PJ Anand, Alcyone Therapeutics CEO

A gene ther­a­py biotech is burst­ing on­to the scene with 12 pro­grams in tow. An ul­tra-rare neu­ro dis­ease is up first

In down­town Low­ell, MA, tucked in­to one of the coun­try’s old­est sur­viv­ing tex­tile mill com­plex­es is a new biotech toil­ing away on next-gen CNS ther­a­pies for se­vere neu­ro­log­i­cal dis­or­ders. And it’s start­ing with Rett syn­drome — a rare neu­rode­vel­op­men­tal con­di­tion that al­most ex­clu­sive­ly af­fects girls.

Kathrin Mey­er

Al­cy­one Ther­a­peu­tics emerged from stealth mode Wednes­day with $23 mil­lion from RTW In­vest­ments and 12 new gene ther­a­py pro­grams in the works. The com­pa­ny was cre­at­ed last sum­mer, short­ly af­ter founder and CEO PJ Anand met Kathrin Mey­er, a prin­ci­pal in­ves­ti­ga­tor in the gene ther­a­py unit at the Abi­gail Wexn­er Re­search In­sti­tute at Na­tion­wide Chil­dren’s Hos­pi­tal.

“We de­cid­ed that there was so much mu­tu­al syn­er­gy,” Anand told End­points News, lead­ing them to ex­e­cute a col­lab­o­ra­tion last year.

The com­pa­ny is in pre-IND en­abling stud­ies for one of its lead can­di­dates, AC­TX-101 — a Rett syn­drome treat­ment us­ing X-re­ac­ti­va­tion tech­nol­o­gy. Its oth­er lead can­di­date, AC­TX-401, is a gene ther­a­py for spinal mus­cu­lar at­ro­phy with res­pi­ra­to­ry dis­tress type 1 (SMARD1), for which it will file an IND this year.

Re­searchers at the Bay­lor Col­lege of Med­i­cine iden­ti­fied mu­ta­tions in a gene called MECP2 as the cause of Rett syn­drome back in 1999. The dis­or­der caus­es se­vere im­pair­ments that af­fect a child’s abil­i­ty to speak, walk, eat and breathe eas­i­ly, a com­mon sign be­ing con­stant repet­i­tive hand move­ments. The chal­lenge with con­ven­tion­al trans­gene re­place­ment, Anand ex­plained, is that over­pro­duc­tion of MECP2 is just as bad as un­der­pro­duc­tion.

“It is one of those Goldilocks in­di­ca­tions where you want to have the right amount of pro­tein,” he said. “The po­ten­tial of this plat­form is to in­crease the ef­fi­cien­cy of gene ther­a­py not by 1 time or 2 times, but by mul­ti­ple times.”

Al­cy­one is cou­pling its pre­cise CNS de­liv­ery plat­form with X-chro­mo­some re­ac­ti­va­tion tech­nol­o­gy, so in­stead of just re­plac­ing the gene in the ac­tive X-chro­mo­some (and risk­ing over­ex­pres­sion of MECP2), they’re se­lec­tive­ly re­ac­ti­vat­ing ar­eas in the in­ac­tive X-chro­mo­some to get MECP2 pro­duc­tion.

Anand has big plans to make this pro­gram a “pipeline in a prod­uct,” where the same gene prod­uct can be ap­plied to oth­er X-chro­mo­some-re­lat­ed syn­dromes. Pri­or to this, he found­ed Anun­cia, a spin­off look­ing to treat hy­dro­cephalus and cere­brospinal flu­id dys­func­tions, and co-found­ed the med­ical de­vice com­pa­ny Arthrome­da.

Al­cy­one’s join­ing a host of oth­er com­pa­nies on the hunt for the first Rett syn­drome ther­a­py, in­clud­ing New York biotech Anavex, which got fast track sta­tus for its blar­came­sine back in 2020. Aca­dia Phar­ma­ceu­ti­cals, mak­er of the Parkin­son’s dis­ease drug Nu­plazid, en­tered its trofine­tide in a piv­otal Phase III study for Rett syn­drome in late 2019. Newron Phar­ma­ceu­ti­cals dropped out of the race last May, culling its Rett syn­drome pro­gram af­ter sari­zotan failed a Phase II/III tri­al.

The 35-per­son team at Al­cy­one is al­so de­vel­op­ing can­di­dates us­ing con­ven­tion­al trans­gene re­place­ment, vec­tor­ized ex­on skip­ping and pro­mo­tor mod­u­la­tion.

“Our next-gen­er­a­tion pre­ci­sion de­liv­ery plat­form shows strong po­ten­tial in over­com­ing the fun­da­men­tal chal­lenge in CNS ther­a­py de­vel­op­ment,” Anand said.

Cor­rec­tion: Al­cy­one plans on fil­ing an IND this year for AC­TX-401, not AC­TX-101. 

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.

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.

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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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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Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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