Chas­ing 'Holy Grail' STAT3 tar­get, Hous­ton start­up re­fu­els with $74M to ze­ro in on liv­er can­cer

Ron De­Pin­ho

Tvar­di launched out of Hous­ton with the promise of fi­nal­ly de­vel­op­ing the right in­hibitors for the Holy Grail tar­get of STAT3 — un­der the guid­ance of se­r­i­al en­tre­pre­neur Ron De­Pin­ho and his col­league David Tweardy, a lead­ing ex­pert in the field. Al­most three years lat­er, they say they have the proof of con­cept da­ta to keep go­ing.

It’s good enough for a $74 mil­lion Se­ries B, a big jump from the $9 mil­lion they got in the last round and, CEO Im­ran Al­ib­hai would add, a re­flec­tion of the rep his team has built.

In Phase I dose es­ca­la­tion stud­ies in­volv­ing pa­tients with sol­id tu­mors who have failed all oth­er treat­ments, the lead com­pound was shown to have down­reg­u­lat­ed the STAT3 ac­tiv­i­ty of in­ter­est: block­ing it from be­com­ing phos­pho­ry­lat­ed by the re­cep­tors it typ­i­cal­ly in­ter­acts with.

“The topline news is that in over half of our pa­tients, we’ve seen clin­i­cal ben­e­fit” in the form of tu­mor sta­bi­liza­tion, shrink­age or even par­tial re­spons­es, he said. “That drove a lot of in­ter­est, but be­yond that what’s been strik­ing has been the safe­ty.”

He be­lieves the se­cret lies in fo­cus­ing on pre­vent­ing the ac­ti­va­tion of STAT3, which dri­ves the nu­clear func­tion re­lat­ed to dis­ease, but not try­ing to re­move it from the sys­tem, de­grade it, or break it too much. The small win­dow, af­ter all, is what makes tar­get­ing STAT3 so tricky de­spite it be­ing a top 5 tar­get for can­cer.

David Tweardy

By the first half of next year, Tvar­di ex­pects to wrap up the Phase I tri­al and ze­ro in on he­pa­to­cel­lu­lar car­ci­no­ma in Phase II tri­als — while al­so start­ing to study the drug for fi­bro­sis.

“When you think about growth and dif­fer­en­ti­a­tion in tu­mors, and metas­tases, there’s prob­a­bly three or four legs to the stool, and STAT3 is def­i­nite­ly one of those. Right? It is a cen­tral node,” Al­ib­hai said. “When it comes to fi­bro­sis, there is one leg to the stool. And STAT3 mod­u­lates that path­way. And so if you could find a safe drug that ac­tu­al­ly tar­gets STAT3, you can po­ten­tial­ly see some re­al­ly beau­ti­ful da­ta.”

Oth­ers have ar­rived at the same con­clu­sion, with a small band of star­tups herald­ing new ap­proach­es such as pro­tein degra­da­tion to tar­get STAT3, Sanofi-part­nered Kymera and Medicxi’s Jan­pix (now part of Centes­sa) among them.

For his part, Al­ib­hai said he wel­comes more op­tions for pa­tients and hopes Tvar­di’s oral dos­ing small mol­e­cule treat­ment can set it­self apart. Be­sides, it is not triv­ial to make drugs that can even get in­to the clin­ic.

“What the true test is: Can you ac­tu­al­ly get in, be safe, and be very very very tar­get­ed in the case of STAT3?” he not­ed. “Be­cause there are mul­ti­ple roles for STAT3 in every cell, and so we need to make sure that we’re tar­get­ing ap­pro­pri­ate­ly for the role that we’re in­ter­est­ed in.”

The small com­pa­ny is al­ready work­ing on a sec­ond-gen­er­a­tion mol­e­cule that will be three to eight times more po­tent than the lead can­di­date, he said. And their new in­vestors are in for the long game, giv­ing them the op­tion to ei­ther jump straight in­to an IPO next or raise an­oth­er crossover round and, more im­por­tant­ly, “do some­thing in­ter­est­ing.”

Slate Path Cap­i­tal, Palkon Cap­i­tal, Ar­row­Mark Part­ners and 683 Cap­i­tal joined the round, with sig­nif­i­cant sup­port from Sporos Bioven­tures and oth­er ex­ist­ing in­vestors.

Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Teresa Graham, incoming Roche Pharmaceuticals CEO

In­com­ing Roche CEO builds out his top team, tap­ping Genen­tech vet to lead phar­ma di­vi­sion

Roche announced another leadership shuffle Thursday morning – the head of global product strategy, Teresa Graham, will take over as CEO of Roche Pharmaceuticals in March while the company’s corporate executive committee will make a spot for Levi Garraway, CMO and executive VP of global product development.

Thomas Schinecker will take over the top spot as Roche group CEO in March, leaving his spot as head of diagnostics.

Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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Te­va drops out of in­dus­try trade group PhRMA

Following in AbbVie’s footsteps, Teva confirmed on Friday that it’s dropping out of the industry trade group Pharmaceutical Research and Manufacturers of America (PhRMA).

Teva didn’t give a reason for its decision to leave, saying only in a statement to Endpoints News that it annually reviews “effectiveness and value of engagements, consultants and memberships to ensure our investments are properly seated.”

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Sanofi CFO Jean-Baptiste de Chatillon (L) and CEO Paul Hudson (Romuald Meigneux/Sipa via AP Images)

Sanofi sees downtick in flu sales as it preps for launch of RSV an­ti­body

Sanofi expects its RSV antibody jointly developed with AstraZeneca will be available next season, executive VP of vaccines Thomas Triomphe announced on the company’s quarterly call.

Beyfortus, also known as nirsevimab, was approved in the EU back in November and is currently under FDA review with an expected decision coming in the third quarter of this year. The news comes as the FDA plans to hold advisory committee meetings over the next couple months to review RSV vaccines from Pfizer and GSK.

Christophe Weber, Takeda CEO (Photographer: Shoko Takayasu/Bloomberg via Getty Images)

Take­da fo­cus­es on ‘di­verse’ pipeline prospects on heels of two ac­qui­si­tions

After a whopping $4 billion asset buy from Nimbus Therapeutics, along with a $400 million deal with Hutchmed for a colorectal cancer drug, Takeda executives touted pipeline optimism on its latest earnings call this week.

That’s because the TYK2 inhibitor for psoriasis Takeda is getting from Nimbus, along with the Hutchmed fruquintinib commercialization outside of China, are just two of what it reports are 10 late-stage development programs of promising candidates.

Regeneron CSO George Yancopoulos (L) and CEO Len Schleifer at a groundbreaking for its new Tarrytown, NY facility, June 2022 (Lev Radin/Pacific Press/LightRocket via Getty Images)

In show­down with Roche, Re­gen­eron gears up for po­ten­tial Eylea ex­pan­sion amid Covid de­cline

Regeneron faced a substantial slump in overall revenue last year, but the focus still remains on some of its biggest blockbusters.

The pharma with several high-profile partnerships — Sanofi and Bayer among them — said Friday that Q4 revenue was down 31% for the quarter, and down 24% for the entire year. However, that won’t stop blockbuster expansion plans.

One of those is Eylea, the Bayer-partnered eye disease drug that has been in major competition with Roche’s Vabysmo. While Eylea is currently only approved in a 2 mg dose, the company recently filed for approval to give a 8 mg dose, in hopes of making a longer-lasting treatment.