Nothing seems to bode very well for Titan. In the absence of probuphine sales exceeding expectations, I don't see how we crawl out of this hole. And I haven't seen anything to suggest probuphine is selling well.

Yes, Pro Neura has potential, but management has utterly failed to move development programs forward, missing deadline after deadline, bungling filings and failing to attract any investor interest.

If things don't change, the writing is on the wall for a buyout in my opinion. At $2 a share, they will have to sell at $1.50 a share in a PIPE to fund 2018. About 7 million shares to fund one year, or about 30% dilution. That would require shareholder consent under Nasdaq rules.

Even if approved, the price will then readjust somewhere below $1.50.

These price drops and levels of dilution are beyond Bhonsle and Rubin's ability to match with issuing themselves new options. They could grant themselves the entire option pool (no doubt they've tried), and still be losing ground financially on a personal level. And it's pretty clear personal is all they care about.

I believe, in the absence of intervening events, they will sell out before year end, probably in the 6-7 range. Someone will get this company for a song.

I know a lot of this is hocus pocus stop losses getting triggered, but its hard not to fault the lack of execution on Parkinsons and Thyroid Disorder.

But we get a mention in Forbes in July, and Beebe does a little promo.


http://fortune.com/2017/06/28/implantables-pills-big-pharma/

Yikes...

I guess the Fortune magazine piece did nothing.

http://fortune.com/video/2017/06/28/titan-pharmaceuticals-proneura/

Stat News Predicts 500k deaths in next 10 years

America yawns.

https://www.statnews.com/2017/06/27/opioid-deaths-forecast/

Just a dream at this point, but if Senators Portman, Capito and Collins (Republican moderates) stick to their guns and vote no unless the senate bill includes $45 billion for opioid abuse, the Senate bill will not pass.

$45 billion over ten years is not much in the big, big picture, and there's a chance the Republicans will go for it to get the bill passed (plus its a PR victory for the Republicans...showing they did way more than the previous administration).

Geez, why not just buy probuphine from Braeburn for $1 billion and provide it at cost and save billions over the next ten years? Titan would get a 20% royalty on the sales price...I'd take it.

Couldn't agree more.

Indivior's results aren't as good as Titan's were in 2013. So why it isn't an automatic CRL?

Big Pharma runs the FDA.

Senate Healthcare bill.

The starting position is an additional $2 billion for opioid abuse funding in 2018 (in addition to the $1 billion approved in this year's budget). To get it passed, they will probably have to agree to Portman's demand of $45 billion over ten years.


http://thehill.com/policy/healthcare/338978-whats-in-the-senate-healthcare-bill

I have to admit, I've wondered whether Indivior's substantial lobbying efforts have worked to dismiss probuphine until...voila..they have an injectable, at which time they will push long acting formulations.

Wow, thanks for the post. Wasn't aware of the details of their trial design.

Rochester NY TV spot...



http://www.rochesterfirst.com/news/local-news/strong-recovery-provides-families-free-training-narcan-kits/747307633

Price Drop?

TTNP getting booted off the Russell 3000, announced 6/10. Possible cause of selling?

https://www.ftserussell.com/research-insights/russell-reconstitution

The first opioid abuse commission meeting was held last week. Funny how they can't bring themselves to use the word "addiction," which sounds like a disease, and use "abuse" instead, which sounds like, well, it's all the patient's fault and why should we pay...

Anyway...all the speakers were strongly for spending tax dollars for evidenced based care (MAT), and against public awareness campaigns, rehab centers, counselors and their ilk. It was positive in my opinion.

The problem being their is an entire industry built on revolving door treatment, and they have plenty of lobbyists.

http://www.medscape.com/viewarticle/881778

Agree totally about the larger company point. Titan fell for the promise of a $50 million milestone upon FDA approval from an unknown, unproven development stage start-up that was willing to pay it because they had nothing else to sell. Big Pharma would have licensed as well, but for less money upfront. As it turns out, Titan lost the big upfront payoff due to renegotiation of the license agreement after the CRL.

“To-Do” List for Mr. Derkacz

Braeburn’s new CEO has a chance to hit the reset button on probuphine. There a some things he can do immediately to change things for the positive. These items would be at the top of my list.

1. Lower the cost of probuphine.

Price is always one of the objections raised to probuphine, and one of the main reasons for the resistance being met by insurers and state medicare and Medicaid formularies.

Per Braeburn’s S-1, four implants cost around $600 to manufacture. And yes, Braeburn has to pay Titan a royalty, pay a specialty pharma its cut and pay for its own expenses, but….$4,950 selling price for something it costs $600 to make? 725% gross profit?

Braeburn’s initial decision on pricing was based on Sheldon’s view that probuphine should be priced competitively with Vivitrol (which cost about $1,000 a month). The thing is, Vivitrol may be long-acting, but it has no buprenorphine in it…it’s for people who have completely de-toxed from opioids. Suboxone is probuphine’s competition, not Vivitrol, and it should be priced accordingly.

The cost of suboxone film is around $480 a month, $2,880 for six months. Braeburn should be charging somewhere in the mid-3000’s for the implants.

2. No More Smiley Faces

Braeburn has used a marketing strategy based on faith in the goodness of human nature and a belief that the merit of a good product will eventually be recognized. Braeburn’s competitors use back-room deals and slandering the competition. I mean, look at these guys. Indivior has been sued by 35 state attorney generals for monopoly practices. Alkermes actively lobbies conservative lawmakers with the “don’t fight drugs with another drug” lie. Meanwhile, thousands more die.

Braeburn doesn’t have to become scum of the earth, but they need to learn to play hardball. No more funding “Advocates for Opioid Recovery” which is essentially a pension plan for Patrick Kennedy and Newt Gingrich, who have done zilch for probuphine. No more funding “Female Opioid Research and Clinical Experts” who are just another voice getting lost in all the confusion.

Hire lobbyists. Contribute to political campaigns. Play the game.

Look at Vivitrol and medicare. $12,000 a year and it is a “covered-preferred” method of treatment in most states. Probuphine is not a preferred method in any state, and some states don’t even cover it. That doesn’t have anything to do with the merits of the drugs. Hardball.

3. Focus on Institutions

They have started this already, but training should not be provided to solo practioners, small practices or others who are unlikely to ever prescribe probuphine. If that means no coverage to rural areas, then too bad. What is the point in having doctors trained in rural areas if they never prescribe?

4. Fire People.

Number one on my list… a tie:

David Byram, VP of Government Affairs and Market Access. One federal government sale in the past 12 months. Market access is a disaster. Case closed.

Craig Brown, VP of Commercializaton and Program Management. His title tells you all you need to know.

I think it will continue for awhile. Not too optimistic about this quarter's numbers.

This is where management's failure to deliver on ropinirole and T3 really hurts. With all eyes on probuphine, it's no wonder that the price lags.
Beebe and Co. still haven't corrected the IND that was supposedly in final form in January, and they got notice of the deficiency in February.

At least the first of the summer training sessions start tomorrow. I love the statement "Due to the skills required for the procedure, the healthcare provider must intend to implant in the immediate future on appropriate patients. Minimizing the time between training and implantation will avoid decay of the newly learned skill set."

https://docs.google.com/forms/d/e/1FAIpQLScoQnOoNLvJ9H5HYNPKIF4l5eG5b5j76F-ZKbYFyGyBLkCOBQ/viewform

No, I haven't seen anything.

Update to Braeburn site

This guy is another 2017 hire...

https://braeburnpharmaceuticals.com/management-user/jim-dipofi/

Who knows if this is accurate, but it's showing a September start date for the Phase 1/2 for ropinirole.

http://adisinsight.springer.com/trials/700257946

NY Times

Drug overdose deaths most likely exceeded 59,000 in the US in 2016.

https://www.nytimes.com/interactive/2017/06/05/upshot/opioid-epidemic-drug-overdose-deaths-are-rising-faster-than-ever.html?_r=0


I use to see these articles as evidence for the need for probuphine; now, it seems more like evidence that no one really cares.

Imagine any event...war, natural disaster, etc. that took 59,000 lives in a single year. How much would be spent to prevent it from happening?

I'm really not sure.

On the pain question, it's entirely Braeburn's responsibility under the license agreement. I heard from Titan's management back in March that there was no pain trial going on. That was odd, because Braeburn's S-1 stated they had started enrollment for one, but maybe it was dropped.

In my opinion, pain is on the backburner for Braeburn because there is no competitive implant on the horizon. They are going forward with pain for injectables because Indivior is doing so, and they don't want to Indivior to have a competitive advantage.

I think it's probably part of her termination package. FORCE is funded by Braeburn, so they are giving her a public role which will probably be helpful.

She hasn't lost all of her stock options, so she has every incentive to make Braeburn a success.

Titan would get the same as it would receive from Braeburn for a US sale. Much lower price in Canada is likely however.

They finally filed an application for Canada...


http://www.biospace.com/news_story.aspx?StoryID=459798&full=1

Alkermes hiring lobbyists to bash buprenorphine...

http://www.npr.org/sections/health-shots/2017/06/12/523774660/a-drugmaker-tries-to-cash-in-on-the-opioid-epidemic-one-state-law-at-a-time

I do have a negative list as well, but for now the positives outweigh the negatives for me. From my own notes:

Why to Sell

1. Time. Although there is a chance for a rebound, it is equally as likely that this is dead money for the next two quarters at least. Likely I can reenter at a later date at substantially the same price.

2. The Addiction Market Sucks. Notoriously difficult patients who are not always interested in getting better. Insurance companies looking for reasons not to fund treatment. Rehab centers and counselors against any treatment that could threaten their income stream. Regulatory hurdles in distributing a controlled substance. A Secretary of Health and Human Services who favors faith based treatment over MAT. Governmental set-asides go to pay the salaries of bureaucrats rather than to the afflicted.

3. Dilution. If probuphine never takes off, Titan will have to look to the equity markets to fund its operating expenses. In the absence of a buyout or another licensing deal for parkinsons or T3, I would expect 10% dilution in 2018, then another 20% in 2019, and another 30% in 2020.

4. Management isn’t going anywhere. Unlike Braeburn, Titan doesn’t have an Apple Tree to pull the plug on rotten management. Rubin and Bhonsle aren’t going anywhere.

5. Management is lazy. Titan moves at a very, very slow pace. They do not seem to have a sense of urgency. I’ve yet to see them meet a self-imposed deadline. It took nearly a year from their pre-IND meeting with the FDA on Parkinsons until they submitted an IND.

6. Management is incompetent. They really don’t seem to know what they are doing sometimes. Filing the Parkinson’s IND without a principal investigator or final test data, and then rushing to supply that information at the last minute. How was it even filed without that critical data?

I’ve seriously considered selling myself, especially because I don’t expect Titan’s management to do anything but infuriate us for the next 18 months. But at the risk of appearing insane, here’s why I am sticking around:

1. Still Too Early to Declare Probuphine Dead. It’s been a really bad start, but there is still the chance that Braeburn will be able to salvage a profitable operation out of probuphine. Yes, there are a lot of people saying I told you so, and they were right. But, hey, worst case scenario Braeburn decides it’s not worth it, and they have to return the drug to Titan under the license agreement (they have an obligation to use their commercially reasonable best efforts to promote the product). If they do that, Titan get’s a second chance to out-license it (Indivior would be interested, especially for pain).

2. Pro Neura is De-Risked. It’s easy to forget, when focusing on the probuphine failure to launch, that Pro Neura has been derisked to a large extent. 5 Phase 3’s for FDA approval when a controlled substance was being used. Two advisory committees. The FDA has only one group of “implant” reviewers (the pharmacological branch of CDER “borrowed” them for probuphine’s review), so the same team that reviewed the implant for probuphine will review the implant for parkinsons and T3. If there was a way to kill it, they would have done so already. So I don’t see any regulatory difficulties.

3. Shorter Trials. The Pro Neura implant can be used anywhere from 3 to 12 months. Titan is pursuing 3 month implants rather than 6 months for parkinsons and thyroid disorder. That will lead to much shorter trials.

4. 505(b)(2). That pathway didn’t work so well for probuphine because opioids are such a hot button and buprenorphine a controlled substance. It should work much better for parkinsons and thyroid disorder, similar to Braeburn’s schizophrenia implant (all that was required to submit the NDA was one Phase 1/2 with 20 patients , one efficacy Phase 3 with 50 patients and one safety Phase 3 with 50 patients).

5. Settled Chemistry. The drugs (T3 and ropinirole) have already been approved. Their efficacy is not in question. And they are not controlled substances, which eliminates the need for special storage, DEA involvement, a specialty pharma, etc. And you won’t have legions of psychiatrists, counselors, rehab centers etc. trying to fight against approval/adoption.

6. Parks looks pretty good. The U.S. Parkinson’s market is around 800,000 patients being treated. With parkinsons, the critical selling proposition for an implant will not be compliance or diversion (which insurance companies don’t care about), but effectiveness. The problems with current drugs relate directly to titration, peak periods and “down time.” Zacks thinks an implant can get 10% of the market . But they also believed probuphine could get 2-3% of the market, which appears to have been overly optimistic, so if we cut that down to 5%, its about 40,000 patients at 4 implants per year for $1,500 ($6,000 a year). That’s about $240 million a year in revenue.

7. T3 looks even better. T3 is a bigger market. 14 million thyroid sufferers in the US, with about 15% of them (2.1 million) unable to break T4 down to T3 through pills (current therapy involves orally ingesting T4 which converts into T3 which corrects the hormone imbalance). For that 2.1 million, they have to take T3 orally along with T4, but T3 pills have an extremely short life, and require multiple dosing throughout the day. So again, titration and effectiveness are the issue. Zacks thinks an implant could capture 6% of the 2.1 million; if we reduce it to 3% to account for optimism, then that’s about 63,000 patients. With a similar pricing as with parkinsons, about $378 million in revenue per year.

8. And we could win the lottery. If Phase 1-2 testing shows that a Pro Neura T3 implant can be used as a “monotherapy ” (i.e., to provide T3 alone without the need to take T4), then the sky’s the limit. That would mean the addressable market is 14 million patients, and even a modest 1% market share would translate to 140,000 patients for annual revenue of $840 million. A 2% marketshare and we would all be bragging about our investment in TTNP for the rest of our lives.

There is no reason that the implant would not be able to be used as a “monotherapy,” but Titan hasn’t promoted that (probably out of justifiable caution).

You're right that the addiction market is very fragmented and contentious. It's a wonder anyone gets clean with all the competing stakeholders fighting over whether MAT is appropriate, and if so, what the best treatment is, and once that is determined, whether insurance will cover it or not.

Reading my tea leaves, realistically, all signs seem to point toward Titan having to do a capital raise sometime in early '18. I would imagine in the $10 million range. Hopefully, at that point, the PPS will have rebounded to the 5's at least, so it will be around 2 million shares in dilution. They have their "at-the-market" prospectus on file, so with some luck they can use that and not take a substantial haircut but involving private equity.

By 3Q 2018, there should be Phase 1/2 results on ropinirole and T3. Combined, they represent a billion dollar market opportunity in a much less difficult market than addiction, with a proven delivery technology using FDA approved molecular entities. About as low risk as you can get in the FDA game. It's at that point that Titan will sell out in my opinion, probably just north of $500 million.

That's why I'm staying around. I'm certainly interested to see how probuphine does, but I don't expect much in the next 2-3 years.

Possible funding source for T3 Phase 1/2?

https://grants.nih.gov/grants/guide/pa-files/PA-15-176.html

Well, we don't know if he will be any better or not. He doesn't have any prior experience as a CEO (and neither did Sheldon). But at least this provides an opportunity for a fresh set of eyes to look at the problems.

It is refreshing to see a little accountability, but I don't expect it to extend to Titan. The lack of any controlling shareholder makes the board beholden to whoever nominates them...Rubin and Bhonsle. They will never take any action to remove them.

New corporate presentation...

Didn't notice anything "new"

http://c.eqcdn.com/_051994db35edeff5c8677db9cd34fe0c/titanpharm/db/325/1182/pdf/Titan+Corporate+Presentation+-+May+2017.pdf

They believe the injectables have twice the potential market share of implants, so I think that's why they get the "flagship" title. They will be going head to head with Indivior on injectables, however, so we'll see how successful they are. Hopefully a little new energy will be put into probuphine.

Well, we could use a little good news!

http://www.prnewswire.com/news-releases/braeburn-pharmaceuticals-names-michael-m-derkacz-as-president-and-ceo-300468690.html

Sheldon out at Braeburn

I think it makes logical sense, but I'm not so sure there is enough of a market for buprenorphine in ROW for Indivior to be interested. Beebe said EU was about 10% of the US market in the last call.

But as long as we are dreaming...Arbaclofen Placarbil. That's not a typo, its a new chemical entity being developed by Indivior. Indivior in-licensed it for alcohol abuse disorder, and conducted a Phase 2a with results in March 2016. As a result of the Phase 2, the oral tablets were reformulated, and now are undergoing Phase 1 to test bioavailability.

If bioavailability is the issue, then an implant would solve the problem, and would fit right into Titan's (alleged) strategy of partnering with companies that have patented drugs with bioavailability issues.

Until some sales show up, dreams are all we have.

Agree that any long-acting formulation will eventually help probuphine, as some people on monthly injections will migrate to implants (but I don't know how much). Braeburn is betting they can go head to head with Indivior on monthly injectables, but I'm no so sure. The good news is Indivior doesn't have an implant (and no plans to make one), but I do wish Indivior had been TTNP's licensee rather than Braeburn.

Indivior

They filed their NDA for injectables. My guess is Braeburn will follow closely behind.

Don't really see how Braeburn is going to compete head to head with those guys, but we will see.

https://www.firstwordpharma.com/node/1475768?tsid=1

Implant update

Update from post in those happier days earlier this month...