Durable, safe and ef­fec­tive long-term kid­ney drug da­ta from Tri­ci­da fu­el block­buster po­ten­tial

Kid­ney drug de­vel­op­er Tri­ci­da’s shares shot up on Thurs­day, af­ter long-term da­ta high­light­ed its lead drug’s durable ef­fi­ca­cy and safe­ty pro­file as a treat­ment for meta­bol­ic aci­do­sis, in which faulty kid­neys are not able to ex­pel the acid caus­ing a buildup in the body.

The drug — TRC101 — is de­signed to bind to hy­drochlo­ric acid in the GI tract, trig­ger­ing the ejec­tion of acid via ex­cre­tion — there­by di­min­ish­ing acid lev­els and stim­u­lat­ing blood bi­car­bon­ate. The com­pa­ny ex­pects to sub­mit an ap­pli­ca­tion to mar­ket the drug by the sec­ond half of this year for the con­di­tion com­mon­ly caused by chron­ic kid­ney dis­ease (and be­lieved to ac­cel­er­ate the pro­gres­sion of CKD), in­crease the risk of mus­cle wast­ing and cause the loss of bone den­si­ty. If ap­proved, it will be the first drug to win the FDA nod specif­i­cal­ly for meta­bol­ic aci­do­sis.

Ger­rit Klaern­er

Da­ta post­ed last June showed the drug in­duced a sta­tis­ti­cal­ly sig­nif­i­cant in­crease in blood bi­car­bon­ate in 208 pa­tients af­ter 12 weeks in a Phase III study, hours af­ter the com­pa­ny ad­ver­tised plans to go pub­lic in a $150 mil­lion IPO. On Thurs­day, Tri­ci­da re­vealed da­ta from a 40-week ex­ten­sion to that study in the 185 pa­tients that com­plet­ed one year as part of the tri­al.

The drug met all the pri­ma­ry and sec­ondary goals of the ex­ten­sion por­tion of the tri­al. The main goal of the ex­ten­sion study was the as­sess­ment of the long-term safe­ty pro­file of TRC101 ver­sus place­bo — and da­ta showed 2.6% of the pa­tients on TRC101 ver­sus 9.8% on place­bo dis­con­tin­ued the 40-week treat­ment pe­ri­od pre­ma­ture­ly.

Sig­nif­i­cant­ly, da­ta on the drug’s dura­bil­i­ty were al­so pos­i­tive. Over 52 weeks, 63% of the 111 TRC101-treat­ed pa­tients ex­hib­it­ed an in­crease in blood bi­car­bon­ate lev­el of at least 4 mil­liequiv­a­lents per liter, or achieved a blood bi­car­bon­ate lev­el in the nor­mal range — com­pared to 38% of the 74 place­bo sub­jects (p=0.0015).

The sta­tis­ti­cal plan al­so called for the eval­u­a­tion of TRC101 ver­sus place­bo for the com­pos­ite end­point of: all-cause mor­tal­i­ty, dial­y­sis/kid­ney trans­plant or a ≥50% de­cline in es­ti­mat­ed glomeru­lar fil­tra­tion rate (a test used to check how well the kid­neys are work­ing) — DD50 when tak­en to­geth­er — over the 52 week pe­ri­od. Of the 124 sub­jects giv­en TRC101, 4% (5) had a DD50 event, in­clud­ing one pa­tient who ini­ti­at­ed dial­y­sis. In con­trast, of the 93 sub­jects ran­dom­ized to the place­bo group, 10.8% (10) sub­jects had a DD50 event, in­clud­ing four deaths and one who ini­ti­at­ed dial­y­sis.

While the tri­al was not pow­ered to as­sess all-cause mor­tal­i­ty and/or the pro­gres­sion of CKD out­comes, Tri­ci­da said it ob­served a 65% re­duc­tion in the an­nu­al­ized event rate of the com­pos­ite end­point of all-cause mor­tal­i­ty and/or the pro­gres­sion of CKD in TRC101-treat­ed sub­jects ver­sus the place­bo group.

“The 52-week…re­sults far ex­ceed­ed our ex­pec­ta­tions,” said com­pa­ny chief Ger­rit Klaern­er said in a state­ment. “We did not an­tic­i­pate that we would ob­serve ev­i­dence of clin­i­cal ben­e­fit be­yond the in­crease in blood bi­car­bon­ate in pa­tients treat­ed with TRC101 un­til the read out of the re­sults of our post­mar­ket­ing tri­al…in the 2022 to 2023 time­frame.”

Shares of the South San Fran­cis­co-based drug de­vel­op­er $TC­DA leapt more than 57% on Thurs­day, clos­ing at $37.80.

Cowen’s Phil Nadeau, who deemed the da­ta ‘im­pres­sive,’ ex­pects TRC101 will achieve $1 bil­lion in rev­enue by 2025.

(T)here is a ma­jor need to con­trol meta­bol­ic aci­do­sis and slow the pro­gres­sion of CKD. Though sodi­um bi­car­bon­ate is ef­fec­tive, its high sodi­um con­cen­tra­tion makes most CKD pa­tients in­el­i­gi­ble for it…With 25 mil­lion peo­ple in the U.S. hav­ing stage 3, 4, or 5 CKD, TRC101 al­so ad­dress­es a large pa­tient pop­u­la­tion, and even mod­est pen­e­tra­tion could yield bil­lions in sales.

(T)he com­pos­ite end­point da­ta com­bined with the phys­i­cal func­tion­ing scores show clear, clin­i­cal­ly mean­ing­ful ben­e­fits to pa­tients. In fact, the dra­mat­ic re­duc­tion in the com­pos­ite end­point im­plies that physi­cians need to treat at most 3 pa­tients in or­der for 1 to de­rive a clin­i­cal­ly mean­ing­ful re­duc­tion in CKD pro­gres­sion.

Sep­a­rate­ly, Tri­ci­da on Thurs­day said it had amend­ed its debt fa­cil­i­ty with Her­cules Cap­i­tal, rais­ing the to­tal amount avail­able to up to $200 mil­lion from the $100 mil­lion agreed in Feb­ru­ary 2018.

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.