Ed Kaye, Stoke Therapeutics CEO

Stoke touts ear­ly signs of ef­fi­ca­cy for Dravet syn­drome drug

Two and a half years af­ter dri­ving his an­ti­sense oligonu­cleotide plat­form to Wall Street, Stoke Ther­a­peu­tics CEO Ed Kaye is paint­ing a fuller pic­ture of the com­pa­ny’s first clin­i­cal da­ta. And though the tri­al wasn’t pow­ered to de­tect sta­tis­ti­cal sig­nif­i­cance, Kaye says the read­out shows ear­ly signs of ef­fi­ca­cy in kids with a rare, drug-re­sis­tant form of epilep­sy

STK-001 was well-tol­er­at­ed in sin­gle and mul­ti­ple dos­es in 22 Dravet syn­drome pa­tients be­tween the ages of 2 and 18 years old, Stoke an­nounced on Fri­day. What’s more, 12 of the 17 evalu­able pa­tients at the time (70.6%) saw re­duc­tions from base­line in con­vul­sive seizure fre­quen­cy, ac­cord­ing to the com­pa­ny.

While that re­duc­tion wasn’t sta­tis­ti­cal­ly sig­nif­i­cant, Kaye ex­plained that it was a small pa­tient pop­u­la­tion, adding they didn’t ex­pect to see any im­prove­ment this ear­ly. Me­di­an re­duc­tions in seizure fre­quen­cy of 17% to 37% were seen across all co­horts, the com­pa­ny re­port­ed.

“Giv­en the num­bers, you would have to see a phe­nom­e­nal change in seizure be­fore you can see a sta­tis­ti­cal sig­nif­i­cance. But when we get more pa­tients, we ex­pect that we’ll be able to re­assess sta­tis­ti­cal sig­nif­i­cance,” Kaye said

Dravet syn­drome typ­i­cal­ly be­gins with­in an in­fant’s first year of life, and per­sists through­out adult­hood. Though it’s char­ac­ter­ized by fre­quent seizures, the dis­ease can al­so lead to in­tel­lec­tu­al dis­abil­i­ty, atax­ia or mo­tor ab­nor­mal­i­ties, be­hav­ioral prob­lems, speech im­pair­ment and sleep dis­tur­bances. It’s caused by mu­ta­tions to the SCN1A gene, which en­codes a pro­tein called Nav1.1.

Pa­tients with Dravet syn­drome have one func­tion­al gene copy and one mu­tat­ed copy — what’s called a hap­loin­suf­fi­cien­cy — re­sult­ing in half as much pro­tein as need­ed to main­tain nor­mal health. Stoke’s Tar­get­ed Aug­men­ta­tion of Nu­clear Gene Out­put (TAN­GO) plat­form is de­signed to ad­dress hap­loin­suf­fi­cien­cies by in­creas­ing — or stok­ing — pro­tein out­put from healthy genes, thus com­pen­sat­ing for the mu­tant copy of the gene.

The plat­form it­self traces back to Cold Spring Har­bor Lab­o­ra­to­ry’s Adri­an Krain­er, who is cred­it­ed as the in­ven­tor of Bio­gen’s spinal mus­cu­lar at­ro­phy drug Spin­raza.

STK-001 binds to pre-mR­NA and helps func­tion­al (al­so called wild-type) genes di­al up pro­tein pro­duc­tion. While an­ti­con­vul­sants like Zo­genix’s Fin­tepla or GW Phar­ma’s Epid­i­olex are de­signed to pre­vent seizures by damp­en­ing the elec­tri­cal ac­tiv­i­ty of the brain, Kaye and the team at Stoke be­lieve up­reg­u­lat­ing Nav1.1 can re­store func­tion­ing neu­rons and al­so treat non-seizure symp­toms.

“The prob­lem with giv­ing a pa­tient an an­ti-epilep­tic is you’re on­ly treat­ing one of many symp­toms of the dis­ease,” Kaye said.

Pa­tients in the open-la­bel Phase I/IIa MONARCH study were giv­en ei­ther sin­gle dos­es of up to 30 mg, or 20 mg dos­es. The an­ti­sense oligonu­cleotide is sus­pend­ed in saline and de­liv­ered via spinal in­jec­tion. The drug ap­peared well-tol­er­at­ed af­ter 12 weeks, with the most com­mon side ef­fects be­ing headache, vom­it­ing, seizure, ir­ri­tabil­i­ty and back pain. Though five of 22 pa­tients (22.7%) ex­pe­ri­enced a se­ri­ous ad­verse event, none of them were found to be re­lat­ed to the drug, Stoke said.

Pa­tients who were in MONARCH are el­i­gi­ble to con­tin­ue treat­ment in the SWAL­LOW­TAIL ex­ten­sion study, which is cur­rent­ly en­rolling. Over­all, Stoke plans to en­roll 90 pa­tients across 20 sites in the US to the MONARCH study.

“One of the things that we want to de­ter­mine from this study is not on­ly what’s the ther­a­peu­tic dose that we can reach, but what we al­so want to know is: Can we give a high enough dose that we can give it in­fre­quent­ly?” Kaye said.

While the es­ti­mate is that they’d dose the drug every four months, it’s pos­si­ble that they could go every six months, he added.

Cor­rec­tion: A pre­vi­ous head­line and ver­sion of this ar­ti­cle in­cor­rect­ly stat­ed STK-001 missed sta­tis­ti­cal sig­nif­i­cance. The sto­ry has been up­dat­ed to clar­i­fy that the tri­al wasn’t pow­ered to de­tect sta­tis­ti­cal sig­nif­i­cance.

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Tony Coles, Cerevel CEO

Cerev­el takes the pub­lic of­fer­ing route, with a twist — rais­ing big mon­ey thanks to ri­val da­ta

As public biotechs seek to climb out of the bear market, a popular strategy to raise cash has been through public offerings on the heels of positive data. But one proposed raise Wednesday appeared to take advantage not of a company’s own data, but those from a competitor.

Cerevel Therapeutics plans to raise $250 million in a public offering and another $250 million in debt, the biotech announced Wednesday afternoon, even though it did not report any news on its pipeline. However, the move comes days after rival Karuna Therapeutics touted positive Phase III data in schizophrenia, a field where Cerevel is pursuing a similar program.

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Who are the women blaz­ing trails in bio­phar­ma R&D? Nom­i­nate them for End­points' 2022 spe­cial re­port

Over the past three years, Endpoints News has spotlighted 60 women who have blazed trails and supercharged R&D across the biopharma world. And judging from the response we’ve received, to both our special reports and live events, telling their stories — including any obstacles they may have had to overcome — has inspired our readers in many different ways.

But change takes time, and the fact remains that women are still underrepresented at the upper ranks of the drug-making world.

Bernat Olle, Vedanta Biosciences CEO

Cit­ing 'chal­leng­ing eco­nom­ic en­vi­ron­ment,' PhI­II-ready mi­cro­bio­me biotech lays off 20% of staffers

The market downturn isn’t just sweeping up public biotechs.

Vedanta Biosciences, a developer of oral drugs derived from the human microbiome, is laying off about 20% of its staff — an unfortunately common occurrence these days. But CEO Bernat Olle took the unusual step of sharing the decision on LinkedIn and offering to connect the employees being let go with any company that’s hiring in their areas.

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Hervé Affagard, MaaT Pharma CEO

One year in­to clin­i­cal hold, FDA has more ques­tions about 'pooled' mi­cro­bio­me ther­a­py

The FDA is still wary about a trial testing a microbiome therapy in patients with steroid-resistant acute graft-versus-host disease (aGVHD).

A year after MaaT Pharma’s IND application in the US was first met with a clinical hold, the French biotech said the agency is maintaining the hold. The crux of the matter, MaaT suggested, has to do with the way it puts together its drug candidate, which is administered as an enema (i.e. an injection of fluid into the bowel).

Up­dat­ed: Amid mas­sive re­struc­tur­ing, Bio­gen looks to re­duce phys­i­cal pres­ence in Boston

Biogen is putting a sizable chunk of office and research space in Kendall Square and Weston, MA up for sublease, marking another big change as the biotech grapples with the aftershock of a disastrous and controversial rollout for its Alzheimer’s drug.

The subbleases are “part of Biogen’s overall implementation of the ‘Future of Work,’ which is allowing us to optimize our footprint and reduce the amount of space we occupy, taking into consideration new elements such as the hybrid work model,” Biogen spokesperson Ashleigh Koss wrote in a statement to Endpoints News, adding that the company has had subleases across several buildings for years.

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Saurabh Saha, Centessa CEO (BIO19)

One of 2021's star biotech play­ers flags an­oth­er big set­back for the pipeline

Two months after scuttling their lead drug, Centessa’s executive team is back with the latest in a series of setbacks that have tanked its stock and blown holes in its strategic lineup of biotech subs.

The company reported in its Q2 post today that it has decided to scrap ZF874 after a patient demonstrated elevated liver enzymes — a classic red safety flag — in a Phase I study for alpha-1-antitrypsin (A1AT).

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Pfiz­er launch­es re­bate pro­gram for rare dis­ease pa­tients who have to stop tak­ing Panzy­ga

Pfizer is launching its second-ever rebate program, this time for Panzyga, its treatment for a rare neurological disease of the peripheral nerves.

The program began last month, according to STAT which first reported the news, and offers a refund of out-of-pocket costs for patients who must discontinue their course before the fifth treatment for “clinical reasons.”

Panzyga was approved back in 2018 to treat primary immunodeficiency (PI) in patients two years and older and chronic immune thrombocytopenia (cITP) in adults. It has since picked up an indication in chronic inflammatory demyelinating polyneuropathy (CIDP), a condition that’s characterized by weakness of the arms or legs, tingling or numbness, and a loss of deep tendon reflexes, according to the NIH.