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.”

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,600+ biopharma pros reading Endpoints daily — and it's free.

Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,600+ biopharma pros reading Endpoints daily — and it's free.

In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Three biotechs price hefty IPOs just be­fore the week­end, while a fourth and a SPAC seek spots on Wall Street

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

A handful of biotechs are hitting Wall Street just before the start of the weekend, with three companies — Caribou Biosciences, Sophia Genetics and Absci — all pricing big raises Wednesday and Thursday. Gamma delta T cell-focused IN8bio relaunched its IPO campaign months after postponing it last November, seeking a slightly lower raise. And another SPAC has filed for a public debut.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,600+ biopharma pros reading Endpoints daily — and it's free.

Victor Perlroth, Kodiak Sciences CEO

Ko­di­ak turns down $125M pay­ment from Bak­er Bros. deal, slash­es roy­al­ty cap by 55%

Following a massive public raise last November, Kodiak Sciences has re-worked a royalty sale agreement with an old partner — and declined new funds in the process.

Kodiak is turning down a planned $125 million payment from Baker Bros. Advisors, according to an SEC filing, cutting short an agreement that saw the biotech hand over a 4.5% stream of royalty sales on its experimental anti-VEGF therapy KSI-301 for retinal vascular diseases. In conjunction with the move, Kodiak is shrinking the royalty cap from just over $1 billion to $450 million.

EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Laurent Fischer, Adverum CEO

Ad­verum faces murky fu­ture af­ter re­view turns up deep­er safe­ty is­sues for gene ther­a­py

Three months after revealing that a patient lost significant vision in one eye after receiving its experimental gene therapy, Adverum announced it found the safety issues were more widespread: Five of 12 patients who received a high dose of the therapy saw “similar clinically-relevant events.”

Three required surgery on their treated eye. And all 12 are being recommended “aggressive immunomodulatory treatments” to prevent further injury.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 112,600+ biopharma pros reading Endpoints daily — and it's free.