Third Rock sinks $59M in­to Cas­ma's 're­cy­cling' tech, with neu­ro on the mind

It feels like launch sea­son, and Third Rock is on a roll. The ven­ture fund and start­up in­cu­ba­tor is un­veil­ing yet an­oth­er biotech — its third pub­lic launch in a num­ber of weeks. This one is step­ping out with a $58.5 mil­lion Se­ries A, and a locked and loaded staff of au­tophagy ex­perts.

Beth Levine

The com­pa­ny, called Cas­ma Ther­a­peu­tics, has qui­et­ly been work­ing on tech­nol­o­gy that it hopes will ar­rest — or even re­verse — the pro­gres­sion of both rare and broad ge­net­ic dis­eases, in­clud­ing the fail­ure-rid­den space of neu­rode­gen­er­a­tion.

To do this, Cam­bridge, MA-based Cas­ma is us­ing new strate­gies to boost the body’s abil­i­ty to break down ma­te­r­i­al it no longer needs, like mis­fold­ed pro­teins, in­vad­ing pathogens, or spare or­ganelles. Think of it as the cell’s re­cy­cling sys­tem. When this slaugh­ter and sal­vage process (called au­tophagy) isn’t work­ing — or when it’s over­whelmed by dis­ease — all sorts of things can go awry.

Cas­ma’s CEO Kei­th Dionne tells me the com­pa­ny is look­ing at us­ing small mol­e­cules to drug var­i­ous pro­teins in­volved in trig­ger­ing au­tophagy. The idea is to in­ter­vene at strate­gic points in the au­tophagy process to boost the re­cy­cling sys­tem. And they’ve got pre­clin­i­cal da­ta that sug­gest turn­ing the di­al up on au­tophagy could lead to treat­ments for a wide range of dis­ease, in­clud­ing lyso­so­mal stor­age dis­or­ders, liv­er and mus­cle dis­eases, in­flam­ma­to­ry dis­or­ders, and neu­rode­gen­er­a­tion.

An­drea Bal­labio

“In pre­clin­i­cal mod­els, we’re see­ing a ma­jor ef­fect in a num­ber of dis­eases,” Dionne said. “And it’s proven to be quite safe. If you ge­net­i­cal­ly in­duce au­tophagy in mice, they live health­i­er, longer lives — freer of dis­ease.”

Cas­ma al­ready has “4 to 5” pro­grams in the pipeline, Dionne said.

James Hur­ley

In­ter­est in this field has been warm­ing up since 2016, when the dis­cov­ery of key mech­a­nisms in au­tophagy earned the No­bel Prize for Phys­i­ol­o­gy or Med­i­cine. Since then, the sci­ence has moved rapid­ly. Many com­pa­nies are now pur­su­ing the idea of au­tophagy’s im­pact on dis­ease.

“There are a num­ber of drugs known to en­hance au­tophagy as a side ef­fect,” Dionne said. “The key thing we want to do is go af­ter the spe­cif­ic mech­a­nism, with­out a lot of oth­er side ef­fects.”

Her­bert “Skip” Vir­gin

Cas­ma’s sci­en­tif­ic founders cer­tain­ly have loads of com­bined ex­pe­ri­ence in au­tophagy. Among them is Beth Levine, di­rec­tor of the Cen­ter for Au­tophagy Re­search, who’s rec­og­nized as a world­wide ex­pert in au­tophagy for her dis­cov­ery of the mam­malian au­tophagy gene, BECN1, and oth­er com­po­nents of the au­tophagy path­way. Then there’s An­drea Bal­labio, a leader in the field of tran­scrip­tion­al reg­u­la­tion of lyso­so­mal bio­gen­e­sis and au­tophagy; James Hur­ley, who per­formed ground­break­ing stud­ies to de­ter­mine the struc­ture and ac­tiv­i­ty of au­tophagy core com­plex­es; and Her­bert “Skip” Vir­gin, who forged new ground in the un­der­stand­ing of au­tophagy’s role in in­flam­ma­tion and im­mu­ni­ty.

Dionne said the com­pa­ny’s Se­ries A should get them 2 to 3 years of run­way, giv­ing the com­pa­ny the chance to de­vel­op spe­cif­ic en­hancers of au­tophagy and val­i­date if they’re work­ing.

Im­age: Kei­th Dionne. Cas­ma

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.

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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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.

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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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.

Rajesh Devraj, Rectify Pharmaceuticals CEO

At­las backs a long­time Ver­tex em­ploy­ee’s quest to bring CF suc­cess to nu­mer­ous oth­er dis­eases

One of Vertex’s longest-tenured employees believes he can take the biotech’s biggest medical and scientific accomplishments and use it to develop treatments for more than just cystic fibrosis.

Three years ago, Jonathan Moore, a scientist and then executive at Vertex from 1990 to 2018, founded a company to develop treatments for diseases that, like CF, are caused by mutations in a “super family” of proteins known as ABC transporters.

Yao-Chang Xu, Abbisko Therapeutics founder and CEO

Qim­ing-backed Ab­bisko makes $200M+ Hong Kong de­but, as a SPAC and Agenus spin­out al­so price on Nas­daq

Three new entities priced their public debuts late Thursday and early Friday, including a SPAC, a traditional Nasdaq IPO and a Chinese biotech joining the Hong Kong Index.

Shanghai-based Abbisko Therapeutics raised the most money of the triumvirate, garnering $226 million in its Hong Kong debut and pricing at HK$12.46, or roughly $1.60 in US dollars. The blank check company followed up with a $150 million raise, while MiNK Therapeutics priced on Nasdaq at $12 per share and a $40 million raise.