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

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.