Arsalan Arif:
好了 大家好 All right.大家好。我是《端点新闻》(Endpoints News)的发行人阿萨兰-阿里夫(Arsalan Arif),很高兴担任今天的主持人。今天的网络研讨会由澳大利亚 Agilex Biolabs 公司赞助,我们的主题是 "澳大利亚的优势"--降低早期试验风险。今天和我一起的是 Agilex Biolabs 公司的 Kurt Sales 博士。他有一个大约 20 分钟的演讲,我们将在演讲后进行快速问答。现在有请库尔特-赛尔斯博士。
Dr Kurt Sales:
Thanks, Arsalan. So COVID-19 really has had an unprecedented global impact on the clinical trials and economy, shutting down many sites and R&D labs globally. Australia, on the other hand, has controlled the coronavirus outbreak pretty well. Bioanalytical laboratories, CROs and sites are open for business as usual. We’re recognized as an essential service by the Australian Government, and we’ve been working quite hard through this pandemic.
Dr Kurt Sales:
So in this webinar, I really just want to discuss the many advantages of moving your early phase trials to Australia, for models of speed and efficiency, cost advantages, to the advanced, most advanced medical facilities available for getting your drugs safely into man and out into the marketplace.
Dr Kurt Sales:
So, why Australia? It really comes down to the three pillars of quality, speed and cost. And in terms of quality, Australia has been conducting clinical trials for over 30 years. So we have an unprecedented technical knowledge around the regulatory perspectives and what you need to do to get your trial up and running, to get your drug safely into man and into the marketplace. We’ve got a track record of quality clinical trial research with world-class key opinion leaders and principal investigators.
Dr Kurt Sales:
The Australian industry is primarily set up to serve global markets, and we work both across the FDA and the EMA in order to track trends and best practices. Bioanalytical laboratories also attend global workshops every year. These in turn, are attended by the FDA and the EMA, and it’s a really good discussion forum for us to be able to discuss the bioanalytical trends and the latest in the regulatory guidances that’s essential for us to develop the assays responsible for PK immunity and [inaudible 00:02:39] biomarkers. Clinical trials themselves around the declaration of Helsinki, ICH, GLP, GCP, NHMRC, National Statement on Ethics Conduct.
Dr Kurt Sales:
We’ve got TGA guidelines and we’ve got local and federal legislation, which governs all of our practices. And all CROs and laboratories have had data submitted to the FDA and the EMA and this goes back for decades. In all the laboratories, and especially the bioanalytical laboratories, are accredited by the National Accreditation Body in Australia, NATA.
Dr Kurt Sales:
In terms of quality, quality of services is paramount. And we are cognizant of the time difference between Australia and the EU and US. And this is sometimes observed as being a bit of a hurdle for clients. However, we actually see this as an advantage because it creates the concept of around the clock working. So whilst we are busy working in the laboratories in Australia, the US and the EU might be asleep or vice versa. So it almost means that by the time you wake up, you’ve got data ready in order to advance your decision making processes. So it almost creates an end to end workflow working 24 hours.
Dr Kurt Sales:
One of the major advantages of working in Australia is the speed in which you can actually get your trial up and running. So the Clinical Trials Notification Scheme is a process by which the approval is established in Australia. And really there’s no lengthy IND that’s required. The burden of the review really is on the Ethics Committee and the Ethics Committee just need a good investigational brochure, a protocol certificate of insurance, some really good preclinical and in vitro data to support the trial. And the decision making around the safety and conduct of the anticipated trial is then reviewed by the Ethics Committee.
Dr Kurt Sales:
And these Ethics Committees, they’re central in Australia and they sit quite regularly. And the review process is around five to 10 days. So within two weeks, you can actually really almost get your approval in order to get your trial up and running. Once the Ethics Committee has approved the trial, the TGA, which is our governing body, will issue a letter of acknowledgement, and this then allows you to move into the planning process with your CRO and get your trial up and running.
Dr Kurt Sales:
So, like I said, there’s no IND required to commence first human trials. You also don’t need GMP grade material. You do need really good quality material, but GMP material is not a requirement for the first human trials. And in most cases, an import permit is not required for clinical trial material itself. And most bioanalytical laboratories have their own permits to facilitate the import of goods for the conduct and the setting up of assays to support the clinical trial.
Dr Kurt Sales:
Bioanalytical facilities generally offer a short turnaround, so this is critical for decision making for single and multiple assays in those studies. So [inaudible 00:06:05] really occur within a short period of time and we work towards a week about dosing regime. So we aim to have, in most cases, that Agilex data ready within three working days to enable the various committees to evaluate the PK data together with the patient’s safety for the next dose escalation.
Dr Kurt Sales:
The third pillar of the Australian Advantage really is cost. And this is where it makes it very lucrative for small biotechs in particular to come and work in Australia. So the Australian Government is now offering and has been for many years, a really attractive R&D incentive, a rebate. And currently it’s around about 43.5%. So this is on all of the activities associated with the clinical trial conducted in Australia. So this will be your trial set up, the trial itself, the bioanalytical laboratory testing, the clinical safety testing, absolutely everything that is done in Australia qualifies for that 43.5% tax rebate. And so not all companies qualify for this.
Dr Kurt Sales:
It’s generally companies that have a revenue turnover of less than $20 million per annum. And in order to qualify for this, you need to register an entity in Australia and appoint a local director. And other parties within Australia can provide a bit of guidance into who to speak to in order to get entities set up. Also, costs in Australia and the exchange rate, particularly in your favor, it’s generally about 15 to 20% less than the EU and US respectively. So not only are you getting a huge amount of money back from the clinical trial from the Australian Government, but the exchange rate and the costs are also considerably less. For small biotech companies in that burning phase and not earning phase of cash turnaround, it really makes your cashflow stretch that much further and allows you to actually also gather some really good first in human data in order to move your studies ahead a lot quicker than you would be able to do in some of the other countries.
Dr Kurt Sales:
So the blue bubbles in this slide really highlight areas of high COVID-19 pandemic status. So you can see in Australia, we have very few of these blue bubbles. So we’ve been relatively unscathed by COVID-19 and this is partly due to the Australian Government really taking cognizance of this potential of the pandemic right early on and putting measures in place. So this data taken from global data just shows, it gives you a snapshot of what’s really happening or has been happening with clinical trials globally. And the purple bowl just shows a huge impact of clinical trials globally. And 50% of those are US studies where the sites have had to shut down and cause a delay.
Dr Kurt Sales:
Australia, as I mentioned before, has been open for business throughout the COVID pandemic and the advantages of Australia is, that we can easily at the moment, get your trial up and running. In terms of the actual response and the incidents in Australia, this series of bar charts just gives you a snapshot of the history over the past 10 weeks, if you like.
Dr Kurt Sales:
And really, we’re above a 100 deaths now, we’ve had a couple more over the last couple of few weeks since we put the slide together. However, that’s quite a low incidence compared with the 7,000 cases that have been reported to date, the majority of those have actually actively recovered from it. So we’re now in the stage to roll back this coming weekend. Certainly in South Australia, where Agilex Biolabs offices and laboratories are, we’re actually seeing that the opening of restaurants now to patrons for in restaurant dining, as well as take aways and outdoor dining. Other places are becoming opened up. So we really are at the tail end of the pandemic, which is a really positive place to be. And we are seeing the reopening of most businesses and everything moving back to a new norm.
Dr Kurt Sales:
So we’re open for business in Australia. As I said, clinical trial industry has been designated by the government as an essential service, hospitals are treating critical cases. There are very few of those, we don’t, I think, actually have any active cases in South Australia at the moment. So even though phase one units generally have to reduce their capacity and this was just basically so that you could actually get the social distancing right between beds. And so that decreased the capacity to about 50%. We are still being able to successfully recruit and move trials forward.
Dr Kurt Sales:
CROs have transitioned to some home-based monitoring as well, but as we see things opening up this will move back to the normality that we knew before COVID. So even though working from home has been implemented as far as possible, we are now seeing a lot more companies opening up and people moving back into the offices, where companies have now put the appropriate social distancing measures in place and cleaning the stations. And video conferencing, certainly, has been ramped up nationally and internationally.
Dr Kurt Sales:
So this really creates a forum for constant dialogue and always on situation where we are constantly being able to engage with our customers and our customers with us through a variety of different forums. So for us, really this, although we have changed a few things recently, we find that generally things haven’t been hugely impacted by the pandemic.
Dr Kurt Sales:
So I thought I’d just use the final few slides to give you an idea of the puzzle and how to put things together for your clinical trial in Australia and the various components of the actual trial. So start with the bioanalytical laboratories more often than not, these are the last bits of the puzzle that are considered and are actually quite critical. To really de-risk your clinical study, especially for the PK immunogenicity biomarker, pharmacodynamic evaluation, these tests really need to be set up well ahead of time.
Dr Kurt Sales:
As I mentioned, the labs work to the EMA and the FDA bioanalytical guidances and these are prescriptive tests, and they take a lot of time. So to develop and then validate the assay to regulatory guidance specifications and allow for some longterm stability to give us confidence that upon collection of the first sample from the clinical trial and the storage within a minus 20 or a minus 80 freezer, that there’s no impact on the actual drug within the serum or plasma in which it’s collected. We really need about 12 weeks before the first patient first dose to comfortably be able to develop and validate an assay.
Dr Kurt Sales:
There are differences between a small and a large molecule in terms of bioanalysis, in terms of timelines. More often, it’s a bit quicker to get a small molecule developed and validated compared with a really complicated biologic that requires us to look at different antigen antibody pairings, and find the best reagents in order to build the assay. So be really cognizant of the fact that it’s essential to be able to plan this ahead of time.
Dr Kurt Sales:
Australia has exceptional quality in terms of bioanalytical laboratories. As Arsalan mentioned, I’m director of immunoassay at Agilex Biolabs and we are the largest bioanalytical laboratory within Australia, and have been focused on assisting clients in bringing their drugs to market for over 25 years. So we have a huge amount of expertise with small and large molecule bioanalysis and I’ll focus a little bit on that in the final slide.
Dr Kurt Sales:
We also have two other exceptional labs within Australia and all labs have their own specialties as well. We have really good central laboratories. These are essential for your safety bloods, clinical laboratory testing. And each state, each territory in which you have different phase one units, have various laboratories within the state that can assist the clinical trial, but it really is up the CRO and how they really want to conduct the trial and where they want to have the safety bloods analyzed.
Dr Kurt Sales:
There are a variety of different CROs from small to large. We work with all of them. I’ve listed a couple of them on the far right hand side. Major hospitals are open for business where we conduct patient studies and I’ve listed the major hospitals in the bottom left hand corner and other really important providers that are part of the puzzle as well. So from clinical insurers to clinical batch trial manufacturers, couriers such as World Courier and Marken and various consultants and regulatory specialists as well.
Dr Kurt Sales:
And we have a lot of knowledge of these individuals and we can provide some guidance and some names to enable you as a customer, to make an informed decision as to who you would like to approach. So we aren’t prescriptive in terms of who we work with. We work with everyone. We’re quite agnostic and we work within all the phase one units across Australia as well.
Dr Kurt Sales:
So just finally, mentioned Agilex Biolabs, one of the largest bioanalytical laboratories in APAC and certainly in Australia. We’re about 85 staff strong at the moment. Over the past nine months, we really have had over 30% expansion where we’ve expanded the footprint of our laboratories. We’ve also expanded the services that we’ve put in place. The immunoassay team, which I manage, we’ve just expanded into a brand new immuno biology division. This encompasses flow cytometry, cell based assays, X-VIVO PBMC stimulation assays.
Dr Kurt Sales:
These we believe are not any critical for inflammatory diseases such as cancer, COPD and various lung diseases that we’re seeing at the moment, but also for immuno oncology. In addition to that COVID-19, which induces huge inflammatory reactions, we’re seeing a lot of drug treatments coming through now into clinic trial settings, where clients are actually looking at how they can treat the symptoms or COVID-19 positive patients to prevent that cytokine storm reaction that’s often associated with a huge inflammatory onset.
Dr Kurt Sales:
And our new immunobiology service enables us to create bespoke inflammatory panels, biomarker panels using either the mnemonics or the Mesa Scale MSD QuickPlex 120 instrument, to be able to monitor the effectiveness of the drug in suppressing the cytokine storm reaction in patients that might have a chronic lung infection or inflammatory reaction due to COVID-19 or inflammatory onslaught.
Dr Kurt Sales:
So this slide gives a bit of our history. We’ve been around for over 20 years. We were initially established out of the University of South Australia and we’ve grown leaps and bounds since then into a state-of-the-art laboratory that we are. Currently we have the latest equipment, certainly in immunoassay, we have Gyrolab, we’ve got the latest [inaudible 00:20:24], we’ve got a BD FACSymphony A320 color flow cytometer in order for us to be able to do receptor occupancy assays, immunophenotyping, in cell sustaining and characterization of a variety of immunological [inaudible 00:20:40] associated with the clinical trial setting.
Dr Kurt Sales:
And really we’re a customer focused company where we really like to be working in a very collegial manner with you, the client, in order to assist you in being able to bring your drug to market. So, happy to take any questions and my contact details, our contact details in the back page here for any follow up. Thank you.
Arsalan Arif:
Thank you, Kurt. Very informative. I appreciate that. You go ahead and end your presentation. We can get on with the Q&A. And really, as someone sitting here in the US and talking to you in Australia, I want to say, congratulations on your response to COVID. You mentioned moving into a new phase and getting work done. I know I talked to a lot of biotechs and I hear from a lot of the biotechs, they’re interested in getting their work done. They’re interested in resuming work, especially biotechs here in the US, so I thank you for that presentation.
Arsalan Arif:
And I’ve been collecting some questions, so I’m going to get to as many as possible so we can get into some detail behind your presentation. But let’s get into something that caught my attention first. So you mentioned 43, 44% rebate on clinical trial spend. That almost seems too good to be true. Can you give a little bit more detail on that? What’s the process behind that? What kind of biotechs are eligible for this kind of rebate? Can you give us some detail on that?
Dr Kurt Sales:
Certainly. It certainly does seem a bit too good to be true but this has been around for many years and it really is an incentive from the Australian Government to get small biotechs globally to bring their work to Australia. And as I said, we’ve been working in this space for 30 odd years and there’s a huge cumulative knowledge.
Dr Kurt Sales:
So really, in order to qualify for this, you need to be a company that earns less than, I think $20 million worth of revenue. This is really designed for the startup companies, the small biotech companies that are burning rather than earning. And it’s quite a simple process. All That you need to do is to register your company as an Australian entity and appoint a local director. And this can be a virtual director. You don’t have to own premises. You can have a virtual premises.
Dr Kurt Sales:
And really, it’s just a case of lodging a tax return at the end of the financial year, which is July, August time for Australia, and you basically get a check in the mail. The R&D tax rebate can be used for anything, you don’t need to leave the money in Australia, obviously we’d like you to do that and conduct more trials. But it really is designed to enable you, the client, to get your drug to market quicker without compromising quality and cost. It’s really designed to springleap your drug into market.
Arsalan Arif:
Wonderful. That should be publicized more. So thank you for bringing that to light. Let me get to another topic here. So how long should a biotech starting a trial allow for assay development?
Dr Kurt Sales:
That’s an excellent question. And this is something that is often left too late, which potentially could impact the trial itself. So we really look at when the first patient first dose is, and we like to draw back a timeline from there. So if we assume that it’s a really uncomplicated assay, an uncomplicated small molecule LC-MS/MS assay or a very simple antibody assay, then you’re looking at about two to four weeks worth of method development. And then you’re looking at about four weeks of validation.
Dr Kurt Sales:
And so the validation really is creating a validation plan. It goes through our quality assurance team, it gets audited. We conduct all of the tests as prescribed by the regulatory guidances. We work to the FDA and EMA guidances, so that allows the client to be able to lodge wherever, even the EU or the US, and then that gets closed out. And we like to include at least one month’s proven stability for being able to give you a really good idea that your drug is behaving in the plasma or the serum in the same way as it would in an assay buffer, and that we freeze it at minus 20 or minus 80, it doesn’t deteriorate and if it does at minus 20, for example, then we can guide you as to the appropriate storage conditions in the clinic. And that just ensures that your sample isn’t compromised. These are very valuable samples. You don’t want to have to repeat a dose group because you haven’t taken into consideration the appropriate storage.
Dr Kurt Sales:
Same goes for urine assays. Urine tends to be very sticky, cerebral spinal fluid tends to be very sticky. So we, as a bioanalytical laboratory, will also test the appropriate collection conditions for these and this then guides the clinical protocol as well, and the clinical trial.
Dr Kurt Sales:
So all in all, you’re probably looking at about 12 to 16 weeks before first patient first dose. We really like to engage clients a lot, even before that. So we’re GLP accredited as well. So we run everything at Agilex Biolabs to the GLP quality standard, even though it’s not a requirement for clinical studies. So we can assist with a preclinical sample analysis as well as clinical sample analysis. So we could actually offer an end to end life cycle for your product to be able to expedite moving into your later phase studies as well.
Dr Kurt Sales:
So, we really would like to engage with clients as soon as they are thinking about their clinical study. And we work in a very collegial way and in a collaborative way during the method development phase, in order to ensure that the assay is the best it possibly can be. The most sensitive has the best assay range that is not only going to be fit for purpose for the phase one, but also for the later phase studies.
Dr Kurt Sales:
And this is where it’s particularly critical for immunogenicity assays, where you marked the dosing a really low dose drug in your phase one, but for an oncology, you might ramp this up quite considerably because you’ve proven the safety profile of your drug and you’re now moving towards looking at efficacy and the actual impact on that patient population. So where you’re dosing a high level of drug, you need a higher drug tolerance, so you need an assay that is also fit for the purposes for which you can measure the antidrug antibodies in that high dosed population.
Arsalan Arif:
Right. Well, let me actually just follow up on that a little bit. And my next few questions are going to be really about the company, about Agilex Biolabs. You have mentioned collegiality and mentioned working with your clients. Now, the sponsors, when they work with your firm, are they working with Agilex Biolabs directly? Are they working through a CRO? How does that engagement typically work?
Dr Kurt Sales:
So we see both avenues. So we see clients that are directed to us through a CRO, and we contract through the CRO and equally, we see clients that prefer to do everything directly with us. So they’ll have a separate contract with the CRO and then they’ll have a separate contract with us. So it really depends on what the customer wants. We are very flexible in the way that we work and it’s whatever is in the best interests of the customer to enable them to manage their own cash position as best as they possibly can.
Dr Kurt Sales:
For us, more often than not, we prefer direct because that enables us to directly engage with the scientific staff, get the assays set up with you. We don’t have to go through the third party all the time in order to ask questions around the molecule, how it behaves, whether there’s any preclinical data, if it’s a small molecule, are there metabolites. If we are directly in contact with a client, it means that we can really speed things up. We’re almost an extension of the client’s laboratory. But in terms of contracting, we’re happy to work through the CRO or directly with the client as well.
Arsalan Arif:
That makes sense. The sponsor directly is going to have that essence of the molecule and you’ll really be able to get that thing, but what I’m hearing is that you’re flexible. And if a sponsor has a certain way of working, they work with the CRO, then you’re willing to play ball really, either way.
Dr Kurt Sales:
Absolutely right.
Arsalan Arif:
Great. Well, so I see that you’ve expanded your labs by 30%. Now I’m just going to ask you a direct question. Now, just tell us about the tech, that equipment and just tell us what sets you apart from other similar biolabs in your region.
Dr Kurt Sales:
So what really sets us apart is not necessarily the equipment. We have the most state-of-the-art equipment, for example, the immunobiology lab, we’ve just established has the latest BD FACSymphony A320 color instrument. It’s a custom built instrument, which we’ve specified specifically for Agilex Biolabs, where we’ve had the laser configuration specifically custom built in order for us to maximize all of the available Fluor for antibodies on the market, really geared towards immuno oncology trials, receptor occupancy, broad immunophenotyping studies, and being able to really delve deeply down into the pharmacodynamic influence and the real workings of what the drug is doing to the patient population.
Dr Kurt Sales:
What sets us apart is the workforce and skill set that we actually have. Cumulatively, we have over a hundred years worth of experience within our company. We have senior method developers that have upwards of 15 years experience working in this industry. They’ve seen pretty much every type of molecule coming through the market, be it small molecule, be it a large molecule antibody, antibody drug conjugate, bispecific antibodies we’re working with, we’re working a lot with biosimilars at the moment.
Dr Kurt Sales:
And the immunoassay team that I manage has an exceptionally high level of skill, especially when it comes down to immunogenicity assays and really understanding the nuances of the drug to be able to develop an assay that can strip out the interferences and still make it sensitive and drug tolerant enough to be able to measure an antidrug antibody within the serum.
Dr Kurt Sales:
So that’s really what sets us apart from all of the other labs with within the region. We have state-of-the-art equipment. We have seven sites, LC-MS/MS machines, we have a Gyrolab xPlore, microfluidic immunoassay reader, we have the Meso Scale QuickPlex 120 electric Kimberley Monessen reader, which enables us to create assays with the logarithmic order of a dynamic range, which is really sensitive and fit for purpose for oncology studies, in particular. The advantages of this, you don’t have to dilute your sample because you have an incredibly long standard curve. We have a brand new BSL-2 laboratory where we can create cell based assays, X-VIVO PBMC stimulation assays, cytokine release assays.
Dr Kurt Sales:
So we have all of the toys and they’re all the latest state-of-the-art, we’ve spared no expense with our expansion in getting the latest equipment, because we believe that that is going to really be beneficial to our clients because we’ll be able to give them the best possible data.
Arsalan Arif:
All right. So you’ve got the technology in place, as I understand it over there. Some of those machines I haven’t heard of but they sound quite advanced. Now let’s just go to our final question. We’re running up on our time limit here. You’ve got the technology and you say that biotechs should talk to you during their preclinical studies as early as possible, just as early as possible. But most people get their funding. They start looking at CRO sites. Why should they prioritize Agilex Biolabs here in this phase?
Dr Kurt Sales:
Well, it’s because we are not only a bioanalytical laboratory, but we’re also a repository of knowledge. So because we’ve been around for over 25 years and we know the landscape in Australia incredibly well, we are not only excellent at being able to develop and validate your assay, but we can provide you with a lot of information, which is public domain anyway, but which would be there to guide you to be able to more rapidly get your trial up and running.
Dr Kurt Sales:
So this could be who key opinion leaders might be and principle investigators for specific disease areas, or who to contact to potentially set up your local entity. Which phase one units are around? Who has done a lot of biosimilar work, for example, the nucleus network and Q-pharm? Have a huge expansion in terms of biosimilars. So it’s not only about the bioanalysis, but it’s about us looking after the client as a whole as well.
Arsalan Arif:
Right. Well with that, we’re going to have to conclude today’s webinar. And I thank you to my guest, Dr. Kurt Sales. Thank you for that and Agilex Biolabs for this detailed presentation. I learned a lot about de-risking your early phase trials in Australia. And for Endpoints News, I’m Arsalan Arif and we hope to see you at the next webinar.