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.

Dan Skovronsky, Eli Lilly CSO

UP­DAT­ED: An­a­lysts are quick to pan Eli Lil­ly's puz­zling first cut of pos­i­tive clin­i­cal da­ta for its Covid-19 an­ti­body

Eli Lilly spotlighted a success for one of 3 doses of their closely-watched Covid-19 antibody drug Wednesday morning. But analysts quickly highlighted some obvious anomalies that could come back to haunt the pharma giant as it looks for an emergency use authorization to launch marketing efforts.

The pharma giant reported that LY-CoV555, developed in collaboration with AbCellera, significantly reduced the rate of hospitalization among patients who were treated with the antibody. The drug arm of the study had a 1.7% hospitalization rate, compared to 6% in the control group, marking a 72% drop in risk.

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Everyone in the cancer R&D arena is looking to build new franchises around better drugs and combos. And one busy pocket of that space is centered entirely on creating an IL-2 drug that can be as effective as the original without the toxicity that damned it to the sidelines.

Alkermes $ALKS formally tossed its hat into the ring of contenders at virtual ESMO today, highlighting the first glimpse of efficacy for their candidate, ALKS 4230, as both a monotherapy as well as in combination with Merck’s Keytruda.

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Albert Bourla (Photo by Steven Ferdman/Getty Images)

Pfiz­er match­es Mod­er­na with their full Covid-19 tri­al blue­print — As­traZeneca says it will un­veil its pro­to­col 'short­ly'

Yesterday, after sustained public pressure as Moderna released its Phase III Covid-19 trial blueprint, Pfizer released its own full trial design for their vaccine trials. The move was designed to boost transparency and shore up public trust in the vaccines, but it also revealed differences in how the two companies are approaching the much-watched studies while failing to satisfy the demands of the fiercest advocates for transparency.

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#ES­MO20: Re­gen­eron, Sanofi eye an­oth­er first for their PD-1 con­tender Lib­tayo with promis­ing da­ta for on­col­o­gy niche

Regeneron and Sanofi took another step forward in the long march towards a greatly expanded market for their late-bloomer PD-1 checkpoint Libtayo.

The two occasional allies posted an objective response rate of 31% for Libtayo among 84 patients suffering from advanced cases of basal cell carcinoma at virtual ESMO. That spotlights progress for 26 patients, 5 of whom had a complete response. The data also reflect a boost in the number of responses seen from the last cut of the numbers.

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Albert Bourla, Pfizer CEO (Steven Ferdman/Getty Images)

Pfiz­er ex­ecs con­fi­dent­ly tap their top 10 block­busters-to-be. But what are the chances of sur­viv­ing PhI­II, let alone hit­ting these big peak sales es­ti­mates?

Pfizer’s top executive team doesn’t lack for confidence.

Where many Big Pharmas would be reluctant to put a peak sales figure on their late-stage drugs, Pfizer CEO Albert Bourla has shrugged off the usual diffidence to outline where the pharma giant expects to get $15 billion-plus.

The list, outlined this week during their investor presentations, is topped by 3 drugs in the $3 billion-plus peak sales category. They are:

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Christian Itin, Autolus CEO (Autolus)

#ES­MO20: Au­to­lus pro­vides glimpse of next-gen­er­a­tion CAR-T pro­gram, show­ing ear­ly pos­i­tive safe­ty da­ta

CAR-T therapies were hailed as a breakthrough when Novartis received the first FDA approval for Kymriah back in 2017. Though highly effective at treating certain types of blood cancers, CAR-Ts are also associated with severe and potentially deadly side effects, including lethal instances of cytokine release syndrome.

With this in mind, Autolus Therapeutics is looking to take a crack at a safer CAR-T and presented Phase II cohort data for its AUTO3 program at virtual ESMO 2020. The data showed that, among the 35 patients in the cohort being treated for r/r diffuse large B cell lymphoma, there were no instances of Grade 3 or higher CRS. Eight individuals saw Grade 1 inflammation while another four patients reached Grade 2.

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Stéphane Bancel, Moderna CEO

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The stakes have always been different for Moderna. They didn’t invest more in the Covid-19 vaccine race than Pfizer, Sanofi or AstraZeneca, and they didn’t have more to lose than Novavax — a $100 million biotech that became a $7 billion company virtually overnight. But they had considerably more to gain than anyone.

Born with grand ambitions and the checkbook to match, Moderna spent its first decade of life attracting as many critics of its vision to remake drug development as it did backers. But the pandemic presented a twin opportunity: to prove its technology on a global stage and to give a still-young biotech billions in annual revenue years before anticipated.

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Seat­tle Ge­net­ic­s' Astel­las-part­nered ADC nails con­fir­ma­to­ry PhI­II in urothe­lial can­cer

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Stronger to­geth­er? Boehringer and Mi­rati team to put first KRAS-KRAS com­bo in the clin­ic

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Boehringer Ingelheim and Mirati have signed a collaboration to combine Mirati’s closely-watched lead KRAS inhibitor, MRTX849, in a clinical trial with the pan-KRAS blocker that Boehringer has quietly developed with high expectations behind their flashier contenders.

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