Arsalan Arif:
Hi, everyone. I’m Arsalan Arif, the publisher of Endpoints News, and I’m pleased to be your moderator today. Today’s webinar is sponsored by Agilex Biolabs in Australia. Our topic is Why Australia is the World’s Leading Early Phase Destination – Rapid Start-up, No IND Required, and a Government-Backed Refund on Almost Half of all Trial Costs. I’m joined by two great guests today. Kurt Sales, the Director of Immunoassay at Agilex Biolabs, and Jane Kelly, the CEO of CMAX Clinical Research.
Jane Kelly:
Hi, lovely to be here.
Arsalan Arif:
Hi, Jane. [crosstalk 00:00:43]
Kurt Sales:
Hello. How you doing?
Arsalan Arif:
All right. So Kurt has a quick presentation for us today. 18 minutes, he says. He’s really good at them, so I’m going to hold him to that. So he’s going to give us that presentation and then, right afterwards, we’re going to get Jane in the thick of things with Jane and Kurt having a Q&A for me. So please get your questions in. You can hit that Q&A button right down there. If we can’t get to it during this session, someone will follow up with you by email. And now I give you Kurt Sales.
Kurt Sales:
Thanks very much, Arsalan. And hi, everyone, and welcome to today’s webinar. I’ll just share my screen.
Kurt Sales:
Welcome, everyone. In today’s webinar, we’ll discuss why Australia is the world’s leading early phase destination, and how Agilex Biolabs and CMAX Clinical Research work together in order to manage timelines and success for your clinical trial.
Kurt Sales:
The contents of today’s presentation generally outline why Australia is the leading destination for clinical trials, a little bit about Agilex Biolabs, what we do, our bioanalytical capability, and how we seamlessly fit in with clinical research organizations such as CMAX in Adelaide in order to deliver your clinical trial.
Kurt Sales:
So really, the Australian advantage is underpinned by three main aspects. Quality, speed, and cost. The quality of our medical system is second to none. Our facilities are incredible, and most of our key opinion leaders have also trained overseas and are well connected with international colleagues. In addition to that, our data from all the trials generated in Australia are compliant with regulatory agencies internationally, and these include the USFDA, EMA, MFDS and TFDA.
Kurt Sales:
The speed of our regulatory process is extremely streamlined, which allows a Sponsor to get their study into the clinic that much faster. For example, a full CMC package isn’t required, but instead of protocol, informed consent, insurance certificate and investigator brochure is all that the Ethics Committee requires, because everything sits within the Ethics Committee for decision-making in order to st the clinical trial. And so, really, a fast process enabling most clinical trials to be started in as little as four to six weeks after the Ethics Committee submission. And typically, and especially contracting directly with Agilex, contracts can be reviewed and signed off in a really short time, enabling us to start the bioanalytical component that much earlier than the clinical trial, first patient, first dose, and to enable everything to be ready for the clinical trial start. In addition to that, we can also perform a fast sample turnaround for studies that require data in real time and for decision-making.
Kurt Sales:
Finally, the cost advantage is really a lucrative incentive, where biotech companies that are earning less than $20 million of revenue per year may be eligible for the Research and Development rebate of 43.5%. And this is generous tax incentive that has been put in place by the Australian government, and it covers all aspects of the clinical trial. So not necessarily just the trial itself or the bioanalytical component, but absolutely everything that is associated with the start-up, the conduct and the closure of that clinical trial within Australia. And it’s a really simple process, and companies need to establish a local entity, and it’s really inexpensive, but takes a number of weeks only to establish the entity, but the cost savings are substantial. And that allows most companies, especially small biotechs, where they’re burning rather than earning, to stretch their cash that much further and be able to conduct formal clinical trials than they’ll ordinarily do elsewhere. In addition, our service provider costs are also about 15 to 20% lower in Australia than in other countries. So thereabout further extending the cash revenue advantage.
Kurt Sales:
Finally, talking a little bit about COVID-19, Australia has fared relatively well during the pandemic. We haven’t experienced the number of study cancellations as encountered in other parts of the world. And in fact, Jane will talk a little bit to this later on, it’s been very much business as usual. With Agilex Biolabs, all the Phase 1 units staying open throughout in order to enable new drug discovery and drug to market.
Kurt Sales:
So a little bit about Agilex Biolabs. We’re the oldest and largest and leading bioanalytical laboratory in Australia. We have over 20 years’ experience and we’ve worked across multiple different projects, cumulative more than 250, and this encompasses both small and large molecule bioanalysis. We work globally across all countries and we’ve grown extensively over the past 18 months, such that we have more than 95 experienced staff. So our service lines really include both small molecule bioanalysis by [inaudible 00:06:03] and usual chromatography, and also large molecule bioanalysis, which encompasses the usual ligand binding type assays, which I’ll discuss a little bit later on.
Kurt Sales:
In addition to supporting pharmacokinetics and immunogenicity, we can also support biomarker analysis and a variety of pharmacodynamic endpoint analysis for clinical trials. We’re a very customer-focused organization. We’ve been FDA inspected, and we’re also accredited by the National Australian Testing Authority for both OECD GLP and also 17025, which is an ISO R&D chemical testing acidity accreditation. We pride ourselves on timeliness and speed. We can provide fast turnaround for sample analysis for clinical trial, enabling the trial to move that much further and faster during the single and multiple escalation dose phases.
Kurt Sales:
A little bit about our bioanalytical expertise. We worked with both the FDA and the EMA bioanalytical guidances for both small molecule and large molecule bioanalysis. We support pharmacokinetic, or PK assays. And here, we can either develop these assays from scratch, or we can transfer the method over from the sponsor laboratory or other CRO. We utilize multiple instrument platforms in order to deliver this. And this ranges from LC-MS/MS, [inaudible 00:07:35] for small molecule bioanalysis, and also ELISA, MSD and Gyro lab for large molecule bioanalysis.
Kurt Sales:
And we have expertise in a range of molecules and cell types, extending from novel chemical entities to biological entities, Anti-Body Drug Conjugates, biosimilars, and a variety of novel antibody constructs. And we can use the method, we measure these in total, or we can measure these three in serum, plasma or multiple other matrices.
Kurt Sales:
When it comes to large molecule bioanalysis, there’s a regulatory requirement to also consider immunogenicity, and we conduct immunogenicity assays in a tiered approach for our sponsors, generally starting with a single ADA assay, or anti-drug antibody assay, for screening, and then a confirmatory and titer assays. And we can move on in that step [inaudible 00:08:28] to also include neutralizing antibody assays for our client. And the team, over the years, has developed substantial experience in a range of non-standard assay formats. These include techniques such as acid dissociation, affinity capture elution, precipitation and acid dissociation, also called PandA, and solid phase extraction and acid dissociation, or SPEAD. And these are really to optimize the assays for drug tolerance, especially an issue in antibody drug trials, where over time, with…
PART 1 OF 4 ENDS [00:09:04]
Kurt Sales:
… drug trials, where over time, with increasing dosage, there’s a huge amount of drug tolerance that’s required in order to dissociate the antidrug antibody from the actual dosed drug, as these complex in the matrix. And we provide statistical analysis to industry standard for our studies.
Kurt Sales:
When it comes to neutralizing antibody assays, here we can do these both by live and binding assay technologies, where we use a competitive approach using, for example, the MSD platform. And we can also provide a cell based assay solution for clients that are wishing to identify more a mode of action associated with the neutralizing effect of the antibody [inaudible 00:00:56].
Kurt Sales:
Finally, and this is a recent addition to our laboratory that we’ve expanded substantially over the past 18 months, we now have enhanced pharmacodynamic assay capabilities. We can develop and validate the usual biomarker assays for clients just wishing to investigate where their drug product has actually impacted a specific pathway, and perhaps modulated an inflammatory mediator.
Kurt Sales:
But over the past year, we’ve developed and installed a brand new immunobiology function, which encompasses mode of action assays and flow cytometry. And this really enables clients within the immuno-oncology space and vaccine space to be able to identify efficacy and look at the effect of the drug in real time in whole blood or PBMCs during the clinical trial.
Kurt Sales:
What is it that we measure? Well, we measure new chemical entities, new biological entities. These include proteins, peptides, and conjugates. We can also measure cells for flow cytometry and oligonucleotides by a variety of techniques, such as [inaudible 00:11:15] mass spectrometry or hybridization techniques. As mentioned in the previous slide, we can measure antidrug antibodies or neutralizing antibodies, and we can also focus on inflammation and immunological assessments. And these include immunophenotyping of peripheral blood and organ material.
Kurt Sales:
And this is really what enables the client to get some quantitative information on the abundance of immune cells and how these might change during the clinical trial situation, either in response to the drug, where it might be a warranted response, such as target engagement, where ligand receptor interaction and persistent, might occupy a receptor on the surface of the cell and the client might want to investigate in real time how long the drug remains on that receptor and how it might wane over time, and the immunological impact of that ligand receptor occupancy on the pharmacodynamic process within the body.
Kurt Sales:
And for here, we can also then provide a variety of really custom-made immunological assays. And I’ve listed a couple of common assays on this slide. More often than not, clients are interested in whether the drug might impact an activation state of immune cells, including a variety of T and B cell activation panels, and also T cell proliferation panels for a variety of our immuno-oncology studies that we are currently supporting.
Kurt Sales:
How do we measure this? And in this slide, it’s very busy, but I’ll take you through it in a stepwise manner. And the close proximity of our phase one unit, CMAX, to Adelaide is really advantageous for a variety of trials, immuno-oncology trials, vaccine trials, where whole blood might need to be processed in real time to isolate, for example, PBMCs.
Kurt Sales:
If we consider that a subject or a patient is dosed at the phase one unit, for example, CMAX, we would then get whole blood from CMAX and we can get blood in a matter of minutes or hours, depending on the trial design. And from here, we can either isolate PBMCs from the whole blood in order for us to do in-life immunological assessments, or we can store these PBMCs frozen for the sponsor for further investigation.
Kurt Sales:
We can extrapolate the cells to measure [inaudible 00:14:03] proteins, and we do this by means of a variety of state-of-the-art technology, such as the Luminex MAGPIX or MSD Quickplex SQ120. We would also get serum or plasma from the clinical trial. And here, we’d actually be able to measure the pharmacokinetics in real time, and also perform fast turnaround of data.
Kurt Sales:
And in addition to that, we can then support a variety of immunological assessments, where we can get whole blood and we can label these [inaudible 00:14:38] tagged antibodies, and we can investigate by means of flow cytometry whether the various markers go up or go down, whether immune cells are activated. And this all ties into safety of the molecule during the trial, and whether it’s having the desired effect by binding to its target.
Kurt Sales:
That just gives a little flavor of the type of assessments that we can support in a buyer analytical environment in real time for the clinical trial to enable the success of the study.
Kurt Sales:
In terms of project timelines, it’s probably a critical path to get the Bioanalytical component set up ahead of the clinical trial. It takes several weeks in order to develop an assay, then validate it according to the EMA and FDA Bioanalytical Guidances, and to put all of the data associated with the development and validation through a quality assurance process to ensure that we are ready for the study startup.
Kurt Sales:
So, we’re probably looking at about eight to 12 weeks, depending on how complex the molecule is, to develop and validate. And this really needs to occur ahead of first patient, first dose within the clinic.
Kurt Sales:
But what makes the advantage of having CMAX in such close proximity within the same city better than working with any other unit is, really, it’s all about the seamless transfer of samples from CMAX to Agilex within the same city to allow fast turnaround. And this is really critical for oncology samples, where whole blood processing to PBMC for immunological assessment is important, and where stability of drugs might be an important consideration for either the PK assessment or PD.
Kurt Sales:
We have integrated sample barcoding, which is advantageous, and we have regular communication. We’ve worked with CMAX for over 25 years. We have a really strong, solid relationship and extensive knowledge and expertise within the clinical trial landscape within Australia. Really, the workflow at the bottom creates a seamless integration from the time that we actually receive the samples from CMAX to processing and being able to rapidly turn the data around in real time to provide information for safety assessment and decision-making.
Kurt Sales:
I hope that the webinar has been of some interest and just given a broad overview and a little flavor of what Agilex does and how we seamlessly integrate with CMAX, which is one of the largest and more established phase one units within Australia with-
PART 2 OF 4 ENDS [00:18:04]
Kurt Sales:
… Phase one units within Australia with extensive expertise in being able to deliver quality for all clinical trials. Thank you. I’ll have you to take any questions.
Arsalan Arif:
All right thank you Kurt. All right let’s get Jane Kelly involved in the conversation. Now, Jane I’ve got some questions for you, Jane. I’ve got questions for you, Kurt up for the presale, but let’s start with Jane first and make sure you unmute yourself Jane when I ask you this. So first, what changes have you seen as a result of the pandemic at CMAX?
Jane:
Hi Aslan. Firstly, thank you to the organizers endpoints and the sponsor AGILEX for allowing me to be part of this exciting webinar. Coming to your question, what changes have we seen at CMAX as a result of COVID, from a site perspective, really there’s been a heightened awareness in respect to the processes that were already in place. Our focus at C-Max of course, is the safety and welfare of the participants and staff. Some of the changes … As I said, it’s just been a heightened awareness, and things, including, and certainly not limiting to a focus on hygiene within the facility monitoring for any signs or symptoms of illness prior to entry to the facility and performing a risk assessment for each study.
Jane:
Now we were already doing these risk assessments, but there’s been a real increased focus on what the mechanism of action of the investigational product in terms of immunosuppression. So if we see a product that has the potential to cause any effect on the immune system, then there’s really that risk assessment to say whether studies can continue as they were planned, does the design need to modify, do they need to be delayed, or in some cases even stopped in the short-term. Social distancing measures within the facility and office space were also established immediately, and we’ve had to be flexible and modify them in line with the government advice as it changes within Australia.
Jane:
Please note that we’ve been very lucky in our facility, that it hasn’t necessitated a change to the bed numbers. In fact, we’re currently in the process of expanding from a current 55 beds to 66 beds in the coming months due to the demand of work coming in. COVID really has resulted in increase in clinical trial opportunities coming into Australia. What we’ve found is that international companies and whether they’re pharmaceutical or biotech companies that were ready to conduct their clinical trials elsewhere in the world in another jurisdiction suddenly found that everything slowed down and in some cases stopped completely.
Jane:
They’d been looking at other opportunities and luckily in Australia, our, our relative incidents of COVID has been very low, so Australia has been as seen as a very attractive destination and in South Australia and Adelaide, the only active cases that we’ve seen recently have been through return travelers that are in very strict total quarantine. Adelaide is a perfect place to, to come to. It’s really been business as usual as Kurt alluded to before. Australia really has demonstrated the resilience and the capacity to not only survive this pandemic, but thrive through the pandemic and beyond.
Arsalan Arif:
All right, glad hear that. I understand you’ve been in this early phase clinical space in Australia for quite some time. Can you give the audience, what changes have you seen in your 27 years in early phase clinical trial research?
Jane:
Yes, I have been very lucky to be involved with CMAX now for 26, actually nearly 27 years. And really the early phase clinical trial space in Australia has certainly grown substantially. The key drivers for the growth are the speed to start up, the quality and portability of the data and of course the very attractive R&D tax incentives that we have in Australia. So just to reiterate some of the points that Kurt made, to commence a phase one program in Australia, including conducting a first time in human study, you don’t need an IND to get started. You can certainly be doing five or 9D in parallel, but what we find for a lot of our particularly smaller companies, they like to get their hands on some human data, which means they can go out and raise some more money.
Jane:
They can get investment, they can make that early go, no go decision. So not having to have IND in place, certainly speeds up that process. The approval to conduct the clinical trial lies solely with the ethics committee. There is no separate regulatory approval. The TGA is Australia’s regulator acknowledged the clinical trial and added to their database. But it does mean as Kurt said, we can go from designing the study, then putting into the ethics submission from ethics submission to first dose in four to six weeks, which is a considerable time saving. The data that’s produced is very high quality. And we know that it is 100% portable to any regulatory jurisdiction. Here at CMAX we’ve been audited by the USFDA on a couple of occasions now with the last being August, 2019. The reason for the audits have been that our data has been … has formed part of an FDA regulatory submission. In the case last year, it was for a biological licensing application.
Jane:
We’ve also conducted studies and we know our data has formed part of regulatory packages to Canada, to Europe, to Japan, to China. There is no doubt that our data is 100% portable. And of course the R&D tax incentive as Kurt has already alluded to one of the world’s most attractive, very, very helpful for SMEs in this space because they can claim back to 43.5%, and there are a lot of expert companies here in Australia who can guide, set up that system and make sure the companies do get maximum benefit for everything they’re eligible for. The benefits have been recognized for some time now, and there’s some real growth and maturity within the early phase industry here in Australia, and there’s a true international focus. Sites and CRA’s have evolved their processes to respond for this need for early, quick up.
Jane:
Here at CMAX we’ve also had a focus and grown our clinical pharmacology capacity, and have very experienced and very knowledgeable PIs available to support the sponsors in that sort of set up, making sure their study is designed to give them the answer that they require at the end of that. The other real noticeable change I’ve seen it in 27 years is really this evolution of adaptive study design and protocols being designed to be able to be modified so that it means …
Jane:
And this is another really good advantage of the collaboration we have with AGILEX is that we can design a study with multiple cohorts. We can actually collect those samples that can be done in AGILEX as Kurt said, they can be processed straight away. We get really quick a turnaround on results, and that means the sponsor can actually use that real time data to actually modify their study design. Hence it results in less protocol amendments, less time spent with ethics, but it’s also really what phase one is all about, is being able to look at your results as they come in and modify your design moving forward. So we see that as a real advantage and that’s something that we’ve seen a lot of growth in.
Arsalan Arif:
Very good. That was some of the questions I had for Kurt right there in terms of your working relationship with AGILEX right there, but let’s get Kurt involved over here. So I understand that you were working on a vaccine study together with CMAX. What can you tell the audience about that?
Kurt Sales:
This is an incredibly exciting time. Our current sponsor is working on a respiratory syncytial virus. These viruses have a huge morbidity impact, especially in causing respiratory illnesses, pneumonia in kids. Agile X is supporting the buyer analytical component of the clinical trial. We’re in the process of setting these assays up for the sponsor. There’ll be multiple ligand binding assays that we’re, setting up and these assays will then be validated to the latest USDA FDA, and [inaudible 00:26:35] guidance documents and then we’ll be ready to deploy these assays on the clinical trial. In addition to the [inaudible 00:26:46] ligand bonding assays, we will also be getting a whole blood and processing the blood to PBMCs in real time, and the advantage of having CMAX almost next door in Adelaide is that we can get …
PART 3 OF 4 ENDS [00:27:04]
Kurt Sales:
… and next door in [Adelaide 00:27:03] is that we can get the whole blood in a matter of minutes, certainly at least within an hour, to process whole blood to PRBCs. This really enables our quality data as the sample is at no time being compromised at all, due to lengthy times being trafficked in an airplane from one country to another or from one state to another. So, yeah, it’s a very exciting time to be a part of the clinical trial network. And especially as we move to support more trials that might also have an impact on COVID-19.
Arsalan Arif:
Okay. Here’s a question for you, Kurt. Through your experience, take us through the selection process from a sponsor’s perspective. Typically, in the past, I understand it’s been the CRO that gets selected, and then the CRO works with the Biolabs. Is that changing in your view?
Kurt Sales:
Yeah. So, we’re finding more complex study designs coming through, where consideration needs to be taken around the actual sample management. So for example, for an immuno-oncology study or a vaccine study, where there’s going to be a requirement to not only look at the PK, or the immunogenicity in the terms of the vaccine study, but there’s also the requirement to look at the pharmacodynamics or the mode of action. And generally, this is done on whole blood, and it’s time critical. And certain cell populations tend to die off after eight hours, certainly after 24 hours. So, the decision making lies in where the local expertise is, where is the phase one unit, and where is the lab in relation to that? And so most sponsors would make the decision on the entirety of the trial, based around the logistics of the clinical trial itself and where the samples are coming from.
Kurt Sales:
So, there’s two ways of looking at it. Often the client would approach a CRO. The CRO would then look at the phase one units, and then look at the lab in relation to that. On the flip side, we have sponsors who like to take charge of everything, and like to piece together the logistics for themselves. Agilex Biolabs, being the largest and most experienced lab, is generally the go-to laboratory for clients within Australia. And then working around the sample management and logistics is another consideration, on how to piece that together in the clinical trial.
Arsalan Arif:
Okay. Well, Jane, can you give us actually an example of a good working experience with Agilex Biolabs, especially you’re in the same city? So any advantages you can speak to about that?
Jane:
Sure. Yeah. I have quite a few examples. But one that really sticks to my mind was in the past, we had a study that involved an opiate medication. And as part of the safety for the participants, we needed some assurance of what the level of the opiate in their bloodstream was, before we actually allowed them to leave the facility and be discharged. So what we needed was a spot PK check, non QC data. We just needed a really quick snapshot of, at that point in time, what was the level of the opiate, and was it safe for us to allow them to leave the facility?
Jane:
So having adjuncts in the same city, and looking out my window, I can just about seeing where Agilex is. So, we’re literally 10 minutes down the road. That was invaluable. That meant that we could then discharge those participants, with a real security of knowing exactly what their blood level was. And then the full assay could happen separate to that, of course. But yeah, it was a really great advantage of not having to send those samples elsewhere, either within Australia or overseas, for sure.
Arsalan Arif:
Okay. Kurt, I mean, similarly, could you speak to that working relationship with CMAX, especially that phase one unit? Why is it important to have that strong working relationship here with this phase one unit?
Kurt Sales:
As Jane alluded to, it’s all around the safety of the participants. Communication and a good working relationship is key in order to, not only deliver on the safety aspects, but also to deliver on the trial itself. We work in the phase one space, which comprises a variety of single and multiple escalation dose studies. And data is really required in real time, in order, not only to make decisions for escalating to the next dose, but also decision around the safety of the participants in the trial.
Kurt Sales:
A good working relationship, such as the one that we have with CMAX, is really imperative to be able to deliver on this, because we need good sample logistics. We need to know when we’re going to be receiving samples so that we can book them into our systems, so that we can have the analysis done in a rapid manner, to enable data to be sent out for safety review committee evaluation, in order to make the decision as to whether to change the study design, or whether to escalate up to the next dose. And it’s only having a strong working relationship with the phase one unit, that enables that to occur in a really seamless manner.
Arsalan Arif:
All right. Thank you, Kurt. So here for our final question, Jane, can you just tell us a little bit more about you and CMAX and how clinical research has evolved?
Jane:
Certainly. We are about to launch a new business called Fusion Clinical Research, which will be part of the CMAX family. Fusion Clinical Research is an SMO, or a site management organization. And it’s a model where CMAX is going to embed staff, process, and systems within primary health practices, within specialist clinics, or even a hospital setting, to assist the investigator to conduct clinical trials. So, it’s ideally suited for investigators who have a keen interest and willingness to conduct clinical trials, have patient populations, but they don’t have the infrastructure to necessarily do so.
Jane:
So, the model we’re using… CMAX is actually owned by a Japanese company called the Iram group, who were actually a pioneer in this area in Japan. So really we’ve taken the model that’s been very successful in Japan, and we’re bringing it to Australia. So we’re leveraging off the success and experience of CMAX, and Fusion will allow us to work with our clients, with our sponsor companies, to take the asset from phase one, into phase two and three, in the community.
Jane:
So, we’ve already conducted a range of studies in the vaccine and diabetes space, and we’re very excited how this fits into the clinical trial landscape in Australia. So this will allow CMAX to diversify our service offering, and differentiate ourselves from other players within the local landscape. But this also will allow for further collaboration with Agilex Biolabs, because we’ll now have samples coming, not only from the CMAX phase one facility, but on the early phase two space, there will be samples coming in from various clinics around Adelaide.
Arsalan Arif:
Very exciting. So, Fusion Clinical Research. That’s the new moniker here, that’s going to be taking it beyond the early stage clinical research for which CMAX is well known.
Jane:
Exactly.
Arsalan Arif:
Very good, very good. Well, that’s all the time that we have for today’s session. I’d like to thank our sponsor, Agilex Biolabs, and Kurt Sales for your very insightful presentation, as always, and really appreciate you, Jane Kelly, with CMAX Clinical Research, for your lending your time and expertise today. For Endpoints News, I’m Arsalan Arif. See you next time.
PART 4 OF 4 ENDS [00:35:45]
