I have no idea what sales will be, but a lot of treatment centers that don't offer MAT are starting to run scared.



https://www.clearbrookinc.com/news/probuphine-license-stay-high/

The latest...

Meanwhile...

https://qz.com/1047785/americas-opioid-mortality-rates-are-24-higher-that-current-estimates-according-to-a-university-of-virginia-study/

Could be a typo, not sure. Certainly wasn't announced.

Another recent academic paper...

http://tandfonline.com/doi/full/10.1080/17512433.2017.1336434?scroll=top&needAccess=true

This study is generally positive, but implies the price has been raised to $5,950 per treatment. Whew...

https://www.ptcommunity.com/journal/article/full/2017/8/505/probuphine-buprenorphine-subdermal-implants-treatment-opioid

Not sure what the odds are, but TTNP's corporate presentations might give you an idea:


May 2017

Initial Phase I pharmacokinetic clinical study expected to start in Q3-2017, following FDA clearance
of the IND

April 2017

• Initial Phase I pharmacokinetic clinical study start delayed to mid-2017

January 2017

-On target to file IND in Jan 2017
• Initial Phase I pharmacokinetic clinical study start: Q2-2017

August 2016

• On target to file IND in Q4 2016, to be followed by initial pharmacokinetic and proof of concept clinical study

June 2015

On target to file IND in Q4 2016, to be followed by initial pharmacokinetic and proof of concept clinical study

May 2016

-On target to file IND with the initial pharmacokinetic and proof of concept clinical study in Q4 2016

March 2016

-On target to file IND in Q4 2016 followed by the initial pharmacokinetic and proof of concept clinical study

January 2016

-Submit briefing material and request a pre-IND meeting with the FDA in Q4, 2015
-Complete non-clinical studies to enable timely submission of IND and commence proof of concept clinical study in H2, 2016

November 2015

-On target to commence initial clinical study in late 2016

Sheldon wasn't qualified for her position, in my opinion. The jury remains out on Derkacz. Di Pofi, their head of sales, has only been in place since April. Think of that...Braeburn had no head of sales until April of this year! I have noticed a lot of new hires/departures on linkedin. Under-performing sales reps. seem to have been let go.

In my opinion, Braeburn's strategy all along has been to have a fully functioning sales force at the time their injectables are launched so they can go head to head with Indivior. They never planned to hit the ground running with probuphine, because probuphine has no competition (no other implants).

There is no way to speculate on what sales will be. If news has leaked, obviously it isn't good.

They only won the "say on pay" 55% to 45%, and that was probably with Robert Mead voting for them.

My guess is they didn't refile the IND until mid-July, and are awaiting a response.

https://www.sec.gov/Archives/edgar/data/910267/000114420417039674/v472140_8k.htm

Every three weeks another 9/11 in terms of the number of deaths...I would think a national emergency declaration is warranted.

The interim report...


The first and most urgent recommendation of this Commission is direct and completely within your control. Declare a national emergency under either the Public Health Service Act or the Stafford Act. With approximately 142 Americans dying every day, America is enduring a death
toll equal to September 11th every three weeks. After September 11th, our President and our nation banded together to use every tool at our disposal to prevent any further American deaths. Your declaration would empower your cabinet to take bold steps and would force Congress to focus on funding and empowering the Executive Branch even further to deal with this loss of life. It would also awaken every American to this simple fact: if this scourge has not found you or your family yet, without bold action by everyone, it soon will. You, Mr. President,
are the only person who can bring this type of intensity to the emergency and we believe you have the will to do so and to do so immediately.



https://www.whitehouse.gov/sites/whitehouse.gov/files/ondcp/commission-interim-report.pdf

White House opioid commission urges Trump to declare federal state of emergency

http://thehill.com/business-a-lobbying/344674-white-house-opioid-commission-urges-trump-to-declare-federal-state-of

Any guesses why Titan posted this on twitter recently?


https://twitter.com/TitanPharma?lang=en

https://www.michaeljfox.org/foundation/news-detail.php?acquisition-may-speed-pd-therapies-to-meet-unmet-needs

It's basically an ad for the competition, and I attribute it to general TTNP stupidity....unless....the Fox foundation is paying for ropinirole implant research? That would be a wow.

The interest rate is pretty harsh, and we have to pay an addition $175 k for the privilege of paying off our loans. But still, agreed, much better than dilution and it takes away the uncertainty in Titan's immediate future.

I checked out the 8-K, and the 750K in royalty revenue and EU deal are conditions to the unfunded $3 million tranche. So if Titan wants that last 3 million, it has to meet those conditions.

I agree these aren't ideal terms, but I do think its about as good as Titan could have gotten. It makes sense to borrow now with some cash in the bank rather than wait until December when, in desperation mode, they would have been forced to accept whatever terms a lender demanded, or take a 30% haircut on whatever the stock price was in order to do an equity infusion that would have been a disaster in terms of dilution.

This will fund Titan through 2018, which means, if they can be trusted to be reasonably competent, through the Parkinsons Phase 1/2 and the T3 Phase 1/2. If those are successful, and they have two new implant applications ready to go into limited 505(b)(2) Phase III trials, my guess is they get bought out.

If they aren't successful, then it doesn't matter anyway unless probuphine sales have done a hockey stick and skyrocketed.

This is good news, and removes a question mark hanging over the stock.

I don't know, but one thing that has my radar up is the lack of insider purchases at these levels. I would expect to see some purchases, even at de minimus levels, by board members, etc. It could be they don't think its a good buy. Or..they could be blocked from trading because of material inside information about a partnership/buyout.

So NuPathe was developing its own ropinirole implant about five years ago. NuPathe got bought out by TEVA, who markets ropinirole, and the project appears to have been dropped.

Although not conducted by Titan, this study shows the benefits of ropinirole implants...

https://www.researchgate.net/publication/269797765_Ropinirole_Implants_Reverse_MPTP-Induced_Parkinsonism_in_Rhesus_Monkeys

Not much out there Turks. I've tried to no avail.

Titan won't respond when asked whether they've resubmitted their IND for Parkinsons.

Braeburn won't respond when asked what happened to the Phase 3 for chronic pain for probuphine they described as enrolling in their S-1.

Actual language of bill...


SEC. 202. SUPPORT FOR STATE RESPONSE TO OPIOID AND SUBSTANCE ABUSE CRISIS.

There is authorized to be appropriated, and is appropriated, to the Secretary of Health and Human Services, out of monies in the Treasury not otherwise obligated—

(1) $4,972,000,000 for each of fiscal years 2018 through 2026, to provide grants to States to
support substance use disorder treatment and recovery support services for individuals who have or may have mental or substance use disorders, including counseling, medication assisted treatment, and other substance abuse treatment and recovery services as such Secretary determines appropriate; and

(2) $50,400,000 for each of fiscal years 2018 through 2022, for research on addiction and pain related to the substance abuse crisis.


https://www.budget.senate.gov/imo/media/doc/BetterCareJuly13.2017.pdf

Not a done deal by any means, but the new proposed healthcare bill just released in the Senate today includes $4.95 billion a year in funding for treatment (counseling and MAT) for the next nine years ($45 billion total).

I think the whole US buprenorphine market is around $2.5 billion, so this would seem to be huge to me, but the market shrugs.

Obama's 21st Century Cares Act passed in November 2016 had $1 billion in opioid epidemic funding over two years, but a lot of that is going to government infrastructure, education etc. None of it goes to the states to actually treat people.

The first version of the Senate bill included $2 billion to the states over 2 years.

This second version is nearly $5 billion a year over nine years, and is aimed at treatment.

http://www.marketwatch.com/story/opioid-abuse-takes-center-stage-from-senate-health-bill-to-yellen-hearing-2017-07-13

And no trials planned for probuphine for chronic pain...

...because no competing implants are in development. They are racing against Indivior, and spending all the R&D money to be able to compete with them.

Why not exploit the market (buprenorphine implant) with no competition?

https://www.biospace.com/News/camurus-and-braeburn-pharma-announce-topline-phase/462724/source=MoreNews

We don't know what the CRADA says. I'm assuming the DOD is paying for some of the expenses of testing, but not for the time spent by Titan working on it. It's likely that Titan paid for all the preclinical testing required to date.

I'm not so sure there is anything to miss. I really don't believe a lot of people are watching TTNP at this point. In my opinion...

How we got here:

1. Too much hype (by Braeburn) on the probuphine launch..."the most successful implant launch in history..." etc. Braeburn's flawed launch...doctors trained but did not prescribe. No sales force until January 2017. Insurance pre-authorization rules making just getting the medicine extremely difficult. The entire rehab/counseling industry speaking out against implants that might adversely affect their revenue stream.

2. The low float allowed shorts to entirely manage the price post-approval. Dumping by Broadfin and Braeburn didn't help.

3. Being included on the index funds was a double edged sword. We didn't get any bump up from buying (funds buy over time to control price movement), but we sure were punished getting kicked off (dumping in June).

4. Management has fumbled, bumbled and stumbled. Delayed Parkinson's trial. No EU deal. Spending precious resources on pre-clinical work for the DOD on a malaria implant that does not seem likely to be commercially viable unless the US goes to war in a jungle environment.

5. I couldn't recommend TTNP to a friend right now, because I'm not sure how they are going to fund next year. It seems dilution is likely, and so why not wait to see how much dilution there is before buying in.

How could management get out of this mess (without just selling the company):

1. Outlicense parkinsons now to GlaxoSmithKline. For GSK, it would essentially allow them to control implant sales for the product they once had the patent on. And it would be cheap for them: although technically pre-IND, this drug is 3 trials away from approval. Get some upfront license cash to take care of 2018. It would also lend some more credibility to the Pro Neura technology.

2. Sign the damn EU license deal. There may or may not be upfront cash, but add some certainty that ex-US development is actually happening.

3. Focus on hypo-thyroidism. That market dwarfs addiction treatment or parkinsons. This is the Pro Neura application that Titan wants to own as an approved drug without a partnership.

4. Stop spending time and money on non-essential development programs. Malaria, autism, etc. are great for the Gates Foundation, but this is a for profit enterprise (despite what management might believe).

5. Communicate honestly and transparently with stockholders. Take all questions on conference calls...it really irks me that this company is owned 80% by street holders, but they will only speak with analysts on conference calls. Fair enough if 80% were owned by institutions, but the stock price lives or dies by the individual investor right now, so stop treating them with contempt.

I was happy to read probuphine is covered by medicare in Indiana!

First I've heard of in Indiana...

http://www.heraldbulletin.com/news/local_news/implanting-treatment/article_f394ba55-6a35-5933-840c-4146e0326b4f.html

I agree it's good news, no matter the market's reaction. Basically, it sounds like the gov't will pay for the next round of testing (non-human primates?) and maybe more than that.

The VA made its first major contract award to Braeburn...$225,000.

https://govtribe.com/project/65-accord-healthcare-inc-65ib-v797d-70137-effective-06012017-05312022/activity

Well, this one came out of nowhere...but I'll take it.

Implantable Drugs Changing Addiction Treatment


http://www.healthline.com/health-news/implantable-drugs-changing-addiction-treatment#1

You have a great 4th too Turks. Check this new article out...reads pretty positive and shows that probuphine is actually helping folks.


http://www.healthline.com/health-news/implantable-drugs-changing-addiction-treatment#1

I agree with you on probuphine's merits, and I'm even more positive about Pro Neura (hypo-thyroidism is a huge opportunity). It's just going to take a long time, and the dilution that will be necessary to fund Titan's operations will be painful.

Hey Turks,

It would be great to see an upturn in 3Q sales, but I'm not so sure. Everything appears to be pointing towards increased demand for probuphine in terms of the worsening opioid epidemic, Congress finally acknowledging the problem and Braeburn's shift in training strategy, but there is not any evidence over the last 12 months that any of that will actually translate to sales.

It seems to me that Braeburn and the insurance companies are playing one huge game of "chicken." Braeburn has priced the implant at $5,000 a treatment, and insurance companies all seem to require prior authorization and do not include probuphine has a preferred treatment (many medicaid plans do not even include it in their formulary). It's infuriating, because by pricing probuphine so high, Braeburn is not allowing it to become a "go to" treatment method. When their injectable is approved, they will match (or go lower) than any price Indivior charges for its injectable. So you will have injectables prices at roughly the same as sublingual therapy, but probuphine will be this unaffordable therapy that only extremely affluent addicts (not a huge population) can afford. Personally, I couldn't justify spending $3,000 a treatment ($6,000 a year) more on having an implant when you could get an injectable at roughly the same price as pills.

I don't think there will be any cash with the EU deal. US sales haven't shown commercial success, so why would anybody pay up front for something that doesn't sell.

If they don't get bought out for pennies on the dollar, Titan's best hope, in my opinion, would be to outlicense Parkinsons now or after Phase 1/2 results are available. That would allow for some upfront cash, and free them up to develop T3 (a bigger market than Parkinsons and Probuphine combined) and own it outright.

http://www.live5news.com/story/35778971/musc-offering-implant-to-treat-opioid-dependence

Pretty significant if it passes, in that Congress only approved $1 billion to be paid out over two years through the Cures Act in December 2016.

This would be $4.5 billion a year for ten years.

$45 billion added to health care bill for opioid treatment

Normally I would think this would help Titan's price, but no....

http://www.cbsnews.com/news/health-care-bill-45-billion-more-in-opioid-money/

Braeburn's new CEO came from TEVA, so maybe you are on to something.

And national healthcare which will negotiate a reasonable price for probuphine (unlike Braeburn's "Rolls Royce" US price), and make it available to anyone who wants it.

Just don't understand Braeburn's pricing strategy...it has cost us huge. I remember in 2013/14 all the analysts (Napadano, Highline) estimated $2,000 to $2,500 per treatment. And Braeburn comes in at $4,950.

Agreed...the IP is the company at this point. Rubin, Bhonsle and Beebe would get one year consulting agreements etc.

The right company could do well with Pro Neura. Titan just can't execute.

My guess is their plan now is to get the Parkinson's Phase 1/2 completed, and, if results are good, raise capital from a stronger position. Problem is, I have no confidence they will be able to get the trial done within a year.

Probuphine has been authorized for sale in Canada...

...authorized for import and sale prior to formal approval due to "urgent public health need."

https://www.canada.ca/en/health-canada/news/2017/06/government_of_canadaenablesnewaccesstodrugsinurgentpublichealths.html

https://www.canada.ca/en/health-canada/services/drugs-health-products/access-drugs-exceptional-circumstances/list-drugs-urgent-public-health-need.html