Dave Greenwald (Deerfield)

Deer­field-backed biotech emerges from stealth with gene ther­a­py de­liv­ery plat­forms from Har­vard and MIT

As a PhD stu­dent at Tufts, Dave Green­wald stud­ied the use of ade­no-as­so­ci­at­ed virus (AAV) vec­tors to de­liv­er gene ther­a­pies to peo­ple with re­tini­tis pig­men­tosa, a group of rare ge­net­ic eye dis­eases that caus­es the reti­na to break down over time.

While he lat­er left lab life, he now sits at the helm of Aper­tu­ra Gene Ther­a­py, a biotech that hopes to cus­tomize AAV vec­tors that are used wide­ly in de­liv­er­ing most gene ther­a­pies. Aper­tu­ra an­nounced its launch from stealth with $67 mil­lion in Se­ries A fi­nanc­ing from Deer­field, where Green­wald is al­so a vice pres­i­dent of busi­ness de­vel­op­ment.

Ben De­v­er­man

The com­pa­ny ac­quired its AAV tech­nol­o­gy from Ben De­v­er­man, a Broad In­sti­tute sci­en­tist who has spent near­ly 15 years study­ing AAV vec­tors.

“When de­vel­op­ing a gene ther­a­py, it has been com­mon to use nat­u­ral­ly oc­cur­ring serotype AAV cap­sids,” De­v­er­man said in a press re­lease.

On the oth­er hand, his lab’s tech­nol­o­gy de­signs “cus­tom AAV cap­sids that have the cho­sen char­ac­ter­is­tics for treat­ing spe­cif­ic dis­eases,” he said, “and we be­lieve this ap­proach will re­sult in new and ef­fec­tive gene ther­a­pies.”

When asked which spe­cif­ic dis­eases Aper­tu­ra plans on go­ing af­ter with the cus­tom AAV cap­sids, Green­wald said, “The nice thing about these plat­forms is that they are ag­nos­tic to cell type and or­gan, so we ac­tu­al­ly use them in pret­ty much any dis­ease.”

How­ev­er, he told End­points News, “we’re not dis­clos­ing spe­cif­ic ther­a­peu­tic ar­eas or in­di­ca­tions at this time.”

Kristi­na Wang

Giv­ing slight­ly more in­sight, Aper­tu­ra’s di­rec­tor of cor­po­rate de­vel­op­ment Kristi­na Wang said, “Nat­ur­al serotype AAVs don’t reach cer­tain tis­sues very well, such as CNS, kid­ney, and a bunch of oth­er tis­sues. We are en­gi­neer­ing AAVs to get to those dif­fi­cult-to-ac­cess tis­sues.”

Aper­tu­ra al­so plans to in­cor­po­rate an­oth­er gene ther­a­py tech­nol­o­gy, known as PESCA, that it ac­quired from a dif­fer­ent Cam­bridge-area sci­en­tist — Michael Green­berg, the chair of Har­vard’s neu­ro­bi­ol­o­gy de­part­ment.

While the AAV tech­nol­o­gy is about what goes on around the cap­sid, “the tech­nol­o­gy from Har­vard is in­side the cap­sid, so it’s more about the reg­u­la­tion,” Green­wald said. “So once we get the gene ther­a­py to the right place, do we turn it on in the right cells at the right amount?”

PESCA can fine-tune the ge­net­ic pay­load of a ther­a­py, “po­ten­tial­ly avoid­ing off-tar­get tox­i­c­i­ties, and com­bined with our AAV cap­sids, can po­ten­tial­ly avoid some of the high sys­temic dosage re­quire­ments as in some of the cur­rent gene ther­a­pies,” added Wang, who worked in Green­berg’s lab while she at­tend­ed grad school at Har­vard.

The tox­i­c­i­ty from high dos­es of AAV-de­liv­ered gene ther­a­pies has been an on­go­ing safe­ty con­cern. In a re­port pub­lished last year, FDA reg­u­la­tors not­ed that 35% of near­ly 150 tri­als with AAV gene ther­a­pies re­port­ed se­ri­ous ad­verse events, in­clud­ing deaths, re­lat­ed to the AAV-de­liv­ered treat­ments.

Aper­tu­ra hopes to present its pre­clin­i­cal da­ta lat­er this year, Green­wald said.

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

FDA's ad­vanced ther­a­pies of­fice pro­vides more clar­i­ty on gene ther­a­py CMC con­sid­er­a­tions

As the Office of Tissue and Advanced Therapies (OTAT) transforms into the Office of Therapeutic Products (OTP), with new user fee funds and “super office” status, the department focused on cell and gene therapies also opened its doors to a town hall Thursday offering clarification on guidance and regulations for manufacturers.

Some of the major concerns from manufacturers were the CMC considerations between first-in-human studies and late-phase studies supporting a marketing approval.

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Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Cell and gene ther­a­pies from acad­e­mia: EMA to help 5 projects go­ing af­ter un­met clin­i­cal needs

The European Medicines Agency said Thursday that it’s launching a new pilot program to help academic and other nonprofit researchers developing advanced therapy medicinal products, which includes cell and gene therapies.

Academics have proven to be enormously useful in feeding new products, like chimeric antigen receptor (CAR)-T cell therapies first developed by Memorial Sloan Kettering, and ushered to the market by biopharma companies. Jean Bennett, formerly with the University of Pennsylvania, also saw her research lead to the approval of gene therapy Luxturna, which Roche now owns.

Gilead names 'k­ing­pin­s' in coun­ter­feit HIV med law­suit

Gilead is mounting its counterfeit drug lawsuit, naming two “kingpins” and a complex network of conspirators who allegedly sold imitation bottles of its HIV meds, some of which ended up in US pharmacies.

The pharma giant on Wednesday provided an update on what it called a “large-scale, sophisticated counterfeiting conspiracy,” accusing two new defendants of “leading and orchestrating” a scheme to sell hundreds of millions of dollars in illegitimate drugs posing as meds such as Biktarvy and Descovy.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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