Avid Bioservices Inc (CDMO)

[biopharm]

Novartis and Nanostring.....now tied into Calico....damn, will AstraZeneca or Novartis just make up their minds...

I knew Calico was not going to give up : ) ...still stealthy quiet though and was surprised to hear The Kraft Group as investors....hmmmmm (longtime friends of Ken Anderson??!!)

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Jan 2016

Jay Bradner
While Jay Bradner is transitioning to head up the Novartis Institutes for BioMedical Research, some of the most important work he did at the prestigious Dana-Farber Cancer Institute is now advancing toward the clinic at a nearby startup that's launching today with a hefty $73 million round and a $750 million partnership with Roche ($RHHBY).

The startup is called C4, which is joining a very exclusive club of biotechs tackling protein degradation, with designs on moving far past protein inhibition. The biotech is being helmed by Jason Fisherman, a venture veteran and former researcher at the National Cancer Institute. And while Bradner's new role at NIBR leaves him outside the circle of founding scientists who will continue to help guide the company, the scientific pedigree of the scientists who are still involved is equally impressive. Ken Anderson and Nathanael Gray, both at Harvard Medical and Dana-Farber, are listed as co-founders.

They'll be working with a big bankroll from a round led by Cobro Ventures, an angel group that seeded the company last year, with Roche and Bradner's new company Novartis taking stakes along with Cormorant Asset Management, The Kraft Group (a conglomerate run by Patriots owner Robert Kraft, a longtime friend of Anderson's) and EG Capital Group.

So with Novartis coming in early as an investor, maybe Bradner won't always be watching C4's progress from the sidelines.

The biotech has plans to head to the clinic 18 to 24 months from now with small molecule binders--dubbed degronimids--that can target, destroy and clear proteins through the ubiquitin/proteasome system. That should provide an array of targets, some of which may be partnered with other top players like Roche, says Marc Cohen, the executive chairman of C4 and Cobro (for Cohen brothers) co-founder. Cobro also backed 2013 Fierce 15 company Acetylon, another Dana-Farber licensee.

"Drug discovery research around the ubiquitin/proteasome system is an exciting and growing field, and the discovery of degronimids represents the first all-chemical solution to ligand-mediated protein degradation," said Gray in a statement.

Back in May, Bradner published his work on degronimids, illustrating how enzymes that attach ubiquitin to them could tag target proteins and then drag them to a proteasome for disposal and recycling. The approach was successfully used on cancer cells, pointing to the possibility of developing conjugates that could defeat drug resistance.

And they're not alone in this space. Just a few months ago Celgene ($CELG) bought into Nurix's work on the ubiquitin/proteasome system. And Cohen isn't in the least bit surprised that 2015 Fierce 15 company Arvinas, a Yale spinout, is already at work on protein degradation as well.

"This is a paradigm shift, a big opportunity with multiple companies in the space coming in," he notes, adding that Bradner made some of the key lab breakthroughs 5 years ago.

Cohen also underscored his long-term interest in the company, looking to foster a biotech that can create 20 to 40 new drugs over the next 20 years.

There's a lot that Cohen isn't talking about right now. Staff? No numbers for now, but hiring fast. Initial targets? Not disclosing at this point. There's also no word on the upfront from Roche, though in most preclinical deals like this the upfront tends to be small with the payoff coming down the road.

http://www.fiercebiotech.com/biotech/dana-farber-spinout-c4-tackles-protein-degradation-73m-round-750m-roche-deal-hand


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March 23 2017
Sleuthy Google upstart Calico forges a rare biotech collaboration on aging with Novartis-backed C4

The elusive but widely buzzed about Calico, a startup bankrolled by Google to find new therapies for aging, has hitched up with protein degeneration-focused C4 Therapeutics with plans to embark on a 5-year, cross country research collaboration.

The deal announcement is long on overarching goals, such as a preclinical focus on cancer, among other areas, but with little insight into the numbers or the work. And that’s just the way Calico likes to keep it, carefully cloaking its activities more like an IT company than any average biotech.

We do know that the companies will work together on preclinical programs, with Calico taking charge of any clinical development work that may emerge.

“I’m not sharing how many things are being worked on,” says Andy Phillips, president and CSO at C4. The goal here is to take a number of projects for targeted protein degradation through IND stage, on to the clinic and eventually people.

But Calico is staying buttoned up. Says Phillips: “We’ve agreed with Calico that we can’t comment on their behalf in regards to these types of things.”

Calico, of course, is the brainchild of Google’s Larry Page, who’s been keenly interested in taking a new approach in developing drugs that will add to our life spans. He brought in one of the best teams in biotech, starting with Genentech legend Art Levinson and following up with his longtime colleague Hal Baron.

The deal is intended to be “highly collaborative,” says Phillips, coming on top of some aggressive growth over the past year that recently included their 53rd (or 54th) employee. And Phillips expects that number to grow into the 60s by the end of the year.

C4 launched a little more than a year ago with a $73 million round led by Cobro Ventures and including Novartis along with a $750 million partnership with Roche. They’ve been working on small molecule binders — dubbed degronimids — that can target, destroy and clear disease-causing proteins through the ubiquitin/proteasome system.

C4 is advancing research work that Jay Bradner did on protein degradation at Dana-Farber before he took the high-profile head job at the Novartis Institutes for BioMedical Research, better known as NIBR.

Calico, meanwhile, is based in The Cove at Oyster Point all the way across the country, a booming biotech development that includes biotechs like CytomX and Denali.

Over the four years since Calico launched, the company has been allying itself with some big labs. The Broad, The Buck, UCSF, and the Jackson Laboratory have all signed on to do basic biology research. But there have been few biotech alliances, aside from a couple of deals with low-profile companies like QB3 and 2M.

Don’t expect any comment from the stellar team at Calico, though. Like any Google startup, mum’s the word.

https://endpts.com/sleuthy-google-upstart-calico-forges-a-rare-biotech-collaboration-on-aging-with-novartis-backed-c4/

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Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy

Protein degradation

hsc-70 (HSPA8) is a cytosolic molecular chaperone, which plays a central role in cellular proteostasis, including quality control during protein refolding and regulation of protein degradation. hsc-70 is pivotal to the process of macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy. The latter requires hsc-70 interaction with negatively charged phosphatidylserine (PS) at the endosomal limiting membrane. Herein, by combining plasmon resonance, NMR spectroscopy, and amino acid mutagenesis, we mapped the C terminus of the hsc-70 LID domain as the structural interface interacting with endosomal PS, and we estimated an hsc-70/PS equilibrium dissociation constant of 4.7 ± 0.1 µm. This interaction is specific and involves a total of 4–5 lysine residues. Plasmon resonance and NMR results were further experimentally validated by hsc-70 endosomal binding experiments and endosomal microautophagy assays. The discovery of this previously unknown contact surface for hsc-70 in this work elucidates the mechanism of hsc-70 PS/membrane interaction for cytosolic cargo internalization into endosomes
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http://m.jbc.org/content/291/35/18096.short