Five Prime claims a big win in topline da­ta for their come­back gas­tric can­cer drug as shares sky­rock­et

Five Prime Ther­a­peu­tics $FPRX has kept a rel­a­tive­ly low pro­file fol­low­ing a flop in pan­cre­at­ic can­cer in late 2017. But the biotech de­clared vic­to­ry in gas­tric can­cer Tues­day af­ter re­leas­ing topline da­ta from a 155-per­son Phase II study.

The South San Fran­cis­co-based com­pa­ny an­nounced that its ex­per­i­men­tal drug be­mar­ituzum­ab, in com­bi­na­tion with chemother­a­py, met all of its pre-spec­i­fied ef­fi­ca­cy end­points. Five Prime was aim­ing for a new path­way in the fi­brob­last growth fac­tor re­cep­tor 2b, which is over­ex­pressed in about 30% of all HER2 neg­a­tive gas­tric can­cers, the com­pa­ny says.

In­vestors were thrilled with the news, as the com­pa­ny’s stock price near­ly quadru­pled with­in an hour of the an­nounce­ment. Ahead of Wednes­day’s bell, the shares re­main up by about 400%.

He­len Collins

For ef­fi­ca­cy, Five Prime set their sights on p-val­ues for a 2-sided al­pha of less than 0.2, rather than the typ­i­cal 0.05. That plan in­volved the three end­points of pro­gres­sion free sur­vival, which was the pri­ma­ry, over­all sur­vival and over­all re­sponse rate. CMO He­len Collins tells End­points News their sta­tis­ti­cal analy­sis plan fol­lowed this strat­e­gy be­cause the tri­al was a small Phase II tri­al, rather than a large Phase III.

“We had pre-spec­i­fied the sta­tis­ti­cal sig­nif­i­cance at 0.2, which is typ­i­cal­ly what you do for a Phase II tri­al be­cause it’s much small­er than a Phase III,” Collins said. “And our goal of this tri­al was to get a greater un­der­stand­ing of ex­act­ly who ben­e­fits and who doesn’t ben­e­fit, so that’s the main thing. And this is in some oth­er ways much bet­ter than a typ­i­cal Phase II be­cause it’s ran­dom­ized, dou­ble-blind, place­bo-con­trolled and that’s why we’re thrilled to see the ben­e­fit that we’re see­ing.”

For pro­gres­sion-free sur­vival, out­comes im­proved from 7.4 months to 9.5 months, hit­ting a p-val­ue of 0.073, while over­all re­sponse rate im­proved by 13.1%, good for a p-val­ue of 0.106. But in over­all sur­vival, which CEO Tom Civik lat­er said in a call to in­vestors would like­ly be the pri­ma­ry for a po­ten­tial Phase III tri­al, Five Prime saw a me­di­an of 12.9 months in the con­trol arm and did not reach a fig­ure in the treat­ment arm. That hit a p-val­ue of 0.027.

Civik not­ed in that call that over­all sur­vival for the stan­dard of care is gen­er­al­ly 5 to 7 months.

Orig­i­nal­ly, Five Prime set out to con­duct this tri­al as a Phase III in­tend­ing to en­roll about 550 pa­tients back in 2018, Civik told End­points News. But af­ter paus­ing en­roll­ment last No­vem­ber, the com­pa­ny con­vert­ed the study in­to a Phase II this past May in or­der to get a look at the da­ta soon­er.

Though Collins said the pur­pose of this tri­al was “not de­signed to be filed” to the FDA giv­en the high­er p-val­ues, Civik said the com­pa­ny is go­ing to ap­proach reg­u­la­to­ry bod­ies to see how they view the da­ta.

Tom Civik

“We’ve got 155 pa­tients and the tri­al was ex­e­cut­ed just like a Phase III tri­al, so we’ve got quite a bit of sub­groups that we can in­ter­ro­gate,” Civik said. “We’re go­ing to take our time and make sure we ful­ly go through all that da­ta, and then we will start talk­ing to reg­u­la­to­ry au­thor­i­ties across the world about what are the next steps. The study was not de­signed as a Phase II to be la­bel-en­abling, but it would be com­plete­ly ap­pro­pri­ate for us to have those con­ver­sa­tions with the au­thor­i­ties as to what they think of the da­ta and to what the po­ten­tial next steps might be.”

For safe­ty, side ef­fects were com­pa­ra­ble in both arms at all lev­els, with grade 3 events oc­cur­ring more fre­quent­ly in the treat­ment arm 82.9% to 74%. More pa­tients dis­con­tin­ued be­mar­ituzum­ab com­pared to place­bo 34.2% to 5.2%.

Cowen an­a­lyst Boris Peak­er is peg­ging peak sales at around $400 mil­lion an­nu­al­ly in the US, with an ex­pect­ed piv­otal Phase III like­ly to take two years. In the best case sce­nario, that could re­sult in a po­ten­tial ap­proval some­time in 2023, he wrote to in­vestors.

Wed­bush’s Robert Driscoll took a high­ly pos­i­tive view of the re­sults as well, writ­ing to in­vestors:

Giv­en the con­sis­ten­cy of the da­ta with oth­er 1L gas­tric can­cer stud­ies, high qual­i­ty na­ture of this dou­ble-blind, place­bo-con­trolled study, as well as the sig­nif­i­cant un­met need, we see po­ten­tial for ac­cel­er­at­ed ap­proval for be­ma in FGFR2b-over­ex­press­ing gas­tric can­cers.

Part­nered with Chi­na’s Zai Lab, be­mar­ituzum­ab is a tar­get­ed an­ti­body that blocks FGFs from bind­ing and ac­ti­vat­ing FGFR2b, and Five Prime hopes that it will in­hib­it sev­er­al path­ways. Though the tri­al was mea­sured for gas­tric and gas­troe­sophageal junc­tion can­cers, the drug could be ap­plied to oth­er can­cers with the FGFR2b tar­get.

Robert Bradway (Photographer: Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Am­gen snaps up can­cer drug play­er Five Prime, adding PhI­II-ready FGFR2b drug in $2B M&A play

Amgen is making a long-awaited move on the M&A side, buying South San Francisco-based Five Prime $FPRX for close to $2 billion and adding a slate of new cancer drugs to the pipeline.

Amgen is paying $38 a share, putting the deal value at $1.9 billion. The stock closed at $21.26 last night, giving investors a 78% premium.

The jewel in the crown of this deal is bemarituzumab, which Amgen describes as a first-in-class, Phase III-ready anti-FGFR2b antibody. Amgen was drawn to the bargaining table by Five Prime’s mid-stage data on gastric cancer, satisfied by PFS and OS data helping to validate FGFR2b as a target. Amgen researchers will now expand on the R&D program in other epithelial cancers, including lung, breast, ovarian and other cancers.

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David Liu (Casey Atkins Photography courtesy Broad Institute)

David Liu has a new big idea: pro­teome edit­ing. It could one day shred tau, RAS and some of the worst dis­ease-caus­ing pro­teins

Before David Liu became famous for inventing new forms of gene editing, he was known around academia in part for a more obscure innovation: a Rube Goldberg-esque system that uses bacteria-infecting viruses to take one protein and turn it into another.

Since 2011, Liu’s lab has used the system, called PACE, to dream up fantastical new proteins: DNA base editors far more powerful than the original; more versatile forms of the gene editor Cas9; insecticides that kill insecticide-resistant bugs; enzymes that slide synthetic amino acids into living organisms. But they struggled throughout to master one of the most common and powerful proteins in the biological world: proteases, a set of Swiss army knife enzymes that cut, cleave or shred other proteins in everything from viruses to humans.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Eli Lil­ly claims a TKO in its long-run­ning ti­tle fight with No­vo Nordisk for the block­buster di­a­betes mar­ket — but there’s a hitch

Eli Lilly isn’t just gunning for a better diabetes drug in tirzepatide. They want to cut ahead of Novo Nordisk’s blockbuster rival Ozempic (semaglutide) on the obesity front as well. But a newly-claimed win in a head-to-head Phase III showdown over reducing A1C while shedding pounds — complete with clear evidence of superiority over the approved rival — could prove a tough sell right now.

Let’s start with the latest data from Lilly.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slapdown, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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Cedric Francois, Apellis CEO (Apellis)

Apel­lis joins the grow­ing num­ber of bio­phar­mas scrap­ping a failed Covid-19 pro­gram af­ter an ear­ly flop

The global pandemic set off a frenzy of R&D activity as biotechs around the world scrambled to see if they could come up with a new medication or vaccine to help fight back. But even as the mRNA standouts are highlighting the market El Dorado open to successful teams, the failures are starting to pile up.

Thursday afternoon it was Apellis’ $APLS turn to deep-six a new drug.

The biotech reports that their C3 therapy APL-9 had failed to move the needle on mortality when combined with standard of care, as compared to SOC alone.

Norbert Bischofberger (Kronos)

Kro­nos seals pact with reg­u­la­tors to hunt AML with pre­vi­ous­ly off-lim­its bio­mark­er end­point

As head of R&D at Gilead, Norbert Bischofberger shelved the SYK inhibitor entospletinib after it proved to need too lengthy a development cycle to win approval. The FDA heard those concerns and will now give entospletinib, once again under Bischofberger’s watchful eye at Kronos, a faster shot on goal.

Kronos has reached an agreement with the FDA to conduct a Phase III trial with a unique primary endpoint, the company announced Thursday, one that it hopes will accelerate entospletinib’s path forward in a certain type of acute myeloid leukemia. The endpoint is measurable residual disease (MRD) negativity, which Kronos says can paint a clearer picture when it comes to the study’s complete response rate.