Show me the money: Which drugs made the top 10 list on upfront deals?

A biotech drug deal can be structured in a lot of different ways. Most companies mix cash with the promise of future biobucks based on development and commercial milestones. Some like to mix a pure upfront with an equity stake. Others shoot for an option with a small ante. And there's always plenty of debate over the relative merits of each type of deal.

Given the eyebrow-raising cash component in Celgene's ($CELG) new deal with Nogra, we thought it would be fun to list the top 10 upfronts paid for experimental drugs, ranked simply according to the cash included in the upfront--no surer sign of what a company really thinks about the potential of an experimental therapy or portfolio.

This ranking includes a group of drugs picked from the top-deal lists of EvaluatePharma and Thomson Reuters. Fierce is using its own criteria, though, on the deals we included, and we're responsible for the results. If you see something that should be here but was overlooked, say something and drop me an email.

You'll notice, though, that I'm leaving out all the big equity deals. Johnson & Johnson ($JNJ) paid $650 million in cash plus milestones to buy Aragon to get one prostate cancer drug, but it's a big down payment for the purposes of this list--not an upfront. And J&J took a billion-dollar stake in Elan (J&J always structures billion-dollar pacts for the drugs it loves) so it could get its hands on the ill-fated Alzheimer's drug bapineuzumab. You won't see it on this list. Also, I'm leaving out the upfronts paid to restructure commercialization rights on an approved drug, like Bristol-Myers' ($BMY) $400 million deal with Otsuka for Abilify in 2009.

You'll find a few big drugs on the list, a few embarrassing failures and a few wait-and-see projects. Curiously, though the list goes back a number of years, you won't see a blockbuster here--at least not yet. With the IPO boom driving up valuations on biotech products as Big Pharma outfits continue to compete for the best programs, it's also possible we'll see some more new pacts make the top-10 list. -- John Carroll (email | Twitter)

George Golumbeski, senior vice president, business development, Celgene

1. GED-301: Celgene buys into Nogra's Crohn's drug for $710 million

Celgene-Nogra. Celgene ($CELG) put Dublin-based Nogra on the map when it agreed to plunk down $710 million upfront to claim commercialization rights to its experimental drug for Crohn's disease. GED-0301 has already completed Phase II. And while the data have yet to be announced, it's certain that they must be very, very good. Celgene is already setting the stage for a pivotal Phase III, to begin later this year. And after committing billions of dollars in deals, the team under George Golumbeski has now claimed bragging rights to the biggest upfront in the industry. Celgene stands to be either a big winner or the industry's biggest loser in this category. The deal total hits the $2.6 billion mark. Story

Reata CEO Warren Huff

2. Bardoxolone: AbbVie's $450 million investment in Reata soured fast

AbbVie-Reata. Bardoxolone (remember that one?) must have looked like a sure thing to Abbott ($ABT) back in 2010 when it bought in for the then-record sum of $450 million--a mix of an upfront payment with near-term cash built in for Reata Pharmaceuticals. But there are no sure things in biotech. Two years later, Abbott Laboratories--which later split off its pharma ops as AbbVie ($ABBV)--had to discount the effort after clear signs of toxicity scuttled the late-stage chronic kidney disease program. Over the last 18 months the work at Reata has gone underground. And AbbVie hasn't murmured a word about it. Report

AbbVie CEO Richard Gonzalez

3. Preclinical compounds: Abbott comes back for more of Reata in $400 million pact

Abbott-Reata. A year after buying into bardoxolone, Abbott (now AbbVie) came back for the rest. Reata's CEO wouldn't say whether Abbott wanted to buy out the company, but with $850 million invested, they may as well have. The whole thing went sky-high, though, when the bardoxolone trial blew up on tox issues. Report

Eli Lilly CEO John Lechleiter

4. Tradjenta (linagliptin)/empagliflozin: Lilly dives deep into diabetes with $387 million upfront deal

Eli Lilly-Boehringer Ingelheim. This was the 2011 deal that brought a quick end to Eli Lilly's ($LLY) long collaboration with Amylin over Byetta and Bydureon. Tradjenta would go on to a quick approval, but empagliflozin--recently endorsed though not yet approved in the EU--has been stiff-armed in the U.S. as the FDA waits and sees how Boehringer resolves some sticky manufacturing issues. AstraZeneca would eventually wind up with Byetta and Bydureon. Report

Fibrogen CEO Thomas Neff

5. FG-4592 (roxadustat): A struggling AstraZeneca jumps in on CKD program for $350 million

AstraZeneca-FibroGen. AstraZeneca ($AZN) has had its checkbook out for some time now, so it's no big surprise to see them in the top 10 with this $350 million upfront deal. Last year the pharma giant grabbed U.S. commercialization rights to FibroGen's FG-4592 (now roxadustat), an anemia drug which has produced midstage proof-of-concept data to demonstrate its first-in-class potential for patients suffering from chronic kidney disease. The drug is designed to kick-start the production of red blood cells by mimicking the body's response to high altitudes. And it fits into AstraZeneca's R&D strategy, which has included a careful focus on the cardiovascular and metabolic fields. AstraZeneca included $465 million in milestones in this deal. Story | 2013 Fierce 15 - Fibrogen

Pfizer CEO Ian Read

6. Eliquis: Pfizer pays $250 million upfront in a blockbuster deal that has yet to pay off big

Pfizer-Bristol-Myers Squibb. Back in 2007, rolling in a pile of Lipitor cash, Pfizer ($PFE) ponied up a rich deal to grab commercialization rights for apixaban, which would go on to approval as Eliquis. Pfizer also agreed to add $750 million in milestones and front 60% of the development costs for this drug, betting that they had a blockbuster on their hands. Eliquis, though, has yet to deliver the kind of big bucks that were anticipated by so many analysts at the time. Release

7. Messenger RNA therapies: AstraZeneca bets $240 million on Moderna's cutting-edge tech

AstraZeneca CEO Pascal Soriot

AstraZeneca-Moderna. New to the helm at AstraZeneca, Pascal Soriot was trying to make a point when he agreed to pay $240 million upfront last year to gain a stake in Moderna's startup operations. Moderna has a plan to transform our cells into tiny drugmaking machines and is turning to some rather complicated ideas from Harvard and elsewhere in its quest. For Soriot, the deal signaled that AstraZeneca was ready to get bold about R&D again, willing to take risks in getting its foot in the door of potentially transformative technologies. Analysts could argue that AstraZeneca was spending its money in the wrong place at the time, as it needed more late-stage work to help make up for years of lost efforts in drug development. Time will tell whether AstraZeneca was right or wrong. Story | 2013 Fierce 15 - Moderna Therapeutics

8. Cancer drug discovery: Celgene puts up $225 million to cement lead role at Forma

Forma CEO Steven Tregay

Celgene-Forma. Celgene had already done one deal with Watertown, MA-based Forma, agreeing to pay $200 million in early-stage payouts for their work on protein homeostasis. In this new deal struck just weeks ago, which is independent of the first partnership they signed, Forma CEO Steven Tregay has hammered out a pact that delivers a $225 million upfront payment for a 3.5-year drug discovery collaboration covering a broad range of protein target families and therapeutic areas. If that big step works out, there are two more collaborations that can follow that will each run two years, backed by a total of $375 million in milestones. About 7 years down the line, Tregay told FierceBiotech​, if the deal makes it to its third and final step, Celgene will have an option to buy the company at a price to be negotiated based on the value of the company at that time. That easily gives Celgene the number one role in top 10 deals, and the money--close to a billion dollars in upfront payments--helps explain why this biotech often figures as one of the preferred buyers in the industry. Report

Medivation CEO David Hung

9. Dimebon: Pfizer blows $225 million-plus on another failed Alzheimer's experiment

Pfizer-Medivation. Here's another disaster of yesteryear. Pfizer's deal team put together a big package for this Russian antihistamine. But even after seeing plenty of positive signals early on--which have been replicated in more recent academic studies--the drug was a flat flop in late-stage testing in 2010. Pfizer footed the bill for the whole thing, leaving its partner Medivation ($MDVN) to go on to find success with the prostate cancer therapy Xtandi. This wasn't Pfizer's only fiasco in Alzheimer's. It partnered on bapineuzumab with J&J, only to see that one fail Phase III as well. Report

Novartis CEO Joe Jimenez

10. Jakafi: Novartis nabs a winner in a $210 million pact with Incyte

Technically, Novartis ($NVS) paid Incyte ($INCY) an upfront of $150 million plus an immediate $60 million milestone to complete this 2009 deal for the ex-U.S. rights to Jakafi (ruxolitinib or INC424), a JAK1/JAK2 inhibitor. But all the money arrived at once, so we combined the figures. Initially approved to treat myelofibrosis, just weeks ago Novartis reported positive results for rare cases of polycythemia vera, a lethal form of cancer characterized by the overproduction of blood cells. A new approval here could easily make this drug a blockbuster. The drug earned $163 million last year, up more than 20% from the year before. That fits well with Novartis' strategy of hammering on a program as it shapes new markets. Story