this and that

We're still alive and (mostly) well. Jonah's bottom is still in bad shape, especially when he poops. He clinches, screams, lifts himself off the table, and flips over, making it impossible to get him clean. Plus, he's in agony, which doesn't help. It does seem the creams are sticking better these last couple days, so at least I know it's not as raw as it was. It's just hard because it seems like every time I have to change a poopy diaper, even with barely wiping him at all, it opens the wound back up. GRRRR. I feel sorry for Jonah but I feel even more sorry for EB kids like Tripp who deal with non-healing wounds in that area all the time. I just can't imagine. Today we couldn't even do bandage change until 3:15 in the afternoon because we were waiting for Jonah to poop so we could soak him in the Baking Soda bath. Soaking is really the one way to get him clean. This past week as been one of the worst I remember. And EB still sucks, just in case you were wondering. 


Overall, we've had a decent weekend though. Matt took me on Saturday night to the Barn Dinner Theatre in Greensboro for dinner and a show. He had given me the tickets on Mother's Day and arranged for Kathryn to come babysit so we could go. Sarah helped babysit too, given his bottom challenges. Thanks to both of you for letting me have a night out. I desperately needed it. 


My sister and Matt's parents were in town (not staying with us, but in town) this weekend, so it was great to see all of them too. Actually, Matt's mom has been in town all week taking care of her dad. He fell last weekend and broke his shoulder. He had a hard time walking even before that. He's in bad shape, staying in bed 22 hours a day, no motivation. Please pray for him and for Debbie too. Most of his care is falling to her, and it's a big load to bear. She has already been here for over a week and has no clue when she might get to return home to Florence.


Other than Barn Dinner and seeing some family, Matt and I have been taking every free moment to sort through all of our drawers, rooms, and closets. We're trying to get ready to have a yard sale to get rid of things/pay for things our new kids will need (bunk beds, dressers, mattresses etc.) and to just make more space in our house! Next up is finding a dining room table that is fairly narrow that will seat at least six and has bench seats (preferably). I'm nesting like crazy and getting really excited about our new addition(s). We still have not been assigned a social worker but I plan on becoming persistent and obnoxious taking care of that this week. God has amazing things in store for our family. I just know it. (And when I talk about the kid(s), I always say "the boys" or "our boys" so I'm sure God will give us a little girly girl and a pet goat. He likes to have his own plans. :) )


Alrighty, gotta run. We're meeting my dad at Ronni's (best wings EVER) tonight for dinner. I think he's having Jonah withdrawal. 


Hope you all had a blessed weekend.

Financings of the Fortnight Puts It In Reverse

LinkedIn? Might as well be in a different universe. From where we sit, it's terribly difficult to go public, let alone do it with investors making the equivalent noise of all those kids who came to see the Beatles in 1964.

There's another way to go public, however. Perhaps you've heard that Radius Health this week merged into an acquisition shell created by life-science venture firm MPM Capital. The new Radius already reports to the SEC and plans to apply directly for a listing later this year, with a goal of transitioning to the Nasdaq by early 2012.

Our Pink Sheet colleagues covered it thoroughly, but the gist is that Radius, spurned by Novartis' decision not to option its anabolic bone-building treatment BA058, now has a financial runway to fund Phase III trials and eventually find a new dance partner. If approved, BA058 would compete directly with Lilly’s Forteo (teriparatide), the only currently approved drug that builds bone mass rather than slowing resorption.

Concurrent with the reverse merger, Radius has raised $91 million in an equity-and-debt Series C round. The first tranche consists of $22 million in equity funding and $6.25 million in debt and includes a doubling-down by MPM, which returned to invest above its pro-rata. MPM's Ansbert Gadicke told our Pinkish colleagues that prostate-cancer developer Cougar Biotechnology provided inspiration for the deal. Cougar reverse-merged into a shell company in 2006; three years later Johnson & Johnson scooped it, and its Phase III drug abiraterone, for nearly $1 billion.

How often does that happen? In the last ten years, never, at least not at that price. At least five others besides Cougar have gone on to reap M&A benefits; the next priciest we could find was Solexa, a genomics company that was acquired by Illumina in 2006 for $600 million in stock.

Of 75 reverse mergers we found in our database since 2001, at least 16 included a round of financing either at the time of the merger or nearly so. Cougar nabbed $47.5 million, for example. Not all are engineered as a way to reach the public markets, of course. (Merck/Schering-Plough was technically a reverse merger, which we had a bit of fun with.) The majority are historical footnotes, as you might expect from companies that can't manage the normal route of attracting public investors.

Then again, the "normal route" doesn't exist anymore for biotech companies. Regarding Radius, the biotech has enough going for it to keep old acquaintances interested; Novartis, through its MPM-managed fund, is a new investor, as is Ipsen, the European drug firm that sold Radius the rights to BA058 in the first place in 2005. Another backer is Nordic Bioscience, a contract research firm with deep expertise in osteoporosis drugs. It's taking equity as part of its CRO fee for BA058; talk about having skin (and bone) in the game.

Spin-outs, reverse mergers, incubators, follow-ons, and A, B or C rounds: Your best bet for boning up on all of them is...

BioCritica: Blockbuster gone bad Xigris (drotrecogin alfa), which was hailed as a new sepsis treatment upon approval in 2001, has a new home. After a decade of minimal sales dogged by serious side effects, owner Eli Lilly & Co. is spinning the drug out to BioCritica, a new firm in Indianapolis that will focus on critical-care medicines. Its backers are Care Capital and NovaQuest Capital, and it also received Indiana state funding and support. No financial details were disclosed, but the NovaQuest connection is interesting, seeing how the firm -- once the investment arm of CRO Quintiles Transnational -- was deeply involved in two of Lilly's Alzheimer's drugs, one of which, semagacestat, failed in late-stage trials. NovaQuest is now operating independently of Quintiles, and as this column reported last December, is raising its own fund. BioCritica, meanwhile, is led by CEO David Broecker, who most recently served at the helm of Cambridge, Mass. biotech Alkermes, but previously worked at Lilly in marketing and product planning. BioCritica will continue Lilly's work to find the best uses of the controversial treatment, which has serious bleeding side effects and questionable efficacy in the broad sepsis patient population, but it hasn't disclosed more detailed plans. Lilly already decided a biotech was best suited for the follow-up to Xigris, a compound Lilly out-licensed to Cardiome Pharma in 2007. -- Lisa LaMotta

GenKyoTex: Edmond de Rothschild Investment Funds led a CHF 18 million Series C for GenKyoTex, a Geneva-based biotech focused on developing small molecule inhibitors of NOX family NADPH oxidases, transmembrane proteins at the beginning of the oxidative stress pathway. New investors Vesalius Biocapital Partners and MH Healthcare Venture Management and existing backers Eclosion, SGAM’s Specialized European Fund for Therapeutic Innovation, and Fondation d’Aide Aux Enterprises chipped in as well. GenKyoTex was incubated at Eclosion, the Canton of Geneva based public-private partnership that helps participating entrepreneurs tap a mix of state, university, and industrial resources. GenKyoTex plans to use the new cash to develop its lead candidate GKT137831, currently on the cusp of going into the clinic, for the treatment of diabetic neuropathy, and to support its preclinical portfolio. GenKyoTex is betting that interfering with oxidative stress by inhibiting NOX will help reduce the formation of reactive oxygen species (ROS) that can contribute to cardiovascular, neurodegenerative and metabolic diseases, cancer, and other conditions. The funding is a coming-out party of sorts for GenKyoTex, which has its roots in a three-way academic collaboration between scientists in -- you guessed it -- Geneva, Kyoto, and Texas. Along with the financing the biotech simultaneously announced a spate of executive changes: Ursula Ney, former Antisoma COO, becomes CEO; Phillipe Wiesel, formerly a medical director at Serono, is CMO; and taking on the role of chairman is PregLem CEO Ernest Loumaye. -- Chris Morrison

SpringLeaf Therapeutics: Start-up SpringLeaf has added $15 million to its coffers through a May 12^th Series B venture roundto continue work on a disposable "patch pump" that allows at-home subcutaneous of intravenous biologics, and also to work on a drug , according to CEO Frank Bobe.The cash comes from return investors Flybridge Capital and North Bridge Venture as well as lead and new backer SR One, whose Brian Gallagher, joins the company’s board. (This is SR One’s first participation in a drug delivery-focused firm since Dicerna Pharmaceuticals’ $29 million August 2010 Series B.)MIT spin-off SpringLeaf was founded as Entra Pharmaceuticals in 2007 and two years later filed a patent application entitled “Skin-Patch Pump Comprising a Changing-Volume Electrochemical Actuator.” Gallagher says the firm's “patient-centric” approach will facilitate more cost-effective therapies and the technology overcomes formulation obstacles associated with delivering existing large-volume biotherapeutics, including highly viscous drugs. CEO Bobe declined to disclose any details on the drug SpringLeaf is working on, but he said preclinical results were encouraging. The biotech, which has now raised about $27 million including a December 2008 Series A round, hopes to initiate a clinical trial by the end of 2012.-- Maureen Riordan

ImmunoGen: Best known for its antibody-drug conjugate (ADC) work, ImmunoGen said May 20 it has raised $84 million before expenses in a follow-on offering, selling 7 million shares at $12 per share. The fundraising comes as ImmunoGen's stock has reached its highest levels since the early 2000s amid growing hopes that ADCs, which attach a strong cytotoxic agent to a therapeutic antibody for a more precise attack on cancer cells, are on the cusp of medical success after three decades of frustrating clinical progress. ImmunoGen is part of the optimism; it has contributed the cytotoxin and "linker" technology used in Genentech/Roche's T-DM1, considered the next iteration of Herceptin. Indeed, ImmunoGen's stock run-up is due in part to new top-line randomized Phase II T-DM1 data released in April that showed improvement in progression-free survival in first-line metastatic breast cancer patients. Good news about T-DM1 is more a boon to ImmunoGen's platform than its immediate finances, as the firm would only receive single-digit royalties from any commercial sales. The targeted antibody, aimed at HER-2 positive breast cancer, is also in non-randomized late-stage trials. Underwriters led by Jefferies & Co. have the option to buy up to 1.05 million more shares. -- Alex Lash

Many thanks to Paul Bonanos and Amanda Micklus, who contributed mightily to this week's introduction.

Photo courtesy of flickr user Rd. Vortex via Creative Commons license.

Deals Of The Week: Outsourcing

Stop the presses! Pfizer has done the unthinkable! The Big Pharma has upended its huge R&D operation!

Reading the headlines and tweets May 26, this blogger anticipated a dramatic pronouncement from Pfizer's head of R&D Mikael Dolsten explaining exactly how the behemoth intended to strengthen its "innovative core." But we were pretty sure Pilates wasn't part of the prescription.

It was just three months ago, after all, that newly installed CEO Ian Read announced sweeping budget cuts to the R&D organization and hinted that certain business units might be ripe for spinning out. But the R&D changes announced Thursday was more ho-hum than a humdinger.

In fact, it wasn't even an R&D shake-up at all. What Pfizer has instead done is winnow its myriad clinical service providers from 17 (!) to 2, moving to a system that is less about buying clinical trials capacity than it is about buying expertise. "We think that expertise can actually help us execute trials more effectively, faster, and with better quality, which will ultimately lower costs," Pfizer's SVP of development operations John Hubbard told "The Pink Sheet" DAILY.

With the looming patent expiration of Lipitor coming in November, there's no doubt Pfizer must cut costs. But it's hardly clear how much Pfizer will actually save via its newly announced preferred provider relationships with Icon and Parexel. It's not as if the drug maker is outsourcing significantly more of its total research and development work to outside organizations after all, a move that would allow for additional job eliminations -- and cost reductions -- in the R&D organization.

According to PSD, Pfizer will increase the percentage of clinical trials work it outsources by only about 10%, with the move really designed to streamline the management of vendors, something Hubbard admits is "complex." Thus, consider this not a revamping of how R&D is done but a consolidation of already outsourced development work into the hands of just a few players. As such, the move sounds a lot like Sanofi's broad 10-year collaboration with Covance. Announced last year, that alliance also met with sweeping headlines but was in reality a more prosaic realignment designed to reduce the complexity of managing development work.

We aren't saying Pfizer's newly announced arrangement isn't noteworthy-- or smart. We're just saying its iterative rather than innovative. (And, maybe, just plain old common sense.)

What's really smart about the set-up is that Pfizer didn't pick just one preferred provider. By signing on two different CROs (can we now call them clinical repair orgs?), the drug maker has created a situation that fosters competition. Financial details of the two new partnerships, which start in June and last until 2016, haven't been disclosed, but Pfizer is apparently keeping a scorecard that benchmarks how well Icon and Parexel each execute on their assigned trials. And as Pfizer gathers data on quality, timeliness -- and perhaps most importantly cost -- that means it can pit the two service providers against each other, potentially further increasing efficiencies. Five years from now, you can imagine CROs jockeying for position to be the next preferred vendor. To merit an alliance, such outfits will be forced to guarantee they can deliver "x" by time "y", and it will only cost "z".

It's a new kind of pay-for-performance arrangement -- and it's definitely a step in the right direction.

But it's far from the sexy R&D shake-up proclaimed in the blogosphere -- and still far from what Pfizer (or any other big pharma, quite frankly) needs to do to solve its moribund R&D productivity problem.

As for the larger changes afoot in Pfizer R&D, it's anybody's guess what model (or what acronym), the drug maker will pursue. We hear CEDDs are out and TAUs and TSUs are the new fashion. (Don't forget OI -- for open innovation -- either. JNJ's promising its externally driven model will yield fruit -- and plenty of products for regulatory approval by 2015.)

Whatever. To be honest, the acronym that most excites us is B-B-Q. Before you quaff your first summer pale ale of the holiday weekend, remember to read...

Elan/Proteostasis: Elan's tie-up this week with Proteostasis replicates last year's mega Celgene/Agios tie-up on a smaller scale. The new deal, potentially worth $50 million to the privately-held Proteostasis, requires Elan to pay $20 million upfront as well as $30 million for R&D expenses over the next five years. In return, the developer of the blockbuster multiple sclerosis drug Tysabri (natalizumab) gets a 24% stake in the U.S. biotech, seats on its board of directors and scientific advisory boards, and the first right to license any neurodegenerative compounds that come out of the collaboration. Yeah, that's right. The privately-held co. has agreed to an option-style deal that gives Elan first dibs on its potentially novel disease-modifying drugs in return for the security of funding. The deal is the first industry collaboration Proteostasis has signed since its splashy debut in 2008: a $45 million Series A financing from high-profile investors, including HealthCare Ventures, Fidelity Biosciences, New Enterprise Associates, Novartis Option Fund, and Genzyme Ventures. (Hmm, wonder what happens to any Novartis options as a result?) The company has stayed under the radar in the interim, using the time and considerable financial backing to build its platform, which is designed to target the biological pathways that regulate the correct folding or placement of proteins within a cell. (For more on protein folding and disease, check out this still-relevant Start-Up feature.) Proteostasis' molecules are still preclinical but the new alliance with Elan could accelerate the biotech's clinical development plans; that's because it marries the biotech's discovery technology with Elan's proprietary animal models, biology, med-chem and clinical development capabilities. --EL

Eli Lilly/BioCritica: Attention biopharma insiders! We interrupt your regularly scheduled programming to bring you news of that rare species observed in the Rx wilderness: the spin-out. On Monday May 23 came news that Eli Lilly was spinning out US development and commercial rights to its commercially underwhelming sepsis drug Xigris to private investors Care Capital and NovaQuest Capital. The new private company, which has been christened BioCritica, will focus initially on the continued development of Xigris but the ultimate goal is to create a portfolio of critical care medicines. To bolster its pipeline, BioCritica has the option to in-license other critical care compounds in preclinical development at Lilly as well as the right to acquire ex-US rights to Xigris. In exchange, Lilly will receive royalties on US sales of the drug and an equity stake in BioCritica. The financial terms of the agreement were not disclosed.The decision to shed Xigris reflects Lilly's effort to focus development resources, according to the company. Though Xigris has been available commercially since 2001, its sales have not met Lilly's or Wall Street's expectations and Lilly has had a spate of expensive late-stage development snafus. BioCritica will continue Lilly's work on identification of the best uses of the controversial treatment, which has serious bleeding side effects and questionable efficacy in the broad sepsis patient population.--Jessica Merrill

Medco/Exagen: Can Medco do for methotrexate in rheumatoid arthritis what it's done for warfarin in the blood thinner market? An interesting alliance announced Monday May 23 between Medco's research institute and the privately-held Exagen Diagnostics shows that it is going to try. Exagen, which has raised a minimal amount of venture money since its 2002 founding, has developed proprietary software to discover and create predictive molecular tests that can aid in disease diagnosis, prognosis, or predict a likely treatment response. One of its tests, Avise PG, helps doctors and patients monitor the effectiveness of low-dose methotrexate therapy in rheumatoid arthritis patients. The oral anti-folate is, of course, decades old --it was first introduced as an oncologic in 1947 and became an important part of the RA armamentarium in the 1980s. And compared to newer TNF-alfa injectables like Humira or Remicade or Simponi the drug is definitely a cost-effective choice for treating the auto-immune disease. The problem is that establishing the right dosing regimen for patients isn't trivial, since individuals metabolize the medicine so differently. (Hmm, methotrexate's profile is starting to sound a lot like another cheap, effective, but difficult to use medicine: warfarin.) And if docs can't get the dosing right in a defined period of time, the default is to move to the costlier biologics. For payers who are increasingly concerned about the cost of specialty products -- and RA is an area of intense interest these days -- new tests that can promote the use of older, cheaper drugs are an obvious solution. But there's got to be data showing the utility. Enter Medco, whose research arm will recruit around 400 patients to participate in a pilot study (called Nimble) gauging the usefulness of Avise in RA patients beginning methotrexate therapy. Docs will send patient blood samples to Exagen's lab, which will conduct the Avise test, and report back on appropriate dosing; outcomes data will be compared to a similar cohort of patients who don't receive the Avise PG test. Why should the drug industry care? Medco's been resurrecting warfarin, conducting a series of observational studies gauging the utility of the medicine plus the genetic test versus newer, pricier drugs like Pradaxa. If the Medco/Exagen team can demonstrate the same utility for methotrexate, it's bad news for newer RA meds, creating a higher bar for adoption with payers.-- EL

Valeant/Sanitas & Watson/Specifar: Need growth? Try a branded generics firm in Central or Eastern Europe. That's the message from a duo of deals this week, both acquisitions by hitherto US-focused firms – and the first of more to come as US growth shrivels up, according to those familiar. Barely a week after Takeda finally confirmed it was forking out €9.6 billion to buy Nycomed, whose attractions also included its strength in CEE and Russia, Canadian specialty pharma Valeant announced it was paying €314 million cash for Lithuania's listed Sanitas, and Watson snapped up Greece's privately-held Specifar for €400 million, plus earn-outs linked to a tablet form of Nexium due to launch in some markets later this year. Europe's ultra-tough pricing and reimbursement environment may make it a graveyard for growth in innovative drugs, but there's plenty of upside in generics, particularly of the branded, specialist kind. The battle for Germany's ratiopharm, ultimately won in March 2010 by Teva, was one of the more high-profile asset-grabs in this field. Valeant had to pay almost four times' sales for Sanitas, a healthy multiple that reflects what was a "dynamic" auction process, according to someone close to the deal. The attraction: for starters, development prowess in dermatology, ophthalmology and hospital injectables (niche, high-margin drugs), formulation expertise, some pipeline, and a portfolio that's 80% non-reimbursed (thus circumventing the government pricing pressures). The deal furthers Valeant's stated goal of doing at least five ex-US deals this year, and follows the February 2011 acquisition of PharmaSwiss, which provided a commercial infrastructure in Eastern Europe. If Sanitas shareholders think they did well, how about Specifar's: Watson appears to have paid over five times 2010 revenues for this group, based in a country whose economy is falling apart and where generic penetration is one of the lowest in Europe. Most of Specifar's revenues come from developing and out-licensing products worldwide, and it’s highly profitable, according to a source involved in the deal. So Watson has paid for a European R&D engine to bolster the sales infrastructure and starter revenue-base it started to establish via its $1.8 billion cash and stock deal in 2009 for Western-European based Arrow. --Melanie Senior

Nestlé/Prometheus Labs: Via its newly formed Nestlé Health Science subsidiary, global food products conglomerate Nestlé SA is buying specialty pharma and diagnostics provider Prometheus Labs as part of its goal of developing personalized nutrition strategies that will help in the management and prevention of chronic health conditions, according to the company’s announcement of the deal. Prometheus, which had been looking to go public, generated revenues of $519 million in 2010 including $316.5 million from the sales of the glucosteroid Entocort EC for Crohn’s disease, which Prometheus licensed from AstraZeneca for the US market in 2004. Prometheus also began distributing Novartis’ cancer drug Proleukin in the US in February 2010, which brought in $64 million. The diagnostic services business, comprising GI tests to differentiate irritable bowel disease (IBD) and Crohn’s from other disorders and oncology services to guide the use of targeted therapies, accounted for $81.3 million for the year, according to an S-1 amendment filed in February 2011. The companies are silent on the deal price, which an analyst cited in a Bloomberg report put at somewhere north of $587 million. Nestlé has also recently added Vitaflo, a maker of nutritional products aimed at individuals with genetic disorders that affect how the body processes food, and CM&D Pharma, which produces IBD, kidney disease, and cancer-related nutritional foods. But unlike those others, the Prometheus acquisition is aimed at the physician market. Nestlé is one of several food and consumer products companies thinking about ways it can leverage its marketing and distribution capabilities to deliver medical diagnostics and personalized medicine. Unilever has engaged the VC firm Physic Ventures to explore opportunities in the area, and for years, Procter & Gamble has maintained a notable presence at personalized medicine meetings. – Mark Ratner

(Image courtesy of flickrer Scott Ingram used with permission through a creative commons license.)

IMPORTANT

You guys are so amazing. The fact that your donations raised about $4,000 in just a few days to bring John and Carson home just blows my mind.


There's big news. Karrie and Donnie's dossier was submitted in Eastern Europe today. They could get their appointment and have to travel in one to four weeks. Because the boys are separated and in two different regions, they have to pay for two adoptions. AND they have to stay longer in the country. That means more expenses over a longer period time and more time that Donnie is out of work.


They still have so much to raise - 
facilitator fees - $18,000
plane tickets for the four of them - $7,000
medical checks for the boys before they can leave the country - $300
passports for the boys - $2,000
the boys' visas - $808
housing while there (8 weeks) - $4,480
food while there - $1,680
in country travel (the boys are 400 miles apart) - $3,000


With the $12,500 they've already raised for this part of the process (they've already had to spend thousands on the stuff that came before this), they still have around $25,000 to raise before they can travel. And that's not including the money that would be helpful to raise for Donnie's lost wages while they're gone. All of that to say, it's a lot. The fact that there are two boys and they are so far apart and in different regions makes the process much more expensive.


They are running out of time to raise the money. The boys know they are coming. They are waiting.

They need better care. Many of the wounds they have could be prevented. From the looks of their photos, I'd say they're most likely anemic. And they may have infections too. So much of it could be prevented and fixed if they could just make it home.

There is no reason the boys should be suffering these huge, deep wounds. With the right bandaging materials and daily care, they will have a life they've never known. One filled with the love of friends and family, the hugs of parents and siblings, the safety and warmth of a real home, and some of the best medical care in the world.

I know $25,000 to $35,000 sounds like an overwhelming amount. But just think if we all shared this story everywhere we could think of (you can direct them to this post if you don't have the time to write one up yourself) and donated anything we could, just think how quickly we could raise this money?

My God is so Big, so Strong and so Mighty, there's NOTHING my GOD cannot do!

I know there are critical people out there (I got a snide comment from one just this week) that think, "Well, if they're going to make it so expensive to adopt the kids they don't even want, why don't we just say no? When is enough enough? Take care of your own kids." 

I didn't respond (trust me, it was better that I didn't), but my thought was, "Well, I guess we say no when we've determined that when Jesus commanded us to take care of the orphans, he only meant the well ones, the convenient ones, and/or the American ones... or maybe when we decide that that command doesn't apply to us at all." The Cannells have stepped up to do an amazing thing. Families like them step up every day to do the same kind of amazing things. What if we took "bear one another's burdens" to heart and did all we could, as a community, to bring these sweet boys home?

What a testimony. What a story we'll have to tell, Friends.  

A couple practical thoughts on raising funds quickly - collect change from your coworkers, ask to hold a special collection at church, get a dollar from everyone you know, post about it on Facebook and/or your blog and ask everyone to give $5, email all your friends and family and ask them to donate (give them a direct link), ask for donations to the Cannell boys instead of gifts for upcoming birthday/graduation gifts, participate in the Cannell's puzzle fundraiser, give your leftover PayPal balance if you have a PayPal account, host a meal for friends/church family and ask them to bring donations, offer your skills/services (photography, organizing, sewing, whatever) for donations instead of payment (if you can afford that)... the list can go on.

Now, please, I know many of you have already donated all that you can. Please know how much I appreciate that and I'm not trying to guilt you into donating more. But if you have felt this tugging at your heart and haven't yet donated, now would be the time to do so. And if you have already donated, we just ask that you please spread, spread, spread the word... anywhere you can think of. (I just emailed a short version of their story and a link to this post to everyone in my contact list. Yep. Sure did.)

You can donate HERE or HERE. Of if you'd feel more comfortable writing a check, you can send one made out to Donnie Cannell to our PO box (right sidebar) and I'll be sure to forward it on to them.

May God bless you as you bless those in great need. Thank you, Friends. I love you all (even you, Snarky Comment Guy).

Peace and love.

The CEDD is Dead. Long Live the TAU

We've now entered a new chapter in the book of GlaxoSmithKline's 'Really Useful Abbreviations For The Way We Organize Our R&D'. In case you missed it: the CEDDs are dead. It's official. The Centers of Excellence for Drug Discovery, therapy-area focused groups spanning discovery through proof-of-concept, which flew onto the scene post-merger in 2001, are gone.

Back in the naughties, the CEDDs were considered quite radical, buzzing of smallness, accountability, and autonomy -- at least relative to the highly centralized, over-corporate, lots-of-corners-to-hide-in-style R&D of the time. They went on to inspire a host of similar initiatives elsewhere.

Now the CEDDs look sooo last decade (although we think the externally-facing CEEDD is still around). This decade the new acronym is fully-integrated Therapy Area Units (TAUs) -- five of them, covering Metabolic Pathways and Cardiovascular, Respiratory, Infectious Diseases, Immuno-inflammation, Neurosciences and Oncology R&D.

We knew which way the wind was blowing when we wrote this January IN VIVO feature. Even then it was clear GSK's R&D chairman Moncef Slaoui and SVP Medicines discovery & development Patrick Vallance wanted to move on from the notion of any sort of divide between pre- and post-proof-of-concept, the point at which the CEDDs passed suitable candidates onto the Medicines Development Centers (MDCs) for the really expensive work.

Slaoui and Vallance instead wanted full visibility from discovery through to registration and reimbursement -- not least so that payer requirements and commercial reality weren't an after thought simply pasted on in Phase III, but could actually influence which discovery programs to advance.

But don't assume the TAUs are a hark back to the pre-CEDD days of large sluggish R&D groups. That would be to forget the DPU chapter (you've still got your acronym cheat sheet right?) By 2008, these even smaller, even nimbler, even more accountable so-called drug performance units (DPUs) had begun to supercede their CEDD cousins. And given there were always a couple of standalone DPUs -- like Ophthiris in ophthalmology, for instance -- one reckons they were a harbinger of the evolving GSK.

Today, these DPUs -- which came complete with investment boards and three-year, milestone-linked funding cycles -- remain the R&D building blocks within GSK. It's just that now they have highly porous borders with downstream development. (And they're also spawning external versions, too, like the academic discovery performance unit set up at Cambridge University.)

So who are the new TAU chiefs? By and large, they're whoever won the battle between the CEDD-head and MDC-head in that particular therapy area: Zhi Hong (CEDD) in infectious diseases; Dave Allen (CEDD) in respiratory, Murray Stewart (MDC) in Metabolic Pathways & Cardiovascular, Perry Nissen in Oncology R&D (so-named because oncology is fully-integrated all the way through commercial, as at Novartis and Sanofi-Aventis). The Immuno-inflammation TAU chief has been appointed from academia but hasn't started yet, and Neurosciences apparently still has two heads.

Almost certainly, TAUs -- whose fully-integrated philosophy is also apparent within Sanofi Aventis' Therapeutic Strategy Units (TSUs?), while AstraZeneca's iMeds are more CEDD-like -- won't be the last chapter in this book. (How would consultants earn their keep?)

The next exciting bit to look forward to, though, is when the 3-year DPU funding cycle comes to an end later this year. That might kill off a few poorly-performing DPUs; indeed, "until and unless GSK actually shuts something down, no one will see the connection between data and funding, and really 'get' the model," opined one external advisor.

Slaoui isn't about to do any culling just to relay a message, though. "I may terminate a DPU even if [it] reaches [its] numbers, because the biggest limitation to numbers is that they don't [necessarily] reflect quality," he said. So by next year a few DPUs may slip away, or be tweaked...but we reckon the overall DPU concept has somewhat longer to run.

image by flickrer purplenina used under creative commons

bandages CAN be adorable. who knew?

When life gives us raw bottoms and lots of vomit...

We make time for the Bandage Baby Boogie!

************

Jonah's hiney is about the same. We picked up our Aloe Vesta wash,  Stomahesive powder, and Baza barrier cream this afternoon and have only had the opportunity to use it all once. It is definitely hard to change his diaper on my own right now. But hopefully this stuff will work well, and his little-baby-bum will be on the mend before you know it. 

This post was brought to you by the letter C (for crazy), lots of puke, two high chair cover washes, and a  therapeutic chocolate milkshake (because for the love of all things sane, Mommy just had to medicate).

ebay items up for anton

Just posted some really nice dress shirts on Ebay (all men's size large). All proceeds to Anton's adoption. Hope on over to http://hopeforanton.blogspot.com for the listing links.

crappy day :(

Whew... it has been a day, Friends. I haven't had an "EB totally sucks" (or "EB is a sonofabitch" as I said on Facebook) sort of day in a long time. As far as Junctional EB goes, Jonah is really blessed with good healing, no corneal abrasions (so far), and only minor breathing issues. Honestly, for us, our biggest issue is that he still has major issues with a terrible gag reflex, throwing up, and having major psychological issues with eating, but we could be dealing with so much more.


And I forget sometimes just how fragile he is.


Last night we let him play outside for too long when it was too hot, and he paid for it today. Last night, when we got him home, we went to change his diaper for bedtime, and an area of skin right around his bum hole was gone. Just gone. No blister, no warning. Just not there. And it is killing him any time I change his diaper. This morning, when he was poopy, he was screaming in agony, raising his whole body off the table when I was trying to clean him (impossible, by the way). Then he starting crying and yelling, "Boo boo! Boo boo!" Broke. My. Heart. All day I've tried to use a Triple Paste/Maalox combo, but it's so raw and in such a tough area, I can't get the ointment to stay on or use a bandage patch. I called the doctor and they've called in some kind of wash, stomahesive powder, and cream that will hopefully help. The pharmacy had to order it, so we'll get that tomorrow. All kinds of creams and treatments are great but don't work when the area is so raw you can't get any of the good stuff to stick. Ugh. Of course, his bottom being in bad shape made bath and bandage change harder than they usually are, and I'm doing things on my own now (my choice), so it just made me a little stressed out.


And then a couple other little things happened that weren't really big deals in and of themselves, but just got to me because I was so down about Jonah's bottom and EB in general. 


And the little boys I fell in love with on adoptuskids.org are no longer there, and it makes me sad. I know it shouldn't have looked so early, but man, they'll steal your hearts. Don't say I didn't warn you.


I'm hoping things (his bottom, my attitude) will be better tomorrow but I do so appreciate you guys sticking with me even through the crappy sorry-for-myself-and-my-baby days. 


And all this tornado stuff sucks too. Enough already.

Abbott Trilipix Demonstrates the Sponsor-As-Bystander

FDA is holding more advisory committees than ever and it’s hard for some not to get lost in the mix.



Take the May 19 Endocrinologic & Metabolic Drugs Advisory Committee meeting, for example. The committee was convened to review data from an outcomes trial that was more than a year old, with no overall safety signal, for a class of drugs that have been on the market for years.



Nevertheless, the panel meeting proved to be an important one, not only for the sponsor involved, Abbott Laboratories, but for drug developers in general.



To recall, the advisory committee was convened to review the results of the ACCORD-Lipid trial and how they relate to the approved indication for Abbott Laboratories’ Trilipix (fenofibric acid) for coadministration with a statin.



The results from the National Heart, Lung and Blood Institute-conducted ACCORD study were released in March 2010. The trial was the first major cardiovascular outcome trial to evaluate the combination of fenofibrate (Abbott’s Tricor) with a statin in a diabetic population and compare it to statin monotherapy.



After an average follow-up of 4.7 years, there were 291 (10.5%) major fatal or nonfatal cardiovascular events in the fenofibrate-simvastatin therapy study arm and 310 (11.3%) events in the simvastatin monotherapy study arm; the results were not statistically significant.



Not a great result for Abbott, to be sure, considering the company’s Trilipix/Tricor franchise generates over $1 bil. in US revenue. Panelist William Hiatt (University of Colorado Denver), a former chairman of the Cardio-Renal Advisory Committee, was blunt: “It’s a clearly negative trial.”



Abbott was clear upfront that the company had nothing to do with ACCORD. James Stolzenbach, Dyslipidemia Divisional VP, who handled the MC duties for the company during the sponsor presentation, made clear that Abbott was not seeking a new indication for Trilipix nor did the company conduct or have a role in conducting the ACCORD study; Stolzenbach “apologized in advance” to the committee if Abbott could not answer all the questions asked of them because the firm was not privy to the full dataset.



Stolzenbach’s comments underscored the fact that Abbott was a bystander for a critical regulatory re-review of one of its most important product franchises. In essence, the company was watching while one agency, FDA, was figuring out what to do with the results of a government-run study conducted by another agency, NIH.



The way the advisory committee review was set up and played out, it appeared clear that FDA has wanted Abbott to conduct another trial of a fibrate/statin combo for some time and the way to do it was take the question to panel in the absence of an overt safety signal that would trigger the agency’s authorities under the FDA Amendments Act.



In a memorandum dated April 25 from Division of Metabolism & Endocrinology Products Deputy Director Eric Colman to the committee, a key question—question 6—was originally proposed with five options for the committee to vote on and the committee could recommend more than one action:



a) allow continued marketing of Trilipix’s indication for coadministration with a statin without revision of the labeling;



b) withdraw approval of Trilipix’s indication for coadministration with a statin;



c) allow continued marketing of Trilipix’s indication for coadministration with a statin with revision of the labeling to incorporate the principal findings from ACCORD-Lipid;



d) Require the conduct of a clinical trial designed to test the hypothesis that, in high-risk men and women at LDL-C goal on a statin with residually high TG and low HDL-C, add-on therapy with Trilipix versus placebo significantly lowers the risk for MACE; and/or



e) other.



But in the draft questions to the advisory committee, question 6 was broken up into two parts, A and B. Question 6A asked the committee to vote first (“yes” or “no”) on whether FDA should require a new study as described above in d). Question 6B asked the committee to vote for only one option of the following: no change to the Trilipix indication, withdraw the indication for coadministration with a statin, or allow continued marketing of Trilipix with a revision of the labeling to include the principle findings from ACCORD.



The panel voted unanimously (13-0) that Abbott should conduct another clinical study. Specifically, the trial should study the hypothesis that in high-risk men and women at LDL-C goal on a statin with residually high triglyceride levels and low HDL-C, add-on therapy with Trilipix versus placebo significantly lowers the risk of major adverse cardiovascular events (MACE).



Now, it appears as though Abbott will have to conduct a large clinical study that, if positive, would show an outcome benefit for a more defined patient population than the broader FDA-approved indication the company already has.



We asked Cleveland Clinic cardiologist Steve Nissen, an occasional Cardio-Renal panelist, for his take on the ACCORD study. “These drugs have done amazingly well in the absence of any evidence of a health outcome benefit,” he said. “Trilipix was approved to ‘reduce triglycerides’ based upon the premise that high trigs are associated with pancreatitis. Only one problem – no one has ever demonstrated that lowering trigs with fenofibrate or fenofibric acid actually reduces the incidence of pancreatitis.”



Nevertheless, the Trilipix advisory committee review highlighted the lack of control Abbott had over the review of its product. That outcome could befall other sponsors as they are further removed from postmarket evaluations of their products.



Call it Bystander Syndrome.

Deals Of The Week Presents Last Week's Deals

Not to go all eschatological on you, but this blogger owes the IVB readership a confession. Religious broadcaster Harold Camping's exhortations (and innumerable billboards and emails) announcing May 21, 2011 as the onset of the Rapture and the ensuing end-of-days offered this blogger an excuse to book out early to enjoy a last supper with friends and family. (At which there was much speculation about the soon-to-be revealed identities of the four horsemen.)

In the blogger's defense, the signs were all there. (And no, we aren't talking about cataclysmic earthquakes, the rise of either false prophets (Beck or Trump?) or the Mississippi River, or the sky-rocketing home prices in the Bay Area tied to LinkedIn's IPO.) How can you deny it's not the end of the world, when the Cleveland Indians are leading their division, Oprah's pulling the plug on her daily tv show, and reality stars like Jersey Shore's Snooki command speaking fees higher than Nobel prize winning writers?

Thus, in the hopes of cramming celebratory fun into the final hours of May 20 (we had until 11pm PT by dear Harold's calculations), DOTW seemed a wee bit, well, unnecessary.

In the face of Armageddon, who really cares about Shire's decision to diversify into regenerative medicine with its non earn-out purchase of Advanced BioHealing? (Dermagraft, after all, can't be used to treat the gnashing of teeth.) And, really, with the world absolutely ending on Oct. 21, it's not like Takeda needs Nycomed to bridge its 2012 Actos patent cliff. (Now if Nycomed sold an OTC product to repair the rending of hair, we might pay attention given its apocalyptic best-seller potential.)

Oh wait, it's Monday May 23-- and we're still here (and so is everyone else). Damn. That means we'll be writing this column until at least December 21, 2012, which REALLY, TRULY is the end of days. With apologies for our tardiness, it's time for another edition of...

Takeda/Nycomed: The Rapture may not have come to pass but Takeda/Nycomed did. On May 19, after a week of speculation and a press release warning journos not to get too hasty, Takeda announced its €9.6 billion ($13.6 billion) purchase of privately-held Nycomed. As IN VIVO Blog told you last week, the deal satisfies a number of strategic and financial imperatives for Japan's largest drugmaker, as it faces generic competition to best-selling diabetes drug Actos from 2012 and seeks to expand its footprint beyond Japan and the U.S. The deal doubles the Japanese firm's European sales, jump-starts its emerging markets presence and provide an immediate 30% revenue boost, increasing operating income by more than 40%, according to the company. Swiss-based Nycomed brings to Takeda not only the fruits of recently-launched chronic obstructive pulmonary disease drug Daxas, but also a more diversified product mix, including OTC and branded generics, regulatory expertise, and an entrepreneurial culture that Takeda President and CEO Yasuchika Hasegawa said he hoped could "vitalize" his firm. As such, the deal helps accelerate the 2011-2013 mid-range growth plan unveiled by Hasegawa earlier this month. The transaction – worth slightly more than initial reports suggested – values the Swiss-based Nycomed at about 3.4 times its 2010 revenues, excluding its U.S dermatology business, which is not part of the deal. The higher price tag means Takeda will take a ¥600-700 billion ($7.33 billion to $8.55 billion) loan to finance the deal, which is the largest yet in the Japanese firm's aggressive ongoing bid to expand its presence and pipeline through M&A. --Melanie Senior

Shire/Advanced BioHealing: Shire/Advanced BioHealing marks the return of the IPO as a stalking horse, a private M&A deal with NO earn-outs, and an ROI greater than 10x for certain investors. True venture like returns --it must be the end of days!! Just before its planned debut on the New York Stock Exchange, Advanced BioHealing instead agreed to a $750 million all cash offer from the specialty pharma Shire, which has a history of using acquisitions to jump quickly into new lines of business. With ABH, Shire dives into regenerative medicine, grabbing the commercial product Dermagraft, a patch that uses natural cells called fibroblasts to heal diabetic foot ulcers. (Dermagraft has a long and painful history, which you can read about in greater detail here.) The current deal builds on Shire's willingness to pay healthy premiums for companies that it sees as cornerstones to new lines of business. The most striking example is Shire's 2005 purchase of Transkaroytic Therapeutics for $1.6 billion, an acquisition that gave the pharma access to enzyme-replacement drugs for rare diseases and a technology platform for further growth. As part of Shire, ABH will be run as a semi-autonomous unit, with retention of top management one of the hoped for outcomes post-integration. The all-cash offer was a 25.6% premium to the amount ABH was expected to raise had it debuted at $15-a-share, the midpoint of its expected range. Since the IPO was reportedly oversubscribed and pricing was on the upswing, a public debut might have resulted in a larger return to investors -- eventually. Still, ABH's backers, which included Canaan Partners and Safeguard Scientific had to be more than satisfied with the terms-- and certainty of exit --offered by the Shire take-out. Canaan apparently reaped a 15x return on the deal, while Safeguard's ROI was a not too shabby 13x. -- Alex Lash and EL

Roche/Merck:The two current heavyweights in hepatitis C therapy got together May 17 with a plan to co-promote Merck’s newly approved protease inhibitor Victrelis , in what was widely viewed as an effort to squeeze upstart Vertex Pharmaceuticals out of the HCV market despite superior efficacy data for its protease inhibitor, Incivek. Boceprevir was approved by FDA on May 13; telaprevir's PDUFA date is today, May 23. Under the non-exclusive agreement, Roche reps will include boceprevir as part of their promotion to health care providers on the use of Pegasys in triple combination therapy for HCV. Pegasys, part of the current two-drug backbone of HCV therapy, commands about 80% of the peg-interferon market in HCV, far ahead of Merck’s competing product, PEG-Intron. Roche will not bundle boceprevir with Pegasys, however, and the deal does not preclude Merck from marketing its HCV drugs in a discounted bundle. (Nor does it preclude Roche from inking a deal with Vertex though analysts think that's unlikely.) The two peg-interferon products will continue to be marketed separately, both companies said, and Merck added that the collaboration will not affect the pharma’s economics for its new product. Merck and Roche, each of which has other HCV compounds in clinical development, also will test their compounds together in combination therapy trials.--Joseph Haas

Stryker/Orthovita: Yes, dear readers, a device deal, which means the rapture must be coming (even though Harold Camping's calculations this time around were off). In 2010 IN VIVO wondered if Orthovita, hit hard by scientific debate about the merits of vertebral compression fracture treatment and allegations of fraud, was giving up its grand dreams. Thanks to Stryker’s $316 million acquisition last week, its independent efforts at becoming the specialty spine player are over. But with a take-out price tag that included a 41% premium, did Orthovita's investors win? The deal allows Stryker to pair its existing hardware with Orthovita’s Vitoss bone graft and Cortoss bone filler. The former can be used along with Stryker’s spinal implants while the latter might serve as a hook to help sell Stryker’s new vertebral augmentation products, giving the med-tech giant another way to differentiate itself from Medtronic’s line of Kyphoplasty products, which use traditional bone cement polymethylmethacrylate (PMMA.)If Orthovita’s products live on, it's fair to say the company never recovered from a series of er, crushing (compressing?) blows. First, in 2009, New England Journal of Medicine published two studies suggesting vertebroplasty – the filling of fractured vertebra with cement (or Cortoss) – wasn’t an effective method of relieving pain from vertebral compression fractures. The studies were published just two months after the company received FDA approval for Cortoss. Then a Medicare fraud investigation by Department of Justice forced vertebral compression procedures to move from in-patient – where Orthovita’s Vitoss and other materials are currently used -- to outpatient settings. The shift caused problems with pricing and, analysts say, distracted Vitoss sales reps. In the end, economic pressures that have been a drag on the entire orthopedics sector also weighed heavily on Orthovita, which had high hopes that Cortoss sales would quickly ramp total sales to $300 million annually. -- Tom Salemi

ThermoFisher/Phadia: The European private equity firm, Cinven, is to exit ownership of the Swedish in vitro diagnostics company, Phadia, after four years by selling it to Thermo Fisher Scientific, reportedly more than trebling its investment in the process. US laboratory equipment manufacturer Thermo Fisher Scientific Inc. aims to strengthen its allergy and autoimmune disease diagnostics business by acquiring Phadia for a hefty €2.47 billion ($3.5 billion) in cash, announced May 19. (In case you are keeping track, Phadia was spun out of Pharmacia in 2004 when Pfizer acquired the parent company, and was acquired by Cinven in 2007 in a deal that valued the company at €1.285 billion.) Phadia markets complete blood test systems to support the clinical diagnosis and monitoring of allergy and autoimmune diseases and chalked up 2010 revenues totaling €367 million thanks to strong sales in Europe and emerging markets. Thermo Fisher is using a mixture of debt financing from Barclays Capital and cash to fund the Phadia acquisition, which is expected to complete in the fourth quarter, and be immediately accretive to Thermo Fisher's adjusted earnings per share. The deal completes a busy week for Thermo Fisher, which completed its $2.1 billion acquisition of Dionex on May 17 and one day later announced the $35 million purchase of UK player Sterilin.--John Davis

Image courtesy of flickrer WarmSleepy via a creative commons license.

our saturday

Yesterday we went to Holly Springs to celebrate Katie's youngest daughter, Quinn's, second birthday. She may just be the cutest (female) two year old in history. She is so laid back and super sweet and got so excited about every present (like fake hyperventilating). I just loved watching her. She has such a sweet spirit, and I have to say, I wouldn't be mad if she ends up being my future daughter-in-law. 


(But for that to happen her future husband is going to have to get over his bad-birthday-attitude blues and learn to share. No nap did not work in his favor yesterday.)

Well, we're off to church. I would have been more than happy for Jesus to have come back yesterday, but since he didn't (shocker), that means He is still has work for us to do. Hope you enjoy your beautiful Sunday and find a way to love on others.

**And if you can't think of anything, I know of two little boys who could use your  $5.00.** :)