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.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Tillman Gerngross (Adagio)

Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

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Iain McGill, Quell CEO

Eu­ro­pean in­vestors pour $156M to beat Blue­stone, Third Rock and RA Cap­i­tal in multi­bil­lion-dol­lar race to the clin­ic

Amid burgeoning efforts to create a new type of cell therapy out of regulatory T cells — whether by channeling or blocking their immunosuppressive power — Quell Therapeutics wants to shoot for a first.

If everything goes well, the Syncona-backed biotech will be in the clinic early next year, marking what it calls the historic feat of dosing a patient with a CAR-Treg with multiple edited genes.

Rogerio Vivaldi, Sigilon CEO (Sigilon via website)

Bob Langer biotech's lead cell ther­a­py re­mains on FDA hold, but re­searchers now may know the cause

Back in July, the FDA placed a clinical hold on the Bob Langer and Flagship-backed biotech Sigilon Therapeutics for its lead program to treat hemophilia A. On Monday, Sigilon reported what caused the pause.

After a patient in the three-person Phase I/II study reported a serious adverse event, Sigilon discovered the spheres used to deliver the cell therapy had fibrosed, the biotech announced Monday. As a result, the treatment contained within the spheres was no longer viable after the patient developed inhibitors to Factor VIII.

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Like the flu vac­cine every year, the FDA could move quick­ly on a vari­ant-tar­get­ed Covid vac­cine

In the same way that the FDA signs off on flu vaccines every year without requiring large clinical trials to measure their efficacy, the FDA may employ a similar strategy in authorizing variant-focused versions of the mRNA vaccines.

As the world braces for more data on the latest variant Omicron, which may reduce vaccine efficacy, top vaccine developers like Moderna and Pfizer-BioNTech have promised they can pull together a new vaccine targeted against a specific Covid variant in about 100 days. Since Omicron emerged last week, Pfizer-BioNTech, Moderna and J&J have all said they’ve begun work on Omicron-specific vaccines, if needed.

Jonathan Montagu (L) and Gerry Harriman, HotSpot co-founders

HotSpot gets hot­ter with $100M raise to push to­ward clin­ic

HotSpot Therapeutics, the allostery-focused biotech that works on what it calls “natural hotspots” — hence the name — is getting a bit hotter in its valuation from investors. And to that end they’ve raised $100 million.

The four-year-old AI computational biotech started by two former Nimbus execs announced this morning that it closed its Series C round right at the line of a 9-figure investment, courtesy of some big investors.

Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; 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.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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