Great day so far.

Short interest appears to have dropped to just below a million, but I'm sure there's additional shorting going on currently given the recent price rise. Dangerous game if approval arrives early.

http://www.nasdaq.com/symbol/ttnp/short-interest

Wow, a pretty solid day! Not sure whether its Sheff-ites or something else, but I will take it.

New publication from CDER...check out the amount of time, effort, etc. spent on guidance for the FDA's pill popping friends about abuse deterrence. The staff that should be reviewing probuphine was probably working on this masterpiece!

http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM492172.pdf




If the FDA is serious about totally preventing abuse 100%, I believe there is an NDA they might pay some attention to...

It's funny the headline talks about a pill, but its really about probuphine.

Listening to the story makes me question the FDA's labeling concerns at the Ad Comm. They were very concerned that the dosage with probuphine was not strong enough for addicts just coming off opioids (hence the focus on rescue meds), and argued probuphine should only be used by addicts who have gradually tapered off the high initial dosages of buprenorphine usually initially required.

However, it's abundantly clear from the story that addicts, especially those in the earliest stages of recovery, cannot be trusted to take their medicine. They miss the high (well, miss is not a strong enough word, they have an uncontrollable craving for the high). So wouldn't a combination therapy of probuphine plus a lower dosage of sublingual buprenorphine be more advantageous than entirely relying on a higher dosage of sublingual buprenrophine that can be abandoned at will by the patient? Essentially, prescribing probuphine as the "fail safe" that takes the possiblity of getting high out of the equation. With such a strategy, the addict could stop taking pills (and feel discomfort), but the probuphine would still prevent the high.

I wouldn't be surprised if many physicians came to the same conclusion and used such a strategy off-label.

New recovery pill helps opioid-addicted firefighter get clean

Not sure if this has been posted already, but I didn't recall seeing it:

http://www.myfoxboston.com/news/new-recovery-pill-helps-opioid-addicted-firefighter-get-clean/201222319

Well, the fact is none of us know when (or if) it will happen. They could be finalizing the press release right now. I'm pulling for you...miracles do happen!

This just stinks.

Six weeks of extra review time and nothing. I've come to the conclusion the FDA is going to take the whole three months of additional review time. Anybody think differently?

I know Braeburn has a risperidone implant in Phase II, so maybe that's why they are not pursuing that particular indication.

Thanks for posting this...I know probuphine hasn't even been approved for opioid abuse yet, but I'm convinced that shortly after approval Braeburn will aggressively pursue an expansion into chronic pain. Incidentally, the Zacks analyst wrote in his email to me that "We anticipate, although not explicitly modelled, that there will be some off label use of probuphine in our current sales forecasts for pain as buprenorphine is already used for this and the benefits of the implantable solution are superior to other methods of administration."

Probuphine Not Approved, But FDA Is Still Busy...

Nice to know they are really clamping down on opioids.

https://www.morningstar.com/news/pr-news-wire/PRNews_20160405CG63096/ani-pharmaceuticals-announces-fda-approval-of-oxycodone-capsules-5mg.html

I'm going to comment as well. I'm not going to appeal for approval of probuphine...HHS will leave that to the FDA...but I am going to request that an exception be built into the regulation: namely, that prescriptions of abuse deterrent formulations of buprenorphine, such as implants or depot injections, not be subject to any numerical limitation at all. This is especially important given the fact that the vast majority of physicians refuse to even deal with bupenorphine. Given that reality, abuse deterrent formulations shouldn't be penalized with the same numerical cap applicable to pill formulations that can be diverted.

I think there is a reason behind the fact that Braeburn's plans for chronic pain have not been highly publicized...it makes Titan more valuable. And I think if probuphine is approved, Titan will be purchased quickly by Braeburn. I would anticipate an offer price of $27.50 per share, which adjusts to $5 per share pre-split, which I think would meet a psychological hurdle for Titan’s board to accept an offer and would be high enough to get 90% of shares tendered. That would mean a fully diluted price of around $660 million, but it would actually be a lot cheaper for Braeburn:

1. They already own 10% of Titan’s stock. So knock $66 million off the purchase price to $594 million.

2. They would be buying $15 million in cash (their milestone payment upon approval) and $14 million in cash from warrants. Knock $29 million off the purchase price to $565 million.

3. Sunil has stated that, with $250 million in annual sales, nearly two-thirds of the $165 million in sales milestones would be reached (approximately $100 million). Say it would take them three years to get to $250 million in sales, and discount for the time value of money by 3% and you get $91.2 million in value of saved milestone payments. So reduce the price to $473.8 million

4. Subtract an assumed value of royalty payments over the next three years: lets say $2 million this year, $20 million next year and $35 million in 2018. Present value = $2 + $19.4 + $32.9 = $54.9. So reduce Braeburn’s “real” price to $418.9 million

5. Other sweeteners/potential savings: save up to $35 million in regulatory milestones on approval of chronic pain. Also get Parkinsons and T3 for “free.”

If they wait a year or so, the price will have increased dramatically, perhaps to the point where it is cost prohibitive for Braeburn. It’s a gamble yes, but much less of a gamble (and much less expensive) than developing your own drug development portfolio.

Yes, I agree that $15-$19 is a reasonable target...immediately after approval. I think what Zacks is saying is that its worth $8.50 now, prior to approval. Once the uncertainty of approval is removed, I'm sure they will revise the target upward.

I did hear back from the author of the report by the way, and he said that, because of the uncertainty of approval, they have not factored in the potential future value of a chronic pain indication. He also indicated he thought it was "very unlikely" that probuphine would not be approved. So they are being conservative.

I really don't know. They won't be issued all at once, but fairly quickly over the next year would be my guess. With the extra $15 million in cash and (hopefully) strong royalties and sales milestones from probuphine, there should be less of a temptation for management to dilute shareholders with a secondary offering (although I realize they can do so with the existing shelf at any time).

There are not that many shares outstanding currently. I can actually see management getting pressure to do a split over the next year (maybe 2 for 1) to add additional liquidity. Kind of ridiculous after the reverse split last year, but stock's that split tend to do well so I'd take it.

Re: $8.50 price target, wow really going on a limb there

I know its a bit ridiculous, but on the other hand they are probably heavily discounting based on the possibility of a CRL. They got burned pretty badly in 2013 (along with myself and many others here), and there's no upside for them sticking their neck out. Still, I do think they could do a much better job accurately reporting what is going on, such as:

-Braeburn's plans for chronic pain;

-upon approval, along with the $15 million milestone from Braeburn, there are warrants to purchase 4 million shares outstanding at very low strike prices that will bring in about $15.2 million in proceeds (and dilution of course).

-Sunil tipped in the last conference call that the $165 million in sales milestones were for the most part "very achievable" and that at 250 million sales per year, two-thirds of the sales milestones would be achieved.

It all hinges on FDA approval. With that approval, the PPS at this level is so good, and the upside so large, that it seems to good to be true. I know if I saw an analyst report for a stock trading in the 4's and the price target was in the 20's or 30's, I would figure the analysis had gone off the deep end.

Hopefully it will do some good. They didn't have any representatives on the last conference call, and so I don't believe they are following Titan too carefully...everything from their research report is ascertainable from reading their SEC reports.

I have no idea how they came up with their probuphine royalty estimates...there are no assumptions provided, no discussion of Braeburn's training of physicians, etc.

Done.

Still no mention by Zack's of Braeburn's plans for chronic pain, which is another catalyst.

So much time and effort going into developing pills that can't be abused. The FDA (and big pharma) really love their pills, don't they? Of course they're missing the boat when it comes to addiction. Under the FDA's logic, an addict will want to get high, but be unable to convert the pill he has been prescribed into a means for doing so, and so will just shrug his shoulders, smile and rationally decide to take his wonderful abuse deterrent pill. That's the end of the story as far as the FDA is concerned.

Completely outside the FDA's grasp appears to be the notion that an addict who wants to get high will just stop taking his pills. They have no fundamental understanding of addiction. To the FDA, no one would simply stop taking their medicine to get high because...that's not included as an option in the labeling. I mean seriously, an abuse deterrent pill? Who cares when cheap Mexican heroin is flooding the streets?

The probuphine implant takes decision making out of the patient's control. That is why there is such a need for it: addicts understand better than anyone else that there will come a moment when they cannot be trusted.

That's not out of the question, but I think it's more likely he will announce that the HHS's new buprenorphine prescription regulations are being released. Because HHS moves so slowly, Congress got out ahead of the executive branch (HHS/White House) with its own bill, and I'm sure the White House will want to make sure the media credits the executive branch with moving on this issue. As anyone here knows, both Congress and the White House have done nothing until the problem is literally out of control.

Still...a guy can dream.

That's a great analysis. It only leaves about 13.8 million shares in the float, and 1.1 million of them have been shorted accordingly to the last short interest report.

Although my guesses about Titan's stock price are wrong more often than not, it would seem that the lack of available shares, creating a lack of liquidity, means that the purchasing that is probable to result following approval is likely to result in a larger spike upwards than most would predict.

...While Short Interest Continues to Climb

Something has got to give!

http://www.nasdaq.com/symbol/ttnp/short-interest

Institutional Base Building....

In September 2015 Titan had less than 1%, and Titan now has over 9%.

http://www.nasdaq.com/symbol/ttnp/institutional-holdings

I hope you're right on that approval date! With all the labeling changes required now for IR opioids for pain, there is no doubt in my mind that Braeburn will proceed with Phase III studies for probuphine for chronic pain post-approval as quickly as possible. It's a market asking for the taking.

Very interesting. I'm sure this initiative was born within the last two months, and so it's impressive they got it done so quickly. I imagine most of the work involved in this new labeling effort for IR opioids has been undertaken by the same division of CDER that is responsible for the review of the probuphine NDA. Makes me think they may take more time to complete the probuphine review if they are being charged with doing other things, but they still have to meet the May 27th deadline.

National Attorneys General Training and Research Institute

Short but sweet, this brief mention in the March 2016 newsletter is about as positive of a prediction as I've seen...

"In the next few weeks, the FDA is expected to approve a cutting edge way to deliver the drug Buprenorphine, a common treatment that helps in recovery. Doctors have been studying a long-acting Buprenorphine implant. "It's implanted into the body, with a very, very simple incision. It's basically placed underneath the skin and it's effective for six months," said Dr. Andy Mendenhall, regional medical director for CleanSlate. "Ninety-five percent of the people who suffer from an opioid addiction are not going to be successful unless they're provided access to opioid replacement therapy like Buprenorphine or Methadone," said Dr. Mendenhall. Typically, those therapies need to be taken daily, and those struggling to recover said it makes them feel like they are using again. This implant can help solve that problem and will require fewer visits to doctors or clinics."


http://www.naag.org/publications/nagtri-newsletters/substance-abuse-news/substance-abuse-newsletter-march-2016.php

I had to gag when I saw this answer...


How much influence does FDA have when it comes to shaping the design of these trials?


FDA gets to see all the trials before they're started, if they're done with the goal of gaining approval or changing the label. This is a very powerful position to be in, with a lot of responsibility. As you might imagine, people don't want to do a trial that the FDA doesn't like, if they need FDA's approval when the trial's completed.

Yes, and it's not too fun to have the FDA issue a CRL, practically design the re-trial themselves, and then complain about it later, and rather than look for "inferiority" as the trial was designed, criticize it for not showing "more superiority."

While we sit in a holding pattern, I’ve been trying to determine whether there is any objective evidence of whether a PDUFA extension is an indicator for how the FDA will eventually act. With the caveat that (a) this is two years old and (b) I have no idea whether this information is correct, I found some comfort in the following statement by Roth Capital commenting on another company's PDUFA extension:

“19 companies have received PDUFA date extensions in the last 1.5 years, and 16 of 19 went on to receive drug approvals. Of the remaining 3 companies, 2 did not receive approval due to manufacturing site issues.”

My understanding is that the FDA has toured and cleared the manufacturing facility that makes the probuphine rods, and so if you exclude the two results where approval was not received due to manufacturing site facilities, that means 16 of 17 PDUFA extensions led to drug approval, or about 94.1%.

http://www.streetinsider.com/Analyst+Comments/Roth+Keeps+Keryx+Biopharma+(KERX)+at+Buy+on+PDUFA+Update%3B+Extension+Preferred+to+CRL/9519317.html

I totally agree. The FDA would have a lot to answer for politically by issuing a CRL at this point in time, after positive results of a redesigned study the FDA designed and a positive Ad Comm vote (albeit with 5 "no" votes from the resident "useful idiots" on the committee). It 2013, the CRL basically got a shrug from the media. Today, it would be huge news.

All the quibbling about efficacy at the Ad Comm was just that: the FDA didn't want to accept results that suggested they were morons for issuing the CRL in the first place. But they fully acknowledge non-inferiority.

So a CRL could come, but I don't think its likely. If I had to guess, the REMS issue is pretty much dealt with but the FDA and Braeburn are negotiating the nature of the post-approval study that will probably be required to monitor the long-term effect of use of the probuphine rods.

As I mentioned earlier, the "telescopic lens" you refer to could work in Titan's short term favor. If approved, I fully expect a lot of publicity coming from the FDA on this, and I'm sure Califf will want to lead the way. That will help giving more exposure to Titan, as there has been a lot of publicity about probuphine, but not much allowing investors to connect the product with Titan.

I hope the FDA does the right thing


Me too! But as much as we may check for news or try to read the tea leaves, none of us can know for sure: the FDA has proven itself time and time again to be illogical and capricious.

That being said, I agree that, if approved, probuphine will be much more successful than I originally thought when I reinvested over a year ago (I lost a lot after the CRL).

The FDA issues a press release with every new drug approval. Given the current climate, I would expect that, if probuphine is approved, it won't be your ordinary press release the FDA issues...perhaps a quote from Califf himself stating this shows how the agency is moving to act quickly on the opioid crisis. Complete BS, of course, but I will take the publicity if we can get it.

Quote: "What are they waiting for?"

Couldn't have said it better myself.

Hey Matthew, I get what you are saying. Remember the uncertainty is a two-edged sword...a definite negative side for sure, but the positive being that it's allowed most of us to buy in at prices that others may dream of just a few weeks from now.

The Ad Comm member quoted, Judith Kramer, is a pharmacist, not a medical doctor, and she doesn't specialize with addiction. It may sound crass, but pharmacists make a lot more on pill prescriptions than they will with probuphine, which will be sold directly to medical personal by Braeburn. And, by the way, just because she and Califf both went to Duke doesn't make them buddies.

Also remember she is not an "FDA Representative." All FDA representatives on the panel were non-voting.

Finally...consider the source of the article. An in-patient rehab center specializing in dual diagnoses. Again, not be be crass, but how many patients will they lose when probuphine assures compliance with treatment. Narcotics Anonymous is entirely not-for-profit and has better success rates than rehab...so someone can take probuphine and go to NA meetings for free and have a better chance at recovery than they would with old school rehab. That fact isn't lost on rehab centers...their employees have bills to pay, kids to send to school etc. and fear can make people do some desperate things (perhaps like publish articles based on their wishful thinking that probuphine won't be approved).

Somehow the author seems to suggest that all the congressional attention to opioids negatively effects probuphine's chances. Fair enough, its a free country and she has her opinion.

http://www.sovhealth.com/addiction-treatment/probuphine-political-showdown-leaves-opioid-implant-hanging-balance/

The HHS could accomplish all of this without the need for Congressional approval by including it in the regulations they are "rushing" to complete. The Senators understand this, and I think this is the Senate's way of saying to the HHS "get going or we will act before you do."

Equally as important as the increase in the prescription cap from 30 to 500 patients is allowing nurse practioners and physician assistants to write the prescriptions. It should really increase the access to bupe, assuming insurance companies go along with it.

NJ-based Braeburn Pharma to hire 52 in Durham County


I don't know if this has anything to do with probuphine: currently, a contract manufacturer makes the rods. It makes sense for Braeburn to take that work in-house and avoid paying the mark-up charged by a third party manufacturer.

http://www.newsobserver.com/news/business/article66393512.html

Sunil's Milestone Comment

For those who didn't listen, this is from the transcript:

In terms of what Titan will receive, as we've indicated in the past upon approval of this product Titan will receive $15 million milestone payment. We will receive royalties that start in the mid-teens and go up to the low 20 percentages on net sales of all products sold in the U.S. and Canada, and this is specific to this partnership with Braeburn. In addition to that, we stand to receive up to $165 million in sale space milestones and this start at relatively modest annual sales numbers. So they're very achievable, and certainly if, we've said in the past that the potential sales projections by analysts where they show peak sales around $250 million to $300 million and even higher. At those levels we would have received almost two-thirds of the sale space milestone.

Point taken. Thanks for that: needed a dose of reality. No sense in putting the cart before the horse. You would think after 2013 and the Ad Comm this year my optimism would have been tempered, but...

OK, I'm convinced I'm right which makes me certain somehow I'm wrong. But if (1) you assume 1 prescription per physician a week hypothesis, (2) allow for 3 months of sales in 2016 and a full year of sales in 2017, (3) assume a 17.5% royalty and (4) assume milestone achievement cliffs of $25 million in annual sales and a $10 million milestone payment for each cliff achieved, then...you've assumed a lot, I guess, but...

For 2016, Titan should have a royalty income of $4.7 million, a regulatory approval milestone of $15 million and a sales milestone of $10 million, for total revenue of $29.7 million against cash expenses of $9 million for $20.7 million in profit, or about a buck a share.

For 2017, Titan should have royalty income of $42 million, sales milestones of $60 million and a regulatory milestone for filing the NDA for chronic pain at the end of the year ($10 Million?)...for revenue of $112.4 million

This can't be right, or can it?

Sunil also described the milestones as "very achievable."

Why do I feel like I'm in the movie "The Big Short." What aren't I seeing here?

Yes, he got a little "off-script" which was refreshing indeed.

Just speculating, but he seemed to say the sales milestones were based on annual sales levels achieved, rather that product lifetime sales. He said at $250 million in annual sales, "almost two-thirds" of the milestones would be triggered. Two-thirds of $250 million is $108.9 million, so to me that means at $250 million, Titan would have received $100 million in milestones.

Break that $250 million down into ten $25 million increments and ten $10 million sales milestones (which seems a logical assumption), and that means, the first year probuphine has $25 million in sales, TTNP receives $10 million, the first year probuphine has $50 million in sales, TTNP receives $10 million, and so on.

$25 million in sales for 2016 is within Zachs ultra-conservative estimates, and so we could see another $10 million in milestones in 2016 alone (or $20 million if they hit $50 million).

2017 should also mean another 3 or 4 milestones hit...$30 to $40 in milestones.

Conference Call

Any thoughts? I only could tune in for the last question where Sunil was characterizing the milestone payments as "achievable" and that, if Titan reached $250 million in annual sales, two-thirds of the milestone payments would be achieved. That is lower than I thought, and a positive in my book.