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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Rafaèle Tordjman (Jeito Capital)

Con­ti­nu­ity and di­ver­si­ty: Rafaèle Tord­j­man's women-led VC firm tops out first fund at $630M

For a first-time fund, Jeito Capital talks a lot about continuity.

Rafaèle Tordjman had spotlighted that concept ever since she started building the firm in 2018, promising to go the extra mile(s) with biotech entrepreneurs while pushing them to reach patients faster.

Coincidentally, the lack of continuity was one of the sore spots listed in a report about the European healthcare sector published that same year by the European Investment Bank — whose fund is one of the LPs, alongside the American pension fund Teacher Retirement System of Texas and Singapore’s Temasek, to help Jeito close its first fund at $630 million (€534 million). As previously reported, Sanofi had chimed in €50 million, marking its first investment in a French life sciences fund.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Time for round 2: Il­lu­mi­na-backed VC snags $325M for its next fund

Illumina Ventures closed off its second investment fund with a total commitment of $325 million, offering fresh fuel to back a slate of startups that have already included a smorgasbord of companies, covering everything from diagnostics to biotech drug development and genomics.

Fund II brings the total investment under Illumina Ventures’ oversight to $560 million, which has been focused on early-stage companies. And it has a transatlantic portfolio that includes SQZ, Twist and Encoded Therapeutics.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 117,600+ biopharma pros reading Endpoints daily — and it's free.

Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Raju Mohan, Ventyx Biosciences CEO

Months af­ter a mam­moth raise, Ven­tyx Bio­sciences dips back in­to ven­ture well

Several months after emerging from what CEO Raju Mohan called “quiet mode” with a mammoth $114 million raise, Ventyx Biosciences is now making its plans for the clinic loud and clear.

The California-based immune modulation player kicked the week off with a $51 million Series B, while also naming some key hires ahead of its big clinical push.

The CMO slot is going to Jörn Drappa, former CMO at Viela Bio before it was bought out by Horizon Therapeutics earlier this year. The AstraZeneca vet stayed on at Horizon for a while as executive VP of R&D before making the jump to Ventyx.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.