Loxo takes cen­ter stage at AS­CO with its ground­break­ing shot at a bio­mark­er-based can­cer drug ap­proval

CHICA­GO — Loxo On­col­o­gy made it in­to the AS­CO show­case over the week­end, boast­ing of a small but grow­ing num­ber of cas­es where chil­dren and adults with TRK fu­sion can­cer re­spond­ed to their lead drug, larotrec­tinib (LOXO-101). And they’re pack­ag­ing it in­to a new drug ap­pli­ca­tion they ex­pect to hus­tle to reg­u­la­tors ei­ther lat­er this year or ear­ly 2018, while show­ing off a next-gen drug com­ing up the pipeline that they’re al­ready claim­ing has es­tab­lished proof-of-con­cept ev­i­dence of ef­fi­ca­cy in two cas­es.

This Stam­ford, CT-based biotech $LOXO is all about hus­tle.

For a small com­pa­ny with just 35 staffers, Loxo has enor­mous am­bi­tions that in­clude shoot­ing at some ground­break­ing ad­vances in drug de­vel­op­ment. At AS­CO, the biotech boast­ed a 76% tu­mor re­sponse rate among pa­tients with mul­ti­tude of dif­fer­ent tu­mor types. Un­like a typ­i­cal can­cer drug fo­cused on the anato­my, Loxo is go­ing af­ter a bio­mark­er — tropomyosin re­cep­tor ki­nase (TRK) fu­sions — and at AS­CO it cob­bled to­geth­er re­sponse da­ta from three ear­ly-stage tri­als.

Specif­i­cal­ly there were 50 pa­tients — 43 adults and 12 chil­dren — with 12% com­plete and 64% par­tial re­spon­ders. That’s a high rate of suc­cess and it fits with their ear­li­er state­ments on progress in the clin­ic. Small groups of pa­tients like this are al­so not un­usu­al for a can­cer type shared by on­ly a few thou­sand US pa­tients.

The in­vestor crowd ate it up. Loxo’s shares spiked 51% mid­day Mon­day.

Just days ago Mer­ck won the first pi­o­neer­ing ap­proval for the ge­net­i­cal­ly de­fined use of a can­cer drug, an­oth­er boost for its glob­al star Keytru­da. Larotrec­tinib is be­ing pushed down the same path­way, but it is ex­per­i­men­tal. And Loxo is the po­lar op­po­site of a gi­ant like Mer­ck, which has been pour­ing cash in­to its well-es­tab­lished Keytru­da pro­gram in si­mul­ta­ne­ous pur­suit of dozens of tar­gets.

Josh Bilenker, Loxo On­col­o­gy

Go­ing af­ter an FDA ap­proval for both chil­dren and adults like this “has nev­er been done be­fore,” Loxo CEO Josh Bilenker tells me. But he is ab­solute­ly con­vinced that the da­ta he has is enough to form the ba­sis of a win­ning ap­pli­ca­tion.

It’s not un­usu­al these days to see bio­phar­ma com­pa­nies use ear­ly-stage da­ta to go af­ter an ac­cel­er­at­ed ap­proval at the FDA. What was once the ex­cep­tion is now the rule. But Loxo — which part­nered with Ar­ray on the pro­gram — is press­ing the en­ve­lope, us­ing small groups of pa­tients across Phase I and II tri­als to pro­vide the ev­i­dence they need that larotrec­tinib works. That strat­e­gy is nec­es­sary to achieve their goal, they say, and they have the agency’s break­through ther­a­py des­ig­na­tion to pro­vide an open door, which Bilenker says led to a meet­ing with the FDA 18 months ago that set them on this path.

As a pub­lic com­pa­ny, Loxo al­so has tout­ed — and ben­e­fit­ed — from just about every scrap of da­ta ex­ecs can lay its hands on, with new in­stances of par­tial re­spons­es used to rev up its stock price.

In Chica­go Sat­ur­day, that strat­e­gy was on full view as they not­ed the first glim­mer of ev­i­dence that its next-gen drug LOXO-195 trig­gered two par­tial re­spons­es af­ter it was used in emer­gency cas­es in­volv­ing re­sis­tance to a TRK fu­sion in­hibitor.

Cour­tesy Loxo On­col­o­gy.

If in fact they can prove that it can work against cas­es of TRK fu­sion drug re­sis­tance, their drug could be­come a reg­u­lar part of the treat­ment land­scape for pa­tients with their bio­mark­er. And they will tout any ev­i­dence of ef­fi­ca­cy they gath­er on their next trip to reg­u­la­tors.

Loxo’s mar­ket cap is up to $1.3 bil­lion as some mar­ket an­a­lysts cheer them at every stage.

Loxo, though, al­so has com­pe­ti­tion in the field. Igny­ta $RXDX has a Phase II un­der­way for en­trec­tinib for TRK-fu­sion pos­i­tive adult and pe­di­atric pa­tients. Just a cou­ple of weeks ago Igny­ta won their own break­through stays for their drug, giv­ing them the same easy ac­cess that Loxo en­joys. And not all an­a­lysts are ig­nor­ing the po­ten­tial for a matchup as these two small out­fits com­pete for the lime­light in can­cer R&D.

“The com­pa­ny guid­ed for NDAs for Trk+ and ROS1+ pts in 2018 and a U.S. launch in 2019 (MAA sub­mis­sion in 2019),” not­ed Jef­feries re­cent­ly. “The break­through des­ig­na­tion for en­trec­tinib helps lev­el the play­ing field some with LOXO-101, which re­ceived BTD in Ju­ly 2016 (NDA sub­mis­sion ex­pect­ed in late-2017 or ear­ly-2018).”

If they do make it to the mar­ket, Bilenker says Loxo plans to set up a com­mer­cial group and launch this it­self. “We own world­wide rights to the drug and that’s our plan,” he says, shrug­ging off the sug­ges­tion of a com­pa­ny sale.

It’s a big goal.

The top 100 bio­phar­ma VCs, Bob Brad­way places $2B bet in can­cer, gene edit­ing pi­o­neer's new big idea, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Before diving in, we had some news to share: Endpoints is launching a premium weekly report focusing on all things regulatory. Coverage will be led by our new senior editor, Zachary Brennan, who joins us from POLITICO. Arsalan Arif has more details in his Publisher’s Note.

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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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Bruce Cozadd, Jazz CEO (Jazz Pharmaceuticals)

Jazz CEO Bruce Cozadd cam­paigned for 6 months to buy GW Phar­ma. A 90% pre­mi­um sealed the deal — along with $17.6M in ‘re­ten­tion’ in­cen­tives

Jazz CEO Bruce Cozadd didn’t beat around the bush.

In his first video meeting with GW Pharma chief Justin Gover last July 8, he offered to pay $172 a share to get the company, which had beaten the odds in getting its remarkable cannabinoid drug Epidiolex across the regulatory finish line for epilepsy. GW’s stock closed at $129 that day.

Cozadd had already done his homework on the financing to make sure he could swing it the way he wanted. He just needed to do some due diligence before making the non-binding bid firm.

UP­DAT­ED: Not 3 weeks af­ter tak­ing Hu­ma­cyte pub­lic, Ra­jiv Shuk­la launch­es an­oth­er blank check com­pa­ny

One of biotech’s earliest SPAC investors is back with another blank-check company, less than a month after his last effort announced its intent to merge.

Rajiv Shukla is intending to take a third lucky winner public with Alpha Healthcare Acquisition III, filing to go public Thursday with a $150 million raise penciled in. The move comes just a couple of weeks after Shukla’s second SPAC said it would jump to Nasdaq in tandem with Laura Niklason’s Humacyte in a $255 million new investment.

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Paul Hudson, Getty Images

How does Paul Hud­son's $13.5M comp pack­age stack up against oth­er CEOs? He's in the 'first quar­tile'

Paul Hudson arrived at Sanofi like a hurricane, chopping off duds in the pipeline, shaking up the C-suite, striking big M&A deals and jumping into the Covid-19 vaccine race — all in an attempt to reboot a pharma giant notorious for its setbacks.

Now, we’re getting a look at what the CEO brought home in his first year on the job.

When all is said and done, Hudson will have made about $6.7 million in 2020, about $2.5 million of which has already been paid. The bigger figure includes a $2.3 million bonus that’s subject to approval at an April meeting, and another $1.8 million in variable compensation that has yet to be paid.

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Af­ter three years of courtship (and turn­downs), Mer­ck pounced on the first glance of clin­i­cal da­ta in $1.85B Pan­dion takeover

It’s almost become cliché for biotech executives to talk about the importance of keeping your options open and being prepared to go all the way. But when it comes to negotiating with a giant like Merck, a little patience can indeed go a long way.

Just ask Pandion Therapeutics.

Days ago we already learned that Merck is shelling out $1.85 billion to pick up the biotech and its slate of autoimmune hopefuls. What we didn’t know until the SEC disclosure dropped Thursday is that the deal comes after Pandion turned down two other proposals from Merck over the past three years and held out until the last minute for a sweetened deal.

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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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