Zachary Hornby. Boundless

'A fourth rev­o­lu­tion in can­cer ther­a­pies': ARCH-backed Bound­less Bio flash­es big check, makes big­ger promis­es in de­but

It was the cel­lu­lar equiv­a­lent of open­ing your car door and find­ing an ac­tive, roar­ing en­gine in the dri­ver seat.

Paul Mis­chel

Sci­en­tists learned strands of DNA could oc­ca­sion­al­ly ap­pear out­side of its tra­di­tion­al home in the nu­cle­us in the 1970s, when they ap­peared as lit­tle, in­nocu­ous cir­cles on mi­cro­scopes; in­ex­plic­a­ble but ap­par­ent­ly in­nate. But not un­til UC San Diego’s Paul Mis­chel pub­lished his first study in Sci­ence in 2014 did re­searchers re­al­ize these cir­cles were not on­ly ac­tive but po­ten­tial­ly over­ac­tive and dri­ving some can­cer tu­mors’ su­per­hu­man growth.

That in­sight and the en­su­ing five years of re­search will now get $46 mil­lion cash and com­pa­ny in­fra­struc­ture to ramp in­to tar­get­ed ther­a­pies as Bound­less Bio emerges from stealth mode with back­ing from ARCH Ven­ture Part­ners and City Hill. Ques­tions abound, from what pre­cise­ly a drug would look like to what even gives rise to these wild DNA, but CEO Zachary Horn­by isn’t bit­ing his tongue on the po­ten­tial.

“We’re think­ing about this as a fourth rev­o­lu­tion in can­cer ther­a­pies,” Horn­by, who was most re­cent­ly COO of Igny­ta, told End­points News. The first three rev­o­lu­tions, by Horn­by’s count, are chemother­a­py in the 1940s, the first tar­get­ed ther­a­pies at the end of the 20th cen­tu­ry, and the re­cent rise of im­munother­a­py.

The road to such a rev­o­lu­tion would be long, but the em­bat­tled on­col­o­gy field may be in need of new di­rec­tion. A study re­leased in April found 97% of can­cer drugs test­ed in clin­i­cal tri­als failed to make it to mar­ket, and this month re­searchers found sys­temic tar­get­ing prob­lems plagued two decades of can­cer re­search.

The con­nec­tion be­tween this loose DNA, of­fi­cial­ly called ex­tra­chro­mo­so­mal DNA or ecD­NA, and can­cer cen­ters around a baf­fling and dead­ly fact about some tu­mors: While nor­mal cells in a high­er-or­der species like hu­mans don’t evolve with­in a gen­er­a­tion, some can­cer cells can evolve rapid­ly, en­sur­ing their sur­vival against at­tempt­ed treat­ments. Why? How? Mis­chel’s map­ping of can­cer genome points to ecD­NA.

Freed from a cell’s chro­mo­somes, the DNA can repli­cate rapid­ly. That doesn’t hurt if they code for noth­ing or some­thing be­nign, but if they code for some­thing that gives the cell an ad­van­tage, such as EGFR (a growth fac­tor), the cells will grow rapid­ly as in any clas­si­cal nat­ur­al se­lec­tion mod­el. This, Horn­by said, ap­pears in over 25% of can­cers, in­clud­ing no­to­ri­ous­ly hard to treat MET can­cers.

EGFR in­hibitors al­ready ex­ist to com­bat can­cer cells that have al­ready evolved (or been “am­pli­fied”), but Bound­less Bio plans to use Mis­chel’s in­sights to de­stroy ecD­NA in its ear­ly stages. Rather than at­tack­ing tu­mors af­ter the cells have al­ready am­pli­fied, the com­pa­ny would jam the process that gives rise to the evo­lu­tion in the first place.

“It opens a whole new av­enue of can­cer tar­gets, in­clud­ing al­low­ing us to pur­sue pa­tient pop­u­la­tions that to this point have been un­drug­gable,” Horn­by said, point­ing to MET and Myc. “That’s just a re­al­ly dif­fer­ent ap­proach than your typ­i­cal tar­get­ed ther­a­pies.”

But how they would do this is still cloudy.

Horn­by said the most promis­ing method was jam­ming the “en­zy­mat­ic ma­chin­ery” — the mol­e­c­u­lar tools and parts that al­low DNA to repli­cate and code pro­teins — as their re­search has shown the ma­chin­ery is slight­ly dif­fer­ent in ecD­NA than typ­i­cal DNA. An­oth­er method they’re ex­plor­ing is to in­hib­it the meta­bol­ic path­ways ecD­NA can use to ful­fill the de­mands caused by its high repli­ca­tion rate; in oth­er words, grow­ing DNA that are hun­gry and de­priv­ing them of food could neu­tral­ize them.

Among the most no­table things about Bound­less’ po­ten­tial ther­a­pies is that they may be ap­proved for tu­mor type, rather than can­cer type, i.e. like the new drug from Horn­by’s old com­pa­ny Igny­ta, it could treat a wide range of can­cers if the pa­tient showed ecD­NA was am­pli­fy­ing in the tu­mor.

The com­pa­ny will al­so in­vest in re­search to dis­cov­er the un­der­ly­ing mech­a­nism giv­ing rise to ecD­NA.

In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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UP­DAT­ED: Have a new drug that promis­es to fight Covid-19? The FDA promis­es fast ac­tion but some de­vel­op­ers aren't hap­py

After providing an emergency approval to use malaria drugs against coronavirus with little actual evidence of their efficacy or safety in that setting, the FDA has already proven that it has set aside the gold standard when it comes to the pandemic. And now regulators have spelled out a new approach to speeding development that promises immediate responses in no uncertain terms — promising a program offering the ultimate high-speed pathway to Covid-19 drug approvals.

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The race to de­vel­op Covid-19 drugs and vac­cines is on — here’s what’s hap­pen­ing in the UK

Weeks away from the results of ongoing US and China trials testing its experimental antiviral remdesivir, Gilead is going to trial the failed Ebola drug in a small group of coronavirus patients in England and Scotland. The United Kingdom is also home to a range of other therapeutic efforts, as the pandemic rages on across the globe.

On Tuesday, Southampton, UK-based startup Synairgen kicked off a mid-stage placebo-controlled study testing its experimental drug, SNG001 — an inhaled formulation of interferon-beta-1a — that has previously shown to be safe and effective in improving lung function in asthma patients with a respiratory viral infection in a pair of Phase II trials.

‘There was a grow­ing weari­ness’: Rush­ing against a pan­dem­ic clock, As­pen Neu­ro­sciences se­cures $70M Se­ries A

Just before Christmastime, Howard Federoff got a tip from Washington: There was a new virus in China. And this one could be bad.

News report of the virus had not yet appeared. Federoff, a neuroscientist, was briefed because years before, he was vetted as part of a group — he didn’t give a name for the group — to consult for the US government on emerging scientific issues. His day job, though, was CEO of Aspen Neurosciences, a Parkinson’s cell therapy startup that days before had come out of stealth mode and gave word to investors they were hoping to raise $70 million. That, Federoff realized, would be difficult if a pandemic shut down the global economy.

FDA puts pe­di­atric aGVHD drug on pri­or­i­ty re­view lane — will they go vir­tu­al with the ad­comm?

Despite worries about regulatory delays due to new work arrangements under Covid-19, the FDA appears intent to go full speed ahead with its everyday work, not only granting priority review to a stem cell therapy for acute graft versus host disease but also plotting an advisory committee meeting for it.

With a PDUFA date of September 30, the journey of the drug — remestemcel-L, or Ryoncil — could shed light on the agency’s capacity to facilitate drug development unrelated to Covid-19.

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

You can add Amgen and GSK to the list of deep-pocket drug R&D players who are tailoring their pipeline work to fit a new age of coronavirus.

Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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Covid-19 roundup: Trump push­es his new fa­vorite, untest­ed drug; CRISPR out­lines crip­pling im­pact of Covid-19

President Trump has a new favorite Covid-19 drug.

After a conversation with Japanese Prime Minister Shinzo Abe, Politico reports, the president is pressuring the FDA to issue emergency use authorization for favipiravir, a flu drug that showed glimpses of success in China but remains unproven and carries a list of worrying side effects. The push comes after a week-plus in which the White House touted a potentially effective but unproven malaria medication despite the concerns of scientific advisors such as NIAID director Anthony Fauci. And Trump ally Rudy Giuliani has been talking up unproven cell therapy efforts on Twitter.

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ITeos nabs $125M as they prep Keytru­da com­bi­na­tion tri­al — if Covid-19 will let them

For iTeos, it turned out, $75 million could only last so long.

Two years after announcing their eye-catching Series B raise, the Belgian biotech is back with an even larger Series B-2: $125 million.

The now $175 million financing – $25 million of the first B round is considered part of the second – illustrates the vast capital available for those with promising new immuno-oncology compounds, particularly those that might be used in combination with existing therapies. In December, iTeos announced a collaboration with Merck to test its lead compound with Keytruda this year. The proceeds will push forward that trial and help fund the ongoing Phase I/II trials for that compound, EOS-850, and a second one, EOS-448.

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