Novavax’s Effort to Vaccinate the World, From Zero to Not Fairly Warp Pace

On a sweltering June morning, Novavax CEO and covid vaccine maker Stanley Erck stood on a stage unmasked and did one thing that will have been unthinkable six months in the past: He shook arms with Maryland’s governor.

Erck was with Gov. Larry Hogan to announce Novavax’s international vaccine headquarters ― a campus anticipated to deal with laboratories and greater than 800 staff. Hogan known as Novavax’s future “shiny” and marveled that greater than 71% of the state’s adults had acquired at the least one shot.

None of these was a Novavax vaccine, which continues to be unavailable for the American public attributable to delayed scientific trial outcomes and different difficulties. Hogan, for his half, acquired his first vaccine dose ― made by fellow biotech upstart Moderna ― in January.

“As you may think about, we’re wanting to obtain our personal,” mentioned John Trizzino, Novavax’s chief business officer and interim chief monetary officer. Its two-dose covid vaccine, which confirmed general 90.4% efficacy in key U.S. and Mexico trials, has but to be licensed. “Within the meantime,” Trizzino mentioned, “we’ve had to make use of one of many present licensed vaccines and we look ahead to the booster” made by Novavax.

Wanting ahead has saved Novavax afloat for many years ― together with its deep ties to grant makers and federal businesses. With its deal with creating vaccines, together with for the SARS and MERS pandemics, Erck argues Novavax is “constructed for this second.” Nonetheless, the 34-year-old startup has by no means introduced one to market.

Novavax’s quest to scale up operations underscores how troublesome it may be to launch a vaccine ― even with the system and expertise in hand. So what occurred? It has had the monetary backing of the U.S. authorities and full religion of worldwide businesses. Every part took longer than anticipated: hiring mandatory researchers and scientists, getting provides and transferring its vaccine expertise. It didn’t transfer at warp pace.

America is awash with vaccine choices, and Novavax doesn’t plan to file for regulatory authorizations till late July on the earliest. The delay might have dire penalties for folks throughout the globe awaiting a vaccine.

“We’re not making aspirin,” Trizzino mentioned. “We’re making a really difficult organic.”

A Moonshot Aim

A yr earlier than the covid pandemic hit, Novavax had a failed late-stage trial on a possible respiratory virus vaccine, after which it reduce its workforce and offered off all its manufacturing capabilities. So, when greater than $2 billion in federal and worldwide funding landed at its doorstep, Novavax discovered itself creating each “a vaccine and an organization” in 12 months, mentioned Dr. Gregory Glenn, president of analysis and improvement.

Novavax’s proprietary secret ingredient is Matrix-M, an immune booster. Executives say the additive ― derived from Chilean soapbark timber ― works so nicely that much less of an antibody-producing antigen could be wanted with it in a vaccine. One monetary submitting mentioned Matrix-M “has the potential to be of immense worth.”

Outfitted with its recombinant nanoparticle vaccine combined with Matrix-M, Novavax deployed a core staff of staff, dubbed “SuperNOVAs,” to crisscross the globe. They assembled a producing community and shared vaccine expertise in India, South Korea, Spain, Japan and the Czech Republic in addition to in america ― about 20 contract manufacturing and check websites in all.

“This takes time and experience,” Trizzino mentioned. “You simply merely can’t hand over the recipe after which stroll away from it and anticipate you’re going to have a high-quality product.”

Novavax is contracted to kind the spine of the COVAX initiative, having promised 1.1 billion doses beginning this yr for creating nations. And whereas President Joe Biden introduced the U.S. would donate 500 million doses of the Pfizer-BioNTech vaccine overseas, Novavax continues to be seen as very important to pressing efforts worldwide to battle the virus and its variants.

Novavax’s moonshot purpose of manufacturing 2 billion pictures a yr more and more seems to be like a pipe dream for 2021. “It is extremely exhausting to simply accept that they may make 2 billion doses as that they had initially dedicated. I’m very skeptical,” mentioned Prashant Yadav, a well being care provide chain knowledgeable and senior fellow at Harvard’s Middle for World Improvement.

One in all Novavax’s largest challenges, Yadav mentioned, is counting on “so many websites” that aren’t absolutely beneath its management, whereas different producers personal their vegetation. The extra locations Novavax produces the vaccine, the more difficult it’s to verify the vaccine and its parts are comparable in each place.

When Novavax executives introduced one other delay in Might, the corporate’s inventory plummeted to $121 a share ― down 62% from a excessive of about $319 in February. As the corporate’s fortunes rose final yr, Novavax executives cashed out tens of hundreds of thousands of {dollars} in frequent inventory, in keeping with securities filings. Final yr, after the corporate benefited from grants and authorities contracts, CEO Erck offered $9.3 million in firm shares, Glenn offered $14 million, and Trizzino offered $11.3 million.

These high executives continued promoting in 2021. Erck offered greater than $22.5 million price of frequent inventory in early July.

Novavax executives use buying and selling plans, and the gross sales usually seem on the identical time every month. In June, after Novavax introduced its long-awaited U.S. and Mexico scientific trial outcomes, Glenn offered greater than 8,000 shares for $1.5 million. As a measure of the corporate’s spectacular rise within the pandemic, Glenn bought 1,000 shares of inventory in December 2016 for the worth tag of simply $1,446.

Novavax spokesperson Amy Communicate mentioned the corporate has packages in place to make sure finest practices on inventory gross sales. “Most individuals, together with our executives, promote inventory for all kinds of causes,” she mentioned, including that Novavax’s executives have “usually offered a fraction of their general holdings within the firm.”

Charles Duncan, a biotechnology analysis analyst at Cantor Fitzgerald, known as Novavax a “present me” funding in Might. “It’s one factor to have a spot to make it,” he mentioned. “It’s one other factor to have the ability to make it there and get it licensed.”

(Left to proper) Dr. Gregory Glenn, Novavax’s president of analysis and improvement, and Dr. Robert Redfield, former director of the Facilities for Illness Management and Prevention, stand with Maryland Gov. Larry Hogan and Novavax CEO Stanley Erck in entrance of the corporate’s soon-to-be international headquarters in Gaithersburg, Maryland. (Sarah Jane Tribble / KHN)

‘Hadn’t Heard of Covid-19’

John Kutney, Novavax’s senior director of producing, joined a BioBuzz video in December, in an effort to recruit urgently wanted expertise. Kutney described the expertise switch as taking a recipe and instructing it to others. With that mission, he has traveled to the Czech Republic, Spain and the UK in addition to Texas, North Carolina and New England.

When Novavax started work on its vaccine in January 2020, “most of us hadn’t heard of covid-19 and we have been solely starting to turn out to be conscious of what was taking place in China,” Kutney mentioned. Novavax tailored its established vaccine platform to the brand new virus after which needed to scale and switch it to bigger manufacturing websites, construct a worldwide provide chain and develop a regulatory technique for emergency use.

“These steps would usually take years,” he mentioned.

The important thing step of transferring Novavax’s vaccine expertise can take three to 6 months, relying on the standard of the associate’s staff. As soon as gear and uncooked supplies are secured, the groups begin with small batches ― first with a 50-liter bioreactor, then a 200-liter and finally a 2,000-liter bioreactor, checking to verify the associate operators know the method each step of the best way.

“What we’re making an attempt to do right here isn’t straightforward,” mentioned Fred Shemer, Novavax’s vp of high quality methods and compliance, within the video: “It’s a difficult scenario.”

In March 2020, Novavax acquired the primary $4 million of almost $400 million pledged by the Coalition for Epidemic Preparedness Improvements. CEPI is a worldwide alliance backed by the Invoice and Melinda Gates Basis, which beforehand supported Novavax with $89 million for a vaccine for a standard respiratory virus.

CEPI’s funding jump-started Novavax’s expertise switch to vegetation throughout Europe and Asia. It helped Novavax associate with SK bioscience in South Korea and paid for ramping up manufacturing at Praha Vaccines, which Novavax finally purchased, within the Czech Republic. It additionally supported scaling up manufacturing of Matrix-M at amenities in Sweden and Denmark.

Operation Warp Pace awarded $1.6 billion in July 2020 to Novavax so it might produce 100 million doses ― one of many largest awards from the Trump administration’s vaccine incubator. It was “form of a surprising quantity for us,” Trizzino mentioned. In December, officers bumped the entire to $1.74 billion with no adjustments to the earlier contract. Novavax additionally has a $60 million contract with the Division of Protection for 10 million doses.

Paul Mango, a former senior official on the Division of Well being and Human Companies, mentioned it wasn’t a “large concern” for the Trump administration that Novavax had no profitable vaccine. In any case, that was additionally true for Moderna, which went on to launch its wildly profitable mRNA vaccine.

Operation Warp Pace’s personnel assets and monetary assist would assist carry the day. “We thought we might do it,” Mango mentioned.

On the time, Trump officers invested in a number of vaccine platforms to hedge bets as a result of it wasn’t recognized what would work, if any. “We didn’t need to put all our eggs in mRNA,” he mentioned. “We didn’t need to put all our eggs in viral vector,” the platform utilized by Johnson & Johnson and AstraZeneca. Novavax’s expertise makes use of a extra established course of with a baculovirus grown inside insect cells in a bioreactor.

“It was crucial to have that array of applied sciences,” Mango mentioned. “We needed to choose those that had the most effective early outcomes and those we thought might undergo scientific trials earlier than the spring of 2021.”

Novavax scientists have spent years collaborating with officers at federal businesses such because the Nationwide Institutes of Well being, Nationwide Institute of Requirements and Know-how, and Walter Reed Nationwide Navy Middle ― typically hiring from their ranks. In 2011, Novavax signed a $179 million contract to develop a seasonal and pandemic influenza vaccine with BARDA, the Biomedical Superior Analysis and Improvement Authority.

As issues about covid-19 rose, Novavax and BARDA started one other negotiation, however Operation Warp Pace officers “stepped excessive,” Trizzino mentioned. They requested Novavax what it might take to ramp up large-scale manufacturing, run a 30,000-subject scientific trial and the follow-on trials, and produce hundreds of thousands of doses.

“They mentioned, ‘Do all this stuff in parallel paths. You do not fear in regards to the funding threat. You do the work and we’ll pay for these actions,’” Trizzino recalled.

Troubles in Texas

It was a tall order. Novavax had labored with Emergent BioSolutions and signed a contract for manufacturing in early 2020, however BARDA pushed Novavax to associate as a substitute with Fujifilm Diosynth Biotechnologies and its vegetation in North Carolina, Texas and the U.Ok.

Looking back, Trizzino mentioned, Novavax “dodged a bullet.” Manufacturing issues at Emergent’s Baltimore plant led to contamination or suspected contamination of hundreds of thousands of Johnson & Johnson and AstraZeneca doses, and in June federal regulators declared 60 million J&J doses unusable, The New York Instances first reported.

Fujifilm’s Texas website, like Emergent’s plant in Baltimore, was arrange within the aftermath of the 2009 H1N1 pandemic to raised put together federal officers for the following one. It acquired $265 million final July to rapidly enhance manufacturing capability, in keeping with a federal contract.

The positioning started manufacturing in January however needed to gradual the cadence of its manufacturing strains for “troubleshooting” throughout Novavax’s expertise switch course of, Fujifilm spokesperson Christine Jackman mentioned. The plant is producing the Novavax vaccine and one other undisclosed covid vaccine.

Trizzino mentioned Fujifilm’s website in North Carolina was up and operating rapidly, however Texas didn’t have as a lot expertise so “it’s taken us a bit longer to ramp that up.” A March inspection by the Meals and Drug Administration discovered overcrowded and unorganized storage areas, a failure to constantly comply with cleansing procedures and questions on why there was a backlog of batches, in keeping with paperwork obtained by KHN in response to a public data request. The backup fashioned as a result of bulk drug substance was being made quicker than the ability might assessment produced batches, Fujifilm’s Jackman mentioned.

FDA inspectors known as Fujifilm’s operations “sub optimum high quality,” in keeping with an April response memo written by Gerry Farrell, Fujifilm’s chief working officer for the ability. He mentioned the criticism resonated and promised an intensive assessment with fixes accomplished in April and Might.

Novavax and Fujifilm work carefully to make sure all batches are reviewed and inspected by each firms’ high quality management groups, mentioned Communicate, the Novavax spokesperson. The variety of doses produced in Texas so far haven’t met projections. Nonetheless, responding to federal inspections in Texas has not delayed Novavax’s vaccine improvement as a result of Fujifilm’s North Carolina plant is the first provider of vaccine doses for the preliminary federal approval, Communicate mentioned.

Novavax’s manufacturing course of is difficult as a result of the vaccine is made in steps in other places. One plant makes the protein antigen, and one other makes the adjuvant. Then the 2 elements go to a ultimate fill-and-finish facility the place they’re mixed into 10-dose vials.

Its Matrix-M depends on quillaja extract from soapbark timber. The extract can also be an additive in root beer and Slurpees. Novavax warned traders in its December 2020 monetary filings that an lack of ability to safe sufficient of the extract might delay manufacturing and stop it from assembly “obligations beneath our numerous collaborations and provide agreements.” Nonetheless, Trizzino mentioned that offer is “not an impediment to whole variety of doses.”

Provide shortages have plagued the business. For Novavax, these provides included 2,000-liter bioreactor luggage, used to tradition cells; depth filters for the purification course of; and the expansion media, which is used to feed the cells.

Not having uncooked supplies pressured Novavax to trim the variety of check batches that manufacturing strains might run. It has additionally taken longer to create high quality management assessments, often called assays, to make sure that vaccines are constant and set up a typical high quality for all subsequent batches. These delays slowed the corporate’s potential to correctly practice operators, Trizzino mentioned.

Novavax is working to succeed in “a stage of consolation that we’re in a position to produce these batches after which go to full capability,” Trizzino mentioned. Novavax is working to finish the ultimate phases of validating these assessments.

Novavax’s international headquarters in Gaithersburg, Maryland, is now a “clean canvas” however is anticipated to deal with analysis and improvement, manufacturing and enterprise operations. (Sarah Jane Tribble / KHN)

Too Late?

On the headquarters occasion, Glenn acknowledged that Novavax is late to the sport. However the international demand continues to be monumental, he pressured.

“We all know that 2 billion folks worldwide have acquired at the least one shot,” he mentioned, “however there are 6 billion folks that must be inoculated.”

The corporate is working to show its vaccine can be helpful even after the pandemic is contained. With its Matrix-M adjuvant, Novavax is testing a mixed flu and covid vaccine, which is exhibiting sturdy leads to ferrets and hamsters. Novavax can also be targeted on booster pictures.

Novavax joined mix-and-match trials this spring within the U.Ok. to check whether or not its vaccine works when paired with Moderna, Pfizer or AstraZeneca’s vaccines. Glenn mentioned the outcomes, to date, have been promising that “we’re going to have the ability to use our vaccine after different licensed vaccines.”

First, although, “the world has to collectively, as one, actually stymie this international pandemic,” mentioned Dr. Dawd Siraj, a College of Wisconsin professor specializing in infectious illnesses.

Siraj mentioned Novavax’s delays shouldn’t solid doubt on the standard of the vaccine itself, given the constructive trial outcomes it has reported globally.

The shot is a “superb vaccine,” he mentioned, that might assist flip the tide in creating nations unable to assist their very own vaccine improvement.

“Allow us to by no means miss crucial level right here,” Siraj added. “Anybody who’s getting a vaccine that’s authorised, the probabilities of dying, the probabilities of requiring ICU care, the probabilities of requiring a ventilator and high-flow oxygen, they virtually disappear.”

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