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.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

BioAt­la rakes in $72.5M Se­ries D, ad­vanc­ing re­search for pH-de­tect­ing can­cer treat­ments

A little over a year after agreeing to a worldwide collaboration with hefty Chinese biotech BeiGene worth up to $270 million, BioAtla is ready for another haul.

The San Diego-based biotech pulled in a $72.5 million haul for their Series D financing, which the company announced Wednesday. Funds will go toward their four main clinical programs developing cancer treatments, two of which are currently in Phase II, BioAtla president and former Celgene COO Scott Smith said.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

‘Plan­ning to vac­ci­nate every­one in the US,’ Mod­er­na out­lines ef­forts to sup­ply their Covid-19 vac­cine as man­u­fac­tur­ing ramps up ahead of PhI­II

Twelve days from the planned start of their Phase III pivotal trial, the executive crew at Moderna has set up the manufacturing base needed to begin production of the first 500,000 doses of their Covid-19 vaccine with plans to feed it into a global supply chain. But the initial batches will likely be ready in the US first, where company CEO Stéphane Bancel plans to be able to vaccinate everyone.

“We have started making commercial product at-risk, and will continue to do so every day and every week of the month,” Bancel told analysts during their morning call on the Phase I data just published in the New England Journal of Medicine.

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Carolyn Loew, Glympse Bio CEO

Gilead-part­nered Glympse snares $46.7M for their NASH-snoop­ing biosen­sors

Since its emergence at JP Morgan six years ago, the NASH field has been held back not only by the question of how to treat the disease, but also by the question of how you diagnose it. It’s simply not that difficult to tell if a liver is fatty or scarred or in full-on cirrhosis.

The method used in most trials is needle biopsy, where you take a hollow needle, stick it through someone’s skin and into their liver and suck out some cells. You stain those cells and examine them under the microscope. It’s safe but very painful, and that pain limits how often you can test a patient in a trial, and, down the line, how many of the millions of Americans suspected to have NASH would actually be tested for the disease and potentially prescribed an approved drug.

Covid-19 roundup: Vac­cine by end of 2020? Ken Fra­zier warns hype do­ing 'grave dis­ser­vice'

When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

Over a month after first casting doubts on the aggressive 12- to 18-month timeframe championed by the US government and his biopharma peers, the Merck CEO again cautioned against any hype around a quick vaccine approval.

In a wide-ranging interview with Harvard Business School professor Tsedal Neeley that touched other big topics such as race, Frazier emphasized that vaccines take a long time to develop. He would know: Out of the seven new vaccines introduced around the world in the past 25 years, four came from Merck.

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Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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