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.

IDC: Life Sci­ences Firms Must Em­brace Dig­i­tal Trans­for­ma­tion Now

Pre-pandemic, the life sciences industry had settled into a pattern. The average drug took 12 years and $2.9 billion to bring to market, and it was an acceptable mode of operations, according to Nimita Limaye, Research Vice President for Life Sciences R&D Strategy and Technology at IDC.

COVID-19 changed that, and served as a proof-of-concept for how technology can truly help life sciences companies succeed and grow, Limaye said. She recently spoke about industry trends at Egnyte’s Life Sciences Summit 2022. You should watch the entire session, free and on-demand, but here’s a brief recap of why she’s urging life sciences companies to embrace digital transformation.

Tom Barnes, Orna Therapeutics CEO

UP­DAT­ED: 'We have failed to fail': Mer­ck gam­bles $250M cash on a next-gen ap­proach to mR­NA — af­ter punt­ing its big al­liance with Mod­er­na

Merck went in deep on its collaboration with Moderna on new mRNA programs, and dropped them all over time, including their RSV partnership. But after writing off what turned out as one of the most successful infectious disease players in the business, Merck is coming in this morning with a new preclinical alliance — this time embracing a biotech that hopes to eventually outdo the famously successful mRNA in a new run at vaccines and therapeutics.

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Bayer's first DTC ad campaign for chronic kidney disease drug Kerendia spells out its benefits

Bay­er aims to sim­pli­fy the com­plex­i­ties of CKD with an ABC-themed ad cam­paign

Do you know the ABCs of CKD in T2D? Bayer’s first ad campaign for Kerendia tackles the complexity of chronic kidney disease with a play on the acronym (CKD) and its connection to type 2 diabetes (T2D).

Kerendia was approved last year as the first and only non-steroidal mineralocorticoid receptor antagonist to treat CKD in people with type 2 diabetes.

In the TV commercial launched this week, A is for awareness, B is for belief and C is for cardiovascular, explained in the ad as awareness of the connection between type 2 and kidney disease, belief that something can be done about it, and cardiovascular events that may be reduced with treatment.

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James Mock, incoming CFO at Moderna

Mod­er­na taps new CFO from PerkinElmer af­ter for­mer one-day CFO oust­ed

When Moderna hired a new CFO last year,  it didn’t expect to see him gone after only one day. Today the biotech named his — likely much more vetted — replacement.

The mRNA company put out word early Wednesday that after the untimely departure of then brand-new CFO Jorge Gomez, it has now found a replacement in James Mock, the soon-to-be former CFO at diagnostics and analytics company PerkinElmer.

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Etleva Kadilli, director of UNICEF’s supply division

GSK lands first-ever UNICEF con­tract for malar­ia vac­cine worth $170M

GSK has landed a new first from UNICEF the first-ever contract for malaria vaccines, worth up to $170 million for 18 million vaccine doses distributed over the next three years.

The vaccine, known as Mosquirix or RTS,S, won WHO’s backing last October after a controversial start, but UNICEF said these doses will potentially save thousands of lives every year.

“We hope this is just the beginning,” Etleva Kadilli, director of UNICEF’s supply division, said. “Continued innovation is needed to develop new and next-generation vaccines to increase available supply, and enable a healthier vaccine market. This is a giant step forward in our collective efforts to save children’s lives and reduce the burden of malaria as part of wider malaria prevention and control programmes.”

Joe Jonas (Photo by Anthony Behar/Sipa USA)(Sipa via AP Images)

So­lo Jonas broth­er car­ries Merz's new tune in Botox ri­val cam­paign

As the lyrics of his band’s 2019 pop-rock single suggest, Joe Jonas is only human — and that means even he gets frown lines. The 33-year-old singer-songwriter is Merz’s newest celebrity brand partner for its Botox rival Xeomin, as medical aesthetics brands target a younger audience.

Merz kicked off its “Beauty on Your Terms” campaign on Tuesday, featuring the Jonas brother in a video ad for its double-filtered anti-wrinkle injection Xeomin.

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Kate Haviland, Blueprint Medicines CEO

Blue­print met all its end­points in bid for ex­pand­ed Ay­vak­it la­bel — but stock trends low­er any­way

Blueprint Medicines announced this morning that the second part of its study on Ayvakit in non-advanced systemic mastocytosis (SM) — a rare disease in which a type of white blood cells known as mast cells builds up — met all endpoints, but the biopharma left key questions unanswered.

In 212 patients, with 141 in the treatment arm and 71 in the control arm, patients who got Ayvakit saw an average 15.6-point decrease in their symptom scores compared to a 9.2-point decrease in the placebo arm at 24 weeks. In an extension study, those on Ayvakit saw their symptom scores drop by 20.2 points by week 48.

Paul Perreault, CSL Behring CEO

CSL CEO Paul Per­reault de­ter­mined to grow plas­ma col­lec­tion af­ter full-year sales dip

As the ink dries on CSL’s $11.7 billion Vifor buyout, the company posted a dip in profits, due in part to a drop in plasma donations amid the pandemic.

However, CEO Paul Perreault assured investors and analysts on the full-year call that the team has left “no stone unturned” when assessing options to grow plasma volumes. The chief executive also spelled out positive results for the company’s monoclonal antibody garadacimab in hereditary angioedema (HAE), though he isn’t revealing the exact numbers just yet.

Blaise Coleman, Endo International CEO

En­do files for Chap­ter 11 as it looks to fin­ish off its opi­oid lit­i­ga­tion

Irish drugmaker Endo International is entering into bankruptcy as it faces the weight of serious litigation related to its involvement in the opioid epidemic in the US.

The company has filed Chapter 11 proceedings in the US Bankruptcy Court for the Southern District of New York, with the company expected to file recognition proceedings in Canada, the UK and Australia. The company’s bankruptcy filing showed the company had assets and liabilities in the range of $1 billion to $10 billion.