Zach Hornby, Boundless CEO

Bound­less Bio rais­es $105M in ef­fort to reimag­ine tar­get­ed can­cer ther­a­py

Bound­less Bio CEO Zach Horn­by was sit­ting in his La Jol­la, CA of­fice last fall, prepar­ing for a board meet­ing when his com­put­er pinged with an email. It was his CSO, Chris Has­sig, email­ing over ta­bles and charts at the best pos­si­ble time.

Their new type of can­cer treat­ment was work­ing. In mice, at least.

“This was a cat­alyt­ic event,” Horn­by told End­points News. The da­ta “re­al­ly said, ‘yes, we can do this.”

Horn­by and his team de­liv­ered the re­sults to the board and then start­ed fundrais­ing for the cash they would need to bring the new tech­nol­o­gy out of mice and in­to peo­ple. They emerged to­day with a $105 mil­lion Se­ries B led by Nex­tech In­vest and RA Cap­i­tal Man­age­ment and plans to be in the clin­ic by 2023.

Chris­t­ian Has­sig Bound­less Bio

Bound­less Bio is go­ing af­ter can­cer cells that con­tain ex­tra bits of cir­cu­lar DNA, float­ing around out­side the tight­ly wound chro­mo­somes where the ge­net­ic code is sup­posed to sit. Al­though sci­en­tists have known about these vagabond frag­ments, known as ex­tra-chro­mo­so­mal DNA or ecD­NA, for decades, new re­search has point­ed to the role they may play in dri­ving many can­cers.

The ecD­NA can act as a ge­net­ic reser­voir for tu­mors. Lib­er­at­ed from the in­tri­cate ma­chin­ery that nor­mal­ly reg­u­lates how DNA repli­cates and tran­scribes, they can run ram­pant pro­duc­ing onco­genes. They can mu­tate quick­ly if doc­tors try to throw tar­get­ed ther­a­pies at them.

Re­searchers be­lieved that up to half of all tu­mor types and a quar­ter of all can­cers have ex­tra-chro­mo­so­mal DNA — many of these can­cers that have been over­looked by the new wave of tar­get­ed and im­munother­a­pies. The ques­tion for Bound­less, first found­ed in 2018 and backed by ARCH and City Hill Ven­ture, was how one turned these new find­ings in­to drugs.

So the com­pa­ny has spent the last two years try­ing to build, in mice and lab dish­es, mod­els of tu­mors with ecD­NA. But that was eas­i­er said than done. For can­cers, the point of these rogue genes is that they can keep cells in a kind of ge­net­ic flux, and the mod­els they built wouldn’t stay sta­t­ic. They’d make a tu­mor with ecD­NA and then watch the ex­tra-chro­mo­so­mal DNA van­ish. Or they’d make two lines, one ecD­NA pos­i­tive and one ecD­NA neg­a­tive and then watch the lev­els ecD­NA rise in the neg­a­tive one and fall in the pos­i­tive ones.

“It kind of left us scratch­ing our heads,” Horn­by said.

Still, the com­pa­ny says it has now man­aged to pull off 20 dif­fer­ent tu­mor type mod­els in lab dish­es and “mul­ti­ple” dif­fer­ent mouse mod­els.

The goal now is to study how ecD­NA tu­mors dif­fer from tu­mors with­out ecD­NA, us­ing a va­ri­ety of ge­net­ic and quan­ti­ta­tive tools. Large­ly, Bound­less will look to find and ex­ploit vul­ner­a­bil­i­ties unique to ecD­NA can­cer — path­ways that on­ly these cells re­ly on to sur­vive and that can be knocked out with small mol­e­cules.

They will look to pair those mol­e­cules they de­vel­op with more con­ven­tion­al tar­get­ed drugs. If a pa­tient had a KRAS-pos­i­tive tu­mor with a high num­ber of ecD­NA, for ex­am­ple, they could give him Am­gen’s so­taris­ib to hit KRAS tar­gets and Bound­less’s drug to pre­vent the can­cer from us­ing ecD­NA to evolve re­sis­tance.

Be­fore last year’s board meet­ing, Bound­less showed such an ap­proach could work in mice. They plan to an­nounce a de­vel­op­ment can­di­date lat­er this year, one they hope will be­gin to change how the field ap­proach­es tar­get­ed ther­a­pies.

To­day, Horn­by said, com­pa­nies ap­proach can­cer like a game of whack-a-mole, de­vel­op­ing a tar­get­ed drug and then de­vel­op­ing a new tar­get­ed drug when the can­cer evolves re­sis­tance to the first one.

“So what we need to do is pull the plug on the game,” he said.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Jason Kelly (Photographer: Kyle Grillot/Bloomberg via Getty Images)

Gink­go nabs $DNA, biotech's most sought af­ter tick­er, for free in sweet­en­er from NYSE

When Ginkgo went comparison shopping for a financial market to list their now $15 billion company, the New York Stock Exchange had a back-pocket sweetener the Nasdaq couldn’t offer: The most sought-after ticker in biotech, $DNA.

DNA — the most famous three letters in biology and the ticker for the world’s first biotech, Genentech, from 1999 until it was bought out by Roche for $48 billion in 2009 — will now be the ticker for Ginkgo, a 12-year-old synthetic biology startup with grand ambitions to change not only how drugs, but also everyday products like meat and perfumes, are made.

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Lark­spur Health Ac­qui­si­tion files to go pub­lic as this year's SPAC flood surges over $14B

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

Another day, another SPAC vying for a spot on Nasdaq.

On Wednesday, OncoSec Medical CEO Daniel O’Connor filed the S-1 paperwork for a new blank-check company he’s leading called Larkspur Health Acquisition. The former Advaxis chief penciled in a $75 million raise, with plans to offer 7.5 million shares at $10 apiece.

BAR­DA slows its $9B en­gine for new Covid-19 ther­a­peu­tics

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.