News & Insights

This MedTech Malta 2025 panel discussion, hosted by AscendCRO (winner of Best CRO of the Year at MedTech Malta 2025), features industry veterans from HiLife Medical, Bariotech, and senior CRO/regulatory experts who reveal why Australia has become the destination of choice for medical device clinical trials, particularly for startups navigating Class III device pathways.

Key Insights from the Panel:

Starting Right: The Holistic Approach

• Define indication for use and patient population upfront—every data point matters, even from first-in-human studies

• Align regulatory pathway (510k/IDE/PMA) with reimbursement strategy from day one

• Avoid the pitfall many startups face: focusing solely on clinical results while forgetting regulatory and reimbursement pathways

• Consider regulatory strategy, clinical endpoints, and market access requirements simultaneously

• 
  

Why Australia Dominates as a Clinical Research Destination:

Financial Advantage:

• 43.5% R&D tax rebate (not tax credit—actual cash rebate)

• A $300,000 trial effectively costs $178,000

• Cash rebate allows startups to reinvest and extend runway

• 
  

Speed & Predictability:

• Single regulatory contact point (TGA) vs. multiple competent authorities in Europe

• Fastest path from regulatory discussion to first patient enrolled (excluding Georgia)

• Predictable timelines for ethics approval, site contracting, and enrollment

• Hospital agreements: 3 months vs. 6-9 months in larger European hospitals

• No 7+ protocol amendments needed to satisfy different country requirements

• 
  

FDA Recognition & Data Quality:

• TGA alignment with FDA = tier-one quality data recognition

• FDA accepts up to 50-55% of pivotal trial data from Australian sites

• Australian sites can serve dual purpose: early feasibility AND pivotal trial enrollment sites

• Eliminates need for separate US early feasibility study before IDE/PMA

• 
  

Enrollment Excellence:

• Real-world example: Australia out-enrolled multiple EU countries combined in multicenter trial

• Dedicated, English-speaking KOLs comfortable with new technologies

• No competition bottlenecks—unlike Germany where companies queue for same limited KOLs

• Enrollment predictions more accurate: "If they say 10 patients, expect 8-9 vs. Europe where 20 becomes 5"

• 
  

Infrastructure & Quality:

• Sophisticated healthcare system with advanced imaging and diagnostic capabilities

• No need to send your own physicians to perform procedures

• Standardized protocols and technology across sites

• Fewer protocol deviations due to missing equipment or tests

• Passionate, engaged clinical research community (research is a passion, not just a job)

• 
  

Strategic Advantages:

Pre-Submission Strategy: Use FDA Q-Subs before first patient to establish protocol, then execute in Australia to generate data for direct IDE/PMA pathway

Regulatory Efficiency: One streamlined approval process vs. navigating multiple European competent authorities under MDR

Time Zone Management: 7-hour difference from California (vs. 9 hours to Europe)—manageable with local CRO partnership

KOL Quality: Eloquent, business-savvy opinion leaders who understand uncertainty of new technologies and excel at presenting to FDA panels

Critical Success Factors:

CRO Partnership: Choose CROs that provide strategic guidance, not just execution—partners who:

• Conduct due diligence on submissions

• Have established relationships with ethics committees, hospitals, and TGA

• Serve as extension of your team on the ground

• Help avoid protocol deviations and data quality issues

  
  

Avoiding Common Pitfalls:

• Don't send your own physician (inventors create biased data)

• Don't compromise on site selection based on available technology

• Don't accept sites where reimbursement incentives drive extra diagnostics

• Don't underestimate the impact of patient competition at overbooked sites

• Don't cut corners on clinical—as panel noted: "Clinical is not the time to cut corners"

Expert Panel:

• Joseph Panetta, AscendCRO (Singapore & Sydney-based CRO covering APAC)

• Vanessa Gallois, Senior Director Clinical Affairs, HiLife Medical (transcatheter mitral valve replacement)

• Pedro Eerdmans, Former Head of Notified Body, veteran of Medtronic, NAMSA, regulatory & QMS expert

• Yousef Biadella, Veteran MedTech entrepreneur & CEO, Bariotech (obesity treatment) — 3 early-stage feasibility studies in Australia across 3 companies

  
  

Bottom Line:

For MedTech startups where time is the most expensive commodity, Australia offers unmatched combination of:

• Speed and predictability

• FDA-recognized data quality
  Significant cost savings (43.5% rebate)

• Superior enrollment performance

• Streamlined regulatory pathway

• Strategic pathway from FIH to pivotal trials

  
  

As the panel concluded: every clinical study must be scientifically valid and answer a meaningful question. For tier-one quality data supporting first-in-human, pivotal, or PMA pathways, Australia stands as the premier clinical research destination.

About AscendCRO: Winner of Best CRO of the Year at MedTech Malta 2025, AscendCRO is a clinical research organization based in Singapore and Sydney, specializing in the APAC region and providing comprehensive support for medical device clinical trials in Australia.

———————————————————————————————————————————————————-

MedTech Malta November 2025 – PANEL TRANSCRIPT

Australasia, a clinical research destination.

We're here to discuss Australasia as a clinical research destination. For those of you who are leading a startup technology company or a medical device company, you already know that quality data is the fuel that propels your next milestone. Whether that's a new indication or a new round of funding or your next stage in your development. Today's panel is actually engineered for you specifically to hear from our experts on things like establishing a trial, selecting sites and PIs, recruiting and enrollment, and finally the many facets of partnering with a clinical research organization.

Speaking of which, my name is Joseph Panetta and I work with Ascend CRO. We are a clinical research organization based in Singapore and Sydney and we cover the APAC region. Taking us on this journey today as our hostess mentioned is Vanessa Gallois who's the senior director of clinical affairs at Highife a trans catheter mitro valve replacement company. Pedro Eerdmans who - I'm just going to truncate a lot of experience here folks – his experience at Metronic, several strategics, global CRO like NAMSA, multiple sponsor side, regulatory and even quality management systems.

And finally, Yousef Biadella, who is a veteran medtech entrepreneur and CEO and currently leading Bariotech, which is a company currently treating obesity.

Correct?

Thank you so much for your role today, panelist. Our goal for you guys specifically is to harness what you know and understand and share that with people who, as Christian on the last panel said, many startup founders don't know what they don't know. So our goal is to help elucidate the many facets that go into clinical trial development, regulatory approval and more.

An old an old boss used to say the way to begin is to begin. So Pedro, when you think about starting clinical trial structure, where do you begin?

Pedro: Yeah, thank you for this question. Uh I always start with the basics and a lot of companies don't think of that. What's your indication for use?  What are you going to use this device for and then also related that of course is what kind of patient population you will need. Often it's seen very broadly and then you get a mix of patients in your study. So be sure that you're focused and clearly know your indication for use. Then you must focus on the patient population you're looking at and start looking where to do this – that, of course, is crucial. Another thing that you need to always keep in mind - and as the ex head of a notified body is all the data, every data point is important - although you think this is just your first study; you will see at the end of the road when you want to submit you will need data from those few patients. So you must to ensure you did them correctly – collected a robust data set and that you can use them.  Very important also is where you do your study – the geographies.

Joseph:  Excellent. Yousef when you are beginning the notion of executing a clinical trial where do you begin?  What's your first step?

Yousef: Um in my case all my experiences (including all three early stage feasibility studies) were  in Australia – across three different companies. In our case, time is the most expensive commodity for a small company and the question main question is how do you generate data in a sophisticated healthcare system that will be recognized in Europe and most importantly recognized in the US in the fastest and most economical way and in most cases out five.

Three out of five. It was it was Australia.

Joseph: I couldn't have asked for a better segue down the road. Vanessa, when you are structuring your trials, when you're thinking about it as a trialist, what is your first this first starting point for you?

Vanessa: Yeah, I totally agree with both of your points. From a clinical and regulatory point of view, and it's been discussed in in earlier panels discussions. I also take into account the regulatory pathway at the very early stage because you don't want to end up with study endpoints that would not match uh a clinical evidence that you need to provide for FDA market access etc. So I try to build that very early on and uh shape the clinical strategy based on that and of course embed everything into your protocol designs endpoints etc. That's also part of the puzzle that is important to take into account.

Joseph: Brilliant. One follow-on question to that. Does any of this change depending on the device designation? Whether you're 510K, IDE, denovo, do any of those considerations change as a result?

Pedro: Yes, I think it it's very important to know already your clinical and your regulatory strategy. I think that's one of the things that is often mistaken with startup companies that they're so focused on the clinical results that they forget is where they want to submit this and then also which regulatory pathway to use and then very important.  Also which reimbursement pathway a fast 510k route can be extremely bad for you if you want to have another pricing than your predicate device. So, it's a very important already to take that into account when you think of studies.

Joseph:  It's a very holistic approach. It sounds like you can't just start at one point. You have to start from all vectors. Yousef, does I'm sure you've done different kinds of device designations. Do any do any of these things resonate with you? Do you feel like you need to start with the holistic viewpoint of regulatory, CMS, and clinical at the same time?

Yousef: In my case most of the devices, except one, were all IDMAS. So it's not like we had a choice in terms of the regulatory strategy because these are implantable devices and some of them life sustaining. So our thought process was a lot easier. it was where can we start as fast as possible in the most economical way in a very sophisticated healthcare system with data that can be recognized when presented to the FDA um so that it allows us to go straight from a first in human to an ID PMA without having to go through an early feasibility study.

So the idea is - your chances of getting that discussion going with the FDA and your chances of getting that data recognized by the FDA without having to go back through another early feasibility study really goes up a lot when you present data for instance either from Europe or Australia - but Europe even for a company based in France is much slower now to generate. So Australia becomes a natural choice.

Joseph: Thank you, Vanessa. Any thoughts on this?

Vanessa: No, my my experience is really the same as Yousef because, you know, I've been working in uh medtech companies where it's about implantable class 3 devices.

So, the pathway is pretty straightforward. Um, but to resonate with what you were saying, you know, Australia is a country is one of those countries that stands out in terms of model. It's not just about how fast you can get your study up and running, but it's also a combination of factors where you, you know, you're generating the data that will be reliable to an FDA or confidence authorities uh in Europe and also very predictable in terms of estimated timelines, site contracting, site budgeting - you name it. And the moment capacity is also very predictable. I've found so far working with Australia. So it it's really a destination that hits a lot of bullet points.

Joseph:  Excellent. Yousef- did you want to add to that?

Yousef:   Yeah, I think that's a really good point. You know having done studies in you know early feasibility and even clinical trials in you know Brazil, Germany, uh a few other countries. The advantage of Australia is that you're really you're only dealing with one contact point and everything is streamlined and even for coming up for timelines whether it's for budgeting or even for discussions with investors or strategics it's a lot easier to present timelines or schedules that are going to match with the reality versus dealing with other geographies where you have to deal with you know ethics committee, hospitals and but also health authorities

Joseph:  And a large part of that is also reliant on the CRO you choose because you want those that have relationships with and can help assure your smooth entryway through ethics committee, governance understandings, the regulatory body, labeling and import. These are all areas that you want your partner to have seasoned and tenured experience handling for you.

Pedro  Yeah. I fully uh agree with you. I always talk about several types of CRO. You have the ones that only execute: You give them something, they push it through to the ethics committee or the competent authority and they execute the study. And then you have CROs that really help you with the thinking - is this the right submission?  Did you do the correct thing for the ethics committee? As said in Australia, you only have an ethics committee. I just want to jump a little bit back on that. In Europe, uh you still have several competent authorities you need to go through . Although the MDR dictates or says that there will be in future one country that will take the lead as competent authority. Uh reality is that you still have to go to the several countries and they can all have their own questions and remarks and demands. So that's a big thing.

Then to have a CRO that can handle all of that and help is extremely rare. I'm still waiting for the one that can do that. And that's the thing with Australia. It is very easy. If you work with a CRO that will do the due diligence on your material, you can have a very fast approval process.

Joseph: Yes. Well, that's what real partnership looks like.  I want to build on something you said - that you were talking about earlier and that was about time and how time is money and we mentioned speed to trial. To that end I want to talk about like time to first patient in Vanessa can you talk about that?

Vanessa: Yeah.  I think speed is important - you know we're in a startup environment where time is money and money is tight. So how can you hit you know your first site initiation first patient enrolled?  And how fast you can hit that is critical - it also helps you maintain investors confidence, competitive positioning, etc. It's really key and how you can achieve that is I would say preparation, preparation and preparation. The more prepared you are, the better. And if you take for example, the submission timelines to get there, well, it's not just about okay, how fast you can get your study up and running again - it's how well prepared you are to achieve that. And having a good understanding; a local CRO partner that helps you along the way  really makes it stand out as an advantage and it really becomes not only a clinical advantage but also a financial advantage and a competitive advantage to start early. So again if you have all the combination and everything that models in it really helps.

Joseph: Yeah, I'm going to tie that back to our prior two panels where Ken on the first panel said - I'm quoting here - they uncovered the most important thing for a startup's focus is funding. And then we just heard from the VC partners that they're looking for those milestones, a clear understanding and a predictable way to deliver them. But when it comes to speed-to-trial in a smart way regarding data and data quality,  Yousef you touched on that when we spoke last week.

Yousef:  yes - I'm still unable to find a place or a geography that allows you to go from first discussion with the authorities to first patient enrolled other than probably Georgia or that geography - The advantage of Australia is that you're able to go really quick from those first contacts to first in human and it's not just to generate early feasibility study - you also have to think about your discussions later on to do a like in in our case an ID PMA a uh PMA route is that that same site or those same sites in Australia can be your first recruiting sites in your pivotal study as well.

That's really important to take into account. So you actually do save some time not only to generate your initial clinical data but later on when you're rolling into and getting involved into a much bigger multi-enter multi-geography clinical study.

Joseph:  So we're going back to that whole holistic thing again, right? Pedro, I want to focus on the whole speed to trial conversation with you like what are the factors that can affect speed to trial?

Pedro: Yeah, the of course there's several I think very important is uh the agreements with the hospitals. Hospital agreements can take a lot of time - and the bigger the hospital, the more lawyers, the more time it will take. I think we talk about three months, but it can go really six to nine months - so that's very important.  Then if you talk about European uh competent authorities, it can take a lot of time.  There are certain countries where we always say don't go there because of this the lack of speed and of course the ethics committee

Maybe going back to the first in human. I think with the first patient in we all celebrate for a millisecond and then we wait for the last patient.  There is often a press release with the first patient is enrolled but I think it's also very important to see how fast can they enroll and what kind of patients can they deliver on a on a on a on a speedy time

Joseph: you know I'm going to borrow from something that you said because.  When we talked last week, you mentioned something I'd never considered, which was competition. That in some countries there are so few sites and PIs available that your device is actually in line with a bunch of others to recruit patients to get on the timeline, the schedule. It seems odd, but do have you ever run into that in Australia?

Vanessa: Maybe I can start. Well, I personally never really encountered that in Australia. So that there's, you know, it's a big country, big sites, a lot of, key opinion leaders, infrastructure to enable research and have, you know, potentially competitive trials running in parallel. Now, it's never great, you know, that that's not something you enjoy having, of course, but it's in a bigger setup, it makes things a little bit easier. And again, you know the I think the overall infrastructure and people working in clinical trials in Australia are very dedicated and motivated and what I've seen so far is very engaged in clinical trials and this is also something we look at in terms of parameters to go to a certain country and initiate trial in that country. Because okay cost, speed are all very good factors but not the only factors you need to take into account and the people the engagement the motivation that will drive enrollment capacity is as important as your speed to initiate the trial.

Joseph: That makes sense. Yousef

Yousef:   I would second that. in past experience when we've done early visibly studies in Germany for instance we had to go to a co but because that co were was influential and experienced we had to basically line up with two other companies in structural heart doing exactly the same indications - And I had a similar experience in a similar device, structural heart, where in Australia we didn't have that; we were the first and the only ones doing a clinical study with the KOL -  so a lot of people think of ‘population size’ - you know for instance Germany being I think 80 90 million people and Australia is probably like 20 I think 20 (Joseph: it's bordering on 30 now is that 24 26)  Yousef -  yeah, but at the end of the day if you're dealing with one KOL who is dedicated to your clinical trial at the time your recruitment is going to go much faster than other geographies.

Pedro:  Yeah, I al also felt the pain from that because what can happen with competition that you get let's say the worst patients. That you just have an ino inclusive criteria that that is not with the others so they go first to the other studies and then you end up with the worst patients and that can really yeah sorry to say screw up your data.

Joseph:     Yeah, it's going to damage your outcomes. And I I think what we're really getting at here is one of the key differences about Australia as a clinical destination is that clinical research is a passion and not just a job, right? And I think that's important and it's very clear that it's a passion because the country itself, this is a very big message for you who have startup technology companies looking for your first trial. The country of Australia, the government offers a 43.5% tax rebate for trials done in Australia. Practically speaking, that means that a $300,000 trial cost you $178,000. And I don't know about only my panelists would know this. Are there other countries that offer such aggressive incentives for research?

Vanessa: Not that I'm aware of.

Yousef:   I think France could do that but uh because for French companies doing innovation you get about the same amount. The issue is that it's almost impossible to do early feasibility study in France for high-risk class 3 medical implantable devices.

Vanessa:  I think the key differences, though, it's rebates it's not tax credit.

So that allows really companies to reinvest that money in, you know, uh maybe another R&D project, extend your runway. I think this is really key for startup companies and it's really a big advantage with Australia.

yeah,

Joseph:  Thank you. While we're on the subject of other countries, one of the things that was brought up during our discussion last week was the fact that there are labs and hospitals and physicians and sites in many countries throughout the world that are capable of executing research, but then there are factors that can thwart that research. I believe one of you brought up a country where some political instability sort of caused a stop to things. We're not mentioning names, but I think it's important to understand that you in some countries you have to send your own physician to do the procedure, but if you have a medical device, don't you want to know how easy it is for other physicians to use it?

I'm just curious, you know, in terms of other factors that may thwart your ability to get good quality data.

Pedro:   Yeah, I agree. If you bring your own physician, he already thinks it's a good product and that everybody can use it because he was one of the inventors often. So you will not get any good data out of that. So it's a waste of time to be honest to do that. Another thing that you see in certain countries is that they have certain technologies, diagnostics, etc. that are not on the same level as other countries. So it would be good to have a very good imaging device that maybe is not there in that country and that will also um yeah will not help you in getting correct data. So it is important to know or you have countries where they have an incentive to use a certain technology because of reimbursement. So let's also use this next to it because that's what's paying us. So you then get extra diagnostics, extra other tools used because that's where the money is for those physicians.

So you need to be very careful and you really need to understand well per country is is what's the standard of care? What's the kind of technologies that they have in house that they can use? H it's so often that I saw deviations, protocol deviations because certain tests were not done. Yeah. Because we don't have this machine in this hospital. Uh it it's terrible that this this site was selected to start with but it happens and you have a lot of loss of data and if you then go to a notified body or an FDA and you show all those deviations then you need to be very good in trying to fix that problem.

Joseph:   Yousef. Um to me um the one aspect that uh sometimes people underestimate is the um the KOLS you're dealing with. So typically if you're doing early stage - what you want is you want a really good ambassador. I find in Australia you have fantastic KOLs that speak the language are comfortable presenting to large panels etc. And especially for companies like I think for all of us, the biggest market is the US and will remain the US for the foreseeable future. So you want people who super understand the culture- you know are very comfortable in English and are able to present. You find a lot of because of the regulatory environment in Australia. You find a lot of fantastic KOLs that are absolutely eloquent; understand the business side and also understand are comfortable with new technologies. So when they're doing treating their first patients or their first few patients, they're comfortable with a certain level of uncertainty that you're not going to find in other geographies.

Joseph:   That's critical. Vanessa, I want to start with you on this question because right now you are running a multi-country trial which means that your regulatory bodies are different in different countries. Help us understand how you and, all three of you by the way have had to do this, where you've had to navigate multiple countries against a single protocol to a specific set of endpoints. Talk to us about that kind of hurdle.

Vanessa:  Yeah, It can be really challenging because each country, especially in Europe, has their own specificity on what they expect in a protocol study design etc. As I was saying earlier, you also need to embed all the reimbursement requirements ahead of time to make sure you hit those when you get your CE mark or FDA approval market access. So this is where it's kind of tricky to pull everything into a study protocol, go through those rounds of submissions, answer a lot of questions and sometimes there's requests to maybe add additional language that is specific to that country and that takes time and energy and when you want to start your study fast – well, in Europe it's complicated because of that. While going and targeting Australia, for example, as your first country to be initiated is much much easier.

You kind of need to sequence each country timelines make sure those timelines are pretty predictable because there's a big variability in Europe in terms of submission timelines and approval timelines. It can shift by months in some countries. So, you need to really be strategic on the choice of the country you choose to go with.

Joseph:  Yikes. When it if what Yousef said is true - time is money and money is time, and you've got to wait months to institute a change, that's tough. But as a former regulator, Mr. Erdmans, can you talk about this?

Pedro:   Yeah. Yeah. Well, I can imagine if you're a startup company, you're very proud with your first protocol. But when you come to a notified body and with seven protocol amendments, I want to know why. What happened with the first patient that you had to change your study? So, I start to feel uncomfortable when I see a lot of changes. And I also think that scientifically it's poor that you have to make those changes. And of course, you don't know this up front. You're happy you have a good KOL that wants to start. You do your first patient then you think let's now go to the other countries and suddenly you get all those questions and those changes you need to do and as I said before you know you have protocol 7 amendment 7, 8, 9 and for being the Medical Director at MCRA evaluating this I have a lot of questions that you need to answer.

Joseph:  Got it. Yousef?

Yousef:  I’d like to address that - what we do is we use a very useful and a free resource and that's called the USFDA. We typically do Q subs before we even touch a first patient and we present a protocol and then we use the basis of that protocol to build our you know clinical protocol and SOPs to collect data outside of the US so that we can present that data and use that data to go and directly into an ID PMA without having to go through an early visibility in the US.

Joseph: You bring up a really good point and a lot of people are unaware that because the TGA which is the regulatory body in Australia is very aligned to the FDA which means that the FDA regards Australia as a center of excellence delivering tier one quality data. So when you have multi-country submission to the United States, yes, the US FDA wants to see the preponderance of data from US sites. However, it will accept up to 50 to 55% of the data from Australia and other countries that are deemed a center of excellence. So that's an important thing to know.

I want to turn to Australasia specifically as we wrap up now that we're sort of ending this and just ask you what you like about Australia as a clinical destination and most of you have already said but Yousef could you recap for us?

Yousef:  When we talk about Australia as a destination even from some investors first thing is it's super far uh it's a 7-hour time difference compared to a 9h hour time difference with California. So if you if you can save 3 months, four months, five, six months in, uh approval time um I believe that uh you know 15-hour flight is well worth it.

Joseph: Couldn't agree more. Now Vanessa, a little bird told me that in this multi-center trial you're executing, Australia out-enrolled multiple EU countries combined. Could that be a reason that you like Australia?

Vanessa:   Yeah, it's definitely one of the reasons. Now, in our studies, Australia has been one of the top enrolling countries. We’re very pleased with the outcome. But it's not only that, as we were saying, it's really a combination of factors that drove the decision to add Australia to the studies. We already discussed a couple of those. And ultimately you need a little bit of foot on the ground and you need your local CRO partner to be the extension of your team because when you're based as Yousef was saying in Europe or the US the time zone difference makes it very difficult for you to manage that yourself. So of course you need your local CRO partner. And you need your therapy development team also on the ground - whether you do that internally or externally through a local your CRO this is really key for driving the entire process. You need to build the relationship with those sites key opinion leaders at a very early stage and again having that local presence helps you stand out and make it happen.

Joseph:    I might know a CRO that could actually help you with all those things. Wrapping up - Pedro given your broad experience set one would imagine that you have a lot of reasons why you might like Australia.

Pedro: Yeah I think key for everybody is predictability. Also, when you have your milestones to your investors nine of 10 times you will not reach them in the clinical studies because things took longer. So I think predictability is really key for a lot of things we do but especially with clinical studies. So if you go to Australia you know how long it will take and you don't have the competition with other studies. So I always say when a physician says I can enroll 20 you can maybe do five. in Australia I have to say I can enroll 10 I he could he will probably do eight or nine so I think it's very important that predictability that you have with like going to Australia is would be for me one of the key factors next to the fact that almost half will be paid back in cash.

Joseph:    There you go.  All right I'm going to wrap up now as we're sort of running over but I do want to echo a couple of the panels that went before us Miss Yancy said something very important she said that every clinical study must be scientifically valid It must answer a question why and then you need the data to back that up.

Another important quote, clinical is not the time to cut corners. So when you're looking at other lands that may be less expensive where you can go and quickly get something done, maybe that's the right place to go for internal data. Maybe that's the right place to go for gathering a clinical signal. But if you are looking for first in human pivotal or PMA, you want tier one quality data dialing back to how we opened this session. So that's where I would invite you to consider Australia as a clinical destination. Thank you. Thank you everyone.