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)

Ven­ture Cap­i­tal as a Strate­gic Part­ner: Fu­el­ing In­no­va­tion be­yond Fi­nance

The average level of investment required for a biotech start-up to succeed is increasing every year, elevating the pressure even further on venture capital to make smart financial investments. Financial investment alone, however, does not always guarantee that exciting innovations can be transformed into real businesses that make a meaningful difference to patients.

Beyond just capital

At Astellas Venture Management (AVM) – a wholly-owned venture capital organization within Astellas, headquartered in the San Francisco Bay Area – capital is just one of the ingredients we offer to add value to our biotechnology investments and partnerships. We generally take a strategic investor approach for companies in our invested portfolio, providing access to expertise, technology and/or resources in addition to the injection of finance. An equity investment from AVM can include access to Astellas’ research and development (R&D) capabilities and expertise, and a global network of partner academic institutions and biotechnology companies, to help advance and accelerate the start-up’s innovation.

UP­DAT­ED: Ver­tex joins Mer­ck, Pfiz­er — re­vamp­ing multi­bil­lion-dol­lar tri­al strat­e­gy as biotech R&D crum­bles

You can add Pfizer, Merck and — as we found out Friday morning — Vertex to the growing list of pharma giants hitting the pause button on a range of clinical trials. But not everyone in R&D is getting a red light.

Vertex says that it’s doing its best to keep working its pipeline strategy, coming up with a plan “to enable virtual clinic visits and home delivery of study drug to ensure study continuity and medical monitoring, and to facilitate study procedures.”

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Covid-19 roundup: In­ter­cept, blue­bird and a grow­ing list of biotechs feel the pain as pan­dem­ic man­gles FDA, R&D sched­ules

Around 100 staffers at Boston area hospitals have now tested positive for Covid-19, spotlighting the growing risk that the pandemic will sideline many of the most essential workers in healthcare as caseloads peak in the US and around the globe. With more than 3,400 deaths, Spain has become the latest country to surpass the official death count attributed to the new coronavirus in China, where the outbreak originated. As of Thursday morning, confirmed global cases had crossed 470,000 and the death count eclipsed 21,000.

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Af­ter crit­ics lam­bast­ed Gilead for grab­bing the FDA's spe­cial rare drug sta­tus on remde­sivir, they're giv­ing it back

Two days after Gilead won orphan drug status for remdesivir as a potential treatment for Covid-19, they’re handing it back.

The company was slammed from several sides after Gilead reported that the FDA had come through with the special status, which comes with 7 years of market exclusivity, the waiver of FDA fees and some tax credits as well. Typically, everyone who can get orphan status lands it without much of a fuss, but Democratic presidential candidate Bernie Sanders, Public Citizen and other consumer groups were outraged.

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Mod­er­na CEO Stéphane Ban­cel out­lines a short path for emer­gency use of a coro­n­avirus vac­cine

NIAID director Anthony Fauci has left no doubts that it takes 12 to 18 months to get a new vaccine tested and in commercial use, in the best of circumstances. But in times of a global emergency — like these — maybe there’s another, faster route to follow.

In an SEC filing on Tuesday, Moderna $MRNA staked out a record-setting pathway to getting their mRNA vaccine into the frontline of the healthcare response as early as this fall. The SEC filing notes that CEO Stéphane Bancel told Goldman Sachs that an emergency use approval could allow the vaccine to go to healthcare workers and certain individuals in a matter of months — presumably provided the NIH sees the safety and efficacy data they would need from the Phase I.

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Caught in a Covid-19 mael­strom, Eli Lil­ly locks down clin­i­cal tri­als as multi­bil­lion-dol­lar R&D ops de­rail

The Covid-19 pandemic has derailed Eli Lilly’s $6 billion R&D operations.

The pharma giant reported Monday morning that it has decided to hit the brakes on most new study starts and pause enrollment for most ongoing studies. Lilly adds that it is continuing dosing for ongoing studies, “but with study-by-study consideration.”

The pandemic has severely disrupted healthcare systems around the globe, says Lilly, making it difficult or impossible to conduct studies at many research sites. And there’s no timeline for when it expects to get back on track.

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As share buy­backs come un­der scruti­ny, what's in store for the bio­phar­ma in­dus­try?

Stock buybacks are not to be permitted for companies that will be bailed out in the coronavirus stimulus package, Congressional leaders have signaled. To what degree the biopharma industry has relied on buybacks for earnings growth in recent years, and if the trend continues, are the big questions as scrutiny into the practice heightens and balance sheets weaken with the coronavirus pandemic wreaking havoc on global economies.

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A Sin­ga­pore VC rais­es $200M for a new round, but will Covid-19 pre­vent it from rais­ing the rest?

A top Singaporean biotech venture fund is nearly halfway toward its largest ever fund, but in a sign of what could be in store for VCs amid a global economic freeze, said they could face headwinds raising the other half.

Vickers Venture Partners has secured $200 million out of a targeted $500 million for its 6th fund, first announced in early 2018. They’ve given themselves 13 months to complete the financing, Vickers founder Finian Tan told Deal Street Asia, but the financial frost settling amid the Covid-19 pandemic could slow efforts.

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Strug­gling Unum ex­ecs are ready to con­sid­er a sale, merg­er or any deal that comes its way

Unum $UMRX is working its way through a survival plan of sorts.

After getting hit with a trio of FDA holds in its brief public history and triggering its second pivot to a new lead drug program while laying off 60% of the staff, the troubled penny stock biotech Unum Therapeutics has hatched new plans to secure financial backing while lining up a go-forward strategy for the company.

First, Lincoln Park Capital Fund has agreed to buy up to $25 million of the long-suffering stock, as Unum directs. And the executive team — led by CEO Chuck Wilson — has put everything on the table for consideration: a sale, acquisition, merger, licensing deal, you name it. The ACTR707 program, meanwhile, is being formally wrapped up — their second failed lead program.