported into the cytoplasm, where then can be translated into proteins. It can be translated into antibodies using the to CRISPR, CAS, subunits or even enzymes in general. mRNA offers many applications such as vaccines where we already have the approved therapeutics. We have the opportunity to use it as cancer treatments and the therapy of enzyme replacement, antibody therapies, gene editing, cellular therapies or even personalized medicine leading the way to also treat previously undruggable targets. On this slide, we summarize the integral components you will require for an mRNA therapeutic and we will begin on the left side with the mRNA which is the drug substance in your product. In general, all these components have to be manufactured according to GMP or CGMP requirements depending on where you are located and for the drug substance, the mRNA is categorized as a biologic and therefore no active substance, master file or drug master file is available. All the information need to be provided in the CMC module 3.2 point S In addition, when we require the lipids, those are categorized as excipients and for example in the USADMF type 4 is applicable. In general, if there are, if the lipids are non compendial or they are novel lipids, they have to be described like an API in CMC modules 3.2 point P These two together then are formulated to the MRNALNP which is basically the drug product. The information need to be collected in the CMC module 3.2 point P and this MRNALMP is finally filled and finished for your final applicable drug drug product. To close this introduction, I will move the spotlight now on the regulatory framework for mRNA Therapeutics and who is influencing it before we will focus on specific guidance. So shown here are different bodies and associations setting the regulatory framework. 1st, we have national and global regulatory bodies such as the EMA, FDA, World Health Organization or MHRA in the UK. They are basically setting the legislations we have to follow when manufacturing these drug substances and drug products. Those bodies also publish the compendia such as EDQMUSP, British Pharmacopeia or VJP, which are setting standards applicable to our manufacturing tasks. As a third part, we have consensus organizations such as VICH, PIX or ISO who are also offering guidances which are acknowledged and are applicable in several countries around the globe. And then finally, we have industry associations such as PDA or ISPE and industry communities such as Bio Forum, which are also offering further guidances on opinions, for example by publishing white papers, also representing the voices from the industry. And with this, I will now hand over to my colleague Mel to give you an insight into the specific regulations. Thank you. A warm welcome from my end as well. We are pleased to have you now that we view the introduction with Oliver, we can now delve into Part 2 for the regulatory framework on MRA based drug substances and drug products. We begin with a high level overview on the categorization of MRA based drugs and differences between the EU and US focus primarily here on the regulations pertaining to manufacturing of MRA drug, substance, drug product and AT&P sorting material. In this high level categorization overview here you see the EU division into 3 categories for M RNA based vaccines, therapeutics and cell and gene therapy. In the EUMRNA based vaccines against infectious diseases are exclusively categorized into a separate class underlying Utrelex Part 2. Next category in the EU are M RNA based therapeutics such As for protein replacement, for example enzyme replacement or oncology or cancer therapies. Underlying Utrelex part four third category in the EU is cell and gene therapy X Fivo in which mRNA is usually are transpected into cells X Fivo and then delivered back in vivo underlying the principles of Utrelex Part 4 in contrast to this convoluted EU approach is the straightforward US approach combining all under one major category under gene therapy both in vivo and ex vivo and including vaccines into biologics underlying FDA's Code of Federal Regulations. After the high level overview, we continue into more comprehensive view on the regulatory framework with overarching regulations they're applicable to environment therapeutics focused primarily on the regulations pertaining to manufacturing and GMP. Beginning with the e-mail governing Utrex volume 4 on GMP guidelines Part 2, Part 4 and Annex One recently revised Annex 1 now also applies to low bio Burton drug substance. Then on to e-mail Q&A guidance document. Next are overarching USFDA guidance, CFR Title 21 Part 210, two 11 and Part 600 and Biological Products. Then World Health Organization Guidance Technical Report Series #1039 and X3IN conjunction with all mentioned here is PIX GMP guidance and X2A which is very similar to Udrelex volume four Part 4 and NX2B which is very similar to Udrelex volume four NX2. While PIX guidance generally is very similar to Udrelex with no fundamental differences between PIX, NX2A and Udrelex Part four, there are some slight differences regarding Atmps then Ema's ICH Q7 GMP 4 APIs. After having looked at applicable overarching guidances, we'd like to now consider in more detail specific guidance applicable to the manufacturing of mRNA trick substance, many of which are draft guidance still progressing and evolving. EDQM recently proposed 3 general texts on mRNA 530-6539 and 5:40. There are interlinked through sequential cross references and published simultaneously as a complete package in the present issue of Pharmacia with scope pertinent to M RNA drug substance. Displayed here are general text drafts 540 and draft 539. At present, however, the most influential guidance is with the most practical relevance come from USB, such as draft analytical procedures for M RNA vaccine quality. The second edition draft now contains proposed key quality attributes for mRNA, drug substance, drug product, as well as serving material including for example identity, integrity, purity and content. Also proposes characterization and release relevant testing for mRNA drug substance, drug product and serving material. The next iteration of these important guidances are recently been forecast to be published by USP around June, July 24 this year. Another influential USP guidance applicable to mRNA drug substance that arrived at a crucial timing point for mRNA starting material this chapter draft 10:40. We very much look forward to the next iterations on these. Next is specific guidance applicable to lipids for LMP formulation. For example EMA's reflection paper on data requirements and FDA's liposome drug products. Note here that for lipids that have not been used in human applications, in the same route of administration or are not described in compendia, now all excipient regulations apply. Speaking of novel excipients, this brings us to our next topic on requirements for novel and non novel lipids in the UN US beginning the non novel, for example compendium lipids that usually are not mandatory to be registered. Exceptions do occur such as specific countries, for example China in the EU excipient qualities part of drug registration dossia in their respective part and in the USDMF type 4 with content similarity to that of API for novel lipids. On the other hand, in the EU excipient qualities part of drug registration Doss EE in the respective part 32P46 on novel excipients and in the USDMF type 4 for excipient the content similarity to API for system use in a drug product or a new route of administration. All details of manufacture, characterization and controls with cross referencing to supporting safety data to be provided according to drug substance format content similarity of completion to an API dossier. Finally, within today's regulatory framework, context is specific guidance pertaining to the manufacturing of mRNA drug product Ed Clems 514 and draft 536, latter which is part of the forementioned Ed Quinn proposed 3 general texts 530-6539 and 5:40 published simultaneously as a complete package in the present issue of Bahamaya. Then again the crucial USP draft analytical procedures for Mr. and E vaccine quality, second edition. We look forward to its publication forecast by USP around June, July this year and hope to see then it's extension of title from mRNA vaccines onto mRNA therapeutics quality as well then FDACMC information for for human gene therapy Imds. In summary, it can be said that US guidance currently leads the front towards establishing critical quality attributes, testing and common set of standards applicable to MRA based therapeutics vaccines and cell and gene therapy. With that we can conclude Part 2. Another quick poll before I turn it over back to Oliver for part three in which he will guide you through the translation of the regulatory framework into practice. So for poll two please, we'd like to get your opinion on which areas you deem regarding the manufacturing of mRNA based therapeutics require more specific guidance to be published. Please select all that apply starting here with option a drug substance, starting material, active substance, encapsulation agents, lipids or recipients, formulation and finished drug products, critical quality attributes for Mr. maybe therapeutic manufacturing and characterization process materials or any other that we may have not listed here. OK, I see we are ramping up and answers. All right. This is sufficient to proceed to the results we see here. Oh, this is interesting. OK, so we have, perhaps not surprisingly, critical quality attributes CQ as followed in equal parts by an encapsulation agents, lipids and excipients. Formulation and finished drug products, then followed by the drug substance serving material, then process materials and finally active substance. Well, thank you very much. Oliver, back to you. Thank you, Mel. So let me take over and thank you for presenting these specific guidances and especially the newly published drafts which are out there. And we will now try to translate those regulatory frameworks into practice. And I want to guide you now through this slide. I know it seems a bit crowded, but we will take us a couple of moments to go through it. So what we have here is basically a simplified manufacturing scheme of an mRNA drug product beginning on the left over here with starting in raw materials to prepare our linearized DNA template. So we have plasmid and potentially primers required for the linearization. And you can see all these boxes are color-coded. So we tried to match them to certain categories. So dark blue will be ATMP or active substance starting materials. Then in yellow we have substance of for pharmaceutical use like GMP great materials or materials which are compendial or according to ICH for example ICH Q7. And until we have basic raw materials and basically according to the newly published guidances by the EDQM, plasmids and primers should be considered active starting materials as they already include the information which will be later be present in the linearized DNA template template which will be translated to the mRNA. In addition then we have like the NTPS, additional enzymes and processing materials both get used for the linearization to get our linearized DNA template over here, which when will be mixed with RNTPS like capping reagents, additional enzymes and processing materials. And now you see that enzymes here are to be considered substances for pharmaceutical use because beginning with this step, we are in the GMP environment for drug substances. When during the beta transcription the mRNA is manufactured, our drug substance as it is, which will then be mixed with the lipids, again considered to be a substance for pharmaceutical use to be formulated into an MRNALMP, the drug product. We hereby then move over to the environment of GMP for drug products before fill and finish and later on then administering to patients in general these steps shown here. So basically the GMP for Drug Substance and the GMP for Drug Product processes. They are have to be inspected for GMP by the Supervisory Authority and for manufacturers located in Europe. This means that this has to happen before the 1st inhuman clinical trial. Upon this inspection, the EU usually will grant the GMP certificate. If the inspection went well, and especially in Germany, indicated here by the German flag, the manufacturer will also receive a manufacturing authorization. These are required in the end to release the materials even for 1st and human clinical trials. In general, we are all have to keep an eye open for the quality of the materials we are using, especially for, for example, enzymes which currently might not be available in a pharmaceutical grade because both materials like PCR enzymes. Restriction enzymes have been used a lot in academic research yet, but have not been available in the pharmaceutical grade and therefore manufacturers are required to have an eye open, for example on RNSDNAS, free statements of the materials they are using, on the animal origin free status to check TSEBSE statuses and risk, and also to keep an eye on chemical compliance, for example with the REACH. This might be especially of interest for enzymes and buffers because they sometimes contain like ketone X100 as a detergent and this for example is banned in the European Union by the REACH regulations. So materials containing those wouldn't be applicable for the manufacturing of an mRNA therapeutic. But having these GMP requirements here what we need to have those applicable as 100% already for our first developmental step steps and the answer to this is no. So there's a flexibility available. It is the face appropriate quality which is indicated in this picture. And you can see that the GMP level indicated here on the Y axis increases starting with research and developmental phases during phase one to phase two until phase three. And during phase three, GMP compliance should be reached completely before then the marketing authorization application is submitted on the bottom. We already also indicated when supposed inspections are occurring and this again year shown is dependent on the region the manufacturer or the manufacturing facility is located. If it's in the European Union, the GMP inspection and recurrent inspections will take place starting with the manufacturing of phase one material. While in the US usually there's a pre approval inspection somewhere around phase three clinical trial materials before when GMP 4 commercial materials goes in place. And this also aligns pretty well with the requirements for process validation As for example indicated in the ICH Q7 guidance where process validation is required during phase three when you are nearly close to manufacturing commercial materials. In this slide to also close out the third part of our webinar, we briefly summarized the comparison of regulation and control for manufacturing in the European Union and the United States in general. In both regions, phase appropriate GMP is expected from phase one on. But the difference as already mentioned before is that in the European Union, the inspection and recurrent inspections start with the fraction of material for phase one clinical trials and this basically has some advantages for customers. So it is certified quality for a Regulatory agency early on. This indicates lower risk profile also through the continuous inspections, but also means an increased preload to the clinic for the manufacturer and for sponsor. In the US the first inspection is usually expected during phase three, the so-called pre approval inspection beforehand. The full responsibility to for the compliance of GMP is with the sponsor and this is not certified by a Regulatory agency. This means it is reduced preload for materials in the clinics as no inspections are expected for phase one and two. But there's also an increased risk for failing at late stage inspections and the early phase quality is not certified through the agency. And with this, I will come now to our last part of this webinar before we can discuss your questions in the Q&A where I want to present you our mRNA integrated offering, so we can support you and your journey to an mRNA therapeutic all the way. Starting with the drug substance manufacturing, the mRNA supplying the excipients, the lipids in high purity of the shelf as well as custom lipids, we can support you with the formulation development of the mRNA and P drug product as well as with fill and finish of your material. In the end I have a liquid or life lized. We can do this through Technical Support where we have extensive expertise in the specific fields of actions of mRNA, lipids and LMPS for more than 40 years with a distinct track record. We can offer you a single contact point for simplified customer experience. So you have one dedicated project manager to contact you taking care of all of these components for your mRNA therapeutic as well as supporting you with our extensive regulatory know how with our regulatory experts supporting you in prepare in the preparation of CMC documents for clinical phase applications and market authorizations. Our team is is global, so we have global experts ensuring the seamless manufacturing of mRNA drug products from preclinical to commercial stages. In Hamburg, in Germany, we can prepare mrnas various concentrations as well as in Darmstadt where we can offer you a bigger manufacturing quantity as well as the manufacturing of lipids and the early formulation screening service for you to find the perfect mixture of lipids for your mRNA therapeutic. In Schefausen in Switzerland we also manufacture distinct lipids and in Indianapolis and the US we have our formulation and fill in finish platform in all of those sites. We also have dedicated regulatory experts to support your on your journey from M RNA drugs, therapeutic development to commercialization. And with this I would like to hand over to Mel again to present to you the take away messages of today. Yeah. Thank you for final conclusions and outlook. Takeaways that M RNA these regulatory framework is currently under construction, noting that M RNA therapeutics utilize the body's innate natural protein synthesis machinery to enable the body to produce its own medicinal proteins. The regulatory requirements for production, CMC and materials are very complex and have not been fully described yet. M Army specific guidance is evolving. Compendial chapters and guidelines specifying quality requirements for starting materials, mRNA, Drug, Substance and Drug Product in development. Drafted and evolving application matters. Depending on the therapeutic application of mRNA, Drug product categorization might differ including regional specific requirements, the outlook for global harmonization of different regulatory requirements and definitions to harmonize disparate classifications and definitions. For example, distinguished transient only interventions such as mRNA that do not alter or edit the genome to decrease complexities towards the joint mission to emerge mRNA beyond vaccines. And with that, we want to thank you for your attention and engaging with us through the Pulse. Thank you, Mel, and thank you, Oliver for this very insightful presentation. Now it's time to start answering a few questions that have come through from the audience. But just before we dive into them, I would like to remind our participants that it's not too late. You can still submit your questions using the QA widget and we will try to answer all of those, but obviously if we run out of time or we need a more detailed answer, we will answer later on individually via emails. Also wanted to remind you that this webinar will be available on demand and you will all receive an e-mail notification when it's available for viewing. So with that I think we can jump straight into the questions. So, so far I have seen that several questions came through and I tried to group by topic and to start with maybe Oliver, can you explain a little bit more in details on how the regulatory requirements differ for mRNA based vaccines compared to other mRNA therapeutics and what are the implications for manufacturing and approval processes? Yeah. So thank you. Very good question. In general, we have to see that these differentiations are mostly applying to the European Union as Mel showed before that for example, the US legislation acknowledges Mrnas as biologics in general. And therefore it is basically one category for European Union. We have to see that there is basically the categorization into ATMP either if it's a gene and cell therapeutic or any related therapeutic application which differs from using it as a vaccine. So for vaccines the EU guidance Part 2 basically applies especially while for everything else the EUGMP guide Part 4 for ATM PS is applicable. And then we have to see that we EOGMP Part 4 is a bit more flexible in that sense that it basically has risk based, risk based approaches included into the guidance. Therefore, putting a lot of, yeah, opportunities for a manufacturer to decide by themselves based on the risk of certain steps which parts of the guidance they are have to follow and and which are basically of minor interest for the beginning. Then basically increasing all of these requirements went through the clinical stages up until the commercial stage. So this is not written in the GMP Part 2 for example. So this appears to be to be a bit more strict in the 1st place because this is when rather yeah, directed to classical vaccines which are produced and which are not basically manufactured by the mrnas kind of not having insights the different manufacturing approach we have to use to get an mRNA to work. So this is basically where it is now good that we get more and more guidances from the different regulators and the different compendials, writing specific guidances on the quality of the starting materials or for the drug substance and also for drug products which we can apply then. Great. Thank you, Oliver. And you know, also kind of related to this, the next question is asking basically which regulatory framework applies on the mRNA incorporated in individualized therapeutic mRNA vaccines since this mRNA is patient specific? That's that's very interesting. So in that case, I just just for sitting now here basically. So it still would be an mRNA vaccine. So if it is basically an mRNA which well, well I wouldn't think that there shall be mRNA vaccines patient specific because normally a vaccine is defined as something to treat an infectious disease. So the basically it is to to treat yeah something like a flu or any other disease which is basically transmitted by a virus or by a microorganism. If it is then still a vaccine then it would be the IT would GMP Part 2 as a vaccine. I would rather see the patient specific mRNA therapeutics rather than an ATMP as they are gene or cell based therapeutics. OK. Great for the answer to the. Question Clarification. Otherwise, please please contact us and we will follow up. If yeah, as I said we capture all the questions. If you know. If you want to know more, if we need to provide more details, we can also follow up via e-mail. So you know, keep the, the, the questions and comments coming through. All right, then let's move to the next one. So obviously during the presentation you explained very clearly that the regulatory landscape for mRNA Therapeutics is still evolving. So how do you anticipate the guidance and requirements to change in the near future and what impact will this have on industry stakeholders? I can take this one. So with the evolving regulatory landscape, we anticipate that we can adopt prior knowledge that was gained from mRNA based vaccines onto mRNA therapeutics specifically the adoption and adapt meant of critical quality attributes for example because the majority of critical attributes are going to remain the same regardless of disease target. So that would that is expected. We anticipate that and we are keep an eye out on the evolving guidance particular to Mr. and E vaccines initially developed. To adopt to mRNA based therapeutics for critical quality attributes but also analytical approaches that would also be adaptable to mRNA based therapeutics. And this overlap would certainly advance mRNA based therapeutics and facilitate such that many previously undruggable diseases will become draggable, which would be a great asset to industry stakeholders of course also for the patient. Great. Thanks, Mel. I will move to the next one. Could you elaborate on the specific quality and safety considerations for the raw materials and components used in the manufacturing of mRNA, drug substance and drug product, especially in relation to GMP compliance and risk mitigation? Sure, I can take this one. It is basically also referring to what we showed you in the section where we translated the regulations over basically what is what we experienced currently. One of the biggest challenges is to identify and and find suppliers for the raw materials and processing materials. As I mentioned, enzymes for example, which are of a suitable pharmaceutical grade, basically matching the requirements we get from the GMP guidelines. So as said, many of those enzymes are out there and commonly known in academia. I mean everyone who basically studied biology and worked in the lab was handling all these enzymes on a daily basis and never gave it a second thought. And now as we are going to use basically the same enzymes for manufacturing therapeutics which will be applied to patients, we have to double check them and see if they are actually suitable or if there is a threat for the patient for example coming from TSEBSE risk. Or if they there are animal materials included in the buffers like BSA which is commonly supplied with buffers for both enzymes or already mentioned the ketone X100 which is commonly used as a detergent. Secondly, what also then comes into focus is for example the usage of certain antibiotics in the manufacturing of these cell based products. So we all know that there is a high sensibility in the population for penicillin and related antibiotics. So we also have to take into considerations and see if potential suppliers have good quality man system applicable to separate the manufacturing from potential sites where they are also working with these better lactam antibiotics or if they are using both even for the selection of the cell lines. Because when there could be a risk that we have a carryover of this contaminant which could risk basically be a risk for the patients. So there's a lot of those components we currently have to consider and there are many companies out there which are currently ramping up also their manufacturing capacities, building new sites or setting up special new lines for Sol term GMP ready or GMP grade materials. Still we need to consider that for those materials there's basically no GMP because with GMP basically applies to drug substances, drug products. And we still then need to check the quality system of a potential supplier, see which documentation they can deliver and if this would suit basically our manufacturing process and our risk mitigation systems. And I expect that this is highly developing and will get much better in in a just few years from now on. I mean already now we can see that also the Pharmaceutical industry in in these parts is developing fast and adopting to the new situation. Very thorough response. Thank you, Oliver. I think we still have time for another question and then we can wrap up. So this is the question, given the complexity of mRNA manufacturing and the evolving regulatory framework, how does your integrated offering address the challenges and provide support for companies developing mRNA based therapeutics from early stage development to commercialization? I can. I can take. Yeah, we can take this together if you like. I can put the start. So in itself mRNA manufacturing is not complex. What what is complex, It's actually very simple and that that is what makes it so great. It's the mRNA regulatory framework that remains still complex because it's still under construction and still needs to be further refined, defined and is evolving. So what how we set ourselves apart is that we offer you an integrated offering with the state-of-the-art and cutting it, employing state-of-the-art and cutting out technologies. And combined with the CMC part as well, you get the complete package with us. And you're also covering different regions, which means we have expert experts that are not knowledgeable in the different regional requirements and specifications. So you can completely just focus on your development and don't have to worry about benchmarking or scaling up for example or what have you. Oliver, if you have anything to add? Please. Yeah. So I I would still highlight basically that our integrated offering makes it much, much easier for customers or anyone who is interested in developing an mRNA therapeutic out there because we can offer you all the components which are required and you don't have to go to multiple persons and discuss with them. So we offer you to have the one project client manager for you who is in contact who knows all basically the parts in our company who has to address it and we can basically prepare you from your development. So offering you mRNA for your basic research up to your starting then with the first clinical trials up to commercial projects and also referring to our early formulation service based in Darmstadt. But we can also support you in selecting really the mixture of of lipids which is when basically working best for your cargo and also for your way of treating and excess of the therapeutic. So that basically the cells you want to target are targeted. And therefore basically whenever there's a new guidance coming up, we discuss it already with all the different stakeholders within the complete process from the beginning till the end. And basically there's no loose end in this whole package. Great. Thank you. We have come a time now. So thanks again Oliver and Mel for the great presentation and this great discussion and also thanks to the audience for joining us. If you need any support for your mRNA based therapeutics or would like to discuss further with our experts, please use the survey question on the side of your screen to indicate your interests and we will definitely follow up. Have a great day. _1732520577758

     

   

       

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