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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Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.