Caremark Federal Employee Program (FEP) for Health Insurance

Probuphine now covered.

https://www.caremark.com/portal/asset/PACover.pdf

At Fabled Addiction Treatment Center, a New Approach

http://www.pewtrusts.org/en/research-and-analysis/blogs/stateline/2016/08/08/at-fabled-addiction-treatment-center-a-new-approach

On further investigation, I'm not really understanding the doctors beef with Braeburn.

Payment terms are net 90 days.

http://braeburnaccessprogram.com/wp-content/uploads/2016/06/Braeburn-Physician-Order-Form-6-1-16-PR0011-002-v2.pdf

Unopened kits can be returned in the first 30 days.

http://braeburnaccessprogram.com/wp-content/uploads/2016/07/Braeburn-Return-Goods-Policy.pdf

So, if a doctor orders a kit for a "no-show," all he has to do is send it back and he will never be charged. I guess that's a hassle, but its far from getting stuck with a $5,000 bill, which is what the posts suggested.

More than that, Braeburn will, on the doctor's behalf, confirm that the patient has been pre-approved for treatment...eliminating all risk for the doctor.

"Braeburn Access Program will offer extended credit terms up to 90 days and reimbursement support services to assist with patient benefit verification and prior authorization approval prior to order shipment."

http://braeburnaccessprogram.com/wp-content/uploads/2016/06/Braeburn-Access-Program-FAQ-_PR0036-001_Final27MAY16.pdf

...that being said, it looks as though insurance companies are beginning to adopt probuphine and issue guidance as to its approved usage.

https://www.anthem.com/ca/medicalpolicies/policies/mp_pw_c191090.htm

On the subject of Braeburn...

I came across some posts by (purported) doctors claiming they wouldn't prescribe probuphine because Braeburn requires the doctor to pay for the drug, and then seek reimbursement from the insurance company. The doctors pointed out, if there is a "no show", then they would have to eat the $4,950.

Not sure if that is true or not, but if it is, it is definitely concerning.

Well said. I was trained, and am now certified. But I do not envision doing any implants. Let's say that health insurers reimburse $150 for the procedure. I would have to do 33 procedures to indemnify myself against one no-show. That is a terrible deal. To be fair, the product could be applied to the next patient and there is a return process. Even so, who in the right mind would purchase a product for $5,000 in order to make $150? That doesn't even address the question of what insurance in their right mind would spend $5,000 every six months when they only need to spend 1/10 that amount?

http://www.suboxforum.com/question-about-new-suboxone-implants-t12691.html

Not Braeburn, in my opinion. I don't think they intend to grow by acquisition (cheaper to just license new products). More likely a BP that wants to jump in on the "pill-free" drug bandwagon. And not until the development pipeline has clinical trials for parkinsons and t3.

I'm not qualified to answer the question. It would seem to me that, with the clamping down on opioid prescriptions, many functioning addicts with legitimate prescriptions may face the alternative of recovery or making illegal purchases. But we've yet to see whether the clamping down is all a lot of noise or whether it makes a difference.

Nurses step in to boost treatment for opioid addiction

http://newsok.com/article/feed/1067054

My instincts tell me you're right, but the market doesn't agree with us right now. I do believe that, of those investors who are aware of probuphine, a significant percentage are not purchasing because it is an implant, and historically, implants have not done all that well.

There are plenty of distinguishing characteristics to refute that argument:

-The typical knock on implants is basically: "why would someone undergo surgery when they can just take a pill." The argument assumes no issue with compliance. I believe the reason over 2,300 doctors were trained so quickly is because of the overwhelming frustration in the medical community of prescribing buprenorphine, only to have the patients stop taking the medication to get high. That's not a judgment, it's just a fact. Addiction is different.

Certainly a significant (and somewhat vocal) portion of the patients in the potential addressable market are vehemently opposed to ever having an implant. For personal reasons, they simply believe it is too instrusive, and object to having the element of choice taken out of their recovery. That is fair enough. No one is claiming we will have 100% market share. Zacks has only predicted a 2-3% market share. Even with that conservative, small percentage, and assuming a stable (not growing) addressable market of around a half a million patients stabilized on 8mg or less of buprenorphine, that's 10 to 15 thousand patients at two treatments a year (30,000 x $4,950 =$150 million). That should mean about $25 to $30 million in royalty income to Titan, with net earnings of about a buck a share.

Personally, I believe that as the opioid epidemic is eventually addressed (albeit much too late), addicts will be moved from "frontline" treatment of 16mg to lower dosages, and the class of patients stabilized at 8mg or less will at least double and potentially triple. The effect of this increase, along with a supplemental NDA for chronic pain, I believe will make probuphine a billion dollar a year drug by 2020, even if only 5% market share of opioid abusers stabilized at 8mg is obtained.

But I could be wrong. For the time being, it will be really interesting to see how many of the 2,300 trained actually make a prescription in the 3Q. Zacks is predicting about 400 prescriptions, and although I'm not expert in the intricacies of insurance coverage or drug roll-outs, I have to think most of those trained will be incentivized to actually try probuphine out as soon as they can.

Yep. And who are they selling to? ETF's hold 2.3% of Titan's shares for the first time I can remember. We've come a long way from the OTCBB days.

https://www.etfchannel.com/symbol/ttnp/

These holdings are in addition to the 2,616,454 shares reported as being held by instutions by Nasdaq as of 6/30.

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

I didn't like the timing of yesterday's filing. Whether accurate or not, it seemed a little rushed. Like they were planning to sell ahead of sales numbers being announced.

On a logical basis, it makes sense. They are just trying to ensure their ability to raise capital in the most efficient manner possible. Yesterday's filing was just a prospectus supplement to a prospectus that had already been filed two years ago. Titan always has had the ability to sell its stock. In the past, its been through PIPE deals on less than advantageous terms: a discount to market price, with warrant coverage. This prospectus allows them to raise capital incrementally with less dilution and less of an effect of the stock price.

My first impression was the same as yours. But the prospectus is good until December 2018...so they may well wait awhile...

Yes...if Braeburn executes on its 3Q goal like it executed on doctor training, I think we will all be pretty happy come November. From the Prospectus:

"Braeburn commenced commercialization activities in support of Probuphine product launch immediately following FDA approval starting with implementation at the end of May 2016 of the Risk Evaluation and Mitigation Strategies directed training program for qualified health care providers. As of the beginning of August, 2,342 health care providers from all 50 states and Puerto Rico have been certified to provide Probuphine to their patients and Braeburn’s stated goal is to have 4,000 certified health care providers by the end of 2016. Probuphine was on the shelves of the distribution center by the middle of June 2016 and the first patients were treated before the end of that month. Braeburn has also indicated that efforts to obtain third party payor coverage are progressing rapidly with meetings already held with several insurance companies, and applications for Medicare and Medicaid coverage already submitted. Braeburn expects to focus on a steady conversion of patients to treatment with Probuphine during the third quarter."

Cantor Fitzgerald

If they are underwriting the offering, I would hope we should see an analyst report coming out from Cantor soon. Roth and Zacks are small potatoes, and Cantor Fitzgerald is a good mid sized firm.

http://www.cantor.com/sales_and_trading/equity_capital_markets/research

I think they see some catalyst coming up (3Q and 4Q sales numbers, Parkinson's Phase I/II) and want to be able to sell some shares into an upswing to provide a comfort zone of cash. And yes, gives them a credible threat in negotiations of pursuing regulatory approval in the EU without a partner, and thereby getting better license terms later.

Offering Terms...


On September 1, 2016, Titan Pharmaceuticals, Inc. (the Company) entered into a Controlled Equity Offering

SM

Sales Agreement (the Sales Agreement) with Cantor Fitzgerald & Co., as agent (Cantor), pursuant to which the Company may offer and sell, from time to time through Cantor, shares of the Companys common stock, par value $0.001 per share, having an aggregate offering price of up to $20.0 million (the Shares).

Under the Sales Agreement, Cantor may sell Shares in sales deemed to be an at the market offering as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended (the Securities Act), including sales made directly on or through The NASDAQ Capital Market or any other existing trading market for the Companys common stock, in nego tiated transactions at market prices prevailing at the time of sale or at prices related to such prevailing market prices, and/or any other method permitted by law. The Company may instruct Cantor not to sell Shares if the sales cannot be effected at or above the price designated by the Company from time to time.

The Company is not obligated to make any sales of the Shares under the Sales Agreement. The offering of Shares pursuant to the Sales Agreement will terminate upon the termination of the Sales Agreement by Cantor or the Company, as permitted therein, but in no event later than the earlier to occur of (i) the completion of the sale of all of the Shares through Cantor or (ii) December 17, 2018.

The Company will pay Cantor a commission rate of up to 3.0% of the aggregate gross proceeds from each sale of Shares and has agreed to provide Cantor with customary indemnification and contribution rights. The Company will also reimburse Cantor for certain specified expenses in connection with entering into the Sales Agreement.

The foregoing description of the Sales Agreement is not complete and is qualified in its entirety by reference to the full text of such agreement, a copy of which is filed herewith as Exhibit 10.33 to this Current Report on Form 8-K and is incorporated herein by reference. The opinion of Loeb & Loeb LLP, the Companys counsel, regarding the legality of the Shares that will be issued pursuant to the Sales Agreement is also filed herewith as Exhibit 5.1.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy the common stock discussed herein, nor shall there be any offer, solicitation, or sale of common stock in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

Item 9.01. Financial Statements and Exhibits.

At the Market Offering

So, Titan wants to sell up to $20 million "at the market price." Basically, they may sell a little stock from time to time on the open market at market prices.

So...now it's not just the MM we have to deal with. It's TTNP also selling into any increase in share price.

Better than a PIPE deal which involves a haircut to the trading price, but basically we have a $20 million overhang to get over from Titan itself before anything good happens.

Pisses me off, because I think with $19 million they have enough in cash.

https://www.sec.gov/Archives/edgar/data/910267/000114420416122519/v448006_424b5.htm

http://probuphinerems.com/probuphine-locator/

Braeburn has apparently taken a hiatus from training health care providers, and so the news well has dried up.

I am dying for some sales numbers, or just an indication of how commercialization is going, but I guess we have to wait until November for 3Q results.

I agree, but I'm tempering my expectations for the short-term. Reflecting back on the last 90 days since approval and trying to understand why the stock price has reacted as it did:

-Braeburn bailed out. Understandable, because Behshad Sheldon and her team will be rewarded based on the success of probuphine (and other drug candidates), not on the increase in value in Titan's stock. That's just they way it is, and I think they did Titan a favor by holding as long as they did. I'm quite sure proceeds of the sale are being used on the probuphine launch, which is fine with me.

-BroadFinn bailed out, but got a solid double. They also exercised 2 million of their warrants, using the "equity" in the warrants as the exercise price (i.e., "cashless exercise), so they were only issued a million shares (which I'm sure they promptly sold). Still, Titan saved its stockholders about 5% in dilution...a fact I think they should have emphasized on the conference call.

-The momentum traders came and went.

-It's the continued shorting which has baffled me given the low float, solid financial position and relatively small trading volume. I agree the answer must be a market maker began issuing options when TTNP was uplisted to Nasdaq (probably based on a formula having nothing to do with probuphine or Titan), and got caught by surprise with approval.

Since that time, they have continued shorting, buying, shorting, buying ad nauseum to keep prices from rising to the level where options could be exercised profitably.

Anyone know how long this can go on? Once 3Q sales are announced, there should be more buy interest, but the MM can continue to short as long as shares are available. The same with announcement of a ROW partner and the initiation of the Phase 1/2 for ropinrole.

What kind of sales volume is necessary to force the MM to finally cover?

I think all of it is the MM...hard to force them to cover when they have an unlimited number of shares to short.

Starting to wonder if the 1.9 million short positions are held by a single entity that is trying to figure out how to cover without taking a total bath on this one. That would explain the continued shorting...buying time hoping for a miracle (or disaster, depending on your point of view).

Well, this is certainly interesting. Not fun, but interesting.

On the positive side, last week's resistance is this week's support, so that's progress.

Yep...short interest is up about 40,000 shares as of 8-15.

A day of reckoning is coming for those guys.

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

Opioid Dependent Mothers

Putting the pieces together, I think I can see a new patient class I was unaware of:

AN OPIATE DEPENDENT BABY IS BORN EVERY HOUR IN THE US

https://www.opiates.com/blog/opiate-dependent-baby/

Buprenorphine Treatment of Opioid-Dependent Pregnant Women: A Comprehensive Review

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4506646/

Results indicate that maternal treatment with buprenorphine has comparable efficacy to methadone, although difficulties may exist with current buprenorphine induction methods. The available fetal data suggest buprenorphine results in less physiologic suppression of fetal heart rate and movements than methadone. Regarding neonatal effects, perhaps the single definitive conclusion is that prenatal buprenorphine treatment results in a clinically significant less severe neonatal abstinence syndrome (NAS) than treatment with methadone.

I think probuphine would completely solve the "difficulties" in "current buprenorphine induction methods."

So, after a little reflection, it doesn't make sense to say "the company believes they will have a partner in place by early next year" unless:

1. There is a single, worldwide partner; and
2. Some event needs to occur by early next year before the partner will agree to license terms.

On #2, I think its the result of the EMA meeting. The EMA is disregarding its own procedure in allowing a uniform, all-EU application for probuphine, which is totally unanticipated and, in my opinion, huge. By 2018, probuphine could be sold in all EU member countries, including the large users of buprenorphine (France, UK, Germany). I assume after the 4Q meeting with the EMA, Titan expects to get confirmation of its approval pathway early next year, at which point in time they will license EU and Australia rights to the partner (and be able to command a very healthy upfront license payment).

"Based on the current pace, the company believes they will have a partner in place by early next year."

This will involve an nice upfront license payment as well...not sure how much, but probably at least $10 million.

EMA EU wide approval is huge...makes it much more attractive for a partner.

New Law Opens The Way For Drug Implants To Treat The Opioid Addiction Crisis

https://www.fastcoexist.com/3062298/new-law-opens-the-way-for-drug-implants-to-treat-the-opioid-addiction-crisis

Norwalk man first in New England to receive opioid treatment implant

The photo subheader makes it seem like this patient got the implant on August 18, but from the text of the article it appears he received it in June.

Really seems like he is taking it for chronic pain rather than dependence.


http://www.thehour.com/news/article/Norwalk-man-first-in-New-England-to-receive-9178181.php#photo-10814165

Pediatric group says doctors should treat teen opioid addicts with medicine

Small mention of probuphine at the end of the USA Today article. It seems to me probuphine would be ideal for teens who would be more likely to have compliance and diversion issues.

http://www.usatoday.com/story/news/health/2016/08/22/pediatric-group-says-doctors-should-treat-teen-opioid-addicts-medicine/89042316/

I believe that is what Yale University is studying, starting two groups of patients at 2mg then increasing to either 8mg or 16mg, and then monitoring the outcomes.

https://clinicaltrials.gov/ct2/show/NCT02187198?term=buprenorphine&rank=14

Turks, I hope you're right, but in my best case in the universe scenario I don't see anything above 10% penetration. That's still a lot of money...north of $500 million in sales, with royalties probably round $100 million per year and all $165 million in milestones paid. I'd say a one in four chance of that happening. I'd say 95% chance of hitting half of that (5%), which is really pretty darn good (especially if parkinsons is in Phase III two years from now).

What's really mind boggling is that Indivior surged from $301 to $361 upon announcement of the news. It's settled at $323 for a market cap of $2.33 billion.

So, at $323, the increase to Indivior market cap at current levels from announcement of phase III trial results is over $150 million (about 50% more than TTNP's total market cap).

And that makes sense how?

Turks, Probuphine has its advantages for sure, but some people are just not going to like the idea of an implant. Even if a depot injection is really giving them an implant formed in situ, they are just going to balk at surgery. It's all good...2-3% market penetration and we've done really, really well, and 10% a home run.

Having some experience with addiction, the main thing for me is with a 30 day depot you're giving the addict six chances to discontinue treatment over the course of six months...as opposed to no such chances with a 6 month implant.

Thanks for posting Truth. I really never understood how some of these depot injections worked, but apparently: "After subcutaneous (SC) injection, NMP diffuses out of the polymer matrix and the polymer precipitates, trapping the drug inside and forming an amorphous solid depot in situ. The depot releases buprenorphine over a one-month period by diffusion as the polymer biodegrades. "

So its injected as a liquid, and transforms into a hardened, amorphous polymer once under the skin, and then gradually degrades, as opposed to Titan's flexible polymer rod that is inserted and then removed.

Just wondering, but what happens if Indivior's solid polymer breaks (a fall or other accident)? Maybe that is what the 2.8% "serious treatment emergent events" alludes to?

I don't think they have a traditional sales force, but not sure. Really, with the doctors investing a whole day in training, the doctors themselves are the sales force in a way. Orders are not made to a sales rep, but directly to the specialty pharmacy. The best way to track sales would be to track shipments from Avella...the specialty pharmacy in charge of supplying rods to doctors.

This one really interesting...Bupe in connection with "group" rather than "individual" care...no wonder counselors don't like probuphine.

https://clinicaltrials.gov/ct2/show/NCT02526212?term=probuphine&rank=12


Seems like a lot of studies being initiated recently on buprenorphine. Hopefully a good sign.

Yale is studying buprenorphine dosage...

https://clinicaltrials.gov/ct2/show/NCT02187198?term=probuphine&rank=14

And Reckitt Benhiser studying in connection with Washington University for depression again:


https://clinicaltrials.gov/ct2/show/NCT02181231?term=probuphine&rank=11

Off Label or New Indication Potential?

https://clinicaltrials.gov/ct2/show/NCT02176291?term=probuphine&rank=9

More Tea Leaves to interpret...

From a bio on Behshad Sheldon posted yesterday:


Probuphine is the first implantable form of buprenorphine, which was previously available only as a pill or as a film placed under the tongue or inside the cheek. Probuphine provides a new treatment option for people in recovery compared to other forms of buprenorphine, such as the possibility of improved patient convenience from not needing to take medication on a daily basis.

The road to the drug’s marketing approval in May was not smooth. After the first FDA advisory committee meeting, the company received a complete response letter.

“And so I had to switch and become clinical and regulatory,” Sheldon says. “I was personally involved with negotiating with the FDA on the design of the new study, the double-blind, double-dummy, path forward and getting it done. For most of the time conducting that study, there were four of us here working on the study. And then we had an office manager and a finance manager. So there were six people in the company for most of the time after the CRL, that led to the completion of the study and then as we got new data that showed positive results, we started to get more people on board and prepare to change what truly was not a very hopeful state of affairs in opioid use and opioid addiction.”

After Probuphine was approved, Braeburn has been “going at a fast and furious pace,” Sheldon says, with the drug being shipped within three weeks of approval.

“And we’ve been working with reimbursement with payers, so far we’ve had really great reception,” Sheldon notes. “There are medical benefits so we have to write coverage policies and that doesn’t happen overnight. But we haven’t had any denial yet, and from pretty big national payers, we’ve talked with over 20 now, have said that they are going to cover it. And even some small regional ones who usually tend to be more persnickety have said they are going to cover it.”

http://www.pharmalive.com/special-feature-pharma-leaders-of-innovation/

I don't think we can count on ROW anytime soon. Titan is meeting with the EMA, which means they are pursuing approval in Europe, probably in an effort to maximize their negotiating position in a license deal. Still, very time consuming.

It really just depends on the rate of adoption. I've searched for any hints online, but found practically nothing. If each one of the 2,342 trained prescribed just one implant in the 3Q, I think we would skyrocket.