Ron De­Pin­ho rais­es seed cash for MD An­der­son col­league's work on a 'Holy Grail mol­e­cule' in can­cer, in­flam­ma­tion

Ron De­Pin­ho has blazed a wide trail in can­cer re­search. As found­ing di­rec­tor of the Belfer In­sti­tute for Ap­plied Can­cer Sci­ence at Dana-Far­ber and for­mer pres­i­dent of MD An­der­son Can­cer Cen­ter in Hous­ton — where he de­part­ed af­ter a rocky tenure which he now fierce­ly de­fends — De­Pin­ho spear­head­ed trans­la­tion­al pro­grams and man­aged, among oth­er things, to build a clin­i­cal tri­al en­gine that proved piv­otal in a num­ber of FDA ap­provals.

That’s why when he learned about his col­league David Tweardy’s work on STAT3 — a pro­tein tied to a wide range of dis­eases — the se­r­i­al en­tre­pre­neur went all in to co-found Tvar­di Ther­a­peu­tics.

“It’s been one of these Holy Grail mol­e­cules that folks have tried to de­vel­op in­hibitors for,” he tells me.

David Tweardy

Us­ing a screen he de­signed 10 years ago, Tweardy, head of in­ter­nal med­i­cine at MD An­der­son, had found a com­pound that pre­vents STAT3 from be­com­ing phos­pho­ry­lat­ed by the re­cep­tors it typ­i­cal­ly in­ter­acts with, mean­ing it can­not then go on to turn on genes that are im­por­tant in can­cer, fi­bro­sis and in­flam­ma­tion. Giv­en that hy­per­ac­ti­vat­ed STAT3 is present in more than 50% of can­cers — of­ten turn­ing up im­muno­sup­pres­sion in the tu­mor mi­croen­vi­ron­ment — he the­o­rized that a po­tent in­hibitor here that doesn’t trig­ger safe­ty is­sues could have a big im­pact.

That seems to be the case through­out the pre­clin­i­cal test­ing done in his lab, which led Tweardy and De­Pin­ho to the Phase I that Tvar­di is cur­rent­ly con­duct­ing. Now, with a fresh $9 mil­lion in Se­ries A fund­ing, the biotech ex­pects to wrap up dose and safe­ty stud­ies in 3 to 4 can­cer types for its lead oral drug, ex­plore an IV for­mu­la­tion for use in non-can­cer in­di­ca­tions, and hus­tle a sec­ond pro­gram to the door of the clin­ic.

Some­where in that time­line are tri­als in­volv­ing check­point in­hibitors, as Tvar­di be­lieves TTI-101 could be used in com­bo or as a fol­low-up to PD-1 agents.

And they hope to do all that by the end of 2019, with the help of a per­ma­nent CEO they are still search­ing for.

It’s not a ton of mon­ey in to­day’s mega-round stud­ded world, but De­Pin­ho says stay­ing flex­i­ble and cap­i­tal ef­fi­cient would be a key strat­e­gy for the com­pa­ny’s ear­ly days — a strat­e­gy that al­so in­volves seek­ing non-di­lu­tive grant fund­ing. Most of the in­vestors in this round will re­main un­named, but he vol­un­teered Mon­i­ca Beam at Alexan­dria as an ex­am­ple of the “very so­phis­ti­cat­ed but pri­vate in­vestors” he chose to work with.

“We don’t have a large bu­reau­crat­ic or­ga­ni­za­tion, so we’re able to make de­ci­sions and be very flex­i­ble which is crit­i­cal­ly im­por­tant here, be­cause STAT3 has so many dif­fer­ent op­por­tu­ni­ties […] that one needs to have a cer­tain lev­el of fo­cus and pri­or­i­ti­za­tion,” he says.

At around a dozen em­ploy­ees, the small com­pa­ny is rem­i­nis­cent of Karyopharm, an­oth­er on­col­o­gy com­pa­ny De­Pin­ho helped start be­fore join­ing MD An­der­son — where he is still fac­ul­ty af­ter step­ping down from a six-year tenure as pres­i­dent. Dur­ing that time, the cen­ter ex­pe­ri­enced re­port­ed op­er­at­ing loss­es of more than $460 mil­lion over 16 months and hun­dreds of staffers were laid off.

De­Pin­ho, how­ev­er, sees it dif­fer­ent­ly.

“It was an ex­tra­or­di­nar­i­ly suc­cess­ful fi­nan­cial sit­u­a­tion,” he tells me, cit­ing “$3.7 bil­lion in mar­gin, the health­i­est fi­nan­cial bal­ance sheet in the Unit­ed States for an aca­d­e­m­ic med­ical cen­ter, record phil­an­thropy and ranked No. 1 in cor­po­rate al­liance rev­enues and IP rev­enues.”

He’s now moved on to new en­deav­ors, in­clud­ing Tvar­di. Once the Phase I da­ta are in, De­Pin­ho ex­pects to ramp up busi­ness de­vel­op­ment talks. He’s al­ready think­ing about the next round, which “would like­ly be our last one en route to ei­ther an IPO or oth­er event.”


Im­age: Ron De­Pin­ho. TVAR­DI

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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Anthony Sun, Zentalis and Zentera CEO (Zentalis)

With clin­i­cal tri­als lined up for Zen­tal­is drugs, Chi­na's Zen­tera sets its sights on more deal­mak­ing and an IPO

As Zentalis geared up for an AACR presentation of early data on its WEE1 inhibitor earlier this year, its Chinese joint venture Zentera wasn’t idle, either.

Zentera, which has headquarters in Shanghai, had already nabbed clearance to start clinical trials in China for three of the parent company’s drugs. In May — just a month after Zentalis touted three “exceptional responses” out of 55 patients for their shared lead drug, ZN-c3 — it got a fourth CTA approval.

Thomas Soloway, T-knife CEO

What hap­pens when you give a mouse a hu­man self-anti­gen? In­vestors bet $110M to find out

T-knife Therapeutics launched last August on a mission to isolate T cell receptors not from human donors, but from mice. Now, with a new CEO and a candidate bound for the clinic, the Versant-backed company is reloading with a fresh $110 million.

“What we are trying to do for the field of TCR therapy and solid tumor therapy is very analogous to what the murine platforms have done in antibody development,” CEO Thomas Soloway told Endpoints News. 

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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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