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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Man­u­fac­tur­ing woes for No­vavax’s Covid jab bad­ly dis­rupt plans for roll­out to the poor — re­port

Production problems at a Novavax facility in Maryland have led to delays in the Covax vaccine sharing program. Now, a shortage of 1 billion doses is expected, as the supplier tries to navigate producing a shot up to regulators’ standards, Politico reported Tuesday.

The company has run into trouble with the purity of the vaccine. Novavax has had trouble proving it can produce a shot consistently up to standards, and it has caused significant delays in the rollout to low- and middle-income countries. This follows several delays at Novavax that has put the executive crew on the defensive.

Break­ing: Bio­gen sells just $300K worth of Aduhelm in Q3, as ques­tions on long term vi­a­bil­i­ty re­main

Barely anyone is accessing Biogen’s controversial Alzheimer’s treatment, with the company reporting just $0.3 million in Aduhelm sales in the third quarter. Although investors will be looking to the longer term, when CMS may decide to cover the drug and open the floodgates for more coverage, use of the drug is currently stalled.

Since June, when the FDA first signed off on the drug under its accelerated pathway, Biogen said Wednesday that it’s sold a total of $2 million worth of Aduhelm. The total sales numbers indicate that likely about 100 Alzheimer’s patients have so far received the drug, which is priced at $56,000 annually.

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Raymond Stevens, ShouTi Pharma CEO

A new Schrödinger-backed start­up emerges from the sci­en­tist who mapped the first hu­man GPCR

One of the most popular targets in drug development, representing about a third of existing drugs, are G-protein coupled receptors — the tiny but integral membrane proteins responsible for recognizing things like light, taste, smell, hormones and pain.

But due to challenges in mapping their structure, the protein family remains largely unexplored.

A slate of companies has emerged over the last few years to change that. If one can figure out the structure of these elusive membrane receptors, it might be possible to create small molecule drugs that overcome the limitations of, say, biologic and peptide therapies. That promise is what gets serial entrepreneur Raymond Stevens out of bed in the morning.

Carl June (Brian Ach/Getty Images for TIME 100 Health Summit)

Carl June lends 'wings' to Chi­nese CAR-T start­up led by for­mer post­doc, pur­su­ing off-the-shelf ap­proach with CRISPR fla­vor

Carl June still has plenty of energy to bring forth new iterations of CAR-T technology — wherever they’re coming from.

Adding another role to his already lengthy list of titles, June is joining the scientific advisory board at Nanjing Bioheng Biotech, where he will serve as chairman.

The appointment, if slightly out of the ordinary, is both a testament to the fruitfulness of June’s lab at the University of Pennsylvania and China’s increasing appeal to biotech entrepreneurs educated overseas.

Bill Gates at the Global Investment Summit in London, Oct. 19, 2021 (Leon Neal/Pool via AP Images)

Gates Foun­da­tion pledges $120M to ramp up gener­ic sup­ply of Mer­ck­'s Covid-19 pill while ac­tivists blast Pfiz­er's dis­pro­por­tion­ate pow­er

Merck’s molnupiravir may not be officially authorized anywhere in the world yet, but who will get access to it has shaped up to be a huge issue. The Bill & Melinda Gates Foundation is now stepping up to ensure lower-income countries won’t be left behind — and calling on others to follow its lead.

The oral antiviral pill, which was shown to dramatically cut the risk of severe Covid-19 disease and death in a Phase III study, is the latest rallying symbol in the battle against not just the coronavirus but the inequality it’s exposed.