CEO Ray Tabibiazar (SalioGen)

Look­ing to take ad­van­tage of 'si­lenced' en­zymes, Sali­o­Gen emerges from stealth with eyes set on gene ther­a­py 3.0

Gene ther­a­py has made big strides over the years, from the first gen­er­a­tion AAV-based ther­a­pies to the CRISPR/Cas9 tech­nol­o­gy that has now tak­en the sci­en­tif­ic world — and No­bel Prize com­mit­tee — by storm. But where ex­act­ly does the fu­ture, or gene ther­a­py 3.0, lie?

That’s the ques­tion a new biotech is aim­ing to an­swer, as Sali­o­Gen Ther­a­peu­tics emerges from stealth Mon­day morn­ing with a $20 mil­lion Se­ries A. And they be­lieve they’ve found a new de­liv­ery sys­tem that can more pre­cise­ly de­liv­er genes in vi­vo than the rel­a­tive­ly large ade­no-as­so­ci­at­ed virus or CRISPR sys­tem: mam­malian-de­rived en­zymes.

Mon­day’s round was led by PBM Cap­i­tal and in­clud­ed oth­er undis­closed in­vestors.

Based in Burling­ton, MA, Sali­o­Gen came about when CEO Ray Tabib­i­azar and co-founder Joseph Hig­gins, who worked on the Hu­man Genome Pro­ject in the 1990s, set out rough­ly a year and a half ago look­ing to find what the nat­ur­al evo­lu­tion of gene ther­a­py might be. They be­lieved that while CRISPR and oth­er tech­nolo­gies like Pre­ci­sion Bio’s AR­CUS were promis­ing, re­searchers could re­al­ly on­ly go af­ter dis­or­ders that in­volve big­ger genes with spe­cif­ic mu­ta­tions, as those plat­forms in­volve cut­ting, knock­ing out or re­plac­ing spe­cif­ic DNA se­quences.

The pair iden­ti­fied three is­sues that need­ed solv­ing in the cur­rent gene ther­a­py field in or­der to get the com­pa­ny off the ground. First was the gene edit­ing it­self, or how Sali­o­Gen could take a dif­fer­ent ap­proach than what’s al­ready out there. Sec­ond is the de­liv­ery method: Tabib­i­azar and Hig­gins felt they couldn’t re­ly on the AAVs. And last was how to make man­u­fac­tur­ing cheap­er in or­der to make the ther­a­pies, which of­ten run up sev­er­al hun­dred thou­sands of dol­lars in costs, more ac­ces­si­ble.

Through these steps came Sali­o­Gen’s pro­pri­etary Ex­act DNA In­te­gra­tion Tech­nol­o­gy plat­form, or ED­IT. The goal, Tabib­i­azar told End­points News, is to es­sen­tial­ly pluck these mam­malian en­zymes that have been “si­lenced” over the course of evo­lu­tion and re­pur­pose them in­to de­liv­er­ing the gene ther­a­py. And the whole pro­ce­dure of tak­ing genes and putting them in­to new cells takes less than a month, sharply cut­ting down on pro­duc­tion costs.

“It puts the ge­net­ic code in­to the genome, and then it’s done, it’s gone,” Tabib­i­azar told End­points.

Not on­ly does that ad­dress the three is­sues they’d hoped to fix, it al­lows for a genome to be rewrit­ten in­side the body with­out the wor­ry AAVs or Cas9s will con­tin­ue mak­ing changes af­ter the tar­get­ed gene has been fixed. Tabib­i­azar is call­ing this process “gene cod­ing,” in that it puts new ge­net­ic code back in­to one’s genome through the en­zyme de­liv­ery.

He likened it to a soft­ware and hard­ware up­grade anal­o­gy — the en­zymes, or the soft­ware, con­tains the up­date and fix­es the is­sues in the body’s hard­ware.

“If you have an Ap­ple [prod­uct] and you get Ap­ple soft­ware, Ap­ple hard­ware, you’re not go­ing to use the app on An­droid,” Tabib­i­azar said. “It’s the same thing here, if you have a mam­malian en­zyme, which rewrites the soft­ware in­to your mam­malian hard dri­ve, you want it to be a fit be­tween the soft­ware and the hard­ware.”

Though Tabib­i­azar says the ap­pli­ca­tion of the plat­form is quite wide, Sali­o­Gen will be fo­cus­ing on fa­mil­ial hy­per­c­ho­les­terolemia and in­her­it­ed mac­u­lar de­gen­er­a­tion first. In FH, the com­pa­ny is tak­ing what it sees as a new ap­proach, aim­ing to re­place the en­tire re­cep­tor gene in the liv­er re­spon­si­ble for the dan­ger­ous­ly high cho­les­terol and LDL lev­els as­so­ci­at­ed with the dis­ease. It’s a field with a few play­ers al­ready, with Verve and Pre­ci­sion Bio both go­ing af­ter HoFH.

Both pro­grams are still in the pre­clin­i­cal stage, but Tabib­i­azar hopes they can be in the clin­ic with­in the next two to two-and-a-half years. The key now is en­sur­ing the ther­a­pies can be safe and build­ing out the plat­form with the fi­nanc­ing. Tabib­i­azar said hav­ing PBM Cap­i­tal on their side, who al­so made ear­ly-stage in­vest­ments in the biotechs that cre­at­ed Lux­tur­na and Zol­gens­ma, pro­vides a cru­cial val­i­da­tion for Sali­o­Gen.

“All our fo­cus is to do it very spe­cif­ic,” Tabib­i­azar said. “Not on­ly do we know how to tar­get it to a spe­cif­ic cell, we know how to tar­get it to a spe­cif­ic lo­ca­tion with­in the genome.”

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Voting in the 2020 election (AP Images)

The right to vote is fun­da­men­tal — a let­ter from biotech­nol­o­gy in­dus­try lead­ers

Biotech Voices is a collection of exclusive opinion editorials from some of the leading voices in biopharma on the biggest industry questions today. Think you have a voice that should be heard? Reach out to senior editors Kyle Blankenship and Amber Tong.

We oppose all attempts to introduce laws that reduce the rights of US citizens to vote or that restrict them from exercising that right. The right to vote is fundamental to democracy. States that have enacted, or are proposing to enact, legislation to restrict voting are undermining our democracy and posing a threat to our nation. As leaders of the life sciences industry, we stand for what we believe is right for our country, our enterprises, our employees and those who benefit from our work. We join the first groups of business leaders who have challenged these laws and will continue to make our collective voices heard on this matter.

Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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Barbara Weber, Tango Therapeutics CEO (Tango)

It takes two to Tan­go: The biotech us­ing CRISPR to dis­cov­er new can­cer gene tar­gets rides a $353M SPAC deal to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

The latest biotech-SPAC deal has arrived, and it’s dancing its way to Nasdaq to the tune of several hundred million dollars.

Tango Therapeutics and its CRISPR-focused search for new cancer genes is reverse merging with Boxer Capital’s blank-check company, the biotech announced Wednesday morning. With a spotlight on three lead programs, Tango expects total proceeds to equal about $353 million in the deal, which includes the roughly $167 million held in the SPAC and an additional $186 million in PIPE financing.

Anand Shah (FDA)

For­mer head of FDA’s med­ical and sci­en­tif­ic af­fairs on Covid: ‘FDA has nev­er been test­ed like this’

Anand Shah has served the American public in a unique way, crisscrossing over the last two administrations between serving as an attending radiation oncologist focused on prostate cancer at NIH, serving as CMO at the Center for Medicare and Medicaid Innovation, and most recently, leading the FDA’s operations on medical and scientific affairs from within the commissioner’s office.

Shah, who stepped down from the FDA in January, caught up with Endpoints News in a phone interview on Tuesday afternoon, offering his thoughts on the agency’s latest decision to pause the J&J vaccinations in the US, and reflecting on his time at an agency during this once-in-a-lifetime pandemic.

UP­DAT­ED: J&J paus­es vac­cine roll­out as feds probe rare cas­es of blood clots

The FDA and CDC have jointly decided to stop administering J&J’s Covid-19 vaccine after reviewing data involving six reported US cases of a rare and severe type of blood clot in individuals after receiving the vaccine.

CDC will convene a meeting of its Advisory Committee on Immunization Practices on Wednesday to further review these cases and assess their potential significance. “FDA will review that analysis as it also investigates these cases. Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, Principal Deputy Director of the CDC, said in a joint statement Tuesday morning.

Launched by MIT grads, a small start­up gets $20M to back a ro­bot­ics rev­o­lu­tion in cell ther­a­py man­u­fac­tur­ing

As co-director of an experimental cellular therapy process development and manufacturing group at UCSF specializing in T cell therapies for autoimmune conditions, Jonathan Esensten has learned a lot about the challenges involved when his group hand-fashions a cell therapy. Esensten — who was a postdoc in Wendell Lim’s lab and counts the legendary Jeffrey Bluestone as a mentor — gives them all high marks at being great at what they do, but time and again there are variations in the treatments they construct.

Kristin Fortney, BioAge Labs CEO

An­ti-ag­ing biotech up­start plucks a drug from Am­gen's dis­card pile, piv­ot­ing from heart fail­ure to mus­cle con­di­tions

Back in April 2019, Amgen quietly shut down a Phase I trial for a drug named AMG 986. There was no safety concern; the molecule just didn’t hit the mark on helping the small band of heart failure patients who received it.

A small biotech, though, believes it would stand a chance in the burgeoning anti-aging field.

BioAge Labs has licensed AMG 986 — now renamed BGE-105 — with plans to parlay the existing IND into a quick Phase I trial teasing out the pharmacodynamic effects and set the stage for mid-stage tests focused on acute muscle indications.