Article from 2013 ( was hard to find) with some interesting comments.
AstraZeneca Makes a Deal With Moderna. Wait, Who?
By Derek Lowe 21 March, 2013
AstraZeneca has announced another 2300 job cuts, this time in sales and administration. That’s not too much of a surprise, as the cuts announced recently in R&D make it clear that the company is determined to get smaller. But their overall R&D strategy is still unclear, other than “We can’t go on like this”, which is clear enough.
One interesting item has just come out, though. The company has done a deal with Moderna Therapeutics of Cambridge (US), a relatively new outfit that’s trying something that (as far as I know) no one else has had the nerve to. Moderna is trying to use messenger RNAs as therapies, to stimulate the body’s own cells to produce more of some desired protein product. This is the flip side of antisense and RNA interference, where you throw a wrench into the transcription/translation machinery to cut down on some protein. Moderna’s trying to make the wheels spin in the other direction.
This is the sort of idea that makes me feel as if there are two people inhabiting my head. One side of me is very excited and interested to see if this approach will work, and the other side is very glad that I’m not one of the people being asked to do it. I’ve always thought that messing up or blocking some process was an easier task than making it do the right thing (only more so), and in this case, we haven’t even reliably shown that blocking such RNA pathways is a good way to a therapy.
I also wonder about the disease areas that such a therapy would treat, and how amenable they are to the approach. The first one that occurs to a person is “Allow Type I diabetics to produce their own insulin”, but if your islet cells have been disrupted or killed off, how is that going to work? Will other cell types recognize the mRNA-type molecules you’re giving, and make some insulin themselves? If they do, what sort of physiological control will they be under? Beta-cells, after all, are involved in a lot of complicated signaling to tell them when to make insulin and when to lay off. I can also imagine this technique being used for a number of genetic disorders, where we know what the defective protein is and what it’s supposed to be. But again, how does the mRNA get to the right tissues at the right time? Protein expression is under so many constraints and controls that it seems almost foolhardy to think that you could step in, dump some mRNA on the process, and get things to work the way that you want them to.
But all that said, there’s no substitute for trying it out. And the people behind Moderna are not fools, either, so you can be sure that these questions (and many more) have crossed their minds already. (The company’s press materials claim that they’ve addressed the cellular-specificity problem, for example). They’ve gotten a very favorable deal from AstraZeneca – admittedly a rather desperate company – but good enough that they must have a rather convincing story to tell with their internal data. This is the very picture of a high-risk, high-reward approach, and I wish them success with it. A lot of people will be watching very closely.
37 comments on “AstraZeneca Makes a Deal With Moderna. Wait, Who?”
21 March, 2013 at 8:33 am
Another company developing messenger RNA therapeutics is CureVac for cancer and infectious disease vaccine platform, well-funded too.
Actively Seeking Work says:
21 March, 2013 at 9:11 am
Why not just design viral vectors that eseentially do the same thing and have a better chance of delivering the desired material to the desired locations. But there you would most likely have a similar or worse immunological response.
With these ideas, I never understand why they don’t try working out the kinks of delivery and immune response before actual research into targets. Seem to spend all that money up front only to lose out in the end.
21 March, 2013 at 9:25 am
And would you need a continuous infusion? Forever? How is it stabilized? Would you want it to be stable? Far out idea. Will keep watching.
Former Merck Chemist says:
21 March, 2013 at 9:33 am
Reminds me of the great deal MSD made with siRNA-high risk, high reward paying bucket loads of cash…for something that didn’t quite pan out.
21 March, 2013 at 9:54 am
Yeah, I don’t see why delivering mRNA would be any easier than delivering siRNA. As far as I know there still is no good solution for siRNA delivery and they have been at it for a long time.
21 March, 2013 at 10:00 am
# 4…..don’t get me started! The venerable academician PK started it off with a big bang and after some 10+ years of dallying, he is gone. Merck is left with a “load of dung,” to hold! Judging by Merck’s experiences in siRNA area, I think AZ will be hard pressed to respond later to a question for which we know the answer already.
21 March, 2013 at 10:25 am
High risk you can say and back with data. High reward you can not.
And as for ‘convincing story to tell with their data’, I have participated in far too many big pharma due diligence deals to know this is often not the key thing deciding as to whether a deal goes through or not.
Company desperation, internal politics and a good press release are often more important to the board than the scientific merits of the research and the realistic chances of delivery of a product within a ~20 year time frame.
This is exactly the kind of thing AZ should not be throwing money at right now – it will not help them out of the hole they are in.
Curious Wavefunction says:
21 March, 2013 at 10:40 am
There’s a story about Moderna in this month’s Boston magazine (click on my blog name for the link). The company has disclosed very little about its technology. Apparently they have employees sign non disclosure forms saying they won’t even discuss their work with their spouses, which to me sounds a little paranoid.
21 March, 2013 at 10:44 am
@7 Anonymous: “too many big pharma due diligence deals to know [good science] is often not the key thing”. At first I was wondering if we have any overlap on such deals but they are so common that the statistics favor us not having any overlap.
@5 ADCchem: Delivery of oligos won’t be a problem: carbon nanotubes. Mark my words. Invest now and buy up as much “nano” stock as you can. I’ve read that it will be a trillion dollar industry by 2020.
21 March, 2013 at 11:03 am
@8, CuriousW, that sort of non-disclosure is pretty normal. If your spouse understands what you do, you have no business sharing that. If they don’t you have no reason to. Have you ever worked in the industry?
21 March, 2013 at 11:13 am
I thought mRNA was renowned for its instability – it’s supposed to be transcribed and then go away quickly so that the organism can control gene expression more precisely. Some of the RNA research (siRNA, etc.) probably tempers that some, but RNA is not exactly a rock, no?
21 March, 2013 at 11:16 am
Wow. Good terms INDEED. From the press release:
Under the terms of the agreement, AstraZeneca will make an upfront payment of $240
million. AstraZeneca will have exclusive access to select any target of its choice in
cardiometabolic diseases, as well as selected targets in oncology, over a period of up to five
years for subsequent development of messenger RNA. In addition, Moderna is entitled to an
additional $180 million for the achievement of three technical milestones.
It never ceases to amaze me that Big Pharma is so willing to drop huge sums of money on wildly speculative startups while at the same time axing and starving their internal efforts. One of the side effects of a layoff threat is that people tend to become timid — they don’t voice opposition to their leaders lest they be seen as “not on the bus.” While Moderna may or may not be worth this kind of investment, you can bet that the deal did not receive the kind of honest scrutiny one might expect. And inside AZ there is no doubt a lot of speculation this morning about just what $240 million could have done internally — hopefully some of those folks will post here.
21 March, 2013 at 11:37 am
@12 “there is no doubt a lot of speculation this morning about just what $240 million could have done internally”.
I should imagine that there’s also a lot of speculation as to why AZ has given $240m to a company it could simply have bought outright – six times over!
21 March, 2013 at 11:41 am
At $200K/FTE, that’s 240 people (PhD’s probably) for five years. I don’t know how many AZ has overall.
21 March, 2013 at 12:34 pm
Nowhere to be found: the modified nucleosides/tides he’s using to prevent degredation, nor the technology for delivery, nor data on efficacy.
Bona fides=great, but we need data.
Curious Wavefunction says:
21 March, 2013 at 12:54 pm
#10: I have worked for three companies including one Big Pharma outfit and I don’t remember anything specific about spouses in any of the formal non-disclosure agreements. Neither do my co-workers. I am not sure if it’s common. I think it’s common sense that you don’t blurt out too many details of your work if your spouse works for a competing organization (there could be an inadvertent slip). Other than that I don’t see a problem.
Rev. Howard Furst says:
21 March, 2013 at 1:00 pm
Some details of the technology are starting to appear in published patent applications. Use your favorite search engine to pull up this one, which includes a bit of everything, from modified nucleotides to in vivo protein expression and secretion: US20120251618
21 March, 2013 at 2:19 pm
According to the patent US 20120251618 they are thinking about using the usual suspects, liposomes and micelles and suggest antibodies for targeting.
As far as I know liposomes have never worked for siRNA and they have been around for years.
21 March, 2013 at 2:52 pm
Unless Moderna has something amazing up their sleeves, I don’t know what AZ is thinking. The modified RNA work has been around for a little while, and Penn has a patent on it http://www.google.com/patents/US8278036
21 March, 2013 at 2:58 pm
I believe Sangamo’s Zinc-Finger Nuclease driven DNA cleavage to force DNA to repair itself is also a similar technology
Their using it for rare diseases (Huntingtons and Hemophilia)
21 March, 2013 at 4:26 pm
On its website Moderna boasts that it has built up a portfolio of 6,500 patent claims, and it even presents a chart of this parameter’s meteoric rise over the last two years. I would be rather wary of any company that thinks the number of patent claims it has made is a reflection of the strength of its IP.
21 March, 2013 at 5:07 pm
The AZ Waltham ID program has been around for 10 years and has never provided a drug (am I wrong about this?). Compared to that, the investment in Moderna doesn’t look so bad. Everyone bashes any research that isn’t old fashioned drug discovery but it too is extremely expensive and high risk. At least if moderna doesn’t work out AZ will have gone down doing something exciting and novel.
Dr. Mindbender says:
21 March, 2013 at 7:02 pm
It never ceases to amaze me that Big Pharma is so willing to drop huge sums of money on wildly speculative startups while at the same time axing and starving their internal efforts.
The irony of this is that with all the cronyism for top 10 schools in big pharma, you’d expect management to fight to save their internal people since they’re “the best.” Instead, they fire everybody and buy up research from smaller companies, where all “those other guys” are working.
Change the hiring practices? Why? They seem to work out perfectly well!
MDA Student says:
21 March, 2013 at 7:21 pm
200mil upfront for something that hasn’t even passed phase 1!!!!????? In an unproven platform!!?? No wonder AZN is broke.
Who ever negotiated that price for Moderna though…they’ve got talent.
C'est curieux says:
21 March, 2013 at 8:35 pm
Related to the just announced $420M-plus deal just announced by AstraZeneca, perhaps someone should tell the CEO at AstraZeneca about U.S. Patent No. 8,278,036 entitled “RNA containing modified nucleosides and methods of use thereof,” which issued on October 2, 2012. As will be clear from reading the patent, the use of modified mRNA comprising any of the various recited naturally occurring modified nucleosides to express a protein in human and other mammalian cells was invented and demonstrated for a variety of therapeutic and other uses by Drs Katalin Kariko and Drew Weissman at the University of Pennsylvania. These modified mRNAs are less immunogenic to the innate immune system, which results in higher translation of protein. Kariko and Weissman have demonstrated higher hematocrits for 1 week after injecting erythropoietin into mice. Their work is also well-known to Moderna and Flagship, as is the fact that this technology is exclusively licensed to CELLSCRIPT, INC.
Pi Shaped says:
21 March, 2013 at 9:08 pm
To all the doubters and haters, this will be AZ’s smartest deal ever. Don’t fear the future, embrace it.
Perfect example of what Booth recently posted. Innovation gets pharma knocking. (Probably because big pharma is crappy at it!)
21 March, 2013 at 10:12 pm
2 years ago, I had image this, but does it come so soon? chemistry down, biotech up, it’s the real world, some people laugh, some people suffer.
David Formerly Known as a Chemist says:
22 March, 2013 at 12:07 pm
If you assume that a full time scientist costs about $240K/year at a pharma company (probably a reasonable estimate), then AZ figured this licensing deal bought them more than what 1,000 man years of scientists at the bench could produce in their own laboratories. That doesn’t say much for the confidence in their internal programs, does it?
22 March, 2013 at 1:21 pm
I still wonder, though, if your own scientists aren’t able to find drugs, why is the management who hired them, equipped them, and directed and organized them brilliant enough to stay on no matter what? And why would anyone be confident that they know how to pick external resources likely to be productive if they couldn’t do it internally (and with, at least for candidates and probably employees, much more data on their usefulness)? If you have four speeding tickets in the last year and a DUI in your past, why does anyone think that having you shuttle Maseratis around is going to end well?
Dr.. Manhattan says:
22 March, 2013 at 2:17 pm
“But again, how does the mRNA get to the right tissues at the right time? ”
Yes, inquiring minds want to know. Particularly with the abysmal track record of trying to deliver any species of RNA into patient’s cells.
I wish them well and will watch this one closely.
25 March, 2013 at 7:40 am
“the people behind Moderna are not fools, either, so you can be sure that these questions (and many more) have crossed their minds already. ”
Frankly speaking, this is a very naïve statement from you. Moderna scientific management has a track record of failure. Also care do Google, and read at Glassdoor. Moderna current and former employees claim of dubious scientific practice by management to increase data accumulation. Moderna is slated to be a failure. It will be an addition track record of failure of its scientific management.
25 March, 2013 at 11:58 am
“I met with quite a number of companies, and nobody I’ve met understood it as deeply as Pascal [Soriot] does, in terms of what this technology can do,” Bancel [CEO of Moderna] says. At a breakfast meeting in December, the first meeting between Bancel and Soriot, they hit it off right away. “He got it in five minutes,” Bancel says. He adds: “Pascal was willing to pay what I was asking because he understands that this technology can do things in a profound way. It can treat disease in a way you can’t with other technology.”
$240MM – one of the biggest deals ever for an untested platform line and the CEO decided without any internal AZ help. Due diligence??? Well would you tell the new boss this is a really bad idea when he is already sacking so many???
A little look at Moderna – they only have 32 staff. And looking at the employee reviews on Glassdoor they are not a happy bunch – every last one of them (#31 -thanks). They raised $40MM last year so those VC’s must be laughing all the way to the bank. Normally doubling your money in 2 years is what they are after. 8 fold increase in 1 year – Wow!!! The main thing Moderna have been doing is patenting, broad and deep. 100’s of claims – this is often poor patent writing but hey, it is just marketing material. The whole area is a patent mess with everyone claiming everything and the attorneys getting rich filing. The only way to sort is out is to go to court but this won’t happen because that only happens when someone gets a product and starts making money. Which ain’t ever going to happen.
What 100% validated targets have AZ got for this expensive, untried platform technology that they couldn’t do with the safer small molecule/biologic routes??? None??!!!
25 March, 2013 at 5:05 pm
“He got it in five minutes,” Bancel says. Hmmmm… AZ Chief, Pascal [Soriot] , got in 5 minutes, which others could not understand? Proper word should be which others refuse to believe of questionable foundation of Moderna. God bless AZ. Pascal is bound to show doomsday to troubled AZ. Bancel may have made exaggerated claims and Pascal must be naïve not to even do proper due diligence. This whole deal looks to me a con-artist selling a fake item to someone on the street.
I look forward to news of AZ firing Pascal and dissolving AZ because of no pipeline or turning into Generic pharmaceuticals producer.
25 March, 2013 at 5:29 pm
@ Pi Shaped “To all the doubters and haters, this will be AZ’s smartest deal ever. Don’t fear the future, embrace it.”
So, you are asking to believe a technology of a company whose foundation publication could not be reproduced by others? This does show that AZ deal will be most stupid deal not “smartest” as you claim.
25 March, 2013 at 5:33 pm
“Their work is also well-known to Moderna and Flagship, as is the fact that this technology is exclusively licensed to CELLSCRIPT, INC.”
@C’est curieux I know it, but I wonder why Kariko and Weissman and Cellscript have not sued Moderna yet, particularly after AZ deal and split the @240 Mln through court?
29 March, 2013 at 4:57 pm
People really need to do their lit reviews before commenting. It’s pretty well understood that they are using the same Kariko and Weissman technology at Cellscript.
As for the efficacy this is a very similar concept as enzyme-replacement therapy. The only difference is that you now theoretically need less drug since the mRNAs should produce several hundreds/thousands of proteins per transcript. In many regards, this class of RNA therapy is very different from the proposed mechanism as RNAi and siRNA.
As for the mRNA delivery, it’s completely reasonable to do ex-vivo transfection similar to that of the recent CARs treatments. That should at least get them into the market and its certainly safer than viral methods.
10 April, 2013 at 10:09 am
@cvl “The only difference is that you now theoretically …” You are talking of theoretically?? The technology had not been proven, nor tested, not even proof of concept. I suspect you are a Moderna’s man??? Making these kind of deals require due diligence and results. Theoretical a lot of things work on paper, but not in real life. You last sentence about delivery is very naïve and based upon theory. Show us results, not a talk for the sake of talk.
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