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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

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Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

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Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

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Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.