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.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; 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.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”

Delaware court rules against Gilead and Astel­las in years-long patent case

A judge in Delaware has ruled against Astellas Pharma and Gilead in a long-running patent case over Pfizer-onwed Hospira’s generic version of Lexiscan.

The case kicked off in 2018, after Hospira submitted an Abbreviated New Drug Application (ANDA) for approval to market a generic version of Gilead’s Lexiscan. The drug is used in myocardial perfusion imaging (MPI), a type of nuclear stress test.