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

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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The lat­est Cin­derel­la sto­ry in on­col­o­gy ends with a sud­den rout as up­dat­ed da­ta dis­play spooks in­vestors

NextCure’s turn as the Cinderella of cancer-focused biotechs was short-lived.
Just a few days after its shares $NXTC zoomed up more than 250% on some very early stage results in a SITC abstract, a more complete analysis over the weekend spiked the hype and left investors in high dudgeon as the stock price collapsed back towards earth Monday.
The focus at NextCure is centered on NC318, an antibody that is intended to shut down the immunosuppressive Siglec-15 — or S-15 — target. After adding a small group of patients to the readout, investigators circled 2 clinical responses, a complete and partial response, along with 4 stable disease cases in non-small cell lung cancer.

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Te­va spin­out rais­es $85M in IPO; No­var­tis beefs up gener­ics unit with $440M deal

→ After Teva spinout 89bio recently announced that its IPO was being held up, the company is back in the game offering 5,304,687 shares at a price of $16 per share. The company has raised $84.9 million IPO in gross proceeds and will be listed under the ticker symbol $ETNB. BofA Securities, SVB Leerink and RBC Capital Markets are the joint book-running managers for the offering. Oppenheimer & Co is the co-manager for the offering.
→ Looking to amp up its presence in Japan’s hospitals, Novartis has struck a deal to buy out Aspen’s portfolio of generics in the world’s third largest healthcare market. The pharma giant is paying $440 million for Aspen’s Japanese subsidiary.
→ Novartis said tropifexor, a non-bile acid FXR agonist, has scored on several key biomarkers of NASH in a Phase IIb trial, including reductions in hepatic fat, alanine aminotransferase and body weight compared to a placebo at 12 weeks.

Break­through sta­tus and promise of a speedy re­view ar­rives for Op­di­vo/Yer­voy com­bi­na­tion as Bris­tol-My­ers bites at Bay­er

Its frontline and single-agent aspirations have been set back, but Bristol-Myers Squibb just took a big step forward in its efforts to apply its checkpoint inhibitor Opdivo to liver cancer. The FDA has granted breakthrough status and priority review to a combination, second-line treatment.

The designation is for Opdivo (nivolumab) in combination with Yervoy (ipilimumab),  for treating advanced hepatocellular carcinoma (HCC), the most common form of liver cancer. The PD-L1 drug was already approved as a single-agent, second-line treatment for HCC. A PDUFA date was set for March 10, 2020 — just 4 months from now.

Third time un­lucky: Lipocine's lat­est quest to mar­ket their oral testos­terone drug snubbed again by FDA

Lipocine’s latest attempt at securing approval for its oral testosterone drug has fizzled yet again.

The Utah-based drug developer on Monday said the FDA has spurned its marketing application, indicating that some efficacy data on the drug, Tlando, was not up to scratch to treat male hypogonadism, a condition characterized by low production of the hormone testosterone, which is responsible for maintaining muscle bulk, bone growth, and sexual function.

UP­DAT­ED: De­cry­ing 'ar­bi­trary and capri­cious' ac­tion, Re­genxBio sues FDA over clin­i­cal holds on gene ther­a­py

When RegenxBio disclosed that the FDA had placed a partial clinical hold on one of its lead gene therapies, execs outlined several customary next steps: continuing assessment and monitoring, delaying a related IND filing, and working with the FDA to address the matter.

As it turned out, they were planning something much less mundane. Two days after announcing the hold in its Q3 update, RegenxBio filed a lawsuit seeking to set it aside, the FDA Law Blog noted.

Roche's SMA chal­lenge to Bio­gen's Spin­raza fran­chise looms larg­er with piv­otal win

Roche has just landed a crucial advance in scoring a come-from-behind win on the spinal muscular atrophy field, giving Novartis and Biogen a run for their money.

The update was brief, but Roche said risdiplam hit the primary endpoint in the placebo-controlled pivotal SUNFISH trial, meeting the threshold for change from baseline in the Motor Function Measure 32 (MFM-32) scale after one year of treatment. The results, which is the second, confirmatory portion of a two-part study, involved 180 patients with type 2 or 3 spinal muscular atrophy between 2 and 25 years old.

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Roche steers Gazy­va in­to a new PhI­II pro­gram af­ter com­bo shows promise in lu­pus nephri­tis study

Roche is working on putting together a late-stage study for its monoclonal antibody Gazyva in patients with severe kidney disease associated with lupus after a combination approach helped patients in a mid-stage study.

The 125-patient NOBILITY trial evaluated Gazyva, combined with standard-of-care treatment mycophenolate mofetil or mycophenolic acid and corticosteroids, versus standard treatment alone. The combo met the main goal of inducing a statistically superior complete renal response (CRR) of 40% at week 76, versus 18% in patients given standard treatment, Roche said.