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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The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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Paul Hudson, Getty Images

How does Paul Hud­son's $13.5M comp pack­age stack up against oth­er CEOs? He's in the 'first quar­tile'

Paul Hudson arrived at Sanofi like a hurricane, chopping off duds in the pipeline, shaking up the C-suite, striking big M&A deals and jumping into the Covid-19 vaccine race — all in an attempt to reboot a pharma giant notorious for its setbacks.

Now, we’re getting a look at what the CEO brought home in his first year on the job.

When all is said and done, Hudson will have made about $6.7 million in 2020, about $2.5 million of which has already been paid. The bigger figure includes a $2.3 million bonus that’s subject to approval at an April meeting, and another $1.8 million in variable compensation that has yet to be paid.

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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.

UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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An Ar­ray co-founder re-emerges as CEO of a small aca­d­e­m­ic spin­out, look­ing to re­make an old class of can­cer drugs

Tony Piscopio hadn’t worked as a bench scientist in years when, around 2011, he got put in touch with a team at the University of Colorado trying to revitalize an old approach to treating cancer.

Piscopio, who had co-founded Array Biopharma before heading to South Korea to launch a new company, was back in the states, unattached and intrigued. He founded a three-person company with two professors, Xuedong Liu and Gail Eckhardt, and while they worked on the biology side, he returned to his old chemist chair and began drawing up potential compounds on a computer, along with manufacturing processes to make them. Outsourcing companies synthesized or analyzed the results.

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Af­ter three years of courtship (and turn­downs), Mer­ck pounced on the first glance of clin­i­cal da­ta in $1.85B Pan­dion takeover

It’s almost become cliché for biotech executives to talk about the importance of keeping your options open and being prepared to go all the way. But when it comes to negotiating with a giant like Merck, a little patience can indeed go a long way.

Just ask Pandion Therapeutics.

Days ago we already learned that Merck is shelling out $1.85 billion to pick up the biotech and its slate of autoimmune hopefuls. What we didn’t know until the SEC disclosure dropped Thursday is that the deal comes after Pandion turned down two other proposals from Merck over the past three years and held out until the last minute for a sweetened deal.

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