The Broken Clock

$AMRN Q2-CC post-mortem [w/ some minor snark]

Thu, 09 Aug 2012 22:58:00 -0400

AMRN Looks for a deal…

Steve Schultz Sr. Director of IR

0:40 Safe harbor statement
Schultz gives $AMRN’s website URL as “triple w amarin corp dot com” <- IR guy is a hipster?

CEO Joseph S. Zakrzewski

7 patents “in play” w/ USPTO [we’re gonna get ‘em even if we have to grease a few palms]
25 patents currently on file w/ USPTO [throw enough shit against the wall, some of it’s gonna stick]
Also received “intention to grant” letter for MARINE method of use patent in Europe
<blah blah blah…>
Ended June 30,2012 w/ $250MM on hand
Getting ready to file sNDA for high triglyceride w/ ANCHOR results
Can file ANCHOR based sNDA when REDUCE-IT (cardiovascular outcomes trial - CVOT) is substantially underway expected in 2012 [why are they linked?]
3 paths to commercialization …(partner, buyout, solo)
Launch anticipated in early Q1’13. Various preparatory steps to take for launch.
Lead suppliers have passed inspections.
Accumulate material for launch.
6:45 yada yada yada <Vascepa is not Lovaza…it’s Lovaza-Plus!>
Vascepa exclusivity will be gained through patents, regulatory exclusivity [NCE], maintaining trade secrets [weak] & taking advantage of manufacturing barriers to entry [riiiiiiight…].
Progress on patent front…
Issuance of 1 patent, notice of allowance for one application & 5 “reasons for allowance” for others.
*** NCE reg exclusivity…still in active dialog w/ FDA. Since approval, AMRN has had continued dialog w/ FDA about NCE. “Hopeful” [is not a strategy] for NCE decision in time for inclusion in August Orange Book supplement…but it’s “also possible that decision may go longer.” At this time, FDA has not advised AMRN of a delay [they also have not told AMRN that they will not be allowed to sell blow on street corners] OR a decision [bullshit].
Since we’re still talking w/ FDA, we’re not going to make any more comments OR field questions about it…so everybody shut your pie holes about this.

Near-term potential newsflow

partnering info
NCE decision
addition of 4th supplier
REDUCE-IT CV outcomes study substantially underway
sNDA filing using ANCHOR data
sNDA submission for expanded supply chain
additional news on patents
scientific publications & presentation of MARINE data in Germany
combination product vascepa + “leading” statin
commercial launch

Financial results update

$250.3 million on June 30.
9:52 <yawn>
increased costs are due to launch and clinical trials
Expect to spend ~ $25 - 35 million to stockpile Vascepa for launch inventory [any ideas on what this translates to in potential sales?]…how long can you keep stockpiled fish oil?

Q&A

Dewey Decimal (JPMorgan) Can you opine [Dewey must be a lawyer] on the recent stock sales? Were they previously planned? Could you have backed out of the sales? How much exposure does Sr. Mgmt still have? Why the F*#(* did you sell??

All sales previously planned. Represent 5% of CEO’s holdings. Fiscal fiduciary management [CEO sounds embarrassed].

You said you were building launch supplies. How much of a supply do you anticipate $25 - 35 million worth of Vascepa will be?

We aren’t prepared to give guidance on that.

Canaccord Genuity (??) Where are you on the hiring of sales people? Managers in place? Interviewing reps?

Large supply of sales people because the job market is in the crapper. Sales piece cranks up in october (if & when we get there) [wink wink].

Will you have “activity” in American Heart Association meeting in the fall?

Yes. Continue CME efforts in many cardiovascular forums.

Status on manufacturing sNDAs?

Hope to have 1 or 2 filed by EOY. Maybe a 3rd sNDA filed in Q1’13. Announce 4th supplier very shortly.

You talked about a statin-combination product? Have you picked a final formulation? Are you only moving forward w/ 1 statin? Or multiple statins?

We *have* a final formulation, but that’s all we’re going to say. We have a statin or statins picked out [depends on partner/buyer?]. Expect to start statin combo study by EOY.

Is the formulation a spray-coated capsule?

Not gonna say.

Tommy Nguyen (Jefferies). Give some color on biz dev. Is there a value creation event (IP/NCE?) that potential partners are still looking for? Or are you beyond that in negotiations? What the F*#*#( is taking so long??

dodge…weave…”discussions continue to increase in activity”…dodge

On timing of filing of sNDA for ANCHOR. Why are they tied to each other? Can you clarify how clear an understanding you have of the requirement to enroll in the outcomes study before filing? Is there some risk to delay from perhaps an incomplete understanding of the requirement?

Believe we’ll have [sNDA ANCHOR] approval in 2H’13…we’re comfortable with that guidance…and that’s all we’re gonna say about that.

Vascepa is listed as 1 of 40 or so cardiovascular medicines on FDA website, but Lovaza isn’t. Does this mean anything significant?

Probably not. FDA is probably just lax on their website [tell me about it].

Ram S (Avis capital?)? Supply situation. Have you had discussions w/ BASF following their acquisition of Equitech? What’s the status of your relationship w/ BASF and their commitment to large scale manufacturing of omega-3 fatty acids? [What the F@#@$ is Ram asking? Just spit it out. Don’t pussy foot around asking touchy-feely questions about your relationship].

CEO’s lips move, but say nothing

REDUCE-IT. What are the other CV outcomes studies being performed with other drugs that are ongoing related to triglyceride lowering and how does REDUCE-IT compare?

Not the best person to ask about other people’s trials.

Can you provide color on higher doses of Vascepa?…you didn’t reach a maximum effective dose. Will you run higher-dose trials?

[Seems lukewarm about higher dose trials.] MDs can dose at whatever dose they want.

What about pricing of Vascepa, esp relative to PCSK9 (e.g., AMG-145) inhibitors?

We’re looking to shift [market] share (eat Lovaza’s lunch) and expand the market…our goal is to get to Tier 2 as quickly as possible.

A lot of exciting times over the next 60 to 90 days [probably shouldn’t read too much into this]

Audio & “Transcript” of $ECYT conference call...

Mon, 14 May 2012 22:11:00 -0400

Audio & “Transcript” of $ECYT conference call (5/10/12). $ECYT should end 2012 w/ > $188MM.

Ron Ellis (CEO) & Mike Sherman (CFO) speakers:

CEO:

Europe: still on schedule for filing for EC145 approval in europe in Q3 for Pt-resistant ovarian cancer in FR++ patients [patients over-producing folate receptor].
PROCEED trial has been on hold due to doxil shortages. Have approval from FDA to import doxil. We are enrolling patients in proceed study.
opened nsclc trial docetaxel (control), docetaxel + EC145, & EC145 alone.
Also presented lung data from Phase IIa trial in Spain. Marty adelman presented results.
SEC clearance for $MRK deal
EU filing: $ECYT has primary responsibility w/ EU filing & is coordinating with $MRK’s european organization.
Other indications: $MRK will pursue other indications aside from ovarian & NSCLC.
$MRK has responsibility for manufacturing for EC145…we’re doing tech transfer on this.

CFO:

Q1: lost 9.8 million compared to 7.2 million “last year”…R & D costs were was up ~$2 million primarily due to CMC work method & process validation associated w/ the EU filing process.
SG & A up $1 million…primarily due to being a public company. This is the last quarter where we compare our finances to a pre-IPO quarter.
Operating expenses for past few sequential quarters have been relatively stable averaging about $10.5MM. This cost was associated with PROCEED trial, but now the PROCEED trial expense has come down due to doxil shortage and has been offset by costs of EU filing.
Pro-forma balance of ~ $238 MM
Prior to deal, would have guided to increased expenses due to ramp up in enrollment of trials.
$MRK reimbursing for all lung trial costs and part of proceed trial costs
Net spending growth will be driven by proceed trial ramp up, but mitigated substantially by $MRK picking up the tab…Expect operating expense growth to be 12% or lower compared to 2011 (< $50MM).
Several sources indicated restoration of doxil supply in 2H2012. Sources include FDA, JNJ, EU regulatory agencies.

Questions:

Semos Semonitis?? Cowen: When will you be profitable? Are you only paying for part of PROCEED? How much is the part that you’ll be paying?

$40 million for PROCEED. We’ll handle the majority (something more than half) of the cost.
Profitability would come after US & EU approval. Expect to have PROCEED PFS data by 1H of 2014. If things go well, we’d expect to file in shortly thereafter.

Where are you in your discussions w/ FDA?

We have agreement w/ FDA on major components of study design…mostly related to endpoint being FR++ only. Agreement that PFS as primary endpoint **could** [could drive a truck through this loophole] lead to accelerated approval in FR++ Pt-resistant ovarian cancer. Most meetings have been w/ FDA imaging group…more “educational” [riiiight]…$ECYT brings nuclear medicine readers to show FDA how they read the images. TFDA imaging group is very engaged & “excited”.
More meetings in the summer…discussions will include submission of the final statistical analysis plan for PROCEED. Will study be limited to FR++ patients or will we also include non-FR++ patients. EU is also interested in this. Both EU & FDA would like to see more data in other patient groups besides FR++. Statistical designs discussed w/ FDA to deal with non-FR++ patients (it’s called a “step-down design”…not worthy of details). Primary endpoints have been agreed to…may be some amendments to trial, but major points are settled.

Single pivotal trial would be sufficient for accelerated approval?

Yes [unequivocal]. Consistent w/ what FDA told us in previous meetings. Can use PFS as a primary endpoint (they will want to look @ OS). Full approval would require a subsequent confirmatory PFS study or a “very very” strong OS benefit in this trial.

Have you communicated w/ JNJ about the doxil shortage? How much doxil are you importing from Europe…how much do you need to avoid another potential delay?

We have enough doxil from Europe to enroll 50 - 70 patients (depends on # of cycles that patients will stay on drug)…ongoing dialog w/ JNJ…it’s a priority for them —[they’re leaving $$ on the table b/c of this shortage]…September [2012] date has been referenced by JNJ & regulatory bodies. As long as doxil comes back by year end, “we should be fine w/o missing a beat” [what does this mean? What happens if it doesn’t come back online by eoy?].
[There’s been some noise about imminent relief of the doxil shortage b/c JNJ has said they are expanding the list of patients waiting for the drug in their “doxil cares” program, but this seems to be more related to existing wait-listees dropping out of the program. So, we still do not expect relief of doxil shortage until Sept 2012.]

Jason Kantor, RBC. You said you have funds available to get you to profitability. Do you need EU approval to get to profitability? Does this assume some average annual spend? [of course it does]. How long will you amortize the up front payment & what method will you use?

Profitability most likely requires both EU and US approval. Our estimates will also depend on our aggressiveness in developing existing pipeline. Depends on what other indications we pursue w/ early stage compounds. Assumptions we’ve made about profitability do actually include substantial investments (another folate-targeted drug moving through a randomized trial) & another inflammation drug through phase I. But we are not in a position to comment in more detail of burn rate beyond 2012.
[doesn’t answer amortization question].

CEO says something strange[honest?] at the end: “[at] one time the [$ECYT] train seemed a little bit off the track, I think we’ve gotten things back on w/ these critical studies enrolling…”

Notes on $ALXA Adasuve CRL CC

Sun, 06 May 2012 10:38:40 -0400

Ladies & Gentlemen, give it up for Mr. Thomas King, CEO of $ALXA!! [crickets]
[Safe Harbor yada yada]
Adasuve CRL was issued by CDER. CRL noted 1 deficiency related to facility inspections & manufacturing:

“during a recent inspection of the mountain view california manufacturing facility for this applicant, our field investigator conveyed deficiencies to the representative of the facility. Satisfaction [sic?] resolution of these deficiencies is required before this application may be approved.” [as others have pointed out, King does not say this is the ONLY issue brought up in the CRL. He just says that there is 1 manufacturing issue in the CRL].

$ALXA believes these deficiencies are medically device specific and readily addressable.
No new clinical or safety issues identified and there were no other deficiencies outlined in the CRL [lots of wiggle room here. Was the old stuff brought up?].
CRL said REMS discussions [related to bronchospasm] can continue after response to action letter has been submitted.
CRL has comments on draft product labeling including what they believe to be a near final draft of package insert [Seems like everybody says this].
Primary manufacturing issue is that Adasuve manufacturing process validation is “incomplete”. $ALXA makes 3 batches of each dosage strength and analyzes each batch to demonstrate “that our manufacturing process is viable [whatever that means. makes no sense.]”.
$ALXA has completed manufacturing process validation for 10mg dose, but not for 5 mg [why the f@#$% not?].
But we still need to talk to FDA about this because our interpretation could be totally wrong. We’re going to talk to them ASAP.
[blah blah blah yada yada yada]

Q & A: Q & A was like a police lineup: 2 hobos and 1 perp (real ‘analyst’)

Q: Tony? Shain. How long will it take to “fix it”? [Tony cuts right to the chase]

We need to understand exactly what FDA thinks they need. Detail in CRL is not specific. We think we know what the manufacturing issue is (as mentioned earlier), but we need to meet with them to make super-extra sure.

[Now nobody wants to ask a question. Lady is now pleading for someone to fill up the lines. 3rd caller gets tickets to see Bachman Turner Overdrive at Bub’s Bar-B-Q this Friday!]

Q: Al Violante? How long until a reverse split to keep business going?

Annual stockholder meeting to discuss reverse split (early june).

Q: Jason Kantor RBC Capital: When do you expect to request a meeting., when do you expect to *get* a meeting? etc. etc. the usual questions. I believe this was asked more succinctly by the guy who said “how long will it take to fix it?”

We’ve already put in a request for a teleconference. Maybe not have to go to a formal meeting [we still like cutting corners]. We hope it’s a 2 month review (type i resubmission).

Theoretically still possible to get approval by EOY?

That would be our goal. [We’re also going to ask Superman to reverse the rotation of the earth so that we can get approval last week.]

[More awkward silence]
[More meaningless prattle from CEO]

For whatever reason, I’m inclined to believe King. I have no position on $ALXA and probably won’t buy in, but I get the feeling that the manufacturing is really the sole issue (or one of the few issues).

A non-fancy rant on Obesity

Sun, 06 May 2012 00:05:00 -0400

Hi. You may be here b/c I just tweeted about a pissing match I got into with Nate Sadeghi-Nejad over his recent comments on obesity.

This is my rebuttal and it is probably the last I’ll say about it for a while.

That being said, there are a lot of words down there and if you don’t want to read them, you can turn back now. My feelings won’t be hurt.

The pissing match started with Nate suggesting that obesity was a ‘disorder’, rather than a ‘disease’. I’m not going to talk about the fact that these terms are poorly defined and if you asked 10 people their definition, you’d get 10 different overlapping answers.

Rather, despite the vague definitions, my guess is that Nate uses disorder to mean a condition that is less severe and more personally controllable (and therefore less deserving of sympathy) than a full-blown disease, whose effects are essentially uncontrollable by the individual. Of course, this is a flawed understanding of disease for the simple reason that many diseases have both environmental (controllable) and hereditary (uncontrollable) contributions (e.g., Alzheimer’s, Parkinson’s, numerous cancers). But Nate reserves his condescension exclusively for the disease (or disorder) of obesity.

The pissing match ended on Friday with Nate’s Incidence Challenge. Nate tweeted:

“Name a disease other than T2DM [Type 2 Diabetes] that has a similar incidence curve. NSCLC being considered.”

Twitter doesn’t give you much room to say what you mean, but what I think he means is this: unlike other diseases (except Type 2 Diabetes) the incidence of obesity has exploded over the past 30 years, so it can’t possibly be a) a disease and b) influenced by hereditary factors.

So, let’s see. First off, Nate tries to tie one hand behind my back by saying that I’m not allowed to use the disease that immediately disproves his argument—Type 2 diabetes. Second, incidence has nothing to do with the definition of disease. Even if we accept his handicap of throwing out Type 2 diabetes, diseases are not defined by whether or not they have a particular type of incidence.

A more appropriate definition of disease (and hopefully Nate would agree) is that it is a pathological condition whose manifestation [sorry, fancy word] is at least partly out of the control of the sufferer. Does this definition hold for obesity? Absolutely. There are truckloads of studies tying obesity to genetic and epigenetic* conditions, with the heritability of obesity ranging from 6% to 85% in different groups (see here here here here here here here here here here here and here for a small sample of studies).

But hey, we can ignore all the research because Nate was chubby once and he started to exercise and he’s not chubby anymore. So it must work for everyone.

Of course, Nate’s view also defies common sense:

I think even he would agree that human hunger and satiety [again, I apologize for using a fancy word] are physiologically controlled.
I’m also sure that Nate has no problem believing that human cancers are basically caused by the body’s derangement of the control of cell division.
And yet, he presumably balks at the possibility that hunger and satiety could also become deranged physiological processes in some people.

Here’s my challenge to Nate: You know the FDA’s criteria for efficacy of obesity drugs? Find me a controlled study showing that diet and exercise alone can achieve the FDA mandated criteria for weight loss in a large group of participants (n > 300) for more than 3 years. And when you can’t find such a study, please speculate as to why that is [here’s a hint: think genetics & epigenetics].

To those who get pissed off because I might be siding with the American culture of victimhood and “my genes made me do it”. I’m not absolving the obese. They have the genetic cards they were dealt and they can partially influence them by their environmental choices. But make no mistake that we are often slaves to our bodies in more ways than we might realize. And I think the obese deserve a little better than condescending snark from people who should know (and behave) better.

And now, back to the stock market.

P.S. Despite my obesity rant, I still think $ARNA is still screwed this week. At least Nate & I agree on that.

*It’s worth noting that epigenetic factors could explain the ‘explosion’ of obesity and T2DM in America & elsewhere (see here for 1 of many examples).

Levadex: A dud in waiting

Sun, 22 Apr 2012 22:28:00 -0400

More snarky thoughts on $MAPP.

Quick! What’s the best selling ergotamine-based anti-migraine drug on the market?

You don’t know?

Neither do I. The reason I don’t know the answer to that question is because the ergotamine market is so small and Balkanized that information about revenue from ergotamine-based meds doesn’t register in various google searches like this and this.

HOWEVER, if you poke around long enough, you’ll see that Valeant Pharmaceuticals, makers of Migranal (dihydroergotamine nasal spray), arguably the best known ergotamine-based anti-migraine drug, sold a staggering $13 million of the stuff in 2008. They haven’t bothered to break down their sales of Migranal since then, but I think we can safely assume that it’s still selling south of $50 million a year.

And yet, there are some Nostradamuses out there predicting that MAP Pharmaceuticals’ Levadex (orally inhaled dihydroergotamine) is poised to sell $400 - $750 million a year (depending on which addled investor is writing about it on seeking alpha)…because…because…well, there’s no good reason to suspect it will sell anywhere near that amount*. And there are plenty of reasons to suspect that Levadex (if approved) with be a ho-hum steady-Eddie $20-50 million-a-year drug.

If you want a sober and cogent analysis of why Levadex will be a dud, see here and here and here.

Alternatively, you can ask yourself the following questions:

What are the current sales of the best selling ergotamine-based anti-migraine meds? It’s not $400 million. My best guess is that Migranal takes the prize here, and even under the most optimistic scenario, it’s probably clocking in at $40 million (see above).
Migranal (same active ingredient as Levadex) has a pregnancy Category X rating. Do you think it’s likely that women (the predominant gender of migraineurs) will cotton to a drug with a pregnancy category of X to the tune of $400 million per year?
Do dihydroergotamine meds have any black box warnings? (here’s a hint: Imitrex has no black box warnings and has a pregnancy category of C, Migranal…and presumably, by extension, Levadex? Not quite so lucky.)

Disclosure: I own $MAPP puts (September expiration).

*To be fair (and I really don’t want to be fair), the argument goes something like this:

The anti-migraine market in the US & Europe is huge (> $3.2 Billion in 2015 & > $4.4 Billion in 2020).
A little more than half of those sales will come from “triptan” meds (so let’s say $1.8 billion in 2015), which leaves a whale load of non-triptan anti-migraine sales ready for the taking (let’s say $1.4 billion) [**cough**BOTOX**cough].
Levadex will take 25% of this remainder because it’s new and shiny and ‘easily delivered’ via inhalation, and the ladies sure enjoy carrying cans of medication around in their purses.

$ECYT $MRK Conf Call on deal for EC145 (suicide bomber version of Vitamin B9)

Fri, 20 Apr 2012 22:43:00 -0400

CEO speaks

……………..zzzzzzz………
…2 minutes in and nothing substantive has been said…
“we’re thrilled to be partnering w/ $MRK”…”first class organization <blah blah blah>”
“We understood each other” $ECYT <3 $MRK (met on eharmony)
“We just had great alignment” (MRK wasn’t doing anything in the onc space this weekend (and through 2018) so they’re going to come over & help us test EC145. They’re also gonna help us move the $ECYT barcalounger into the basement).
………4 minutes in and nothing of substance has been said….
………$MRK funding development program beyond ovarian….
[I think the word “thrilled” has been used in every sentence so far.]

Meeting should have started at minute 6

CFO Speaks

$120 million up front (not quite as much as mega millions).
$MRK has world wide rights to develop EC145.
$MRK and $ECYT will co-promote EC145 in US w/ equal sharing of costs and profit.
$MRK has exclusive rights to EC145 outside US & $ECYT gets double-digit royalty.
$ECYT retains rights to EC20 & will ensure EC20 is available to $MRK for development of EC145.
$ECYT is responsible for “full value chain” for EC20.
Clinical trial execution: ecyt will continue to execute phase 3 PROCEED trial in ovarian and $ECYT will be responsible for the majority [not sure what this means] of the costs…all other development will be responsibility of $MRK.
Phase 2 lung study is already active…we’ll continue to execute on this trial and hand off to $MRK [does this contradict the previous bullet point?].
$MRK has committed to develop EC145 in other indications.
Previously, we had enough $ to complete PROCEED, complete the phase 2 lung trial & bring another pipeline drug into clinic.
Now, our near term cash burn will be lowered b/c $MRK’s picking up the tab.
The $ infusion also allows us to be more aggressive in pipeline development + allows us to develop commercial capability related to EC20.
No need to raise $ in foreseeable future.
We are developing drugs in inflammatory space…another folate drug and a prostate drug.
Financial guidance will come at another time.

Questions:

Chris Raymond of Baird. Amazing deal. Is there any change to the plans of filing in Europe?

Is filing now driven by $MRK?

We’ll be collaborating on reg filings…still on track to file in late Q3 or early Q4

Color on your decision to keep development of EC20 in house?

EC20 is an important element of the platform. We have other folate-targeted drugs (onc & inflammatory)…we need to have total control of EC20
$MRK obviously has rights to use EC20

Cowan? Royalty ex US? Above 20%?

CFO: All I can say it’s double-digit outside US

Remainder of PROCEED costs & phase 2/3 for lung. How much are those trials going to cost now?

Cost of trials…we’re responsible for a majority [what does this mean?] of the PROCEED trial costs (some sharing)…still have some discussions w/ FDA about finer elements of study that will affect total size of PROCEED…historically identified $40 million dollars for the TOTAL cost of that trial and we’re responsible for the majority of that. Lung cancer trial: $MRK is responsible for the cost of that trial. Lung trial size is ~180 patients. We had estimated that it would cost 50? million dollars, [so we’ll save that amount].

You retained right to co-promote in us…are you seriously going to do this? 50/50?

[CFO makes noises with mouth, but says nothing]

Have you decided on the 4 remaining cancer indications?

We’re still evaluating the 4 possible cancer indications w/ $MRK.

You’re not gonna answer this, but here goes: $880MM in milestones…how much of that treasure chest is from commercial milestones vs. non-commercial milestones?

You’re right. We’re not gonna answer. Nice try.

Leerink Swan. Does this agreement with $MRK limit any indications or settings that you can pursue with your other folate-receptor targeted drugs that are earlier in your pipeline?

Agreement is very specific to the agents involved.
Agreement also includes 2 other “vinta” agents in the pipeline that weren’t our priority. This includes ECO489: folate targeted vinta (similar to EC145 but w/ different linker). Also includes ECO225: folate targeted vinta w/ mitomycin c as a payload.
We plan on bringing forward ECO531 ourselves. ECO531 = folate targeted tubulysin.

w/r/t EC20, do you need an EU presence to market this in Europe?

We’re responsible for commercialization…we gotta do it some way, [so probably yes]

Mark ????? Someone else really. Conditional filing w/ EMA will be later this year? Is it conditional on PFS or OS?

Filed later this year (you’re correct)….based upon phase 2 PFS data. Full approval based on results of PROCEED trial…primary endpoint is PFS in the folate++ group.

U gonna get an SPA from FDA?

That’s a longer discussion for another time [I don’t wanna talk about it]. FDA isn’t giving out SPAs for our endpoint in ovarian…only SPAs when OS is the primary endpoint [so why the @#@#$ are you doing PFS?]…No SPA, but we’re comfortable moving ahead [why?].

Jason Cantor: RBC Capital. Congrats. Excellent deal. How much milestone is associated w/ ovarian & do you get more $ if you get early approval?

Not gonna answer the milestone questions.

w/r/t development of other indications outside of ovarian and lung, how long until you start a trial in a new indication?

[It’s in $MRK’s hands.]

Do you have enough material for trials?

Yep.

Is there a standstill agreement w/ respect to buying you guys out?

There are provisions in the agreement, but i can’t say anything else.

Do you now have enough $ to run the company forever (assuming you get approval and successful launch)?

[of course that’s theoretically possible, but I’m not nostradamus.]
CEO: “about the standstill…” [then says nothing].

???? You talked about the competitive nature of the deal…was there any change in the intensity of interest vs. time [did people run for the exits after you updated the phase 2 trial back in December 2011?]?

Multiple parties were looking @ the asset for different geographies.
Many many companies.

Closing comments: We’re going to use the word “exciting” as much as possible for another minute now.

Disclosure: Long $ECYT

Sinatra & The Boys Discuss $VVUS. I am now long $VVUS.

Mon, 09 Apr 2012 23:31:00 -0400

Sinatra & The Boys Discuss $VVUS. I am now long $VVUS.

Why $VVUS's Qnexa will be approved sooner rather than later

Mon, 09 Apr 2012 07:29:14 -0400

Vivus’s anti-obesity medication, Qnexa, has a 4/17/12 PDUFA date looming.

Here’s my abbreviated rationale for why it will be approved.

Vivus’s 1/9/12 announcement indicating that the FDA had asked Vivus to remove the contraindication of childbearing-women from the proposed Qnexa label was a strong positive indication.
The advisory committee vote recommending approval was also strongly positive (20+, 2-), and it provided political cover for FDA decision makers.
Qnexa results meet/exceed FDA guidelines for development of anti-obesity meds. You can’t keep moving the goalposts on people.
Qnexa’s active ingredients (topiramate & phentermine) are already on the market.
There’s nothing else approved on the anti-obesity front except for orlistat, which is about as effective as a waterproof towel.

There have been rumors about a possible delay in Qnexa approval due to haggling over REMS issues. I don’t know anything about that, but the simpler view is that the FDA keeps its word and renders a + verdict on 4/17/12.

I currently have no position in $VVUS.

This is a permanent link to the $KERX call (Keryx’s version will...

Sun, 08 Apr 2012 00:02:00 -0400

This is a permanent link to the $KERX call (Keryx’s version will be removed on 4/17/12). Call was listen only (no questions, only 10 minutes). They’re definitely burying Perifosine (they imply they’ll have difficulty recruiting for their multiple myeloma trial) & playing up Zerenex, but see here for a bearish opinion on Zerenex.

$AVII Conference Call / Postmortem

Mon, 02 Apr 2012 21:51:00 -0400

My take home message: There’s more uncertainty surrounding the functionality of the exon-skipped version of dystrophin than I had initially suspected. They are hoping[praying] that their version of dystrophin is still somewhat functional and that they will see a clinical benefit after 24 weeks.

CEO:

dystrophin protein can be produced w/ [our] drug therapy
highly statistically significant
american academy of neurology (AAN) meeting on 4/25. AAN meeting/presentation will give more data.
primary endpoint was dystrophin production as a % of normal
p = 0.002 for 30mg/kg/week cohort
average of > 20% of dystrophin + fibers…medical literature suggests this level is associated with better clinical outcomes…based on animal models and in Becker’s (milder) muscular dystrophy.
consistency across all of patients…range of 15.9% to 29.0% of novel dystrophin fibers in 30 mg cohort. Results determined in blinded fashion by histologists and multiple samples per patient.
We asked the question, “Can higher dose (50mg/kg/week) also increase dystrophin levels in a shorter timeframe (12 weeks)?” No. Results are clear. [ed: Why is this true? Shouldn’t you start making dystrophin more or less immediately? Maybe ‘interesting’ biology here.]
Rollover extension study will assess whether 50mg/kg/week shows dystrophin and a clinical benefit.
Through 24 weeks, no treatment related adverse events, no serious adverse events either.
[CEO sounds strained. “LOOK YOU BASTARDS, THESE ARE GOOD DATA! STOP SAYING THE GLASS IS HALF EMPTY!!!!]
Didn’t see clinical benefit in running walking tests.
Extension study is now open label. Expect more biopsy data and other clinical benefit data in 2H of 2012.

[operator now sounds stoned]

Lazard: Congrats! Ages of patients? Any color? Were they really sick?

Baseline characteristics consistent across cohorts. Avg age ~9 years. “good distribution” of ages [what exactly is a “good” distribution here?]. Still evaluating each individual patient [post-hoc mining].

Is the dystrophin that is produced diffuse across biopsy/muscle sample?

Very consistent across many samples, but we haven’t looked at other muscle groups [aside from bicep].
Other speaker: Ed Kaye, CMO. Very happy that dystrophin levels were about 20%…should see clinical benefit “over time.” [because we didn’t see it @ 24 weeks].

What about secondary outcomes related to immune infiltrates?

We’re still evaluating [sounds like bullshit]…”we were focused on …dystrophin”

Marco ??? Congrats. What data do you expect to have when you meet w/ FDA?

[no real answer. dodge, weave] We’ll be working on a briefing document for FDA & pivotal trial design. We continue to collect data from open-label extension. Aw shucks, I guess > 24 weeks might be better for us.

What kind of data do you think you’ll have from trial extension? Will you have 40[sic] week data?

[ed: Interesting comment, though. Basically says, ‘if we had better data, we’d be chomping at the bit to meet w/ FDA, but as it stands, we’re gonna let the extension study continue and hope[pray] that we see a clinical benefit…Then we’ll be chomping at the bit to speak with them again. So, we’re gonna drag our feet a little bit about setting up the FDA meeting’]. 1st patient enrolled was August, 2011. 48 week analysis for this patient would come in July…[so expect a little bit of delay in our interaction w/ FDA].

What kind of patients might you enroll in a pivotal study? Same type of patients (presumably sicker, more advanced?) or will you go for patients who haven’t progressed as much?

We picked the ‘correct’ patients, but we have to wait longer.

What will your pivotal studies look like and how will they compare to what Prosensa [competitor] is doing?

[no answer]…everything is riding on what we learn from extension study. We’ll be making our decision on a trial based on *our* product [fuck Prosensa].

Rodman? [Fix your phone]. How many biopsies do you have? How long/consistent is dystrophin expression happening during course of Rx? Is the dystrophin that’s produced *functional* [or is it just a non-functioning version of dystrophin]?

We can’t keep taking serial biopsies of the kids: therefore, we can’t measure half-life etc. We just don’t know if we’re at steady-state or if we have room to increase dystrophin levels. W/r/t whether our dystrophin is functional, Francesco Muntoni (The Lancet 378:595-605) has published analysis of biopsy data…it’s in all the right places [in muscle tissue]…There’s nothing to lead us to believe that the mutant version that we produce is non-functional [but this is really an argument based on a negative result]. We see some [sketchy] evidence suggesting that our mutant dystrophin is actually functional [alterations in some specific mRNA’s. This all sounds like really weak evidence].

How do the biopsies look? Is there a concentration of expression at the injection site?

[Look, Einstein] we did injections in the old study. *Now*, we infuse the drug over 60 minutes. We do bicep biopsies.

Okay, let me rephrase…is dystrophin evenly distributed?

We’ll share examples of the muscle biopsy at AAN, but we see positive fibers across many many samples [this sounds like a difficult question to assess ]…as far as the BICEP is concerned dystrophin seems relatively evenly distributed…but we haven’t looked at other muscle tissues.

You can’t do serial biopsies, but you *can* do multiple measurements of secondary clinical measures, so did you see anything [good] during the intermediate timepoints (immune infiltrates? anything else?)?

We captured a lot of data, but you’ve got it backwards…since we didn’t see much until about 24 weeks, we’re probably not going to see much of anything using these secondary measurements until AFTER 24 weeks. We need to look *beyond* 24 weeks. [more lipservice of examining existing data on secondary endpoints].

Edward? Cowen? Congrats. Chris. You said > 20% dystrophin levels beat your expectations. What levels were you expecting?

We were expecting levels similar to those found in Becker’s patients. We know that DMD is defined by <= 5% dystrophin (as a % of normal). We know there are Becker’s patients who have high single digit % dystrophin and they have markedly better clinical outcomes than DMD patients, so…we were thinking anything [roughly] > 10% would be positive! [ed: However, the exon-skipped form of dystrophin probably isn’t identical to Becker’s dystrophin, so even if the percentages are as good as (or better than) some Becker’s patients, there may be functional differences between the 2 types of dystrophin that make it unfair to compare the 2 proteins]. Just give us more time.

Of the 8 patients you said who reached a high level of dystrophin…they were all > 10% dystrophin?

[dodge weave] we didn’t say exactly what you’re suggesting. We need to look at data from extension study.

What about higher dose for longer period (> 50mg/kg/week)?

Is it really about the dose level or is it about the duration [this is AVII’s new mantra]? [want to find the minimal dose that is effective]. Maybe we shouldn’t wait for progression of the disease. Maybe we should start earlier [handwaving and contradicting earlier statement about ‘we picked the right patients’].

Canaccord. How much preclinical tox coverage you have as far as extending dosage? [WAT?!?]

Have completed long-term animal tox dosing. 9 month primate study (up to 300mg/kg/week) and 6 month mouse study (up to 900mg/kg/week). Doing pathology work currently and will report finding in next couple of months (by end of Q2). None of the subjects died, but still need to perform pathology studies. But our human trials have been really clean (no treatment related AEs and no serious AEs).

Open label extension phase…what’s going on w/ the dose? Are you changing the frequency or outcomes analysis in the extension trial?

Not changing dosing. Every patient stays in their original cohort, except for placebo group which is now split amongst 30 and 50mg/kg/week group [2 patients into 30 mg group and 2 patients in 50 mg/kg/week groups]. Have lessened frequency of efficacy endpoints [not sure what he means]: We were capturing data every 4 weeks, but now capturing every 12 weeks. Biopsy samples will be done similarly to the blinded study.

What should we be expecting on 4/25 at AAN meeting? What will be notably *absent* in the AE profile?

Still evaluating full data set. We only get 3 minutes & 3 slides at the AAN presentation + a poster. [managing expectations: You’re not going to get much data]. Safety treatment effect will be shared in full detail because there’s not much to report [we’ll only show you the good stuff].

What has the FDA communicated to you about the importance of dystrophin levels vs. “efficacy”. What does the DMD community want from you w/r/t dystrophin levels vs. “efficacy”?

[dodge, weave, obfuscate] non-answer. FDA will want *some* level of evidence of clinical benefit [trying to insinuate that even though FDA will want some evidence of clinical benefit, the bar may be low for meeting that criterion]. Safety profile gives FDA a little more latitude about assessing benefit [i.e. maybe we can thread the needle of FDA approval w/ shit efficacy b/c the drug is relatively benign].

What about cystic fibrosis patients? What do they think about exon skipping?

[dodge, weave] DMD community is well informed.

Wedbush: Historical data. In an earlier study you looked at 10 & 20mg/kg/week and you saw effects. Your earlier studies suggested that you’d see dystrophin accumulation around 24 weeks, so are you going to keep your eyes trained on >= 24 week analysis? [not sure what he’s driving at].

Our older study told us that dystrophin production was low (most of the patients had < 10% dystrophin and there was a lot of variability). Muntoni (UK study director) was espousing *duration of treatment* as opposed to *dose* [using Muntoni to rationalize away the ‘bad’ data in the 50mg/kg/week cohort].

That’s a wrap.

Notes on $MAPP Conference Call Regarding Levadex CRL

Wed, 28 Mar 2012 13:01:00 -0400

My notes [with snarky comments].

MAPP requesting meeting w/ FDA to address issues on CMC & inspection issues w/ 3rd party manufacturing facility.

FDA not able to complete review.

Wedbush. All that’s left to do is inspect 3rd party manufacturing facility? What about royalty from $AGN?

We believe [cya] that 3rd party has alredy provided response OR issues are addressable. FDA has 14 days to respond to our request for meeting. ”We think that the information we provided [to FDA] is complete…we need to confirm that [I’ve got lawyers breathing down my neck]”. $50MM milestone from AGN upon approval. Additional $25MM milestones possible.

Lazard: More detail on usability of inhaler? Inadvertent dosing an issue? General usability? Does FDA want to know ‘how did patients interact with the device?’

We believe we have what they’re looking for.

Will there be any changes to the device?

We don’t believe so

Leerink. CMC issues…were they questions about process and process control? Can you clarify?

We need to talk to FDA and then we’ll provide more information. Based on CRL, we *believe* we have the data that they want, but need to talk to FDA.

Manufacturing issues…How standard are the issues? How many issues? What is this facility? Did the other facilities pass? Is another inspection needed? When was last inspection of this facility?

1 specific facility is involved. We *think* that we’ve already provided a response [actually 3rd party has]. Either 3rd party has provided a response or the questions are addressable. Nothing in the letter says there’s a need for another inspection.

BofA. When will you seek FDA meeting? How long does it take for meeting to happen?

Sending a request today to meet with FDA. Up to 60 to 75 days to set meeting after their response. We hope [pray] it will be quicker.

Identify the 3rd party? Issues with drug or inhaler?

3rd party issues were raised around “can[ister] filling”.

Confidence in eventual approvability [leading the witness]?

Extremely encouraging. We’ll work through the CMC issues. FDA gave us full markup of carton, carton labeling, etc. [so it’s in the bag!!!].

Canaccord. Feedback from AGN? What’s the Refile Process? DHE products are [pregnancy] category X. Are you going to have a Category X drug?

See our previous answers. W/r/t Category X, we’ve provided a comprehensive package [We really don’t want a category X, but you can bet your ass the FDA will give us an X].

What’s the process on refiling timeline?

We don’t know how long

How are you going to update “the street” on what’s going to happen?

We’ll have conference calls around material events…& press releases.

JPM. Cash on hand today? Burn for 2012? IND for another drug planned…are you going to stall your IND to save $?

Ended Q3 with $112MM…burn was ~$50MM. Don’t anticipate new significant spending. Don’t see an impact on moving other drugs forward.

Matt ?? Any effects on contract w/ AGN?

What’s the rate limiting step in getting Levadex to market?

[reading between the lines…] our response to FDA.

Will you get a class I or class II review or is it something less formal?

No idea.

User/usability studies…will you have to do any additional usability studies?

We believe that the information we provided to the FDA is [enough]…even if we had to do so, it would be quick.

Kevin Tang / Tang Capital [please pronounce my name correctly]. How many pages is CRL?

No comment

How many 483s were subject to this 3rd party supplier [zing!]?

We haven’t provided a number, but it’s a manageable group

But you can’t comment on how many 483s there are?

[geologically looooooong pause]

Who is the 3rd party?

We’re not disclosing info for competitive reasons [we secretly hope our competitors use them, so they can get a CRL and some 483s, too!].

Is it true that the inhaler has 4 doses (8 puffs / inhaler)?

Any questions from FDA about taking too many puffs/doses?

[dodge, weave, stonewall, obfuscate, but eventually says] “no.”

Adam Feuerstein. FDA didn’t have time to review it all. Why not just delay PDUFA date?

Delay in review time was just on 1 piece. CRL is really related to CMC issues. FDA doesn’t dialogue with sponsors the way they used to [sniff, sniff. Not our fault].

Usability data came late? But didn’t you submit a usability study w/ original NDA?

We did submit usability study data…tested on naive patients…96% correct usage. But there were additional questions about usability…we pulled data from our other studies into a smaller package, but FDA couldn’t review in time.

Did you really have an SPA? & what’s going on w/ 10-K?

SPA- we reviewed our phase 3 study under SPA process. We believed at the end of the process that we adhered to FDA guidelines. FDA said we didn’t have an assigned number w/r/t SPA [probably lost between FDA’s sofa cushions]. But they’re not asking for additional studies, so it’s moot, bitch!

So that was a misstatement, right?

[Look, we’re tired of playing Sarah Palin to your highfalutin’ northeast liberal blamestream media]. We reviewed protocol and thought we executed properly

You don’t get a letter from the fda saying you’re “SPA”?

There isn’t the full clarity you’d hope or expect [somebody dropped the ball…not us].

10-K?

It’s an accounting issue [stop breaking our balls over penny ante crap] w/ recognizing payment from AGN.

How long have you had the issue back & forth w/ SEC?

Not gonna talk about this [You’re dead to me Feuerstein]. Other people have similar issues [if everybody jumped off a bridge with inappropriately recognized revenue, would you do it, too?]

Bill Tanner/Lazard. What about the other, non-partnered part of Levadex?

CRL provides more clarity for our potential partners [now we can say, “Look at all the crap we *don’t* have to do!”]. Not sure what we’ll do preapproval or post-approval.

BofA Gilber. Zings Adam about SPA (I’m not gonna ask sour grapes questions about SPA)! Will FDA turn down your request for a meeting b/c there’s not enough to meet over?

Possible, but we’d like to have a ‘sit down’ with them anyway, [b/c they’re batshit crazy…and as Michael Corleone said, “hold your friends close, hold the FDA closer.”]

Does this affect any key hiring decisions?

We have sales reps we’re prepared to hire on a contingent basis.

Wedbush Securities. What about slowing of launch expenses b/c of CRL? Talk about timing of inventory build, etc.

Havent’ given any detail about preapproval launch expenses. Most cost has been shared w/ AGN. Most costs are research related.

When will you report Q4?

As soon as we can. get on file by end of week.

David Chen? CMC questions is solely on this 1 3rd party manufacturer?

No. additional CMC questions “around…around…the product”

3rd party makes the canister?

Yes.

No redundant supplier?

We’re getting one [we’re gonna bury the existing manufacturer next to Feuerstein], but there isn’t a redundant supplier in the NDA

Are the other CMC questions related to device?

[negative answer]. we think we’re clear on the device, except for 3rd party issues [implying drug related cmc issues].

Mike ?? Sun America. Did CRL provide any recommendations of actions for approval or did they just point out the issues?

CRL identified additional information they need. Want meeting to clarify.

Mostly CMC issues then since you’ve provided usability issues?

We believe so.

Joe Schwarz Leerink. Does 3rd party manufacturer already manufacture similar canisters via GMP? Do 483s opine on whether 3rd party is in accordance w/ GMP?

FDA observations revolve around GMP.

Concluding Remarks: [Thanks for keeping the stock price up!]