Specialist
C-level Executive at at Replicate Bioscience Inc
Agenda
- COVID-19 vaccines’ competitive positioning and scientific discoveries – Moderna (NASDAQ: MRNA), AstraZeneca (LON: AZN), Pfizer (NYSE: PFE) and BioNtech (NASDAQ: BNTX) and Johnson & Johnson (NYSE: JNJ)
- COVID-19 vaccines' CD4 and CD8 T cell responses
- Efficacy on elderly vs young populations
- Risks and unknowns
- 2021 vaccine candidate outlook and efficacy on the new COVID-19 variant
Questions
1.
Is it fair to argue that the initial AstraZeneca results faring at around 60% efficacy is cause for concern with vector vaccines holistically, including the J&J platform? How should we reconcile these results?
2.
Has anything changed in your comparative assessment of the Pfizer, Moderna, AstraZeneca and J&J vaccine candidates? What parameters are particularly important to compare, whether antibody quality and volumes, the CD4-CD8 responses or the duration of the antibody and T cell responses?
3.
Were you surprised by the high durability of the antibodies reported by Pfizer and Moderna? You have been fairly negative about mRNA vaccine candidates when comparing Pfizer and Moderna in the past. How would you assess the assays in which we’re comparing the two, with one showing CD4 and the other not showing both T cell responses? How significant is that in our evaluation of the different vaccine candidates?
4.
You referenced Moderna and Pfizer’s T cell responses being significantly lower than those of AstraZeneca or J&J’s candidates. We’ve heard historically that the assays used and the parameters to compare measuring neutralising antibodies vs T cell responses may be a bit difficult, as the assays are different across the mRNA candidates, J&J’s viral vector and the AstraZeneca candidates. Would you agree with that, and how significant
is it that the T cell responses are lower for the mRNAs?
5.
How concerning is it that the T cell data for Moderna and Pfizer vaccines may be distorted, or amplifying a smaller pool? Is this an atypical method of analysing responses when compared with historical vaccines?
6.
How could you assess the efficacy of different vaccine candidates in accordance with patient age data? Do you expect better efficacy in the most at-risk, 65-plus elderly category as more pipeline candidates appear?
7.
Do you expect more meaningful decay to the Pfizer and Moderna vaccines with larger sample sizes? Could a candidate such as Merck’s – a company with a historically efficient uptake in the elderly – be expected to eventually replace Pfizer or Moderna as the go-to option for COVID-19? Novavax is another example which could potentially be more durable in the elderly.
8.
It seems like some of your concerns around mRNA have been assuaged with the increased data, but there are still a lot of unknowns around that method. With live-attenuated vaccines, there’s a theoretical risk of a supposed immunity to the vector. How should we consider the risks, unknowns or potential limitations across the various candidate types, be it mRNAs, adenoviral vectors or the subunit adjuvants?
9.
You mentioned that all the platforms to date have been receptive to the new variants. Do you still have doubts around the receptiveness across some of these candidates? Are you more confident in the long-term durability potential of the traditional platforms than you are for the mRNA candidates?
10.
How could this potential superior durability of traditional platforms inform vaccine uptake? We’re already noting storage and administration issues with the Pfizer vaccine, and other logistical issues with Moderna’s. How would the traditional platforms coming online impact the configuration of administration? Is that when we can expect an acceleration towards mass-scale vaccinations, in the US and worldwide?
11.
AstraZeneca is continuing with the two-dosing regimen, despite higher protection than the mRNA candidates after the first dose, as you said. J&J has shifted to a two-dosing regimen. What are the read throughs here? Does the one-dose trial result show that a two-dosing regimen is essentially better in efficacy? How does that define your expectations for J&J vs mRNA vaccines, and then other vector vaccines?
12.
Is it fair to summarise that two doses offer a better response in immunity, but essentially a one-dosing regimen would be preferable for eliciting greater protection? Do you envisage any pipeline candidates faring better with the one-dosing regimen than J&J and AstraZeneca, or that they could even lead with a one-dose?
13.
Where would comparatively shorter durability and a need for this third addition to the regimen or booster shot situate mRNAs vs ex-mRNA candidates? Would you eventually expect a phasing out of first-generation mRNA candidates, or a reformulation of the dosing regimen to expand that durability?
14.
How do you define a shorter vs a sufficient period of protection, to contextualise the mRNAs potentially having shorter durability? Is this all relative to what other pipeline candidates demonstrate, or is there a defined time frame – whether six months-plus or one year – that you would consider a long duration?
15.
We have discussed the concept of antibody-dependent enhancements in previous Interviews [see COVID 19 Vaccines – Q4 2020 Update – Johnson & Johnson, Pfizer, Novavax, Moderna, BioNTech, Inovio & AstraZeneca – 29 September 2020]. This is especially key in the context of discussing poor durability, and the period where the patient can essentially be more susceptible with the waning antibody responses. Is there a specific risk with antibody-dependent enhancements relating to any of these vaccine candidates?
16.
Would you describe Novavax demonstrating little-to-no CD8 responses as being particularly concerning?
17.
Some literature theorises there is potential for an autoimmune reaction with mRNA candidates. As it administers cells that produce the antigen, it’s unclear how many times the recipient can get their own host cells to produce an antigen for their own immune system to attack the antigen. Do you think this is a major concern – if not with the initial vaccinations, than with secondary booster vaccinations, or even a third potential round of vaccination with the mRNA?
18.
What do the new COVID-19 strains originating in the UK and South Africa imply for efficacy across candidates, particularly vector vaccines vs mRNAs?
19.
We discussed Novavax’s lack of CD8 responses in the context of the antibody-dependent enhancement mechanism. How should we frame it in the context of overall efficacy? To what extent is this a concern here?
20.
Are there any further key outstanding differences across the various candidates that we have yet to touch on today? How are you segmenting the individual mRNA candidates vs the DNA platforms, in particular?
21.
Is it fair to argue that the initial AstraZeneca results faring at around 60% efficacy is cause for concern with vector vaccines holistically, including the J&J platform? How should we reconcile these results?
22.
Can we conclude with your assessment of the logistical and administration delays associated with the vaccine roll-outs in the US and the UK?
