Hear from a panel of Life Science experts on the latest advancements and innovative modalities paving the way in the global vaccine development space. What has been COVID-19’s impact on drug development and the regulatory landscape? Key factors contributing to Asia Pacific being recognised as the hub for vaccine development and opportunities for biotech’s to leverage. Key considerations for pre-clinical and clinical planning to accelerate vaccine development, supporting a robust global strategy.


Kari Abitbol: Hi, everyone. I'm Kari Abitbol, Director of Client Success at Endpoints News. Thank you for joining today's webinar, Keeping Pace with the Evolving Global Landscape in Vaccine Development. We're sponsored by Novotech, which is internationally recognized as the leading Asia-Pacific-centered biotech CRO with global execution capabilities. I'm excited to moderate today's expert panel.

Joining us we have from Seoul, Korea, Dr. Sushant Sahastrabuddhe, Associate Director General with the International Vaccine Institute. From Brisbane, Australia, Dr. Paul Griffin, infectious disease physician and Cinical Director of Infectious Diseases at Mater Health Services, and Associate Professor at the University of Queensland Medical School. From Sydney, Australia, Dr. Babaji Yadav, Senior Consultant with Novotech Drug Development Consulting, and from Manila, Philippines, Jenny Arellano, Novotech's Director of Clinical Services in the Philippines.

Our panelists will explore the latest advancements and innovative modalities paving the way in the global vaccine development space. For instance, what has been COVID-19's impact on drug development and the regulatory landscape? They'll also discuss key factors contributing to Asia-Pacific being recognized as the hub for vaccine development, and opportunities for biotechs to leverage. Finally, they'll touch on key considerations for and clinical planning to accelerate vaccine development and support a robust global strategy.

If you have any questions during today's webinar, please hit the Q&A button at the bottom of your screen to join the discussion. This webinar will also be available to watch on-demand tomorrow. We've heard a lot of buzz around mRNA, cell and gene therapies, immunotherapy, and future vaccine development. Let's start by sharing some insight on the latest advancements and innovative technologies and modalities paving the way in the global vaccine development space. First question is for you, Sushant. Can you start us off with your thoughts on the focus for IVI and where you are seeing a lot of opportunities and innovation in the vaccine development space?

Dr. Sushant Sahastrabuddhe: First of all, thank you, Kari, for the introduction, and thank you Novotech for inviting me for this webinar. It's going to be quite interesting. Let me start by introducing a bit more about the International Vaccine Institute, which I represent in this webinar. IVI by its mission, it works on the research and development of vaccines for global public health. We have six major components in our mission. One, is discover, develop, and deliver. These 3Ds are quite important for us, and safe, effective, and affordable vaccines.

We are around 25-years old organization and our focus has been to work on the disease or work on the vaccines for diseases for the global public health. We started our work with cholera, typhoid, dengue, chikungunya, and now we have a spectrum of more than 26 different vaccine candidates that we are working either in the laboratory, in the preclinical work, clinical work, or in the delivery or immunization space.

Coming to second part of your question, we certainly as a facilitator for global public health, we actually welcome a lot of innovation that has come up in last few years, specifically after the response to COVID-19. I think mRNA, being one of the prime example of that, how it had changed the way the vaccines are being developed and being delivered for outbreak potential, or pandemic disease. We certainly have brought a lot of attention during this COVID-19 on the gaps that we see in the healthcare industry and the issue of equity that has been highlighted quite a bit.

We are committed from our side as a global public health organization, global R&D organization to close those gaps because, at one point in time, we have a lot of innovation that is happening, but at the same time, we also have a lot more gaps that we have seen in some of the countries where the vaccine have not been reached. We still are committed with our partners, including WHO, GAVI, UNICEF to make sure that the people who need the vaccine will get the vaccine.

Certainly, there are a lot more opportunities now for helping countries to be more vaccine self-reliant because there has been a lot of regulation during COVID-19 that the countries need to develop certain capabilities to cope or to get ready for any future pandemic. We are working with a lot of countries now to make sure that they have some sort of self-dependency, self-reliance on vaccine development as well as procurement. We are collaborating with global partners to be battle-ready for the next pandemic if and when it happens. It should not happen but we should be ready.

We have learned the lesson quite early on with COVID-19 that although we delivered the vaccine, I think the first response that came out, the first vaccine was licensed within 260 days after the first case was diagnosed for COVID-19, which is quite good, if you look at the traditional way of vaccine development. But in response for a pandemic like COVID-19, this is still quite late. There is a discussion about from US government for 60-day mission, from CEPI, there is a 100-day mission, that we are talking about and we are working on that space.

I think having these new technologies around mRNA, new methods of routes of administration, which includes the intranasal vaccines as well as the MAPs, which is the microneedle patch. This is something that we are quite excited about, but at the same time, we want to make sure as a global health organization that people who are left without vaccination during COVID-19 should have the access as well as there was lot of focus given on the COVID-19 vaccination.

There were a lot of kids and a lot of people who actually missed the routine immunization in some of the developing countries. We need to put our attention back on those EPI vaccines and making sure that people are actually getting those vaccines. I'll probably pause there and see if there are any more questions on this.

Kari: Thank you. Paul, question for you, what do you consider the most innovative areas of focus in vaccine development?

Dr. Paul Griffin: This is a tough question because there's just so many at the moment. I guess the first thing to say is the fact that we are continuing to develop new vaccines doesn't at all detract from the efficacy and safety of the vaccines we have now. I still think the currently approved COVID vaccines are going to be some of the biggest accomplishments we've ever seen in medical and scientific research. It's really clear there are some properties we'd like to improve upon with those vaccines.

There's a lot of different approaches to trying to address some of that in terms of what I think is most innovative and potentially promising, we've just heard about some of them. I really think intranasal vaccines are going to be a really important part of not only what we do with COVID, but other respiratory pathogens as well. There's some really good approaches that are progressing well through clinical trials with intranasal vaccines.

I also think that vaccines into the skin, the patches are going to be a really important part of our strategy moving forward. They have a lot of really interesting properties in terms of being stable at room temperature for long periods of time, et cetera. What's been shown to be really clear with COVID is we've done a great job in a lot of high-income countries with vaccines, but a lot of countries that haven't had that capability have really struggled to get vaccines. If we have vaccines that might have some of those properties, that will be a lot easier.

I think improvements on the current technology we are relying on. Things like self-amplifying mRNA for example, is also going to be a huge step forward. Even things like tweaking the lipids around mRNA vaccines and there's a lot of great work happening in that space as well. As I say, I think we've been really fortunate to get the vaccines we have for COVID in particular in recent times, and I'm really looking forward to the improvements that we're seeing in the ongoing development in a very large number of technologies.

Kari: Great, thank you. Follow-up question for you. There are some suggestions that the advancement in genomics will be an impactful trend into 2023. What role do you see genomics playing over the next 12 months?

Dr. Paul: I think that's true. It's really clear and again, that's been a really big part of our response to COVID. It was huge in that we had essentially plug-and-play platforms. The technology that was first to be approved really relied on getting that genomic sequence and being able to plug that in really quickly to respond. As we heard, we did that relatively quickly, but it would be great to be able to do that more rapidly. The stronger our genomic sequencing is, the better we understand what's happening with existing viruses.

We're obviously mapping the evolution of covid essentially in real time, largely because of the access to sequencing in many parts of the world, but also looking at even predicting what might happen and increased surveillance, so that perhaps we could find pathogens like this more quickly and maybe have vaccines ready to go before we get to the stage that we, unfortunately, have with COVID. Genomics is going to be a huge part of that.

We also need to make sure we continue to have capability there and even strengthen that once again look at doing that in parts of the world that don't yet have access to a lot of that technology and make sure that we not only do that work, but also share that information readily, so that we can all remain prepared.


Kari: Great. Babaj, where do you think the real opportunity or where do you consider the real opportunities for advancement in drug development for novel therapy is?

Babaji Yadav: I agree with my fellow panelists' Paul and Sushant's lot of points. I think there always will be opportunities and room for improvement in drug development to make vaccines that are safer and more efficacious. If you look at over the last few years we have seen development of all these mRNA vaccines, DNA vaccines, protein peptide-based vaccines, personalized cancer vaccines, lipid nanoparticle-based vaccines. Some of these vaccines are still under investigation and with some we have got mixed clinical success.

People are trying different ways to improve these vaccines, deliver these vaccines in a way to make them more efficacious or enhance the immunogenicity, durability, and overall efficacy. A lot of things are being tried and tested. For example, technologies like electroporation, microneedle technology, is coming quite nicely. Then self-administration vaccines, that is something being tried and tasted where you can just take a vaccine at home. That home technologies are being developed to accelerate the clinical development of vaccines. In terms of COVID, people are trying to figure out if we can give these COVID vaccines in combination with seasonal flu vaccines. There's a lot of things being tried and tested.

Kari: Thank you. Looking at COVID-19 is impact on drug development and the current regulatory landscape. Sushant, back to you. In what ways do you consider the COVID-19 pandemic to have impacted vaccine development?

Dr. Sushant: Again, thank you for the question. As Paul mentioned, this is a very big topic. COVID-19 probably has affected every single aspect of the life that we have known before. I think there is to be pre COVID-19 and post COVID-19, and you'll see the life had changed quite a bit. Vaccine development is one of those areas which has been affected in both positive and negative.

Let me explain the positive points first and then we can probably go to the cons or the negative point that we have seen during COVID-19. One big positive point that we have seen during COVID-19 is the way the regulatory agencies, they showed the flexibility in terms of reviewing the protocols, giving the clear guidance to the manufacturers, to the developers, to the governments, and having a very clear strategy in terms of how and when to license the products. Not only for vaccines, but also other products for COVID-19, which was quite unique.

If you see, traditionally we talked about eight to 10 years for any vaccine development. A major part of that was generating the clinical trial data, but at the same time, there were a lot of steps involved in the regulatory approval of one particular product. That regulatory flexibility was something which was amazing and we should continue with some sort of that.

The second point I see is the clinical trial, the way the clinical trials were designed. There were standardization of protocols across multiple manufacturers, WHO, CEPI, they played a role in that. There were discussions on successful conduct of solidarity trials where we can do the clinical trials using different vaccine candidates in the endemic countries, which never happened before. That I think was quite unique.

We also agreed on the clinical trial endpoints quite early on and because of that, the manufacturers had a very, very clear target in terms of how to design the clinical trials and how to get the regulatory approval in those things. One of the other things, which I think is very important from the delivery perspective, because development is one part of this, but delivery is very important. If there are vaccines, but they're not being utilized, they're useless. It's not the vaccine that saved the lives, it's the process of vaccination. COVAX, the mechanism that was developed jointly by WHO and by CEPI was quite instrumental in getting the number of doses to the countries which needed those vaccines.

Adoption of innovative technology. We talked in the first part of this webinar, having mRNA vaccines, having some of the-- If there is one DNA vaccine which is licensed in India. Having this new technologies respond in a positive way during COVID-19 has been the positive point. One thing that we realized somehow in the initial part of the pandemic, the world became one. This became a global problem, and it did not remain the regional problem that we have seen for some of the other outbreaks that has been affecting the African continent per se. Ebola, for example, it always remained an African problem rather than becoming a global priority.

At least in the initial part of the pandemic, I will say that the global unity was unprecedented and I think we responded as humanity to a problem which was affecting almost all the countries. Those are the positive points. A lot of other things, but I'll focus on some of the vaccine development part.

What we see as the negative point or the differences that came out during COVID-19 was I mentioned as previously vaccine inequity. There are still almost a billion people who haven't received even a single dose of this vaccine. Probably, now they will not receive even a single dose of this vaccine because the pandemic is almost over in most of the countries. Vaccine inequity is something that we need to work on.

Otherwise, what happens is the global unity that we have seen in the initial part of the pandemic, it'll never happen if the next pandemic come because countries will look more inwards. They will try to be more self-reliant, they will try to develop capabilities in the countries to make sure that they can respond because they cannot depend on the global partners for helping them in the time of crisis. This is something that we need to take very seriously and we need to have a plan for that.

What we have also seen is initial part of the pandemic, again, there was lot of interest in getting the vaccine. As the pandemic fizzled off, there was a lot of cases of vaccine hesitancy been increased, not only for COVID-19 vaccine, but also for the routine vaccination, which was happening in those countries. This is something we need to tackle as a problem because this is for the first time in our history, that almost everybody on the planet was trying to get vaccinated. And because of that, there were a lot of other things that we should be quite cautious and we need to work as a global public health community to take care of the vaccine hesitancy that is out there now in many countries, and how that should not affect the routine vaccination.

I think what we also see is that trust in the global leadership. We are part of the global organization as IVI, but the trust in global leadership to tackle problems like COVID-19 because of the different policies, different strategies, different opinions from different agencies that have eroded the trust of the public, in terms of a common source, the trusted source of information. People were going back again, to different sources of information. That's something we need to be prepared, not only from the pandemic point of view, but also in general for the vaccine field.

The last thing I'm quite worried about is, as I mentioned, the countries are looking more inwards. They're trying to be more self-reliant. If the next pandemic happened, rather than responding as a global community, we might be responding as individual countries or individual region rather than a global entity. That I see as the positive and negative points from COVID-19. Thank you.

Kari: Follow-up question for you, actually. Has the changing environment changed your pipeline prioritization and future direction in any way?

Dr. Sushant: Multiple ways. If you see before COVID-19, 2019, obviously, nobody had COVID-19 in their portfolio as a vaccine development priority. 2020, 2021 until last year, almost 75% of our research priority, they were on COVID-19 vaccine. Other vaccines got deprioritized. We still had a healthy portfolio of vaccines, working on typhoid, on cholera, on chikungunya, and some other disease. COVID-19 took a lot of space for us, in general for last few years, like many other companies and many other agencies.

Now I think we are coming back on the vaccine priorities. We are diversifying, again on the diseases that are important for the global public health. Moving forward for the future studies, since we have learned and there seems to be some sort of precedence in the regulatory agencies, in the sites, and in the developers who have some sort of flexible clinical trial design. Which not only includes the adaptive clinical trial design but also having more remote monitoring, which was not part of the discussion before COVID-19.

There were some companies, there were some sponsors, and some CROs like Novotech, who are using this option. I think during COVID-19, we realized that we can do much more by managing things remotely, as much as we were doing before. This is something that we see moving forward. In general, about the immunological understanding of vaccines, how they react in the body, and how to get some consensus on those parameters is something that we have seen in COVID-19. That's going to affect the way we design our clinical trials in the future.

Kari: Great, Jenny, over to you. How have you seen the regulatory and ethnic timelines evolve in APAC? Are there specific countries where there has been a big change?

Jenny Arellano: Yes, thanks for that question, Kari. Like the rest of the world, Asia-Pacific regulatory bodies have also responded positively to the call for the solidarity during this period. The regulatory and ethics bodies quickly put an infrastructure for continued service to review clinical trial applications during the pandemic. Moreover, for COVID-19 in particular, regulatory authorities in Asia-Pacific have actually opened the doors for rapid review and put in place, technical experts to support the review process.

In Australia, for example, the pre-pandemic ethics timeline was about six to eight weeks, was reduced to one week for COVID vaccine trials. In the Philippines, the local FDA traditional review process was about four to six months, and now it has been reduced to 30 days during the pandemic period. Similarly, in Malaysia, for example, a fast track lane has been defined for the pandemic-related clinical trials.

We had review timelines of 22 working days for biological products and for the ethics, the review process was about 20 working days. What has changed really is in the recent months, most of the regulatory bodies in Asia have reverted back to the pre-pandemic review cycle, except for Malaysia, where they have retained this fast track lane for the review process.

Kari: Great. Thank you. Babaji, What are you seeing as the challenges in getting investigational vaccines approved for initiation of clinical studies?

Babaji: From my experience of handling these regulatory submissions at Novotech. We mainly face two types of challenges, one is a regulatory challenge, another was a scientific challenge. From the regulatory point of view, when we started working on COVID studies, COVID clinical studies in the beginning of 2020. We received a lot of queries from companies around nonclinical data package requirements to start a COVID clinical study. At that point of time, we did not have any COVID-specific guideline or regulatory guidance published by any major global regulatory agency in the world. We were relying on this general vaccine development guideline by WHO.

Of course, eventually the COVID-specific guidelines were published, regulatory timelines were condensed and COVID applications were accelerated. I think having that COVID-specific guidelines or any specific guidance, regulatory guidance, regulatory strategy, regulatory pathway, it helps in developing a robust nonclinical and clinical strategy. From a science point of view, I think we all know that you still got to figure out, you've got to understand the biology of the virus and it's virulence. Also, you've got to develop and validate an antigen that can produce robust immunological response.

You've got to make sure you have a pharmacological relevant animal model to study safety and efficacy of the vaccine under development. Then platform technologies. This is something, if you are working on then you got to figure that out. All these things you've got to take into account. If it's a public health emergency situation, then you're pretty much racing against time. You got to figure out all these things in a very short time.

Kari: Great. Jenny, another question for you. What regulatory authority challenges impact the conduct of vaccine trials in Asia?

Jenny: While regulations in Asia have been evolving with speed to adapt to the trends, some of the fairly recent concepts such as decentralized clinical trial principles or the use of digital technology. Artificial intelligence is one, evolution of medical technology, as well including the use of wearables to track real-time medical data may impact on the regulator's speed to review, and confidence to approve the trials with speed. Additionally, regulators have given much attention, actually to quality of data and participants rights and welfare. Thus recruitment of high number of participants in vaccine trials may increase the scrutiny through regulatory inspections.

Kari: Thank you, Jenny. Pivoting now to the contributing factors to Asia-Pacific being recognized as the hub for vaccine development. Another question for you, Jenny, what has contributed to the attraction of Asia-Pacific to run vaccine trials?

Jenny: I went actually across a paper that described the 10-year retrospective review of the WHO clinical trial database. That was published in a prospective and clinical research paper in 2019. In this study, it showed that there was a sevenfold growth in the number of clinical trials in Asia, which translated to about 125,000 registered trials conducted. This number represented about 28% of all registered trials in the WHO database. It also demonstrated an increase in trial in some of the Asian countries.

For example, in Thailand, there was a 14% increase in this trial. In South Korea about the same 13%, and in Malaysia, 8% from that period of 2008 to 2017. Allow me to also cite the data for the Philippines. The Philippine clinical trial registry that was established in 2012 listed more than 600 trials in that database over a period of 12 years. There's a notable upward trend in the number of clinical trials from 2019 to 2021, which gives an average of what? 66 trials per year in this country. This increase in the number of clinical trials is driven by several factors that make Asia-Pacific a destination for vaccine trials.

We know that Asia-Pacific region is a host for more than 4 billion people, which represent 60% of the world's population. There's also large number of treatment-naive participants or individuals. If you combine this with the presence of heterogeneous population, it makes these characteristics attractive for vaccine trials. Couple this with also the research environment for vaccine requiring large study population, there's a rich trial experience in these regions as well.

Enthusiastic investigator is another factor. The high success rate in recruitment delivery, high retention of participants in the clinical trial, and as such, the high compliance to protocol required visits. In parallel, the improvement in the regulatory landscape and increasing investment in trial infrastructure and the lower cost of running clinical trials, are all contributory factor in the attractiveness of the region for vaccine trials.

Kari: Great. Paul, next question for you. For Australia, what are the regional advantages for biotechs to leverage to accelerate their Phase I study?

Dr. Paul: Thank you. I think Jenny's outlined a lot of those for Asia-Pacific that apply well to Australia. We know to do clinical trials well, there's a lot of moving parts and you need a lot of different groups with unique expertise to really work well together to get the most out of your clinical trials. I think Australia is well-positioned to have that. As COVID for an example, I think we've done 36 or so COVID-19 vaccine clinical trials in this country, which puts us in the top five in terms of countries and their experience with COVID-19 vaccine studies.

One of the approved vaccines actually started this journey with the Phase I happening in Australia, so we clearly a good country for contributing to the development of particularly vaccines. I think it's across the spectrum of what you need to run clinical trials. Well, I think in terms of investigators, we have highly trained and highly experienced investigators. That experience is something that is hard to come by unless you have people working in the area, and we have a lot of investigators that have spent a long time working in this space that have a lot of experience and expertise.

We have really good sites from larger Phase I units to a lot of sites out in the community and associated with our hospitals, for example, that do a great job of successfully running these sorts of studies. We have great CROs to support those sites and we know that you really need to have a lot of really good support and CROs that you can trust and work well together in terms of being an investigator or a site, so we're fortunate there.

In general, we have a very good healthcare system like the majority of the Asia-Pacific, I guess would be in the same situation there. We have a lot of academic and industry collaborators, so we can get a little bit more out of our studies and know that we have the support there, should that be required. We have a regulatory system that I think is well set up. For this it's appropriately rigorous that you can trust it and know that the decisions are being made on the right grounds, but it's also agile enough that things are turned around quickly enough and it's not an unnecessary barrier to getting through your clinical trials.

Most importantly, I think we have an engaged population, people that are typically keen to come along and participate in clinical trials and particularly with our vaccine studies, usually for the right reasons because they want to help develop these products, and so things like appropriate recruitment and as already mentioned, retention is really important. We tend to have high rates of both of those, so we can successfully do our studies as planned on time safely and successfully. I think like most parts of the region, we are really well set up to do that.

Kari: Thank you. Babaji, further to this, how does the USFDA view Phase I data from Australia? Can data from Phase I trials in Australia support an IND application? Is it true the other way around?

Babaji: It's an interesting question. We get asked this question all the time. I have been personally involved in doing a number of regulatory submissions for the USFDA, and also to their [unintelligible 00:28:34] in Australia. In general, USFDA looks at the Australian clinical trial data quite favorably for a lot of reasons. One of them is the Australian clinical trials are obviously, they're conducted to the global ICH-specific guidelines.

Australia has this diverse patient population, which in general represents the US one in terms of ethnicity, and also Australia, as Paul mentioned, has very good clinical trial facilities and infrastructure. We also have good, well renowned and accomplished KOLs, key opinion leaders to help sort these clinical trials out. Even the other way around from my experience, the USFDA, the clinical trial data obtained in the US is very well-accepted and recognized by the Australian Ethics Committees, as long as of course, these clinical trials are conducted to the global ICH-specific guidelines.

Kari: Sushant, from a South Korea perspective, what has changed in recent years to support vaccine development?

Dr. Sushant: Good question. I think from South Korea, I'll probably divide that into three major categories. One is from the vaccine manufacturer's side and I can talk about that. Second is from the support from the government, and third is the regulatory situation in the country. If you know about South Korea vaccine industry, probably 10 years back, they had the ambition to play the global role, but there were not many companies. If you see post-COVID and just before COVID, there are a lot of companies in Korea which have products which are licensed beyond Korea. They certainly have the global ambitions. The target from the government is to make the Korean biotech industry as one of the top five in the world, especially focusing on the vaccines.

I think that's working out quite well. We did not have a lot of collaboration before COVID-19 with the Korean vaccine industry. Now we are working very closely with the Korean government, with the Korean manufacturers, and we can see that the Korean companies are going to play a larger role in the global public health in the coming years or probably next decade or so.

From the Korean government side, after the MERS and SARS outbreak in South and Southeast Asia, and the MERS outbreak was right here in Korea. Korean government started to invest a lot in their vaccine industry as well as the biotech industry. I think that investment is what's emphasized during the COVID-19 response also. Korean government is supporting the vaccine manufacturer. They are playing the role in the global entities, whether it's IVI, WHO, GAVI, UNICEF, or MSF. They are playing a role in that.

I think they will continue to contribute in that development. From the regulatory perspective, I think recently, the KMFDS, which is the NRA in Korea, was recognized or assessed as the maturity level 4. Which means that any manufacturer who is located in Korea can export the products outside and the prequalification can happen. Having this ML4 for recognition for MFDS will pave the way for a lot of additional vaccines that can be shipped or that can be produced in Korea and shipped for the global public health.

I see this to be a three-way strategy from a Korea side, and I certainly see a lot more opportunities and a lot more scope for the Korean vaccine manufacturers.

Kari: Great. Jenny, do you have any examples of how biotechs have been able to springboard their global vaccine program by incorporating Asia sites?

Jenny: Absolutely. Let me share the success of our Phase II/Pre-COVID vaccine trial with a target of 7,000 participants in the Philippines. Philippines is one of the three countries participating in this particular trial. The proportion of recruitment allocation at the onset of the planning of the trial was 40% to the Philippines and 60% to the other two countries.

However, there was some skepticism from the sponsor as Philippines was unfamiliar territory to them, and the lack of confidence in the regulatory and ethics approval process for the COVID-19.

At that time, the FDA of the Philippines was not very transparent in terms of what's the definition of a fast track for COVID-19 trials. However, this skepticism eventually turned into confidence as Philippines was able to obtain regulatory approval faster. The first country actually to initiate the recruitment. Eventually, the sponsor decided to reallocate the additional recruitment target to the country to shorten the overall recruitment timeline. The end result, Philippines was able to deliver 70% of the global recruitment target and in six weeks time only. This delivery performance demonstrated value for the inclusion of Asia sites in the clinical development plan of vaccines.

Kari: Great. Thank you all. As we wrap up, let's discuss some key considerations for preclinical and clinical planning. Babaji, first question is going to be over to you. In terms of defining a robust preclinical program, what non-clinical safety and toxicology aspects need to be considered?

Babaji: Thank you, Kari. This is a very interesting question. We get this question asked all the time by our clients. When it comes to designing preclinical studies or preclinical program to support your clinical program, I would say, know your product very well first and do your homework. Follow the original as well as global or international guidelines on non-clinical CMC and clinical requirements for vaccines to support your clinical studies in humans.

When you do clinical trials, essentially, you've still got to conduct first your proof of pharmacology studies, immunogenicity studies, safety studies to support your clinical application. There are guidelines. There's a guidance published by the USFDA, as well as EMA and internationally by WHO on non-clinical CMC and clinical requirements to support vaccine studies.

In case when there is no regulatory guidance published, or in case you need a product-specific guidance, then I would say you can still follow the general scientific principles outlined in these current guidelines, or you can just reach out to any major global regulatory agency, seeking their advice on adequacy of your non-clinical data package. For example, the USFDA, they offer what they call an INTERACT meeting or pre-IND meeting to review your non-clinical data package or your overall clinical strategy and give you an advice on whether the package is adequate or not, to initiate a clinical trial.

Kari: Follow-up question for you. When looking at developing vaccines against new virus strains, can platform technology accelerate non-clinical development for already approved vaccines?

Babaji: It's a very interesting question. Platform technologies can certainly be used to leverage some of the clinical safety and efficacy data established with your prototype vaccines to support or accelerate the clinical development of your modified vaccines or subsequent vaccines. Platform technology is basically a machinery or a tool that effectively delivers an antigen, enhances its immunogenicity. Essentially, what you've got to do in the beginning is, establish the proof of concept and safety of these platform technologies.

When you make a slight change in the antigen or you modify vaccines, then all you got to do in this case, being just upbridging or abbreviated pharmacology, immunogenicity studies to support the clinical trial application of the modified vaccine. From my experience here at Novotech and I am working with a number of clients, we have seen this approach being very well-accepted by the regulatory agencies around the globe, for mRNA vaccines, DNA vaccines, even personalized cancer vaccines that used plasma DNA or lipid nanoparticles as a platform technology.

USFDA actually also has published a guidance on public health emergency use of vaccines where they have stated that if you are developing a modified form of vaccine against a new viral strain, and as long as you keep the manufacturing process same, then you can submit an abbreviated data package with just the pharmacology and immunogenicity studies with your modified vaccine without having to repeat concepts of toxicology studies, which may take time and it costs some money as well.

Kari: Thank you. Paul, are there any specific technology and pathway considerations for GMO products in Australia?

Dr. Paul: Yes, thanks. A little bit like our general regulatory environment. We're very fortunate to have a robust regulatory environment for GMOs. We have an office of the gene technology regulator that has well-established pathways, different pathways for different types of GMOs, but there is one that we use for GMOs that are going to be used for clinical purposes, which involves being planned to not be intentionally released into the environment and because a lot of other countries and sponsors may not be familiar with that. We have a lot of IBCs or Institutional Biosafety Committees that are approved and able to provide support this, work with sponsors to put in all the right documents that we need to get that approved.

I guess we are very fortunate that we also have sites that are familiar with the rigors of conducting clinical trials with GMOs. I've worked with those IBCs to help support the approval process, document development, et cetera, and are very familiar with the conduct of those studies so we can be assured that that regulator will be satisfied when they come and do visits and make sure those sites are well set up. We have sites that have done a lot of that work and so we can be confident that they'll be able to do that successfully.

Kari: Great. I have a follow-up question for you, Paul, there. Jenny, I think your expertise would be good here as well. If you'd like to follow up after Paul, what key patient population considerations are needed to best support rapid patient enrollment for vaccine trials?

Dr. Paul: Thanks. It's always a bit of a balance when we are looking at what patient populations to put in. We obviously want to try and have healthy volunteers and the healthier, the cleaner, the data. We also want to try and incorporate a population that's very representative of who the intended population to receive the investigational product or vaccine will be once it's approved.

I think COVID has accelerated our ability to have adaptive design and broader protocols to include different cohorts. For example, commencing with healthy volunteers and once their data supports are progressing to, adding in different demographics, whether it be increasing age starting to permit comorbidities to be, people with comorbidities to be enrolled, for example.

As I say, you don't want to have a population that's too clean in your study so that we don't know how the product or vaccine's going to perform in the real world. You also don't want to start with populations where there might be too many confounders. I think that's been something that has been accelerated by COVID and that we often do well in our clinical trials.

Kari: Thank you. Jenny, did you have anything to add to that?

Jenny: Yes, if I may add on that, Kari. Rapid enrollment for vaccine trials requires really a careful assessment of several factors. One of that Sushant has mentioned earlier, but in the context of mass vaccination. In clinical trial also, the population's uptake on vaccine or maybe the familiar terminology is vaccine hesitancy, which may impact on the success and the speed of recruitment. Another is the openness of the government actually, or the institution where the site is located and supporting the health research vis-a-vis addressing certain beliefs of the community, such as [unintelligible 00:40:44] use as guinea pigs in research.

Additionally, the receptiveness of vaccine trials differ from other therapeutic areas such as oncology, where largely due to the lack of the need for an immediate treatment option. As such, the government or medical researchers' effort to foster appropriate knowledge about the clinical trial is an important factor. Another is the involvement of vulnerable populations such as pediatric or the elderly that may require special attention or the additional process that may be driven by ethics regulations. For example, additional timeline may be needed to secure assent from the pediatric population or consent from the legal representatives.

When carefully planned and recruitment process and flow at the site are tested prior to the actual recruitment initiated, these additional steps may actually not necessarily impede the speed and ability of the sites to recruit participants for the vaccine trials. Lastly, if I may share the understanding of government vaccination program also in the location where the vaccine trial is planned is going to be conducted is an important consideration to ensure that there would be no conflict or overlap with the vaccine used in the clinical trial. This was particularly an important consideration during the conduct of the COVID vaccine trial and the simultaneous rollout of the government of COVID vaccination programs.

Kari: Paul, back over to you. Having been a PI on many vaccine clinical trials, what do you find the most attractive and interesting in a new vaccine IP?

Dr. Paul: That's a great question. I think what we get most excited about is when there's a really exciting mechanism of action that will address an unmet need, for example. We've mentioned a few of the vaccine types that we're most excited about, intranasal, for example. I guess associated with that is a biological plausibility that's likely to be both safe and effective and ideally if it comes with preclinical data, that suggests that is in fact the case. Seeing a vaccine that has a novel mechanism of action that it looks like it's going to do something in addition to what we've already got with great preclinical data certainly does get us excited and keen to take something into the clinic as quickly as we can.

Kari: Thank you. One last question for the group. Considering what we've heard today, what is your key piece of strategic advice for a biotech to support asset development in the current climate? Paul, do you want to take the first crack at that and then pass on to somebody else?

Dr. Paul: Thanks, look, another great question. I think it's really clear we've learned a lot of lessons from COVID. We've seen how we can do this a little bit better, a bit more quickly. I think one of the main things there is collaboration and working together and that goes across, I guess, clinical trial sites, academia, industry, for example. I think that's something that we really need to continue doing as much as possible, even as we now transition to perhaps a non-pandemic state of the agency, might not quite be there and I guess apply those same lessons to other pathogens and even potentially for investigational products outside of infectious diseases.

The other thing is we have a lot of great teams, CROs, sites, investigators, for example. I think it's really important to involve those people early to come up with the right design to make sure that you're approaching the right sites to successfully conduct your clinical trials. Again, just reaching out to people who might be able to help you as quickly as possible, so that you get off on the right foot.

Kari: Anyone else like to add to that?

Babaji: I can go next. I agree with Paul. I would just like to summarize stressing on three points. First is, know your product very well because the drug development strategy and regulatory strategy is customized to an individual product. Second, I would say follow the regional as well as global or international guidelines on non-clinical CMC or clinical requirements to do all the studies and initiate a clinical trial.

Third thing I would like to say is, if you're not sure, just reach out. Reach out to any global regulatory agencies and seek their guidance and advice on adequacy of your non-clinical data package to support your clinical studies or reach out to CROs or consultants who specialize in that particular area of vaccine development. This will not only just de-risk your program, but will also give you a higher chances of regulatory success. Doctor Sushant, do you want to add anything?

Dr. Sushant: A couple of things. If we had to draw some silver linings from this terrible tragedy that was happening over the last couple of years. One of the thing is now almost everybody in the general population knows what different vaccine types are, knows about various stages of clinical trials, and there is a lot more awareness about vaccine development, vaccine delivery than that was before 2019, which is a great thing.

At the same time, it can be a double-edged sword. That means lots of people know about that, and that's probably going to be not a complete knowledge. There are a lot of errors that are done from people side, when there is a judgment in terms of half-knowledge. I think what we need to do as a community is to keep that momentum on the vaccine science and vaccine policy being discussed in the general population in the general forum.

At the same time, as Babaj mentioned, we need to really from, the onus lies on the companies or the biotech to know the disease quite well, that they're developing the vaccine against, to know the product or platform quite well, and as Babaj mentioned, to really know the community, the regulators and be more, or should I say, aggressive in terms of the development of various clinical development strategy. I think there is more openness now from the regulators and as from the public for these kind of initiatives.

Jenny: If I may top up that Kari, I would say the careful selection of partners or for the biotech company with really strong footprint across the geographies, and having the bandwidth of expertise that would complement really, the biotech companies on in strategically mapping their clinical development of their assets.

Kari: Thank you. That's all the time we have for today. Thanks to everyone in the audience for tuning in, and thanks to our panel for sharing their time and expertise. We appreciate Novotech for sponsoring the discussion at Endpoints Webinars. Again, today's webinar will be available to watch and share with colleagues on demand starting tomorrow. All registrants will receive an email from zoom with access instructions.

I'm Kari Abitbol for Endpoints News. Thank you for joining us, and we hope to see you at a future Endpoints Webinar.

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