Unum plays its first glimpse of hu­man da­ta in an $86M IPO, re­veal­ing two deaths and an FDA hold

Chuck Wil­son

Af­ter pro­mot­ing one of his top ex­ecs to pres­i­dent and bring­ing in two new board mem­bers, Unum Ther­a­peu­tics CEO Chuck Wil­son end­ed the week by putting the first snap­shot of pos­i­tive hu­man da­ta from their lead cell ther­a­py for can­cer on dis­play in an $86 mil­lion IPO fil­ing. But with just a hand­ful of pa­tients in the first round of clin­i­cal tri­als, Unum is al­so re­veal­ing pub­licly for the first time that it ran square­ly in­to lethal rates of dose-lim­it­ing tox­i­c­i­ty that killed two pa­tients in one arm and forced it to aban­don their high dose af­ter the FDA slapped a clin­i­cal hold on the study.

That hold was on­ly re­cent­ly lift­ed some­time last month, ac­cord­ing to the fil­ing. Unum kept word of the deaths and the hold out of the news for three months while it was on a road show for the IPO.

In re­sponse to a query, pres­i­dent and CFO Chris­tiana Sta­moulis said in an email:

As you know we are in the qui­et pe­ri­od and un­for­tu­nate­ly we can­not pro­vide any com­ments at this point.

The biotech — one of many that has built a rep around a top team and re­li­able ven­ture back­ers — has been build­ing a new cell ther­a­py that en­gi­neers pa­tient’s T cells in­to a dou­ble wham­my on can­cer cells. The cells are first de­signed to ex­press AC­TR, a chimeric pro­tein en­com­pass­ing pro­teins from T cells and nat­ur­al killer cells, then com­bined with an­oth­er tu­mor-spe­cif­ic drug, whip­ping up a cy­to­tox­ic as­sault on can­cer cells.

The lead drug is AC­TR087, and Unum is al­ready com­par­ing it to Gilead’s Yescar­ta and Kym­ri­ah, the two pi­o­neer­ing CAR-Ts on the mar­ket. A com­bi­na­tion with Rit­ux­an, re­searchers test­ed a low dose (0.5 x 106 AC­TR T cells/kg) in 7 NHL pa­tients and tracked 6 re­spons­es, in­clud­ing two com­plete and a par­tial re­sponse. That looks good com­pared to 39% and 32% com­plete re­sponse rates re­port­ed at three months for Yescar­ta and Kym­ri­ah. And they re­port­ed no se­ri­ous ad­verse events.

The high dose (1.5 x 106 AC­TR T cells/kg) was lethal, killing 2 of just 9 pa­tients in that arm. That’s not the first time se­vere tox­i­c­i­ty has killed pa­tients in an ex­plorato­ry ear­ly-stage cell ther­a­py study, but the lengthy de­lay be­tween the deaths and the SEC fil­ing is like­ly to spur in­tense crit­i­cism. The FDA re­spond­ed by putting the study on hold, some­thing Unum nev­er pre­vi­ous­ly dis­closed. From the S-1:

The se­vere AC­TR087-re­lat­ed SAEs we ob­served in Dose Lev­el Two re­sult­ed in the FDA plac­ing this tri­al on clin­i­cal hold in De­cem­ber 2017 pend­ing sub­mis­sion of cer­tain in­for­ma­tion re­lat­ing to the ATTCK-20-2 clin­i­cal tri­al. The clin­i­cal yy­hold was re­moved in Feb­ru­ary 2018, fol­low­ing re­view of this in­for­ma­tion by the FDA. Sev­er­al pro­to­col and dos­ing changes were made in ear­ly 2018, which we ex­pect to re­duce the in­ci­dence of ad­verse events and bet­ter man­age those events that do oc­cur.

Re­searchers con­clud­ed that there were two cas­es of AC­TR087-re­lat­ed se­vere CRS — one fa­tal — and one pa­tient died from AC­TR087-re­lat­ed neu­ro­tox­i­c­i­ty. There was one fa­tal case of en­te­ro­coc­cal sep­sis con­sid­ered re­lat­ed to AC­TR087 and “one pa­tient sub­se­quent­ly ex­pe­ri­enced a fa­tal case of sep­sis con­sid­ered not re­lat­ed to AC­TR087,” ac­cord­ing to the S-1.

Cy­tokine re­lease storms and neu­ro­tox­i­c­i­ty are not new in the cell ther­a­py world, as Juno found out through a string of deaths linked to their first dead­ly, and now dis­card­ed, CAR-T. Gilead’s Kite and No­var­tis, though, were able to com­plete reg­is­tra­tion stud­ies with­out rais­ing the same con­cerns.

Safe­ty con­cerns are a key fea­ture in cell ther­a­py re­search, but the FDA rules put a wall around in­for­ma­tion and pre­vent the agency from dis­cussing any of this, leav­ing biotechs some wide dis­cre­tion on how they han­dle this in­for­ma­tion. As we saw with Sol­id Bio­science’s 11th hour up­date about a par­tial tri­al hold for their Duchenne MD gene ther­a­py due to safe­ty con­cerns, pri­vate biotechs can re­ly on the FDA’s si­lence to keep safe­ty is­sues a se­cret, wait­ing un­til SEC rules re­quire a dis­clo­sure. And for promi­nent bioethi­cists in the field, that’s a prob­lem­at­ic is­sue.

I asked bioethi­cist Arthur Ca­plan at New York Uni­ver­si­ty’s Lan­gone Med­ical Cen­ter what his per­spec­tive was. His an­swer, by e-mail:

Don’t know Unum case, but I do know of nu­mer­ous in­stances in which com­pa­nies had deaths dur­ing ear­ly clin­i­cal tri­als that they chose not to pub­licly dis­close. They told the FDA but FDA does not re­veal in­for­ma­tion in­clud­ing deaths that are of­fered as part of com­mer­cial de­vel­op­ment.

Ab­surd­ly more weight is giv­en to keep­ing deaths a se­cret in or­der to bol­ster the fi­nan­cial prospects of new com­pa­nies and their in­vestors than to pro­tect­ing the wel­fare of hu­man sub­jects and ul­ti­mate­ly the safe­ty of the pub­lic should drugs or ther­a­pies be ap­proved in the USA or oth­er na­tions.

At a min­i­mum re­searchers ought to know if a path they are pur­su­ing has re­sult­ed in death(s) so as not to repli­cate the risks for their sub­jects.  How best to do this I am not sure but putting trade se­cre­cy over hu­man wel­fare is a sad or­der­ing of pri­or­i­ties.

Unum has three dif­fer­ent Phase I pro­grams in the clin­ic, with an­oth­er head­ed to hu­man stud­ies in the near fu­ture. The biotech has a col­lab­o­ra­tion deal in place with Seat­tle Ge­net­ics which com­bines a BC­MA ther­a­py with AC­TR087 for mul­ti­ple myelo­ma.

Seat­tle Ge­net­ics has paid over $32.5 mil­lion in the deal so far, with ven­ture back­ers com­ing up with $77.3 mil­lion.

One of the big ad­van­tages that Unum hopes to prove is that by con­cen­trat­ing on CD16 bind­ing they can use the same ba­sic ap­proach for all their ther­a­pies, mak­ing it sim­pler to de­sign and man­u­fac­ture than the break­through drugs now on or close to the mar­ket.

For a ven­ture-backed com­pa­ny, Unum al­so re­vealed an un­usu­al­ly high re­serve of stock for two key play­ers at the biotech: Dario Cam­pana, the sci­en­tif­ic founder and a well known cell ther­a­py ex­pert, and CEO Wil­son. Each owns 21.7% of the stock.

At­las, mean­while, owns 13.9% while F-Prime is in it for 9.9%.

Karen Fer­rante and Robert Perez joined Uum’s board last week, while CFO Chris­tiana Sta­moulis added the pres­i­dent’s ti­tle to her re­sume. Bruce Booth at At­las is chair­man of the board.

Albert Bourla appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

UP­DAT­ED: Pfiz­er CEO Al­bert Bourla is back in the M&A game, but why is he pay­ing $11.4B for Ar­ray?

Pfiz­er $PFE has cut short its time on the side­lines of bio­phar­ma M&A.

Mon­day morn­ing the phar­ma gi­ant un­veiled an $11.4 bil­lion deal to ac­quire Ar­ray Bio­Phar­ma, beef­ing up its on­col­o­gy work and adding a new re­search hub in Boul­der, Col­orado to its glob­al op­er­a­tions.

At $48 a share, Ar­ray $AR­RY in­vestors will be get­ting a 62% pre­mi­um off the Fri­day close of $29.59.

Pfiz­er, which has strug­gled to gain all the up­side promised in past buy­outs like Medi­va­tion, high­light­ed the ac­qui­si­tion of 2 ap­proved drugs in the deal — Braftovi (en­co­rafenib) and Mek­tovi (binime­tinib).

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Gene ther­a­py R&D deals turn red hot as Big Phar­ma steps up to play

This September will mark the 20th anniversary of the death of Jesse Gelsinger, a young man suffering from X-linked genetic disease of the liver. He was killed in a gene therapy study conducted by Penn’s James Wilson, and the entire field endured a lengthy deep freeze as the field grappled with the safety issues inherent in the work.

Some thought gene therapy R&D would never survive. But it did. And this year marked a landmark approval for Zolgensma, a new gene therapy for spinal muscular atrophy Novartis priced at $2.1 million.

“Gene therapy is the hottest item on the block now. But there was a time when we first got into this trial, where there wasn’t a person in the world who believed that gene therapy would work. We have to remember that,” noted gene therapy investigator Jerry Mendell told SMA News Today.

We’re still right on the pioneering frontier when it comes to getting approvals for gene therapies and launching marketing campaigns with the European green light for bluebird's leading program last Friday underscoring the nascent nature of the field. But gene therapy R&D is booming, and has been for several years now.

The rapid growth of gene therapy clinical development is well known, but we decided to put some numbers on it, to quantify what’s going on. DealForma chief Chris Dokomajilar took a lot over the past 10 years, as the number of deals, R&D partnerships and buyouts steadily gained steam, spiking last year and on track to maintain the surge in 2019.

The upfronts and totals for the dollars on deals so far in 2019 is already close to the 2018 mark, underscoring a new phase of negotiations as the major players step up to gain a piece of the late-stage and commercial action.

Once again, we’re looking at an “overnight” biotech success story, decades in the making.

At some point, that may start to brake the numbers we’re seeing. But for now, as rivals line up to compete for frontline prominence across a range of diseases, the arrows are all pointed north.

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Exterior of the 1 million square foot Discovery Labs in Upper Merion, PA (PR Newswire)

Philadel­phia cham­pi­ons life sci­ences 'co-work­ing,' re­viv­ing for­mer GSK cam­pus in $500M makeover

In a boost to Philadel­phia’s thriv­ing life sci­ences scene, a for­mer Glax­o­SmithK­line cam­pus and a near­by site has been turned in­to what its de­vel­op­er calls “the largest cowork­ing ecosys­tem” for health­care com­pa­nies in the coun­try.

The Dis­cov­ery Labs, a com­pa­ny spawned by MLP Ven­tures, has se­lect­ed two lo­ca­tions in the King of Prus­sia area as the $500 mil­lion test case for its strat­e­gy of ac­quir­ing and con­vert­ing old phar­ma­ceu­ti­cal R&D fa­cil­i­ties world­wide. The sites add up to 1.64 mil­lion square feet.

A uni­corn stalks Wall Street in search of IPO cash; CASI Phar­ma in-li­cens­es CD19 ther­a­py from Chi­na’s Ju­ven­tas

→ A herd of up­start biotechs will look to Wall Street for some ma­jor wind­falls this week as a burst of new of­fer­ings con­tin­ues to feed cash in­to the R&D sys­tem. To­day we learned that Bridge­Bio will look to raise in the neigh­bor­hood of $225 mil­lion by of­fer­ing 15 mil­lion shares for $14 to $16 each. And they have a string of joint bookrun­ners: J.P. Mor­gan, Gold­man Sachs, Jef­feries, SVB Leerink, KKR, Piper Jaf­fray, Mizuho Se­cu­ri­ties, BMO Cap­i­tal Mar­kets and Ray­mond James. If suc­cess­ful, Bridge­Bio will emerge with a mar­ket cap of around $1.7 bil­lion. There are 5 biotechs look­ing to IPO this week, in­clud­ing Akero and Pre­vail.

UP­DAT­ED: Sanofi Gen­zyme deserts gene ther­a­py de­vel­op­er Voy­ager Ther­a­peu­tics

While gene ther­a­py com­pa­nies re­joice as the sec­tor gains trac­tion with ap­provals and a flur­ry of M&A ac­tiv­i­ty, one play­er is feel­ing the heat.

Back in 2015, Voy­ager Ther­a­peu­tics joined forces with Sanofi Gen­zyme in a deal worth up to $845 mil­lion ($100 mil­lion up­front + a po­ten­tial $745 mil­lion in mile­stones) to co-de­vel­op gene ther­a­pies for se­vere cen­tral ner­vous sys­tem dis­or­ders. But two years lat­er, the French drug­mak­er re­treat­ed, elect­ing to not pick up the op­tion to work on Voy­ager’s Parkin­son’s dis­ease pro­gram. (Last year, the FDA dis­ap­point­ed Voy­ager, telling the com­pa­ny that it was not open to an ac­cel­er­at­ed fil­ing on the Parkin­son’s drug on the ba­sis of Phase II da­ta — in­stead of re­quir­ing an ad­di­tion­al piv­otal study.)

In­vestors fret as VBI's hep B vac­cine fails key sec­ondary PhI­II study goal

Sobered by mount­ing costs, Dy­navax $DVAX last month made the de­ci­sion to fo­cus all its re­sources on its 2017-ap­proved he­pati­tis B vac­cine Hep­lisav-B, which ri­vals and su­per­sedes the ef­fi­ca­cy and con­ve­nience pro­file of GSK’s $GSK es­tab­lished En­ger­ix-B. The Cal­i­for­nia-based com­pa­ny will be on the look­out for an­oth­er com­peti­tor — VBI Vac­cines, which on Mon­day un­veiled late-stage da­ta on its hep B vac­cine: Sci-B-Vac.

John Oyler, Founder & CEO of BeiGene, at the US-China Biopharma Innovation and Investment Summit in Shanghai on October 23, 2018; Credit: Endpoints News, PharmCube

UP­DAT­ED: As Bris­tol-My­ers/Cel­gene tie up loose ends, BeiGene pock­ets $150M from PD-1 breakup

As soon as Bristol-Myers Squibb announced its $74 billion buyout for Celgene, BeiGene emerged as a prominent example of a player whose pact with the big biotech could sour, as its PD-1 candidate seems to overlap with Opdivo. After six months of suspense, the partners say they are finally bringing the 2-year-old deal to an amicable end.

BeiGene $BGNE gets $150 million for the termination in addition to full global rights to tislelizumab. In 2017 Celgene had paid $263 million in upfront license fees to develop the PD-1 inhibitor for solid cancers in the US, Europe, Japan and the rest of the world outside Asia. It also threw in a $150 million equity investment in exchange for BeiGene handling its commercial operations — think Abraxane, Revlimid and Vidaza — in China.

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Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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