SO MUCH WINNING!:

Now, in the final days of the Trump administration, their "MP2" -- later redubbed "Operation Warp Speed" -- occupies a peculiar place in the annals of the administration's ill-fated response to Covid-19: In many ways, it was successful, living up to the highest expectations of its architects. The Trump administration did help deliver a pair of working vaccines in 2020, with more shots on the way. But the officials who expected to be taking a victory lap on distributing tens of millions of vaccine doses are instead being pressed to explain why the initiative appears to be limping to the finish.

Governors say the Warp Speed effort has made promises it didn't keep, with deliveries of doses falling short and reserve supplies exhausted. Physicians and logistics experts have critiqued the disorderly rollout, arguing that the Trump team should have done a better job of coordinating the nation's mass vaccination effort. The incoming Biden administration on Friday morning announced they'd even do away with the initiative's branding, which President Donald Trump has touted for months.

Operation Warp Speed "is the Trump team's name for their program. We are phasing in a new structure," tweeted incoming White House press secretary Jen Psaki, adding there's an "urgent need to address failures of the Trump team approach to vaccine distribution."

It's a deflating end for the Trump officials who conceived of Operation Warp Speed last spring, hanging themed posters inside the health department that boast the slogan "Because Winning Matters!"

POLITICO spoke with 11 officials closely involved in the conception of the vaccine project, in addition to other government officials and outside advisers, about how that optimistic vision of "MP2" became "Operation Warp Speed" -- and where the rollout went astray in recent weeks. Many expressed frustration and disappointment, but also a faith that the long arc of history will prove they succeeded -- pointing to data that roughly 1 million Americans per day are now getting vaccinated under Trump's watch, ahead of President-elect Joe Biden's own vow to accomplish the same.

The recent news about distribution problems "just sucks," said one health official. "This time it was supposed to be different... it still can be."

A U.S. defense agency that specializes in turning science fantasies into realities jump-started technologies and nurtured companies that are now at the forefront of the response to the COVID-19 pandemic.

The Defense Research Advanced Projects Agency (DARPA) has taken risks where others wouldn't. Its pursuit of high-risk, high-reward technologies, combined with its mission-driven approach to managing projects is promising to pay off in the fight against COVID-19.

DARPA was behind the creation of DNA and RNA vaccines, funding early R&D by Moderna Inc. (NASDAQ:MRNA) and Inovio Pharmaceuticals Inc. (NASDAQ:INO) at a time when the technologies were considered speculative by many scientists and investors.

The military R&D agency believed nucleic acid-base vaccines could be developed much faster than conventional technologies. Its funding, project management and vote of confidence helped de-risk the science and attract investments and partnerships.

NIH selected Moderna as its partner for COVID-19 vaccine development. This week, an RNA vaccine produced by Moderna became the first COVID-19 candidate vaccine to be administered in a Phase I trial.][...]

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DARPA deserves at least part of the credit for the fact that it's no longer an extraordinary idea to encode an antigen in DNA or RNA so the human body can create the protein, rather than injecting the antigen as part of a conventional vaccine.

When DARPA began pursuing nucleic acid vaccines in 2011, it was far from clear that they would work.

"A lot of people said that would be great if it works, but we don't think it could work, there are too many things that can go wrong," Amy Jenkins, a program manager in DARPA's Biological Technologies Office, told BioCentury. She said DARPA scientists concluded "there are scientific reasons why it may not work, but there are also scientific reasons why it may work, and that's absolutely the right place for DARPA to be investing."

Jenkins highlighted DARPA's high tolerance for risk. "It was something that was much too risky for groups like the NIH to fund."

In addition to a high risk tolerance, DARPA operates on a very different model than NIH. Instead of giving multi-year grants that require only periodic progress reports, it awards milestone-based contracts.

DARPA project managers like Jenkins speak with the groups they fund "once a month, sometimes even once every other week, and during something like the coronavirus [outbreak], almost once a day," she said.

Another difference from NIH is that DARPA is highly focused on achieving its goals, not on advancing science. "We monitor progress closely, but we don't necessarily chase science where it wants to take us. We stay laser-focused on building the capability we need to build. If the path we were taking to getting that capability is not working for scientific reasons, we divert and we take a new path to that same capability."

CureVac AG became one of the first RNA vaccine companies, in part because of DARPA funding; it was one of the agency's early bets on the technology. CureVac was also one of the first companies to begin work on a COVID-19 vaccine.

In November 2011, DARPA awarded a $33.1 million contract to a collaboration among CureVac, the Sanofi Pasteur unit of Sanofi (Euronext:SAN; NASDAQ:SNY) and In-Cell-Art S.A.S. to advance CureVac's RNActive technology platform and evaluate vaccine candidates.

CureVac demonstrated proof-of-principle in a Phase I trial launched in 2013, when its mRNA-based rabies vaccine induced antibodies when delivered with a needle-free device. The study was reported in the Lancet.

CureVac was founded in 2000 and had raised about $84 million at time DARPA selected it to lead the consortium.

DARPA also played an important role in helping Moderna establish its mRNA platform, awarding the biotech a contract for up to $25 million in October 2013. In addition to a vote of confidence for an edgy technology, the DARPA award added non-dilutive funding to the 2012 $40 million venture funding from Flagship Pioneering.

Moderna raised over $600 million in a 2018 IPO and has a market cap of $11.6 billion.

DARPA's funding was directed towards Moderna's development of RNA vaccines against the chikungunya and Zika viruses.

Moderna's Phase I trial of a chikungunya vaccine, completed in September 2019, was an important inflection point for the platform and for RNA vaccine technology. It was, the company reported, the "first systemic mRNA therapeutic to show production of a secreted protein in humans."

"The researchers have demonstrated that it is feasible to use mRNA sequences to produce and scale a highly potent antibody response against an infectious disease target," said DARPA's Jenkins in a statement released in September 2019.

Jenkins added that Moderna's chikungunya vaccine results were encouraging validation of the "prospects of creating a new, platform-based prophylactic and therapeutic approach that might better protect civilians and service members alike against the relentless threat of pandemic disease."

In addition to RNA vaccines, DARPA helped advance DNA vaccines from concept to reality.

In 2015, the agency allocated $45 million to a project led by Inovio to develop a vaccine and therapies for Ebola. The program funded development of a DNA-based mAb, a conventional protein-based mAb and a DNA-based vaccine.

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