RA Session II, Taysha Gene Therapies CEO (Taysha)

Taysha Gene Ther­a­pies gears up to ap­proach reg­u­la­tors with a new can­di­date for a de­bil­i­tat­ing neu­rode­gen­er­a­tive dis­ease

Af­ter launch­ing ear­ly last year, Taysha Gene Ther­a­pies quick­ly went about check­ing off key mile­stones. With­in five months, it pulled in a hefty Se­ries B round and made the jump to Nas­daq. And now, it has a late-stage can­di­date that CEO RA Ses­sion II says is just about ready for reg­u­la­tors.

The Dal­las-based biotech on Mon­day un­veiled a deal for glob­al rights to TSHA-120 — a gene ther­a­py dis­cov­ered in the lab of UT South­west­ern’s Steven Gray to treat a de­bil­i­tat­ing neu­rode­gen­er­a­tive dis­ease called gi­ant ax­on­al neu­ropa­thy (GAN). It’s the first gene ther­a­py to be ad­min­is­tered in hu­mans in­trathe­cal­ly (in­to the spinal canal), ac­cord­ing to Ses­sion, who’s cur­rent­ly lin­ing up an end-of-phase meet­ing with the FDA.

“It ba­si­cal­ly, for us, val­i­dates the sci­en­tif­ic ap­proach that we cur­rent­ly use on the rest of the port­fo­lio,” Ses­sion said.

The AveX­is and Bridge­Bio vet­er­an found­ed Taysha back in Jan­u­ary 2020 with the help of for­mer AveX­is CEO Sean Nolan. At the time, they want­ed to take what they learned build­ing the first-ever gene ther­a­py for spinal mus­cu­lar at­ro­phy and scale the process. The com­pa­ny launched in April with $30 mil­lion in Se­ries A fund­ing and a pipeline of gene ther­a­pies from UT South­west­ern, which Ses­sion has called an “un­der-rec­og­nized gem.”

Suyash Prasad

A Se­ries B round and $181 mil­lion IPO fol­lowed in Au­gust and Sep­tem­ber, re­spec­tive­ly. CMO and R&D chief Suyash Prasad called it  “three years of fi­nanc­ing in six months.”

“RA and I chat­ted fre­quent­ly dur­ing our ear­ly fi­nanc­ings,” Prasad said. “We just re­al­ized things were go­ing so well af­ter the Se­ries B, we just turned around and said, ‘Let’s go pub­lic.’”

TSHA-120 is now Taysha’s 26th pro­gram. So far, 14 pa­tients have been dosed with the AAV9 can­di­date in an open-la­bel dose-es­ca­la­tion study launched in 2015 by the NIH and the pa­tient ad­vo­ca­cy group Han­nah’s Hope. Re­searchers ob­served a halt in dis­ease pro­gres­sion at the sec­ond-high­est dose lev­el one year post-treat­ment, and six pa­tients have shown dose-de­pen­dent im­prove­ments for more than three years, ac­cord­ing to Taysha.

The biotech has rough­ly 6 months of da­ta on the high­est dose co­hort, and ex­pects to read out more da­ta lat­er this year.

“If we con­tin­ue to see that dose im­prove­ment, who knows what we would ex­pect,” Ses­sion said.

GAN is a rare au­to­so­mal re­ces­sive dis­ease of the cen­tral and pe­riph­er­al ner­vous sys­tems caused by mu­ta­tions in the gene cod­ing for gi­gax­onin. Chil­dren with GAN usu­al­ly show symp­toms be­fore the age of five, in­clud­ing pro­gres­sive sco­l­io­sis, con­trac­tures, and at­ro­phy of the spinal cord. Some pa­tients lose their abil­i­ty to walk, and end up in a wheel­chair. And too of­ten, pa­tients die in their late teens or ear­ly 20s.

There’s cur­rent­ly no treat­ment for GAN, and an es­ti­mat­ed 2,400 pa­tients in the US and Eu­rope.

“When you think about brain dis­eases and dis­eases of the cen­tral ner­vous sys­tem and the pe­riph­er­al ner­vous sys­tem, and in fact, philo­soph­i­cal­ly, for any drug ap­proach — you should re­al­ly tar­get the or­gan that’s mal­func­tion­ing, to try and lim­it any kind of off-tar­get tox­i­c­i­ty,” Prasad said.

That’s why Taysha is dos­ing the can­di­date in­trathe­cal­ly, he said. The process al­so al­lows them to start on the right side of the blood-brain bar­ri­er.

“The biodis­tri­b­u­tion of AAV9 from an IV per­spec­tive, on­ly 1% to 3% of the drug ac­tu­al­ly cross­es in­to the blood-brain bar­ri­er,” Ses­sion said. “And so as Suyash said, we could de­liv­er … a low­er to­tal dose, but put the drug ex­act­ly where it needs to be.”

Taysha is giv­ing Han­nah’s Hope $5.5 mil­lion up­front, plus up to $19.3 mil­lion in mile­stones. The ad­vo­ca­cy group stands to make low sin­gle-dig­it roy­al­ties on net sales.

“With the da­ta that we have in-house to­day, we’re ex­treme­ly ex­cit­ed about what the pos­si­ble reg­u­la­to­ry path­way could look like,” Ses­sion said. “With that be­ing said we need to have the con­ver­sa­tions with the reg­u­la­tors.”

He plans on dis­cussing with reg­u­la­tors in the US, Eu­rope and Japan “as soon as pos­si­ble.”

Up­date: Han­nah’s Hope is el­i­gi­ble for up to $19.3 mil­lion in mile­stones

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.

Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.