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Rajeev Venkayya MD Profile picture
Rajeev Venkayya MD
@rvenkayya
CEO, Aerium Therapeutics; CEPI & IAVI Boards. Fmr Head Takeda Vaccines; Fmr White House & Gates Foundation; Pulm & Crit Care; @ucsf @umich; views mine.
4 subscribers
Jul 29, 2022 • 4 tweets • 5 min read
I'm excited to share new data showing that one of @AeriumTx's monoclonal Abs (P2G3) is as potent as Bebtelovimab at neutralizing *all* SARS-CoV-2 VOCs to date, including BA.4/5.

Phase 1 begins in August. 1/

biorxiv.org/content/10.110…

@Turelli_EPFL @Trono_Lab @CHUVLausanne Image While P2G3 is similar to bebtelovimab, there are important differences. Virus escape studies show that P2G3 neutralizes BA.4 viruses that "escape" bebtelovimab, but bebtelovimab does not neutralize P2G3 escapees. CryoEM helps explain the different behavior. 2/ @Turelli_EPFL ImageImage
Aug 26, 2021 • 5 tweets • 2 min read
This is why monoclonals are a linear tool in an exponential fight:
- Hard to scale, esp when HCWs are in short supply, and linear relationship between patients:resources; and
- They don't touch transmission, so exponential growth quickly outstrips treatment capacity. 1/ An exponential fight requires exponential weapons that control the transmission driving exponential growth: vaccines for all eligible, universal masking, TTI, ventilation, etc. This makes it possible for treatment capacity to keep up with demand. 2/
sun-sentinel.com/coronavirus/fl…
May 6, 2021 • 13 tweets • 4 min read
It was good to discuss this with @HelenBranswell. Patents aren't a constraint to access. These things are:
🔹Lack of capacity at originators to support more tech transfers;
🔹Partners w/proven global vaccine manufacturing experience; and
🔹Raw material/component shortages. 1/ Scaling up vaccine manufacturing is *far* more complex than HIV medicines or other drugs. And the safety and benefit/risk calculation is completely different because vaccines are given to healthy people including children. 2/
Apr 6, 2021 • 9 tweets • 4 min read
THREAD

In light of the situation in #Brazil and reports of more severe #COVID19 in young persons, we should consider whether antibody-dependent enhancement (ADE) is playing a role.

It has important implications for the rest of the world. 1/🧵

nature.com/articles/s4156… In ADE, an initial mild infection can be followed by more severe illness upon reinfection. Non-neutralizing antibodies are thought to play a role. The potential mechanism for #SARSCoV2 is likely different from #dengue. See "b" ⬇️

Antibody-independent mechanisms also exist. 2/ ImageImage
Mar 31, 2021 • 8 tweets • 3 min read
THREAD

Some say life will only get better at a "herd immunity" threshold, others say we only need to vaccinate high-risk people.

Bottom line: every additional person vaccinated helps everyone in the community, *including those already vaccinated.* 🧵 1/

Direct protection from vaccines (protection of the vaccinated person) goes a long way toward limiting illness and death, but indirect protection massively amplifies the impact. Here’s a good explainer from @ZoeMcLaren. 2/

Mar 4, 2021 • 13 tweets • 4 min read
THREAD: Vaccines & transmission

The emerging, expected evidence that #vaccines reduce transmission is a game-changer, but the focus on herd immunity can give the impression that we won’t see a benefit until most are vaccinated. Not true. 1/ @apoorva_nyc
This thread describes a world in which vaccines reduce transmission. Early evidence is promising, although more data is needed to understand magnitude of reduction and differences between vaccines. 2/
nejm.org/doi/10.1056/NE…
@mlipsitch @angie_rasmussen
nytimes.com/2021/02/23/opi…
Feb 21, 2021 • 4 tweets • 4 min read
This is an excellent overview of the complexity of mRNA vaccine manufacturing.

An mRNA batch currently takes 110 days from start-finish.

“Traditional” vaccines (recombinant, vectored, inactivated) can take months longer. 1/

@eweise @kweintraub

usatoday.com/in-depth/news/… More about the complexity of "traditional" vaccine approaches below.

These timelines assume the process has been "scaled up" and everything is in place & ready to go: facility, equipment, raw materials, etc. Unexpected issues can add weeks or months. 2/

Feb 8, 2021 • 11 tweets • 4 min read
THREAD: Vaccine Escape

As variants spread and #vaccines are deployed, we’re not sequencing enough to keep up w/the virus.

As a stopgap, we should sequence viruses from every vaccinated person who develops #COVID to identify vaccine escape mutations. 1/
washingtonpost.com/health/2021/01… We call these “vaccine breakthroughs,” and we’ll see more of them as the B.1.351 and P.1 variants spread. Sequencing all breakthrough viruses will help us to track those variants and identify new mutations that might contribute to vaccine escape. 2/
Feb 1, 2021 • 16 tweets • 5 min read
THREAD: Vaccine Manufacturing

Back in October, I said the Warp Speed timelines were extraordinarily optimistic given the inherent risks of vaccine development, manufacturing and distribution. All of those risks and others have materialized. 1/
Much of the risk is in "scaling up" production to produce large volumes of vaccine in a facility, and “scaling out” to manufacturing partners to expand capacity. This thread is about vaccine manufacturing and the challenges we’ll continue to face. 2/
Jan 29, 2021 • 8 tweets • 3 min read
THREAD
In light of the exciting & sobering news from @Novavax and @JNJNews, some thoughts on implications for future vaccine development.

As I've said, the Ph3 trials will provide the highest-quality data on vaccine efficacy against the new variants. 1/ Multiple lines of evidence strongly suggest mutations in B.1.351 confer some escape from natural and vaccine immunity.

Unless shown otherwise in efficacy/effectiveness studies, we should assume this is a class effect for all spike-targeting vaccines. 2/
Jan 6, 2021 • 8 tweets • 18 min read
@BhadeliaMD @kavitapmd @ashishkjha @ASlavitt @RanuDhillon @RebeccaKatz5 Manufacturing partnerships are necessary for any company to ramp up manufacturing of #COVID vaccines, since no company has enough capacity to meet the world’s needs. Nearly all vaccines in late-stage trials have partnerships in place for this purpose. 1/ 🧵 @BhadeliaMD @kavitapmd @ashishkjha @ASlavitt @RanuDhillon @RebeccaKatz5 .@Novavax is a good example (@AstraZeneca is another). They listed their network of partners when they announced the partnership with @SerumInstIndia, with a goal of manufacturing >2B doses/yr. (@TakedaPharma is one of those partners.) 2/
ir.novavax.com/news-releases/…
Jan 3, 2021 • 18 tweets • 7 min read
THREAD
I created a simple table to illustrate the individual impact of the "flexible second dose timing" now recommended in the UK.

Coincidentally, @bob_wachter & @ashishkjha just tackled the US policy question in this important piece. 1/
I based this on recent statements from the UK chief medical officers, JCVI, and what we know from prior vaccine development. 2/

JCVI: app.box.com/s/iddfb4ppwkmt…

UK Chief Medical Officer (CMO) statement: gov.uk/government/new…

CMO letter to the profession: gov.uk/government/pub…
Jan 1, 2021 • 14 tweets • 5 min read
THREAD
There’s much debate around the UK's recommended use of the AZ vaccine with a two-dose schedule and flexible timing of second dose. Some thoughts on the AZ recommendation (not Pfizer) based on available data with refs to some excellent threads. 1/
UK’s MHRA and JCVI are highly-experienced in vaccine assessments and recommendations, and they've surely weighed the benefits & risks of this recommendation carefully. That said, it would be good to see all the data underpinning their recommendation. 2/
Dec 28, 2020 • 11 tweets • 3 min read
THREAD
As scientists race to understand the new COVID variants, we have a valuable tool at hand: multiple ongoing Phase 3 vaccine trials. These can provide valuable insights into vaccine protection as well as the natural epidemiology of the variants via the placebo arms. 1/ The first indication of whether vaccine protection is affected will come from the lab: neutralization studies assessing whether vaccine-induced antibodies are as effective at neutralizing the new variant as earlier strains of SARS-CoV-2. Similar activity will be reassuring. 2/
Dec 12, 2020 • 7 tweets • 7 min read
I've participated in some great discussions on #COVID19 and #vaccines on #Clubhouse recently. I’ll use this thread to share some references I’ve mentioned and/or plan to bring up in future rooms. @joinClubhouse 1/

@JorgeCondeBio First up is a new tool from @bhrenton that tracks #CovidVaccine allocations to US states, and *some* distribution sites, based on publicly-available sources and pending a federal tracking website. 2/

Dec 6, 2020 • 6 tweets • 5 min read
THREAD

Swiss cheese is great for explaining how to slow a virus, as @MackayIM's fantastic graphic shows.

There's a history. Dr. Carter Mecher first applied Swiss cheese to pandemics in 2006 at the White House. I told the story @statnews in April. 1/

statnews.com/2020/04/24/swi… Carter came across James Reason's work in human failures and complex systems when he worked on patient safety at the Dept of Veterans Affairs.

Swiss cheese was a good way to explain the power of early coordinated NPIs in a pandemic, which was called "community mitigation." 2/
Dec 1, 2020 • 6 tweets • 2 min read
Fully agree that a human challenge trial *would not* have resulted in an authorized/approved vaccine any sooner.

Disagree that every smart person was recommending a human challenge trial to speed up the approval process. 1/ It is not a simple undertaking to establish a human challenge model, particularly with a novel virus for which the pathophysiology is not well-understood and where a targeted therapeutic is not available for what could be a lethal disease. 2/
Nov 29, 2020 • 10 tweets • 8 min read
@bnallamo Fair question. Here are a few thoughts from a non-regulator. First, @US_FDA, led by Peter Marks and Operations Warp Speed, led by Moncef Slaoui, recognize that every day matters for HCWs and high-risk groups and are moving with extraordinary speed. 1/ @bnallamo @US_FDA An EUA (Emergency Use Authorization) for a vaccine is not the same as a therapeutic, given that the vaccine is being given to subgroups of people who are “healthy” and may or may not be exposed to the virus. The bar for safety & efficacy data is therefore higher than for Rx. 2/
Nov 12, 2020 • 24 tweets • 9 min read
THREAD
In light of the Pfizer #vaccine news, a natural question is whether it's feasible to develop “better” #COVID19 vaccines after the first ones are approved?

The answer is yes. It can be complicated but there are ways to do it. 1/

First let’s break this down into three questions:
▪️ Why might we want better vaccines?
▪️ Why would it be hard to study new vaccines?
▪️ What are the options for doing this? 2/
Nov 9, 2020 • 8 tweets • 3 min read
This is very good news indeed, and the *potential* implications go well beyond the @pfizer #COVID19 vaccine.

While we just have the press release, it's worth reviewing what this *could* mean for the pandemic and beyond. A thread. 1/

@BioNTech_Group First, it shows vaccines *can* prevent COVID illness in humans, and it validates the spike protein target. We didn't know these things before today, and it's good news for all #COVID19 vaccines in development. 1/
Oct 23, 2020 • 5 tweets • 2 min read
This is extraordinarily optimistic. To be clear, it's not impossible, and OWS surely has assumptions to support this. And yes we must be ambitious.

But many will assume and/or communicate that these *targets* are what they can *expect* to happen, when there are many unknowns and execution risks. 1/