Terns Phar­ma­ceu­ti­cals touts safe­ty da­ta from an ex-Eli Lil­ly can­di­date in the hunt for NASH treat­ment

While many oth­ers have tried — and failed — to get a NASH can­di­date across the fin­ish line, Terns Phar­ma­ceu­ti­cals thinks its FXR ag­o­nist will even­tu­al­ly earn its wings with­out the safe­ty is­sues that have slowed oth­ers down. Now, a mid-stage safe­ty read­out could help add some va­lid­i­ty to those hopes.

No pa­tients in the Phase IIa LIFT study dis­con­tin­ued TERN-101 due to side ef­fects, CMO Erin Quirk said dur­ing a call with in­vestors on Mon­day morn­ing. That in­cludes pru­ri­tus, an un­com­fort­able itch­ing sen­sa­tion that fre­quent­ly leads pa­tients to drop out of oth­er FXR ag­o­nist stud­ies.

Senthil Sun­daram

“This is the first of sev­er­al im­por­tant mile­stones that pro­vide val­i­da­tion for Terns’ pipeline over the next 12 months or so,” CEO Senthil Sun­daram said.

NASH, or non­al­co­holic steato­hep­ati­tis, refers to fat buildup in the liv­er that caus­es in­flam­ma­tion and scar­ring. TERN-101 tar­gets FXR, a nu­clear re­cep­tor in the liv­er, in­tes­tine and kid­neys that reg­u­lates the he­pat­ic ex­pres­sion of var­i­ous genes in­volved in lipid me­tab­o­lism, in­flam­ma­tion and fi­bro­sis.

Eleven out of the 74 pa­tients treat­ed with TERN-101 came down with pru­ri­tus, in­clud­ing four in the high­est dose group, Terns said. Pa­tients re­ceived one of three dos­es — 5 mg, 10 mg or 15 mg — over 12 weeks. There were no treat­ment-re­lat­ed se­ri­ous ad­verse events, as two cas­es of Covid-19 and a UTI that sent pa­tients to the hos­pi­tal were not linked to the can­di­date.

“TERN-101 is more high­ly liv­er-dis­trib­uted than oth­er FXR ag­o­nists that have been stud­ied in NASH pa­tients,” Quirk said dur­ing the call, adding that da­ta sug­gest the can­di­date pri­mar­i­ly ac­ti­vates FXR in the liv­er, rather than the in­tes­tine or oth­er or­gans. “We be­lieve that TERN-101’s dif­fer­en­ti­at­ed safe­ty and tol­er­a­bil­i­ty pro­file and im­proved tar­get en­gage­ment, rel­a­tive to oth­er FXR ag­o­nists, is be­cause of its ac­tiv­i­ty in the liv­er.”

Oth­er NASH can­di­dates have run in­to trou­ble with raised LDL cho­les­terol, which in turn can raise car­dio­vas­cu­lar risk. No change in LDL cho­les­terol was re­port­ed in the first two dose groups, but a sta­tis­ti­cal­ly sig­nif­i­cant change (15.9%) was seen in the 15 mg group.

Re­searchers al­so not­ed im­prove­ments in a bio­mark­er known as cor­rect­ed T1 (cT1) re­lax­ation time, an MRI-based test mea­sur­ing free-wa­ter con­tent in liv­er tis­sue. Im­prove­ments of at least 80 mil­lisec­onds were seen in a sig­nif­i­cant pro­por­tion of pa­tients in the 5 mg and 10 mg groups at Week 12 com­pared to place­bo, and sig­nif­i­cant de­creas­es in cT1 were re­port­ed at Week 6 for all dose groups, ac­cord­ing to Terns.

Erin Quirk

“LIFT is the first con­trolled NASH tri­al to show sig­nif­i­cant cT1 im­prove­ment as ear­ly as Week 6,” Quirk said.

Mean rel­a­tive changes in MRI pro­ton den­si­ty fat frac­tion (MRI-PDFF), an imag­ing mark­er that mea­sures liv­er fat con­tent, were -8.4% in the place­bo arm, -15.1% in the 5 mg arm, -19.7% in the 10 mg arm, and -12.9% in the 15 mg arm at Week 12. While the rel­a­tive changes were sig­nif­i­cant at Week 6 for the 10 and 15 mg groups com­pared to place­bo, they weren’t sta­tis­ti­cal­ly sig­nif­i­cant at Week 12, Terns said.

Mean changes in ala­nine transam­i­nase lev­els (ALT), which can in­di­cate a liv­er prob­lem, were -5.3% (place­bo), -2.6% (5 mg), -18% (10 mg), and -13.2% (15 mg).

Terns $TERN stock was up 9% up­on shar­ing the news ear­ly Mon­day morn­ing, then slipped 4% about an hour lat­er.

Terns bagged the rights to TERN-101 back in 2018, along with two oth­er NASH can­di­dates from Eli Lil­ly. Its TERN501, a thy­roid hor­mone re­cep­tor be­ta ag­o­nist, is cur­rent­ly in Phase I, and a com­bi­na­tion tri­al of the two is ex­pect­ed to kick off in the first half of next year.

While 2019 was ini­tial­ly dubbed “The Year of NASH” by Gold­man Sachs, the year quick­ly turned in­to the year of NASH fail­ures, the most no­table among them Gilead’s. CymaBay went from a $1 bil­lion com­pa­ny to a $100 mil­lion com­pa­ny af­ter they found their drug ap­peared to be mak­ing pa­tients worse. Cir­ius with­drew an $86 mil­lion IPO bid af­ter a bad read­out.

The bad luck con­tin­ued in­to 2020, as In­ter­cept, which pulled ahead with pos­i­tive Phase III re­sults, wound up with a re­jec­tion for their long-watched NASH drug last June. And af­ter fail­ing a Phase III show­down, Gen­fit ex­it­ed NASH al­to­geth­er and made plans to lay off 40% of its work­force back in Oc­to­ber.

Ab­b­Vie cur­rent­ly has a Phase I FXR ag­o­nist for NASH, which it in­her­it­ed in the Al­ler­gan buy­out.

At first, the idea be­hind Terns — named af­ter the small, tough wa­ter bird — was to part­ner a Cal­i­for­nia-based dis­cov­ery team with a small de­vel­op­ment group in Chi­na to ef­fi­cient­ly de­vel­op new drugs pri­mar­i­ly for the Chi­nese mar­ket. But back in Jan­u­ary, a spokesper­son for the com­pa­ny told End­points News that the com­pa­ny has since shift­ed to fo­cus more on build­ing a head­quar­ters and de­vel­op­ment team in Cal­i­for­nia.

While Terns con­tin­ues to “have an eye on ad­di­tion­al glob­al mar­kets,” their cur­rent fo­cus is on the US, where clin­i­cal tri­als for their three lead pro­grams will oc­cur, the spokesper­son said.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UP­DAT­ED: Roivant bumps stake in Im­muno­vant with a $200M deal. But with M&A off the ta­ble, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

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Sanofi preps a multi­bil­lion-dol­lar buy­out of an mR­NA pi­o­neer af­ter falling be­hind in the race for a Covid-19 jab — re­port

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

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Alan Hirzel, Abcam

Drug sup­pli­er Ab­cam brings a long­time col­lab­o­ra­tor in house as part of $340M buy­out pact

BioVision has supplied Abcam with research tools since 1999, and now the two are making it official as part of a merger unveiled Monday.

Abcam will buyout BioVision as part of a $340 million acquisition deal to bring aboard the supplier’s biochemical and cell-based assays for biological research, as well as recombinant proteins, antibodies and enzymes.

The deal will give Abcam control of BioVision’s portfolio and allow for both the expansion of research existing areas of focus such as oncology, neuroscience and epigenetics and preparation to expand into new products. As a part of the deal, Abcam will develop and supply products and services to NKY, the previous owner of BioVision and receive support for ongoing development and commercialization of in vitro diagnostic products.

Tib­so­vo clears an­oth­er hur­dle for Servi­er, but can it make Agios' old drug prof­itable?

When European regulators saw the data Agios used to win US approval for their AML drug Tibsovo, they sent the more than decade-old biotech back to the drawing board. A single, single-armed trial was not going to cut it.

On Monday, though, the drug’s new owners announced it had cleared a more rigorous study. In a randomized, Phase III trial of certain newly diagnosed patients, those who received a combination of Tibsovo and chemotherapy lived longer than those who received a combination of placebo and chemotherapy. Those patients also had higher response rates and complete remission rates.

UP­DAT­ED: Watch out Glax­o­SmithK­line: As­traZeneca's once-failed lu­pus drug is now ap­proved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

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Not all mR­NA vac­cines are cre­at­ed equal. Does it mat­ter?; Neu­ro is back; Pri­vate M&A af­fair; 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.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

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Bris­tol My­ers pulls lym­phoma in­di­ca­tion for Is­to­dax af­ter con­fir­ma­to­ry tri­al falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

Rick Pazdur (via AACR)

FDA's on­col­o­gy head Rick Paz­dur de­fends the ac­cel­er­at­ed ap­proval path­way, claim­ing it is 'un­der at­tack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

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