Sage plots come­back plan for its ex­per­i­men­tal oral an­ti­de­pres­sant

Tri­als test­ing de­pres­sion drugs in­vari­ably tend to dis­ap­point. Per­haps the most keen­ly-an­tic­i­pat­ed de­pres­sion tri­al of 2019, de­spite great an­a­lyst and in­vestor op­ti­mism, al­so failed in pa­tients with ma­jor de­pres­sive dis­or­der (MDD), evap­o­rat­ing bil­lions from its drug­mak­er Sage Ther­a­peu­tics’ mar­ket val­ue in ear­ly De­cem­ber.

The com­pa­ny — which last spring se­cured the land­mark ap­proval of its in­jectable post­par­tum de­pres­sion drug Zul­res­so — now has an FDA-en­dorsed path for­ward for its ex­per­i­men­tal oral an­ti­de­pres­sant.

The plan is to pur­sue two new in­di­ca­tions for the drug, zu­ra­nolone (or SAGE-217), on the ba­sis of two-week tri­als: post­par­tum de­pres­sion and the acute treat­ment of MDD, in com­bi­na­tion with an ex­ist­ing an­ti­de­pres­sant. These in­di­ca­tions are ex­pect­ed to sup­ple­ment the orig­i­nal plan to get the drug ap­proved for the treat­ment of MDD as an episod­ic ther­a­py.

“Over­all we be­lieve SAGE’s up­dat­ed ‘217 plan makes sense: it of­fers two more in­de­pen­dent shots on goal in MDD and one ad­di­tion­al study in PPD, with­out the need to im­mi­nent­ly raise cash at a dis­tressed val­u­a­tion,” Stifel’s Paul Mat­teis wrote on Wednes­day.

In De­cem­ber, Sage re­port­ed that SAGE-217 had failed to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment over place­bo in the 581-pa­tient late-stage MOUN­TAIN study in pa­tients with MDD. In the tri­al, pa­tients were ei­ther giv­en a 20 mg or 30 mg dose of the drug, or place­bo, once-night­ly for two-weeks.

The hope was the drug would help MDD pa­tients quick­er and more ef­fec­tive­ly than the ex­ist­ing crop of an­ti­de­pres­sants, which can take weeks to kick in. Al­though the 20 mg dose was not ac­tive, the per­for­mance of 30 mg dose was “di­rec­tion­al­ly” pos­i­tive, Sage chief Jeff Jonas had as­sert­ed in an in­ter­view with End­points News.

This da­ta is “like win­ning the sil­ver medal,” Jonas said. “This is not a gi­ant step for mankind we thought we would take, but it is a step in the right di­rec­tion.”

In re­sponse to the MOUN­TAIN fail­ure, Stifel’s Mat­teis had stressed that all hope was not lost for the drug.

“The fail­ure is a sur­prise in one sense, but in an­oth­er sense, not at all un­prece­dent­ed: even Prozac failed in a num­ber of ef­fi­ca­cy stud­ies,” he wrote in a note. “It’s for the lat­ter rea­son that we’re re­luc­tant here to throw in the tow­el on the SAGE bull case that ‘217 still has the po­ten­tial to be­come a block­buster drug.”

Jonas, mean­while, hint­ed that giv­en the 30 mg dose was well tol­er­at­ed, Sage could po­ten­tial­ly en­hance the size of the dose in the oth­er tri­als en­com­pass­ing the larg­er SAGE-217 pro­gram.

The new path for­ward for the drug does ex­act­ly that — the three ad­di­tion­al tri­als will eval­u­ate 50 mg dose of SAGE-217, and are all ex­pect­ed to read­out in 2021.

“Giv­en the state of the world, there’s po­ten­tial­ly some risk to 2021 time­lines (as is the case for all biotech tri­als), how­ev­er, we note that the MOUN­TAIN study on­ly took 8 months to com­plete,” Mat­teis said.

The so-called Rapid Re­sponse Tri­al as­sess­ing co-ini­ti­a­tion of SAGE-217 with a Se­lec­tive Sero­tonin Re­up­take In­hibitor in MDD is es­sen­tial­ly a first-of-its-kind tri­al re­flect­ing the FDA’s re­cent dis­tinc­tion be­tween rapid-act­ing and slow­er-act­ing main­te­nance an­ti­de­pres­sants. “We like this tri­al since it aligns with how we think many psy­chi­a­trists would like to use the drug in the re­al world,” he added.

Sage, which end­ed 2019 with $1 bil­lion in its cof­fers, has con­cerned in­vestors with its spend­ing — last year’s op­er­at­ing ex­pens­es hit $719 mil­lion — as Zul­res­so’s launch has been slow­er than an­tic­i­pat­ed. Spend­ing could be cut for Zul­res­so giv­en the dif­fi­cul­ties of that launch, Mat­teis said.

The Cam­bridge, Mass­a­chu­setts-based com­pa­ny’s shares $SAGE have lost more than 80% of their val­ue since Zul­res­so’s March 2019 ap­proval, clos­ing at $28.80 on Tues­day. The stock was down more than 9% at $26.11 on Wednes­day morn­ing.

“Bot­tom line, the stock looks cheap ($1.5B cap) and we think it just takes some pa­tience, giv­en our view that it isn’t a ques­tion of “if”, but “when” ‘217 be­comes ap­proved for PPD/MDD,” Jef­feries An­drew Tsai said.

So­cial im­age: Jeff Jonas (NBCU Pho­to Bank via Get­ty Im­ages)

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Dif­fu­sion to hand Nas­daq spot to EIP Phar­ma for PhI­Ib de­men­tia study of ex-Ver­tex drug

One of the more than a dozen bidders for Diffusion Pharmaceuticals’ spot on Nasdaq has prevailed.

Boston biotech EIP Pharma will merge with Diffusion in an all-stock deal, with plans to start a Phase IIb clinical trial in the coming months in a common form of dementia with no approved treatments. The combined company will be renamed CervoMed.

The nine-year-old privately-held EIP is working on a former Vertex drug that it will test in a 160-person Phase IIb in patients with dementia with Lewy bodies, or DLB. The National Institute on Aging is expected to fund that trial with a $21 million grant. With the reverse merger, slated for closing in the middle of this year, EIP will be funded through that readout in the second half of 2024. EIP’s equity and debt holders will own about 77.25% of the combined company.

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Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

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See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

Alec­tor cuts 11% of work­force as it dou­bles down on late-stage neu­ro pro­grams part­nered with GSK, Ab­b­Vie

A month after revealing plans to concentrate on its late-stage immuno-neurology pipeline, Alector is trimming its headcount by 11%.

The layoffs will impact around 30 employees across the organization, the company disclosed in an SEC filing, adding that the plan will “better align the company’s resources” with the new strategy. With $712.9 million in cash, cash equivalents and investments as of the end of 2022, Alector believes the reserves will now get it through 2025.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

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