photos

At least we're teaching this kid something...

Drunk on DP?

The first cool not sweltering evening in FOREVER. Thank God for highs in the low 80's.

This smile is the result of seeing DEAC!

Doing it all by self.

This Charming CEO

Well, well, well. Of all the people to replace CEO Jim Mullen, the ever-more-Icahnized Biogen Idec tabbed George Scangos, the chief of Exelixis. Scangos' replacement is less of a surprise (small hint above), but more on that in a moment.

There are plenty of fun juxtapositions -- East Coast/West Coast, rumpled Mullen/dapper Scangos -- but one that can't be waved away is that Biogen Idec is squarely a commercial company, squeezing as much revenue as possible from its multiple-sclerosis leader Avonex and turning more and more to business development to bolster its pipeline; while Scangos, for all his revving of Exelixis' oncology discovery engine, has never brought a drug to market, let alone run a four-billion-dollar commercial operation.

"The Pink Sheet" Daily will dissect the major move in greater detail, so we don't want to steal our sister publication's thunder. [UPDATE: Here's the PSD piece.] Meanwhile, we point you to the other man behind the Exelixis engine, Michael Morrissey, the R&D chief who now steps into Scangos's CEO shoes.

Morrissey? We can't help wonder which song he'll use to take the stage at his first investor conference as CEO...

"A Rush and a Push and the Kinase is Ours"
"How Soon is NDA?"
"Please Please Please Let Me Get XL184 Approved"
"Panic" (Hang the VP, hang the VP, hang the VP...)

Feel free to suggest your own. If you're not a Smiths fan, just tap your foot to whatever song is in your head.

Photo courtesy of flickr user Djenan.

VEGF & Colorectal Cancer: How Do You Know When to Stop?

Fifty million Elvis fans can't be wrong. What about nine Phase III trials?

Avastin is a $5.7 billion drug, with activity in at least five tumor types with every indication of gaining more (it's pending for approval in gastric cancer based on data presented at the 2009 ASCO annual meeting [it is not (Herceptin is!); IVB regrets the error] and positive data in ovarian cancer was presented at the plenary of the 2010 meeting). Some projections have it becoming the top selling drug in the world in 2014 with annual sales of $9 billion. (For more on Avastin's performance in ovarian cancer, check out "The Pink Sheet.")

But it all started out with colorectal cancer.

With success like that, and the VEGF mechanism of action seemingly proven in the setting, of course other drug development projects followed. "There is clearly room to improve on anti-angiogenic therapy in CRC," Scott Kopetz from MD Anderson Cancer Center said at this year's ASCO meeting, and agents with oral bioavailability and lower production costs could have real market advantages.

But, as Kopetz reminded us during an ASCO session on novel possibilities for treating colorectal cancer, small molecule angiogenesis inhibitor options – including the multi-targeted receptor tyrosine kinase inhibitors – haven't worked. Fourteen small molecule VEGF receptor antagonists have been tested (and failed) in CRC – among them early disappointments like AstraZenenca/Schering's PTK787 and more recent failures with Pfizer's sunitinib, GlaxoSmithKline's pazopanib, Bristol-Myers Squibb's brivanib, and AstraZeneca's vandetanib and cediranib just weeks ago. (see Pharmaceutical Approvals Monthly). That includes a total of nine Phase III trials and over 10,000 patients studied, by Kopetz's calculations.

And - "despite over 10,000 patients enrolled," he said, "unfortunately there's no evidence yet that anti-angiogenic agents, besides bevacizumab, confer benefit."

With such a host of attempts and no positive results, maybe it's time to move beyond VEGF in colorectal cancer. After all, there's scads of other pathways to pursue – from MEK to PI3 kinase to Src to Notch to Hedgehog, as Wells Messersmith from the University of Colorado mapped out.

Maybe it isn't quite time to call it quits on angiogenesis, though. Kopetz held out a little hope – and from the back of a McCormick Place hangar it was hard to see how much of a veil of Avastin glory was in his eyes – there's still the large molecule angiogenesis projects out there.

The Phase III on VEGF-Trap, sanofi-aventis/Regeneron's aflibercept, should report out in December. So perhaps we should all keep our hopes up a little longer.

squash muffins

I am about to be your new best friend. I thought this was Matt's sister's recipe, but she says she got it from Matt's Aunt Katherine. Katherine, you are my hero.

I don't know about you, but I can only take so much fried squash, baked squash, and sauteed squash... enter Squash Muffins.

Yellow Squash Muffins

2 lbs. yellow squash (about 8 medium or 5 large)
2 eggs, beaten
1 cup melted butter
1 cup sugar
3 cups all purpose flour
1 tbsp and 2 tsp baking powder
1 tsp salt

Preheat oven to 375. Wash squash, trim off ends, cut into slices. Cook in boiling water 15-20 minutes or until tender. Drain WELL and mash.

Measure out 2 cups of squash and mix with eggs and butter, set aside.

Combine remaining ingredients in large bowl, add remaining squash and the squash mixture, stir just until evenly moistened.

Spoon into greased muffin cups, filling 3/4 full. Bake for 20 minutes or until golden brown on edges (not whole muffin).

This recipe makes 18-24 muffins.

I used Country Crock Lite instead of butter, and they still tasted great. Next time, I think I will try replacing at least some of the sugar with apple sauce and see how that goes. I had to bake them for 25 to 27 minutes, which is a little longer than the recipe says. But it's definitely true about just baking them until the edges are brown, not the whole muffin. They were PERFECT!

I didn't have enough yellow squash from my garden, so I combined yellow squash and zucchini. Matt was a little concerned about how that would taste, but I told him, "If a recipe calls for a cup of butter and a cup of sugar, it's going to taste like butter and sugar."

And he was pleased, as you can see.

It really is a great way to use some of your garden (or Farmer's Market) squash if you are tired of the same old thing. And they freeze well too. Kim says she always makes a double batch, freezes them and then just thaws them and heats them in foil in the oven. Tasty, even the second time around. Let me know if you try them!

a fun friday

On Friday, Jonah finally got his playdate with the two cute twin girls Kathryn nannies for (er... for whom Kathryn nannies... who actually says that?). We were supposed to do it last week, but their Mommy got sick, and then they got sick, so it just wasn't a great time. But Friday was so much fun.

This is Juliana.
And her sister, Jasmine.

They are ten months old and ON. THE. MOVE. It really made me realize how slow Jonah crawls. Honestly, I'm okay with it. :) It was so neat to see them be able to move and explore and get to what they wanted (quickly!). Jasmine loved the stairs and was SUPER fast. Juliana was all about Deac and just followed him everywhere. He was only partially amused.

It was hard to get them all three in the same frame, but they finally converged at the activity table.

And at one point, we just had a roundup. This was the only shot I got that didn't include the top of one of their heads.

I thought this one was adorable. What's that? Where's Jasmine?

Oh, there she is... enjoying some shoes and diaper salve with Jonah.

Jonah and one of his best buds, Kathryn.

Then, on Friday evening, we met our friends, Shawn and Jen (who, for some reason, were Jawn and Shen every time I said their names on Friday... it was a slow brain day.) Anyhoo... the Winston Salem Children's Museum has some $3.00 Friday nights, so Shen invited us to come along.

Shawn and Jen's little boy, Jude. He's four months older than Jonah, and I have high hopes that they'll be best buds.

I think the daddies had more fun than the (littler) boys.

This was a Scarf-Shooty-Outy thing that you could put soft balls and scarves in. It would shoot them all through the tube...

and then they'd pop right out.

Jonah was not amused with his hard hat (along with most of the rest of everything we did).

Jonah pushed the trucks. Jude went with a less conventional approach.

I don't know where this was, but it was soft and padded, so we hung out there for a while.

More of being NOT amused.

He did take a break of being Fussy McCrabby pants to play the laser harp.

But then he was back at it for Daddy's photo-op. (Matt may or may not have just shoved Jonah under Carmen's utters for some practice milking thus inducing a screaming fit, I couldn't rightly say.)

Jude loved the kitchen area. Steak in a bowl. Spaghetti straight on the table. Stacking the larger cup INSIDE the smaller cup. This boy lives on the edge.

"What's that? You wanna look up my nose?"

Driving the Krispy Kreme truck. Did you know Krispy Kreme started in Winston Salem? You're welcome, America. For those of you who don't know Krispy Kreme, you better hope you never taste a KK doughnut. You'll hate yourself for wasting all those years with your measly Dunkin' Donuts.

When we went into the Food Lion part of the museum, this little girl said, with a sassy attitude, "Um... Excuse me. I need someone to check me out please." So Jen and Shawn politely obliged. It was laugh out loud funny, but maybe you just had to be there.

Anyway, we stayed for about an hour and a half, and even though Jonah wasn't so into it, I was still so glad we went. The more we get Jonah out and experiencing new things, the more he'll get comfortable being other places besides our house. And I LOVE getting to spend time with Shawn, Jen, and Jude. I think the six of us (almost SEVEN!) are going to check out the Greensboro Children's Museum next month. They have $5.00 Friday nights and are even better. Hooray for fun outings and new experiences!

While You Were Getting Eliminated

Ah, the World Cup Not a pleasant weekend to be an American or English fan of the beautiful game; we could, um, parrot the experts, but we'll spare you. Let's just say it was very disappointing. Of course if you read the press in England, you could be forgiven for thinking it was the end of the world.

But life goes on. ADA continues this week in Orlando -- plenty of GLP and insulin news, below -- and our very own EuroBiotech Forum starts Tuesday in Paris. It's not too late to sign up for two days of partnering and excellent content, including keynote talks from Novartis Pharma CFO Jonathan Peacock and Teva Pharmaceuticals Europe president and CEO Gerard van Odijk.

While you were watching the drugs that watch your blood sugar ...

• Morphosys has licensed a Phase I anti-CD19 antibody from Xencor. The last time we checked in with Morphosys regarding its in-licensing ambitions, CEO Simon Moroney told us "The review isn't complete and we're optimistic, but the ground isn't littered with jewels." We're glad they finally found something shiny enough to pay $13mm u/f for. Xencor will run Phase I for what is now known as MOR208 and then Morphosys picks up development, paying Xencor milestones and royalties on worldwide sales.


• Will Novartis need to up its bid for the eyecare giant Alcon? That company's independent directors committee certainly thinks so, and it has an expert backing it up, reports Reuters.


• Boehringer Ingelheim will work with Marinomed to commercialize in various markets an OTC nasal spray for the common cold. Marinomed gets about €1 million u/f and could receive milestones based on market entry and royalties.


• AstraZeneca and Medicines for Malaria Venture announced a partnership whereby MMV will have access to AZ's compound library for discovery efforts against malaria parasites.


• ADA: Novo Nordisk's diabetes drugs were on display at ADA -- liraglutide bested Januvia as an add-on to metformin and proof of concept achieved for ultra-long-acting insulin Degludec. Analysts report this morning that Novo also began talking about liraglutide Depot, a longer-acting version of the peptide.


• ADA: BMS and AZ put out a trio of releases on Saturday with Onglyza and dapagliflozin data. Onglyza and metformin as first line combo therapy? Check. Onglyza/metformin non-inferiority study vs glipizide/metformin? Check. Dapagliflozin add-on Phase III? Check.


• ADA: There's plenty more from Byetta, Januvia, canagliflozin, taspoglutide and all your other favorites. News roundup here.

image from flickr user baldheretic used under a creative commons license

crazy jonah

So we had a great weekend, and I have many a cute photo to share, but I have to interrupt my (not so regularly scheduled) post to share this video.

You know how your kids just seem to stay the same and not learn anything new for several weeks, and then they learn like five new tricks in two days? We've had that kind of weekend. In the last three days, Jonah has waved bye-bye (although it was only one time... but was most certainly a bye-bye wave... I have witnesses), learned to give kisses, learned to high five, and lastly...

... has developed a strong preference for the color purple... as you can clearly see.

(And no, we don't usually sit around torturing our child for kicks and giggles and good video material... but sometimes we do.)

Kids are SO crazy. I just can't believe how he's changing and growing and learning so many new things. I mean, I know he's delayed (obviously), but I'm just so proud of the huge strides he's made in this last week or so.

On that same note, he ate his ENTIRE breakfast, lunch, and dinner BY MOUTH, and we only had to use the g-tube for his water and meds. (You can pick your mouth up off the floor now.) I know it probably won't last but HOLYCOW HOTDANG WOOHOO my child ate over 1,000 calories of SOLIDS today.

He's also pulling up to his knees and playing that way regularly these days. And today he was crawling around (mostly chasing after the purple ball) more than ever. He was so active compared to even a week ago. It's like he's just had this burst of energy and learning. Maybe that's what eating will do for you!

And on a two-steps-forward-one-step-back-that's-Jonah-for-you kind of note, although he now opens his mouth for food, he's started lifting his tongue up and getting confused about how the mechanics of eating go. Before, he knew how to open and swallow, but the psychological aversion was our problem. Now it seems that we've made some strides in that department (I'm not so naive to think this will for sure last), he's forgotten the physical skill of opening his mouth and taking the spoon. So, needless to say, that's frustrating and food goes everywhere, and feedings still take about ten times longer than they should, but we'll take what we can get! It's still a huge victory overall.

I'll blog about our weekend later on in the week. Jonah had a play date on Friday with some cutie twin girls (La-dies Man, I tell ya) AND got to go to the Children's Museum on Friday night. Fun times. Hope yours was as great as ours. Cute photos to come (tomorrow hopefully?).

Deals of the Week in a Parallel Dimension

It's ADA season, and this week didn't disappoint with diabetes deals coming out of the woodwork. But if FOTF can go a little off-piste, permit your favorite deals roundup to stray as well , straight into uncharted regulatory and reimbursement territory. (We promise to get to the juiciest deals eventually.)

This week FDA and CMS agreed to routinely share data in what could serve as a first step toward parallel reviews by FDA and CMS for marketing approval and medicare coverage. We're already seeing reimbursement milestones popping up in deal terms, and we can imagine that a parallel review by the massive government insurer would only mean they'd be even more common.

To be sure this isn't a new discussion, as our colleagues from "The Gray Sheet" wrote this week. But there may be more substance to this new effort, under which the agencies are "seriously exploring the ability to start, at a manufacturer's request, a Medicare national coverage determination process" while a medical device is under FDA review. That remark, from FDA center for devices and radiological health director Jeff Shuren, was made before a device-oriented audience, but he clarified that the memorandum of understanding between FDA and CMS will apply "FDA-wide."

Hmmm. Who will be the first to channel his/her inner Ray Stantz and order FDA and CMS to "cease any and all supernatural activity and return forthwith to your place of origin?"

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Before we get to the deals this week please allow us a moment to say GOOOOOOOOAAAAALLLLLLL!

Oh and yes, we did the movie thing last week, but it's hard to resist this one. We had the same reaction as Derek Lowe to the idea of Lilly launching a statin in 2010 -- surely someone threw us in a DeLorean, cranked up the Huey Lewis, scored some Lybian plutonium and sped up to 88 miles per hour, because we all went Back to the Future this week.

Never mind that Biff guy, it's time for ...


Sanofi/Regulus: Sanofi-Aventis made its first foray into the emerging microRNA field by forging a collaborative development agreement with Regulus Therapeutics, a startup co-owned by publicly traded Alnylam Pharmaceuticals and Isis Pharmaceuticals. For an upfront payment of $25 million and an equity investment of $10 million, Sanofi received options to license four Regulus compounds, beginning with a co-development agreement targeting fibrosis. If all milestones are reached on all four, Sanofi could pay Regulus more than $750 million; Sanofi also has a $50 million option to expand the partnership into a broader alliance that to us recalls the first broad RNAi deal between Alnylam and Novartis. MicroRNAs regulate gene expression by binding to target messenger RNA transcripts and developers hope that disruption by a single microRNA can interfere with disease pathways. Nearly all microRNA-based therapies have yet to reach the clinic. Regulus, which has programs in oncology, cardiovascular and metabolic diseases, also has two separate partnerships with GlaxoSmithKline. One gives GSK four options in Regulus’s immunological and inflammatory disease portfolio, and the other pertains to a specific hepatitis C treatment. The deals collectively are a sign of Big Pharma’s renewed interest in innovative early-stage technologies.--Paul Bonanos

Valeant/Biovail: While complementary lines of business played an important role, it was probably Biovail’s advantageous tax setup that led larger specialty pharma Valeant to merge with it in a deal announced June 21. Canada (and hockey?) will be a major focus for the newco – to be named Valeant Pharmaceuticals International but based in Biovail’s hometown of Mississauga, Ontario, rather than Valeant’s current home of Aliso Viejo, Calif. The new Valeant’s four main business areas will be specialty central nervous system (comprising Biovail’s CNS franchise and Valeant’s neurology business), dermatology, Canada, and branded generics/emerging markets. Valeant CEO J. Michael Pearson, who will run the new company, said each firm currently has a roughly $100 million business in Canada, and both are experiencing a better than 20% growth rate. Asked to estimate what the new company’s effective tax rate would be, Biovail CEO Bill Wells, who will be chairman of the new company, said Biovail currently pays in the 5 percent to 8 percent range. The combined company’s rate will be somewhat above that but far below Valeant’s tax rate of 36 percent, he said. Biovail has done its manufacturing in Canada, generating excess net operating losses. Now, those NOLs will help shelter Valeant’s considerable income in Canada. The new company also will retain Biovail’s principal subsidiary in Barbados, where intellectual property is developed, funded and managed, taking advantage of that country’s very low tax rates. The merged company also should realize $175 million in cost synergies in 2011 before tax savings are even factored in, derived partly from combining commercial operations in Canada, which will detail both specialty and primary care products.—Joseph Haas

J&J/Metabolex: Metabolex's first deal this week sees Johnson & Johnson taking time out from their OTC recall issues to boost its diabetes pipeline. In addition to licensing a type 1 diabetes vaccine from Swedish biotech Diamyd (see below), J&J's Ortho-McNeil-Janssen unit snapped up worldwide rights to several undisclosed first-in-class preclinical drug programs for type 2 diabetes from Metabolex. The deal is the companies' second, following on a 2006 alliance around two Metabolex PPAR-gamma programs, which are now both in Phase II development. In the current deal, Metabolex gets an undisclosed up-front payment and the typical assortment of development, regulatory and sales milestones plus royalties. If the stars align, the biotech could see up to $330 million.--CM

J&J/Diamyd: The same day OMJ inked its deal with Metabolex it also signed up Sweden's Diamyd, paying $45 million up-front for that company's Phase III type-1 diabetes vaccine. The vaccine could slow or halt the disease by protecting insulin producing pancreatic cells. Development and commercial milestones on the deal total $580 million, and Diamyd is eligible for tiered royalties on potential sales. The companies are sharing the costs of the vaccine's ongoing EU Phase III trial, and J&J can take over development if it chooses based on the results of that study. J&J's strategy is clearly one designed to leverage its presence in diabetes devices -- it does not market any diabetes drugs, yet, but its two deals this week augment an internally and externally sourced suite of compounds the roots of which goes back at least ten years to a research deal with Mitsubishi-Tanabe in 2000. --CM

Sanofi-Aventis/Metabolex: Sanofi-Aventis may not be making big news at this year's 70th Scientific Sessions of the American Diabetes Association but that doesn’t mean it isn’t creating its own buzz—and no vuvuzelas required. On June 25, the company announced its third deal since March 31 in the diabetes space, becoming the second pharma to ink a deal this week with Metabolex. The global licensing agreement is for the biotech’s Phase II, oral GPR119 receptor agonist, MBX-2982, for the treatment of type 2 diabetes. Specific deal terms of the Sanofi partnership weren’t disclosed but biobucks could total $375 million. It’s no secret that Sanofi has grand ambitions to become one of the leading players in diabetes but to do that, the company will need to diversify beyond its juggernaut Lantus. As Sanofi bolsters its pipeline, the focus has been on novelty and diversification—the March alliance with Agamatrix gives the French firm a foot in the blood glucose monitoring space; the tie-up with privately-held CureDM gives Sanofi a potentially first-in-class compound in the islet cell regeneration space. Agonists of GPR119 represent a first-in-class oral treatment for type 2 diabetes that simultaneously increase insulin secretion while stimulating the release of GLP-1 from the intestines. (They are also an au courant target as evidenced by last week’s deal between Neurocrine and Boerhinger Ingelheim.) —Ellen Foster Licking

Gilead/CGI: Finding a use for some of the $4.6 billion of cash it has on hand and also seeking some diversification beyond the antiviral space, Gilead Sciences June 25 announced that it would buy privately held CGI Pharmaceuticals for up to $120 million in cash. Gilead said the majority of the payment would be an upfront purchase price with the remainder paid out in clinical development milestones but did not break down the exact amounts. CGI, formerly known as Cellular Genomics, has nothing in the clinic but is doing discovery and development in three platform areas, of which Gilead seems most intrigued by its spleen tyrosine kinase inhibitor (Syk) program, which includes a lead preclinical compound with potential to treat rheumatoid arthritis. Under the deal, CGI would continue operating as a fully-owned Gilead subsidiary at its current headquarters in Branford, Conn. Gilead Chief Scientific Officer Norbert Bischofberger cited CGI’s scientific expertise as “a strategic fit with Gilead’s existing research organization” and said Gilead will work to move CGI programs into clinical development. Standard & Poor’s analyst Steve Silver called the transaction a “modestly priced opportunity to broaden Gilead’s long-term pipeline.” GCI's backers are probably seeing about a 2x multiple on the deal, should those milestones materialize; the company had not raised money since a 2004 Series C led by Lilly Bioventures that brought in $34.9 million.—JH


Bristol-Myers Squibb/Exelixis: Exelixis revealed June 21 that Bristol is walking away from its late-stage partnership on the biotech's lead compound XL184, a multikinase inhibitor in Phase III trials for medullary thyroid cancer (MTC). GlaxoSmithKline had an option on '184 but passed in late 2008, soon after which Bristol swooped in with a lucrative deal, $240 million in upfront and near-term milestones. With Bristol's decision, the question becomes whether Exelixis can find another home for the drug. It insisted the data were sound, and officials on both sides of the no-deal talked vaguely about portfolio conflicts and pipeline reviews. Two investigators working on XL184 trials told "The Pink Sheet" they knew of no clinical problems serious enough to merit BMS's decision, but some analysts were skeptical that Bristol would give up rights, given what it has already spent, on a drug with serious potential. Fresh from layoffs of nearly 30% of staff, Exelixis said it will push on with XL184 and start a Phase III trial in glioblastoma by the end of 2010 and file an NDA for MTC in the second half of 2011. The firms' partnership on XL281 remains intact. -- Emily Hayes

Image courtesy of flickrer TheAlieness GiselaGiardino23.

it was just the battery!