Kamel Khalili (Joseph V. Labolito/Temple University)

Ex­clu­sive: Af­ter four decades, one re­searcher's rad­i­cal HIV cure fi­nal­ly gets its shot

In the downtime between experiments, Kamel Khalili and his mentor traded their wildest ideas for curing HIV. It was the mid 1980s and Khalili was a postdoc at George Khoury’s National Cancer Institute lab, where he studied links between viruses and tumors, then one of the hottest fields in cancer research. But the epidemic was raging through New York and San Francisco, mounting the largest public health threat in decades. A couple buildings over, Robert Gallo was sequencing the virus for the first time. It felt impossible to stay away.

There was one idea Khalili couldn’t stop thinking about. HIV posed a unique challenge in part because it integrated itself into human DNA, coiling away from the body’s defenses. Khalili had spent his grad days tinkering with one of the earliest tools biologists invented to manipulate DNA inside a living cell. In fact, the first experiment he was assigned to when he moved from Tehran to Philadelphia as a 27-year-old graduate student was to take a bacteria-infecting virus and use it to inactivate a gene inside E. coli.

He wondered if he could do the same to the HIV genes inside a patient’s cells — an idea, he knew, was as ludicrous as it was elegant.

“Obviously the tool wasn’t there,” Khalili recalls. The tools they had struck DNA randomly, subjecting the recipient to a scattershot of genetic artillery. “You’d kill the patient.”

Then in 2012 came CRISPR, the so-called molecular scissors that could cut DNA wherever a researcher wanted. Khalili, who had risen to run a vast neuroscience department at Temple University without ever giving up on his youthful whim, rushing to examine a new gene editing tool whenever it appeared, got to work. Within a year and a half of Jennifer Doudna and Emmanuelle Charpentier’s Nobel-winning Science paper, he submitted a manuscript to The Proceedings of the National Academy of Sciences that would send ripples through the HIV field.

He had taken CRISPR and used it to excise HIV out of human DNA. When he put it in HIV-infected mice a few years later, about a third were cured.

“I’ve been working on HIV for close to 40 years,” says Khalili. Now 69, he has an easy, avuncular laugh even over Zoom and large expressive eyebrows, though colleagues tell me he can have a far harder edge in the lab. “For the first time we realized a cure was possible.”

In November, Khalili gave the first evidence the approach could work in monkeys. Investors are now getting on board. Excision BioTherapeutics, the company founded around Khalili’s work, announced today a $50 million Series A to push the therapy into the clinic. If it works as intended, it could provide a long-sought single-shot cure for a virus that now infects 38 million people worldwide and set the stage for a similar approach for other chronic viruses, such as herpes and hepatitis B.

In a field already burned countless times, outside researchers are understandably cautious: CRISPR is a powerful tool, they say, but trying to excise all the viral DNA lurking in a patient’s cells is like trying to plumb an oil spill; there’s always a bit left, tucked in hard-to-reach places. Still, many were impressed he got this far, having discounted the approach years before. And they broadly agreed that Khalili may have invented one of the weapons for the multi-pronged assault they think will one day take down the virus.

The first test will come later this year, when a group of patients will be injected with Khalili’s therapy and, eventually, taken off the anti-retroviral medicines that have kept their infections at bay. If the infections don’t return, they will owe it to an immigrant scientist, who flung himself into a crisis much of his adopted country ignored and for four decades never let go of a brash and maybe even brilliant idea, even when the tools didn’t exist and the NIH told him it was impossible.

Skepticism still runs high, just not as high as when Khalili first started sketching out the idea to friends and colleagues on napkins nearly a decade ago.

“We have to be very careful,” says Fyodor Urnov, a gene editing expert at Cal-Berkeley who worked on early HIV gene editing studies. “But I think, overall, the field can move from hypothetical to realistic optimism.”

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Qual­i­ty Con­trol in Cell and Gene Ther­a­py – What’s Re­al­ly at Stake?

In early 2021, Bluebird Bio was forced to suspend clinical trials of its gene therapy for sickle cell disease after two patients in the trial developed cancer. As company scientists rushed to assess whether there was any causal link between the therapy and the cancer cases, Bluebird’s stock value plummeted – as did those of multiple other biopharma companies developing similar therapies.

While investigations concluded that the gene therapy was unlikely to have caused cancer, investors and the public may be more skittish regarding the safety of gene and cell therapies after this episode. This recent example highlights how delicate the fields of cell and gene therapy remain today, even as they show great promise.

Brad Bolzon (Versant)

Ver­sant pulls the wraps off of near­ly $1B in 3 new funds out to build the next fleet of biotech star­tups. And this new gen­er­a­tion is built for speed

Brad Bolzon has an apology to offer by way of introducing a set of 3 new funds that together pack a $950 million wallop in new biotech creation and growth.

“I want to apologize,” says the Versant chairman and managing partner, laughing a little in the intro, “that we don’t have anything fancy or flashy to tell you about our new fund. Same team, around the same amount of capital, same investment strategy. If it ain’t broke, don’t fix it.”

But then there’s the flip side, where everything has changed. Or at least speeded into a relative blur. Here’s Bolzon:

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Sen. Patty Murray (D-WA) (Graeme Sloan/Sipa USA/Sipa via AP Images)

Sen­a­tors to NIH: Do more to pro­tect US bio­med­ical re­search from for­eign in­flu­ence

Although Thursday’s Senate health committee hearing was focused on how foreign countries and adversaries might be trying to steal or negatively influence biomedical research in the US, the only country mentioned by the senators and expert witnesses was China.

Committee chair Patty Murray (D-WA) made clear in her opening remarks that the US cannot “let the few instances of bad actors” overshadow the hard work of the many immigrant researchers in the US, many of which have won Nobel prizes for their work. But she also said, “There is more the NIH can be doing here.”

Law pro­fes­sors call for FDA to dis­close all safe­ty and ef­fi­ca­cy da­ta for drugs

Back in early 2018 when Scott Gottlieb led the FDA, there was a moment when the agency seemed poised to release redacted complete response letters and other previously undisclosed data. But that initiative never gained steam.

Now, a growing chorus of researchers are finding that a dearth of public data on clinical trials and pharmaceuticals means industry and the FDA cannot be held accountable, two law professors from Yale and New York University write in an article published Wednesday in the California Law Review.

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Novavax CEO Stanley Erck at the White House in 2020 (Andrew Harnik, AP Images)

As fears mount over J&J and As­traZeneca, No­vavax en­ters a shaky spot­light

As concerns rise around the J&J and AstraZeneca vaccines, global attention is increasingly turning to the little, 33-year-old, productless, bankruptcy-flirting biotech that could: Novavax.

In the now 16-month race to develop and deploy Covid-19 vaccines, Novavax has at times seemed like the pandemic’s most unsuspecting frontrunner and at times like an overhyped also-ran. Although they started the pandemic with only enough cash to last 6 months, they leveraged old connections and believers into $2 billion and emerged last summer with data experts said surpassed Pfizer and Moderna. They unveiled plans to quickly scale to 2 billion doses. Then they couldn’t even make enough material to run their US trial and watched four other companies beat them to the finish line.

JP Gabriel, Ocugen

JP Gabriel watched from the bleach­ers as the pan­dem­ic raged. Now head of sup­ply chain at Ocu­gen, he's ready to bat

The world was in the middle of the most pressing public health risk his generation had ever seen, and JP Gabriel felt like he was sitting on the sidelines. As a VP of biologics and mRNA manufacturing at Ultragenyx, Gabriel watched from the sidelines as players like Pfizer/BioNTech and Moderna used mRNA tech to chase their own Covid-19 vaccines.

This month, Gabriel got the chance to get his hands dirty against the pandemic — but it won’t be with mRNA.

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Jenny Rooke (Genoa Ventures)

Ear­ly Zymer­gen in­vestor Jen­ny Rooke re­flects on 'chimeras' in biotech, what it takes to spot a $500M gem

When Jenny Rooke first heard of Zymergen back in 2014, she knew she was looking at something different and exciting. The Emeryville, CA biotech held the promise of blending biology and technology to solve a huge unmet need for cost-effective chemicals — of all things — and a stellar founding team to boot.

But back then, West Coast venture capitalists didn’t see in Zymergen the one thing they were looking for in a winning biotech: therapeutic potential. Rooke, however, saw an opportunity and made her bets. Seven years later, that bet is paying off in a big way.

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FDA of­fers scathing re­view of Emer­gent plan­t's san­i­tary con­di­tions, em­ploy­ee train­ing af­ter halt­ing pro­duc­tion

The FDA wrapped up its inspection of Emergent’s troubled vaccine manufacturing plant in Baltimore on Tuesday, after halting production there on Monday. By Wednesday morning, the agency already released a series of scathing observations on the cross contamination, sanitary issues and lack of staff training that caused the contract manufacturer to dispose of millions of AstraZeneca and J&J vaccine doses.

Covid-19 man­u­fac­tur­ing roundup: Mary­land looks to grow biotech ca­pac­i­ty with $400M check; Rus­sia lands sec­ond Sput­nik V part­ner this week

A Maryland real estate project has added three new biotech-focused manufacturing and research buildings to an office park to keep up with demand created by the pandemic, the Washington Business Journal reported.

The Milestone Business Park — located off of I-270 in Germantown, MD — will see the new buildings and a total of 532,000 square feet as the campus rebrands to Milestone Innovation Park.