Specialist
Former divisional head at German Centre for Infection Research (DZIF)
Agenda
- Review of genetically engineered vaccine candidates, and key advantages over inactive and live attenuated
- DNA, recombinant and protein subunit vaccines and their potential in COVID-19
- Key advantages of mRNA vaccines and remaining hurdles in delivery, formulation and capacity constraints
- Case studies on Moderna (NASDAQ: MRNA) vs CureVac vs BioNTech (NASDAQ: BNTX)
Questions
1.
Based on our chat ahead of this call, you seem to hold a contrarian perspective on the COVID-19 coronavirus vaccine development programmes. To kick us off, how are you looking at the situation today?
2.
It seems you’re saying the vaccine is as good as the antigen used, and therefore there may be little difference in efficacy across the different platforms, whether we’re talking DNA or mRNA, as all are using the same antigen. Can you dive deeper into that? As a follow up, to what extent is demonstrating pre-clinical immunogenicity a very low hurdle, and not predictive of real-life human efficacy?
3.
It’s well-documented that cellular immunity protects from Sars [severe acute respiratory syndrome] and Mers [Middle East respiratory syndrome]. It seems that DNA and mRNA vaccines induce both the humoral and cellular immune response, so on paper they should be effective in COVID-19? Or is the real question around whether they can induce the appropriate cytotoxic T cells?
4.
What are the safety signals we should be paying attention to, and how are regulatory authorities approaching that? By way of example, during the Ebola pandemic, a live vector vaccine was injected into patients without any knowledge of the long-term safety data. Today, do you expect the regulatory authorities to likewise go ahead without long-term safety precautions?
5.
Moderna’s lead mRNA vaccine candidate, as you’ve highlighted, is likely to elicit a double-adjuvant effect and also a potentially worse safety profile than non-mRNA platforms. What does that mean for the timeline before it hits the market? Are we likely to see a lag given the need for additional safety data that we might not need for some of the more traditional vaccine technologies?
6.
Moderna dosed its first patients in the clinic in mid-March. What do you think is the risk that, by the time we get all the data and manufacturing is scaled out, this particular pandemic may have died out, to the point regulators will re-instate all the typical standards?
7.
It seems key advantages of genetically engineered vaccines over traditional live attenuated and inactive vaccines are the versatility and the very fast GMP scale-out. But within this category of genetically engineered vaccines, what are the respective advantages and disadvantages of the different technologies?
8.
Is there a difference between DNA and mRNA vaccines in manufacturing cost or the cost per dose?
9.
How hard is it to scale production of lipid nanoparticles for these mRNA vaccines?
10.
No mRNA-vaccine trial has ever fully read out. When the data is released, what should we pay attention to? If we’re not going to get any conclusive efficacy data, what data will we actually get?
11.
Moderna, CureVac, BioNTech and Translate Bio have all publicly announced they have mRNA assets in the clinic. Is there any differentiation across their programmes?
12.
The purification stage is critical for mRNA vaccines to the extent that longer or shorter strands can elicit an undesired immune response. Is this an area where one player may have an edge here, whether on overall product purity or better quality control technology?
13.
Are mRNA players able to effectively bring these products to market or will they need to partner up?
14.
We’re just on the hour, so before we end the call, do you have any closing thoughts?
