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>You can have your own watch list and get email alerts.<
That's exactly what I'm looking for. Thanks!
Is anyone aware of a service that provides free alerts for insider trading? I know Form 4 Oracle provides this service, but the $19/month fee isn't worth it to me.
Interesting article from The Street
http://www.thestreet.com/pf/newsanalysis/biotech/10332153.html
Any implications stemming from the bolded text below? I just don't know.
The crowds have finally thinned in the halls of the Westin St. Francis in San Francisco, the home of JPMorgan's annual health care conference.
There is a sense of urgency at the gathering, where seemingly every health care investor and executive spends at least part of the week. Everyone is looking for an edge, and the CEOs of both publicly traded and private companies are all too eager to explain why their organization deserves investors' attention and dollars.
The big-cap names mostly presented Monday and Tuesday. I discussed my observations of that part of the show earlier in the week.
The last two days concentrated on the smaller names, and here are some of the highlights of what was said -- and what wasn't.
Mum's the Word
Shire Pharmaceuticals (SHPGY) discussed the strength of Adderall XR, which it said was the U.S. marketshare leader in Attention Deficit/Hyperactivity Disorder, or ADHD, with 26.8% of the market.
Shire's new drugs include Lialda for ulcerative colitis and SPD465 for adult ADHD. The Food and Drug Administration is supposed to release its decision on Lialda by Jan. 21 and on SPD465 by May 21.
CEO Matt Emmens reviewed Shire's rich product portfolio and pipeline, and the presentation and breakout session appeared well-received.
However, if you've followed my rants on the shares of Shire partner New River Pharmaceuticals (NRPH) , you know that I was chomping at the bit for Emmens to address the labeling issue of NRP104, now known as Vyvance.
When asked if Vyvance needs to have the anti-abuse label in order to be successful, Emmens said that Vyvance simply needs to be effective and "show anti-abuse potential." He refused to comment on the label specifically.
MGI Pharma (MOGN) was more than willing to talk about 2007, which executives expect to be a big year for the company. While the company preannounced disappointing revenue for 2006, its Aloxi drug, which treats nausea caused by chemotherapy, could see improved sales this year.
In a sit-down with TheStreet.com, MGI Chief Financial Officer William Spengler explained that Aloxi's flat $250 million in sales in 2006 was the result of several factors related to competition from generic versions of GlaxoSmithKline's (GSK) Zofran.
Spengler said that MGI was aggressive in offering rebates to compete with the cheaper alternatives. Some clinics held off placing orders for Aloxi, expecting MGI to continue to lower prices as the end of the quarter drew closer.
While the competition was expected, the company has been hurt by clinics and physicians who can make an additional $80 to $90 per vial by prescribing the generic anti-nausea medication instead of Aloxi. However, in the third quarter this year, physicians will have to pay more for the generic, closing the price gap between MGI's drug and generic competition.
The company also plans on filing a new drug application for Aquavan, a sedative for use during gastrointestinal procedures such as colonoscopies, midyear. MGI hopes to launch the product next year. Spengler believes sales for Aquavan could reach $250 million just in GI indications.
MGI has been cash flow positive for six months, is expected to earn a profit this year and "has no financing needs," according to Spengler.
New Ideas
An interesting (and very well-attended) presentation was made by CombinatoRx (CRXX) . Thirty-five-year-old CEO Alexis Borisy discussed his novel approach to finding new drugs.
He noted that traditional drug discovery focuses on agents that target a single pathway. CombinatoRx combines drugs (or other agents) to attack from multiple pathways. The company tests millions of combinations to discover previously undiscovered and unusual mixtures to treat various illnesses.
For example, its lead product candidate, CRx102 for rheumatoid and osteoarthritis, combines steroid prednisolone with cardiovascular drug dipyridamole. The steroid component is in doses so low that it would be ineffective if used alone. However, combined with dipyridamole, the steroid had a positive effect. The drug is currently in phase IIb trials.
CombinatoRx also is in phase II trials with CRx170 for chronic pain. It currently has eight drugs in the clinic, although none expected to reach the market for several years.
I had a fascinating discussion with a successful health care investor who believes a new trend may arise in biotech in the coming years. He expects some companies to be dissolved in order to form royalty trusts, similar to what you see in the energy industry or REITs. These companies are essentially shells that collect and distribute royalties.
The hedge fund manager says royalties from companies with viable products or compounds but weak management could be returned to shareholders in the near future. He named Ligand Pharmaceuticals (LGND) , MGI Pharma and SuperGen (SUPG) as potential candidates.
MGI's Spengler said the idea was interesting but was more likely to occur in earlier stage companies than in companies such as MGI that have existing products.
HNAB
HNAB has short- and intermediate-term issues.
They discontinued development of ropidoxuridine and are returning the rights to the university they licensed it from.
Ondansetron is going generic just in time for HNAB's oral spray (Zensana) to come onto the market. Nobody knows what the impact is going to be but it can't help.
Marqibo, while probably effective, is a long way in terms of time and money from making it to market. Sphingosomal topotecan is even farther from market.
Their other products (Talvesta and Alocrest) are in phase I and II. Again, they're a long way from the market and there are lots of risks in these programs.
All of this is contributing to the decline. I think Hana is a good company, and has long-term potential, but the opportunity cost of leaving your biotech money in HNAB is high considering what's going on with the rest of the sector. Which is a nice way of saying there are probably better places to put your money right now.
YMI
Lungman,
Regarding YMI, the jump is almost certainly due to the cetuximab news.
DVAX
Randy,
The failure of the trial isn't a mystery. In fact, no conclusions can be drawn from the Tolamba trial except that it was a mild ragweed season.
This is a perennial problem with trials of any agent that purports to reduce symptoms of an environmental allergen. Patients are prescreened and enrolled well in advance of predicted peaks in environmental allergens, but there is no way to predict whether there will be sufficient allergen to elicit symptoms.
Speaking anecdotally, I participated in a failed randomized, double-blind, one-day trial of an oral allergy medication when I was an undergrad. They screened us and paid us $200 to sit in a park for a day. I don't know if I received placebo or active treatment, but none of the people I was with had any symptoms whatsoever.
XNPT
Now, I know nobody here cares about XNPT except me (despite the fact that it's gone from $16 to $27 twice), but these results are good. XP19986 has great potential--GERD market is huge, and a lot of patients don't respond adequately to proton pump inhibitors. In fact, XP19986 has far greater market potential than the company's gabapentin analog.
There's a read me first I prepared on XNPT somewhere on BV, if you want to know more.
XNPT has a lot of things to like about it. Lots of cash, two drugs (and a a third coming) with little efficacy risk, and it appears to be extremely well managed.
Please note that this is not a pump. In fact, I do not own XNPT at the moment because, despite all the nice things I have to say about it, I felt it was fully valued at $26. Nevertheless, it's worth keeping an eye on.
By the way, the third product the CEO refers to (XP21279) is a levodopa analog. Could be big bucks.
************
XenoPort Announces Advancements in Clinical Development Programs
Monday January 8, 8:01 am ET
SANTA CLARA, Calif.--(BUSINESS WIRE)--XenoPort, Inc. (Nasdaq:XNPT - News) announced today that it will report several developments in its XP19986 and XP13512 clinical programs at the JPMorgan 25th Annual Healthcare Meeting. These advancements include identification of a new tablet formulation for XP19986 that may be suitable as a once-a-day treatment for gastroesophageal reflux disease, or GERD, as well as updates on clinical trials that are part of XenoPort's XP13512 development program.
In a single-dose Phase 1 clinical trial, XenoPort evaluated different sustained-release tablet formulations of XP19986. All formulations provided good absorption of XP19986 and conversion to R-baclofen. One formulation demonstrated a pharmacokinetic profile similar to the prototype capsule formulation used in previous studies, and a second formulation provided a pharmacokinetic profile that may allow once-a-day dosing of XP19986. XenoPort plans to conduct an additional Phase 1 escalating repeat-dose clinical trial of the potential once-a-day formulation in healthy subjects prior to initiating a Phase 2 clinical trial in patients with GERD in the second half of this year.
Ronald W. Barrett, Ph.D., chief executive officer of XenoPort, stated, "We are very pleased with the early results with the new formulations of XP19986. While we believe that patients would accept twice-a-day dosing for the treatment of GERD, the new once-a-day formulation might further enhance the therapeutic utility of, and commercial opportunities for, XP19986."
XenoPort also indicated that it remains on track with its Phase 3 clinical program of XP13512 as a treatment for patients with restless legs syndrome, or RLS. XenoPort announced today that enrollment for study XP060 will be completed this week. XP060 is a Phase 3 trial that is designed to demonstrate the long-term maintenance of efficacy of XP13512 in the treatment of RLS patients. In October 2006, XenoPort announced the completion of enrollment of a 12-week Phase 3 clinical trial, XP052. A second 12-week Phase 3 clinical trial, XP053, was initiated in August 2006. Top-line results of study XP052 are targeted for release in the second quarter, with top-line results of study XP060 planned for the fourth quarter of this year. Top-line results of study XP053 are targeted for the second half of this year.
In addition to these Phase 3 efficacy trials, XenoPort is conducting additional clinical trials of XP13512 to further assess safety and tolerability. In a recent Phase 1 clinical trial of single doses of 2400, 3600, 4800 and 6000 mg of XP13512, XenoPort gained further evidence that XP13512 can provide higher exposure of gabapentin than that which has been previously reported for oral gabapentin itself. This property of XP13512 could afford advantages in the treatment of neuropathic pain conditions. A previously reported Phase 2a trial of XP13512 in post-herpetic neuralgia patients demonstrated that patients switched from oral gabapentin to XP13512 had higher gabapentin exposure and additional relief of pain. XenoPort plans to initiate a clinical trial of XP13512 in painful diabetic neuropathy, or PDN, in the second half of this year.
Dr. Barrett stated, "We have made extremely good progress in our clinical programs over the last year. We believe that these programs have the potential to provide significant patient benefits and represent substantial commercial opportunities. We are executing our plans based on the priorities of advancing our XP13512 Phase 3 RLS program, adding another indication, PDN, to the XP13512 program and moving XP19986 forward in the GERD indication this year. We also plan to file an IND and initiate a Phase 1 clinical trial on our third clinical development candidate, XP21279, in the second half of this year."
XenoPort will present its progress and clinical development plans at the JPMorgan 25th Annual Healthcare Conference on Wednesday morning, January 10, 2007, at 8:00 a.m. Pacific Time. To access the live presentation via the web, please go to www.XenoPort.com or to https://events.jpmorgan.com. The XenoPort presentation can be accessed through the "Conference Webcasts" link for the JPMorgan Annual Healthcare Conference. Please connect to the website at least 15 minutes prior to the live presentation to ensure adequate time for any software downloads that may be necessary to listen to the webcast.
A replay of the webcast can be accessed for a minimum of one week and will be available approximately 24 hours after the live presentation.
About XenoPort
XenoPort, Inc. is a biopharmaceutical company focused on developing a portfolio of internally discovered product candidates that utilize the body's natural nutrient transport mechanisms to improve the therapeutic benefits of existing drugs. XenoPort's most advanced product candidate, XP13512, is the subject of a Phase 3 clinical program for the treatment of RLS, and has successfully completed a Phase 2a clinical trial for the management of post-herpetic neuralgia. XenoPort has also reported positive results of a Phase 2a clinical trial of its second product candidate, XP19986, in patients with GERD.
>I had the procedure myself: no visible change. Zilch. Nada.
The procedure is expensive, but I considered it an investment investment.<
Now that's dedication. Now, where do I sign up for the Phase III of Proellex? Guarantee I won't suffer from a thickened endometrium.
BCRX
In case you missed it, this is big news. I made very good money on BCRX last year, and was contemplating buying it again when it was around $9.00.
http://tinyurl.com/ykvsv5
In retrospect, this contract was almost inevitable and I shouldn't have missed that opportunity...oh well.
*************************************************
BioCryst Awarded $102.6 Million from U.S. Department of Health and Human Services to Develop Peramivir for Seasonal and Pandemic Influenza
Thursday January 4, 12:21 pm ET
U.S. Government Award Highlights Potential Importance of Peramivir as an Antiviral Therapy to Protect Nation Against Seasonal and Pandemic Influenza
BIRMINGHAM, Ala., Jan. 4 /PRNewswire-FirstCall/ -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX - News) today announced that it has been awarded a $102.6 million, four-year contract from the U.S. Department of Health and Human Services (DHHS) to develop the influenza neuraminidase inhibitor, peramivir, for the treatment of seasonal and life-threatening influenza, including avian flu.
(Logo: http://www.newscom.com/cgi-bin/prnh/20030414/BIOCRYSTLOGO)
"BioCryst is pleased to be working with the U.S. Government to further strengthen pandemic preparedness through the development of peramivir, a potentially safe and effective therapy for the treatment for seasonal and life-threatening influenza," said Charles E. Bugg, Ph.D., Chairman and CEO of BioCryst. "We are dedicated to working together to address the potential health crisis of an avian flu pandemic, as well as the annual threat of seasonal influenza."
Peramivir is an antiviral agent that inhibits the enzyme neuraminidase, potentially preventing the spread of the influenza virus.
The award made to BioCryst is part of a larger HHS initiative to pursue the development of new therapies and vaccines which may expand the ability of the United States to respond quickly to a potential pandemic. Receiving this contract from HHS further confirms the potential importance of peramivir as an effective antiviral agent for the treatment of seasonal and life-threatening influenza, including avian flu.
This contract commits $102.6 million to support the full development of both intravenous and intramuscular formulations of peramivir. The contract also funds the validation of multiple U.S.-based manufacturing facilities.
The company will sponsor a conference call at 4:30 p.m. Eastern Time today. The call is open to the public and can be accessed live either over the Internet from http://www.biocryst.com or by dialing 1-800-822-4794 (U.S.) or 1-913-981-4912 (international). No passcode is needed for the call.
About Peramivir
Peramivir is a member of the class of antiviral agents that inhibit influenza viral neuraminidase, an enzyme that is essential for the spread of influenza virus within the host. In laboratory tests peramivir has been shown to be more potent than, and with activity against viral strains that are resistant to, currently available neuraminidase inhibitors. Peramivir is an inhibitor of influenza A and B neuraminidases. At the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) injectable formulations of peramivir were shown to be safely administered at high dose levels to healthily subjects and, in preclinical studies, peramivir has been shown to promote survival in animals infected with highly pathogenic strains of the H5N1 virus. The availability of an intravenous form may be important in treating patients hospitalized with severe life-threatening influenza; the intramuscular formulation will avoid dosing issues with currently available oral or inhaled agents.
About Influenza
The influenza virus causes an acute viral disease of the respiratory tract. Unlike the common cold and some other respiratory infections, seasonal flu can cause severe illness, resulting in life-threatening complications. According to the Centers for Disease Control and Prevention, every year in the United States more than 200,000 people are hospitalized from flu complications, and about 36,000 people die from flu. Most at risk are young children, the elderly, and people with seriously compromised immune systems.
H5N1 avian influenza is caused by a subtype of the influenza A virus. Circulating among birds worldwide, the virus is considered extremely contagious in birds. It is believed that all species of birds are susceptible to avian influenza, but domestic poultry, including chickens and turkeys, are among the most susceptible to the highly pathogenic strain. According to the World Health Organization, at least 261 people have contracted H5N1 avian influenza, of which at least 157 have died. Almost all of these infections have resulted from contact with infected poultry.
About BioCryst
BioCryst Pharmaceuticals, Inc. is a leader in the use of crystallography and structure-based drug design for the development of novel therapeutics to treat cancer, cardiovascular diseases, autoimmune diseases, and viral infections. The company is advancing multiple internal programs toward potential commercialization including Fodosine(TM) in oncology, BCX-4208 in transplantation and autoimmune diseases, peramivir in seasonal and life- threatening influenza and BCX-4678 in hepatitis C. BioCryst has a worldwide partnership with Roche for the development and commercialization BCX-4208 and is collaborating with Mundipharma Holdings for the development and commercialization of Fodosine(TM) in markets across Europe, Asia, Australia and certain neighboring countries. For more information about BioCryst, please visit the company's web site at http://www.biocryst.com.
Forward-looking statements
These statements involve known and unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include that DHHS could reduce or eliminate funding for peramivir through the contract announced today, that we or our licensees may not be able to enroll the required number of subjects in planned clinical trials of our product candidates and that such clinical trials may not be successfully completed, that BioCryst or its licensees may not commence as expected additional human clinical trials with our product candidates, that our product candidates may not receive required regulatory clearances from the FDA, that ongoing and future clinical trials may not have positive results, that we may not be able to complete successfully the Phase IIb trial for Fodosine(TM) that is currently planned to be pivotal, that we or our licensees may not be able to continue future development of our current and future development programs, that our development programs may never result in future product, license or royalty payments being received by BioCryst, that BioCryst may not reach favorable agreements with potential pharmaceutical and biotech partners for further development of its product candidates, that BioCryst may not have sufficient cash to continue funding the development, manufacturing, marketing or distribution of its products and that additional funding, if necessary, may not be available at all or on terms acceptable to BioCryst. Please refer to the documents BioCryst files periodically with the Securities and Exchange Commission, specifically BioCryst's most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, current reports on Form 8-K which identify important factors that could cause the actual results to differ materially from those contained in the projections or forward-looking statements.
RPRX
>I could have done without the pretense of a Chinese Wall. It just serves to remind us all of the differences between Ph2 and Ph3 studies and the risks extrapolating.<
I thought that was a little bizarre too. Like she can't go home and listen to the webcast herself?
>Can anyone expand on the discussion about the endometrial changes that were not obviously pathologic but could only be described as "weird?"<
I can't based on the information from the presentation--perhaps Dewophile can? 'Weird' may be okay as long as they don't see changes consistent with endometrial intraepithelial neoplasia. Dewophile or Xrymd may be able to provide more color.
[OT] Dew,
Given that E-Trade's Power Pro offers semi-sophisticated investors the ability to hide both their order and the true size of their order, do you consider Level 2 even useful any more? I don't find that it even remotely reflects the true supply/demand for a stock.
>I predict they will end up offering Power Pro unconditionally to all accounts or all accounts that meet a net-asset threshold.<
Hopefully the latter. I'd hate to see grandpa or junior try to enter a complex trade with Power Pro. The low-float, low-volume stocks many of us buy trade irrationally enough as it is.
RPRX
Comments anyone?
Aside from the qualitative stuff from the doctors, I didn't think there was anything new in the presentations other than the fact that we got a good look at the endometrial thickening results.
I saved screenshots of each of the key results for Proellex; if I have time later I'll post them for archival purposes.
Bladerunner
>Small trial, Eastern Europe. Take this stuff to Yahoo, will ya.<
Do some DD before succumbing to posting Tourette's. The UF trial (which I was talking about) was 150 patients, conducted in the US.
RPRX
I won't try to convince you.
My experience with the CEO is that he's been brutally honest since I've had an interest in the company. Perhaps lessons learned from the ZONA years?
RPRX
I didn't hear anything. Bastards wouldn't let me go to the meeting in person or I would have asked myself.
Given the QoL results, fibroids must have shurnk.
Overall, that was one of the most positive R&D days I've ever heard. The key result (aside from the incredible efficacy, which we already know), is that the upper bound of endometrial thickness in the UF trial was lower with both doses of Proellex than with placebo. This is in ~150 patients, so it's likely a real effect.
RPRX
The presentation for the phase II/III in UF couldn't be better. Very, very positive. The endometrial thickness results were spectacular--less thickening among Proellex patients at both doses than with placebo.
Presenter (a doc that treats UF, not an investigator or an RPRX employee) said that the results for UF symptom survey were "highly clinically significant."
>4) Discussion of how/why the secondary end points of libido and distress were not positive, as well as discussion surrounding the measures used to assess libido and distress.<
Talking to myself...should have specified that the above statement relates to Androxal.
Julescat,
Belief is good, but the data say otherwise.
Number and total volume of fibroids are not related to pain or dysmenorrhea.
What are you looking for, a cure?
Since I hate unsupported statements, here's the best published evidence to date:
Lippman SA, Warner M, Samuels S, Olive D, Vercellini P, Eskenazi B. Uterine fibroids and gynecologic pain symptoms in a population-based study. Fertil Steril. 2003;80:1488-1494.
OBJECTIVE: To determine the association between dyspareunia, dysmenorrhea, and noncyclic pelvic pain and the presence and characteristics of uterine fibroids. DESIGN: Population-based cross-sectional study. SETTING: Desio, Italy. PATIENT(S): Six hundred thirty-five non-care-seeking participants of the Seveso Women's Health Study with an intact uterus who underwent transvaginal ultrasound. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Ultrasound-detected presence of uterine fibroids and fibroid characteristics including volume, number, location, and position. Current dyspareunia, dysmenorrhea, and noncyclic pelvic pain was measured by self-report on a visual analog scale. RESULT(S): Uterine fibroids were detected in 96 women (15%). Women with fibroids were more likely to report moderate or severe dyspareunia (adjusted odds ratio [OR] = 2.8, 95% confidence interval [CI] = 0.9-8.3, statistically significant trend) and moderate or severe noncyclic pelvic pain (adjusted OR = 2.6, 95% CI = 0.9-7.6, statistically significant trend) than women without fibroids. Moderate or severe dysmenorrhea was not associated with the presence of fibroids (adjusted OR = 1.1, 95% CI = 0.5-2.6). Number and total volume of fibroids were not related to pain. CONCLUSION(S): This is the first population-based study of gynecologic pain symptoms and fibroids. Dyspareunia and noncyclic pelvic pain, but not dysmenorrhea, increased in severity with the presence of uterine fibroids. Fibroid-associated pain symptomatology in a non-care-seeking population may be different from that of a clinic population.
RPRX
Things to look out for tomorrow, if you're going to make the time to listen to the webcast:
1) Information on uterine fibroid volume (a secondary end point). While far from critical because bleeding and pain are what drive women to the clinic, substantial shrinkage would be nice to see.
2) Whisker plots for endometrial thickness in the uterine fibroid trial. Would be spectacular to see that the thickness range for the 25-mg dose fits inside the range for placebo patients.
3) Any additional color around the pain end points for endometriosis and uterine fibroids.
4) Discussion of how/why the secondary end points of libido and distress were not positive, as well as discussion surrounding the measures used to assess libido and distress.
Anything I'm missing? Hopefully the CEO won't open his mouth. While I admire the management's openness and honesty, Podolsky could use a course in diplomacy. In short, if there's anything bad to say you can trust him to say it, and in the worst possible way. On the other hand, if he doesn't hedge and hem and haw the outlook must be really good.
After today, we're <50% of the way to where I think RPRX should be valued. I also find it a little ridiculous that RPRX is trading at less than what it was 10 months ago.
Ha ha ha....I'm not the only one to make that mistake
And I apologize...would have done so right after that post but had to go to "lunch." Must have been temporary hypoglycemia and/or an extended hangover that was making me crabby.
I don't know why I keep responding to these.
1) Who will step up to the plate and pay for marketing and manufacture of the 5-mg dose?
2) Who will pay for additional clinical trials?
3) Who will pay for NDA submission?
Answer: nobody will for a stigmatized drug like RU-486.
In short, the risk/reward isn't there.
>What makes you and RFJ so sure these results won't translate quickly into FDA approved indications<
This question is either dumb or disingenous, I can't decide which. Twenty-one patients? Open-label? Take it to Yahoo.
RPRX
You should note that the decision to discontinue the asoprisnil trial was a business decision, and was in fact strongly disagreed with by the independent DSMB.
I would not be at all surprised if some small biotech licences asoprisnil and takes it through phase III with dosing amendments and the provision for intermittent withdrawal. Hell, if I had the money I might consider it myself.
Also note that comparing asoprisnil and Proellex is apples and oranges. Asoprisnil is a mixed agonist/antagonist; both RU-486 and Proellex are pure antagonists. Therefore, if you're going to make comparisons make them with RU-486. Although evidence is mixed for RU-486, the most recent article you cited from the Green Journal (a randomized, controlled, though small trial) suggests it is effective at very low doses (5 mg) and does not elicit hyperplasia.
Even comparing RU-486 and Proellex is comparing apples and oranges to some extent. Beyond the obvious structural differences, RU-486 does not appear to be antiproliferative in the primate endometrial epithelium or stroma. Both Proellex and Lupron provide fairly profound suppression of proliferation.
Note that RU-486 is avaiable in 200-mg tablets right now. Prescribing 5-mg dosages will require either a compounding pharmacy or someone will have to take the 5-mg dosage through clinical trials so that it can get a formal indication. Either way, it eliminates any pricing advantage for RU-486 in endometrosis and/or UF.
AEZS
Dunno,
As long as you're checking I-Hub right now, thought I'd ask for your thoughts on AEZS. Why do you like it, what short- and intermediate-term milestones can we expect, what's up with the 30% drop a few weeks ago, etc.
I haven't done any serious DD on it, just looked at the rather impressive pipeline. Interested in your views.
J
RPRX
Think Equity went from a $31 May price target to $18 and dropped Androxal from the future valuation model. I think I know why. It had heretofor been the larger part of the future revenue model. Do you have access to their report in making that move?
No, I do not have access to that report. However, it came out after the R&R conference; suggests they thought twice about the soft end points for Androxal.
What penetration level and % does their royalty revenue from Proellex presume?
Royalty value is not the issue here. Sale of the program and/or the company is.
Does Think Equity seem to be aware that the Schering Plough P3 trial for Asoprisnil is not on Schering's planning horizon due to long term effects that showed up only in longer term trials?
One would hope, although the endometrial thickening issue showed up at 3 mo. Not sure where you're getting the LT crap.
Do you know when the adverse side effects of RU 486 became apparent in their fibroid testing?
In the most recent trial of RU486, there was no thickening after 6 mo.
>Stop trading what is surely an undervalued 2007 prospect and enjoy the ensuing 3-6 month ride.<
I have to admit that RPRX was a tempting one to trade. I picked up a lot more shares, mostly on margin, last Friday and sold enough to get myself off the margin train today. Still holding my entire core position plus a bunch of bonus shares from the trade.
I hate margin, but it was fricken' ridiculous it didn't pop on Friday morning. I'm not going to make a habit of this--having so much money at stake turned me into a browser lemming for an entire week.
RPRX
It's going to be an interesting battle between the January effect, the outcomes of the analyst meeting (there's gotta be some upgrades after that), the potential financing, any Androxal news, takeover talk, profit taking, and the results for the key secondary end point of fibroid volume.
In short, you may, or may not, see a transient buying opportunity on Wednesday.
I did say *almost* religously.
I started buying at ~$8.00 in September and October (?) but bought the bulk of my shares much more recently. I disobeyed my rule because the big drop was obviously the result of one rather ill-informed and ill-mannered hedgie.
I've disobeyed my rule three times in the past 1.5 years. Once with YMI (which was a very good idea) and once with POTP (bad idea). For the life of me, I can't remember why I liked POTP.
*****
That was most certainly not a biotech pick list. I wouldn't buy anything on it. I was just saying that if I had to buy, it would be either NBIX or AVNR.
I do have three ideas that I'm working on...we'll see what happens.
*****
Regarding RPRX: the company has estimated that it will require $50 M to get all 3 indications through to submitted NDA. There are several factors to consider:
1) Will the Androxal program be sold ex-US, and if so will it attenuate the need for cash?
2) When will RPRX sell the Proellex programs?
3) Burn ex-clinical trials is extremely low. Depending on how their contract is structured with their CRO, they may very well be able to avoid raising cash long enough to sell Androxal and/or until after the March results.
I have very little doubt that there's significant acquisition interest out there, but as I've said elsewhere I think the only thing that's standing in the way of an acquisition tomorrow is management. They're going for a super home run. I'd personally prefer to skip the risk and dilution and take $250 or $300 M. Pocket change for big pharma. In fact, Pfizer could buy 52 RPRXs at that price.
Anyway, they're not going to drop a $50 M bomb on us all at once. Instead, they'll raise money in a stepwise manner.
And PS: another insider buy at RPRX in the high 11's.
I obey this rule almost religiously. In fact, as I've said to Dew before, I'm better at loss cutting than stock picking.
I'd attribute the fact that I haven't lost money on a portfolio basis in the last 5 years almost entirely to the 10% rule. True, I haven't made as much as I could have either.
Learned the hard way--as did many others--in 2000.
Anyone watch David? I'm primitive: no television.
I think you should relax a little...lots of near-term catalysts coming up. Plus--and this should have occurred to me earlier--RPRX is one of the few stocks that is insulated from the Medicare debate (because, of course, Proellex is for reproductive-age women).
Analysts See More Biotech M&A in 2007
I wish I was smart enough to be an analyst.
No news here for us. Posting for archival purposes.
Tuesday December 26, 3:35 pm ET
By Damian Troise, AP Business Writer
Biotech Industry Poised to Continue Buyout Trend on Promising Technology, Developing Pipelines
NEW YORK (AP) -- Who will be the next biotech takeover target? That's the question Wall Street is asking as a year of innovative developments and heated competition in several of the industry's markets draws to a close.
This was the sector's second active year in a row in terms of buyouts, as large biotechnology and pharmaceutical companies went beyond licensing agreements to fill out development and product pipelines. So far in 2006, there have been 15 M&A transactions with biotech companies, just one fewer than in 2005.
"The huge premiums that big pharma is willing to pay for biotech innovation reflects their pipeline problems," said G. Steven Burrill, chief executive of San Francisco-based Burrill & Co., a life sciences venture capital firm.
Drugs typically cost between $1.2 billion and $1.8 billion to bring to market and can take up to 15 years to develop, Burrill said in a Dec. 1 report reviewing the sector. Buyouts are a "cheap and efficient" way for companies to cut both time and costs.
They might not seem so cheap at first glance though.
This year, Foster City, Calif.-based Gilead Sciences Inc. bought Westminister, Colo.-based Myogen for $2.5 billion. Cambridge, Mass.-based Genzyme Corp. beat cross-town rival Millennium Pharmaceuticals to buy Canadian drug developer AnorMed Inc. for $584 million. Merck & Co. is buying San Francisco-based Sirna Therapeutics Inc. for $1.1 billion and Abbott Laboratories agreed to pay $3.7 billion for Kos Pharmaceuticals Inc.
The hefty prices suggest buyers are becoming more aggressive, said Merrill Lynch analyst Eric Ende, in a note to investors. Venture capitalists are pushing deals harder, he said, and licensing agreements are becoming more expensive, prompting partners to become potential suitors.
"The capital markets have become increasingly accessible for biotech companies," says Ende, "which has allowed large-cap biotech companies to build war chests for cash for acquisitions."
The backdrop to this surge in buyout deals is the growing competition between biotechnology companies. Genentech Inc. received FDA approval for its age-related macular degeneration drug Lucentis in June, pitting it against OSI Pharmaceuticals' Macugen. Meanwhile, Regeneron Pharmaceuticals is in late-stage development for its own treatment.
Genentech again made a splash in the lung cancer market after receiving expanded approval for Avastin. The drug is pitted against another newcomer, Amgen's Vectibix, which is poised to take market share from Imclone's Erbitux. Merck's Januvia, a dpp4 inhibitor, entered the market against Byetta, made by Amylin Pharmaceuticals and Eli Lilly, and Novartis and OSI are working on drugs of their own.
The competition is also being fueled by new developments in targeted gene therapy, such as DPP4 inhibitors and RNAi technology. These next-generation treatments are helping small biotechnology companies gain more licensing agreements -- and attention from large biotech companies and big pharma.
Ende believes the acquisition trend will continue in 2007, due to increasingly expensive licensing deals, strong balance sheets at biotech companies, shifting management philosophy, and continuing pressure from venture capitalists.
RPRX RMF
Anyone may update this file; feel free to e-mail me for the source file with the formatting. Permission granted to cut, paste, slice, dice, or repost elsewhere.
Warning: opinions ahead. Take it for what it’s worth.
Edits:
*Added information from Dewophile on Lupron for uterine fibroids.
*Added information on near-term catalysts
*Added information from Dunno and Bladerunner on GnRH analogs in development
I would appreciate any additional comments via private message or e-mail…no need to clutter the board.
Company
RPRX is a biopharmaceutical company focused on the development of new drugs to treat hormonal and reproductive system disorders. The company’s name was changed to Repros Therapeutics Inc from Zonagen, Inc, “in order to more appropriately reflect [a] focus on the reproductive and hormonal health technology market.”
RPRX management has been upfront about their desire to sell the company or individual programs. Provided continued positive results in clinical trials, this company will be sold eventually.
From a brokerage report:
Proellex and Androxal represent exactly what we look for as investable assets in biotechnology: they address very large markets, are in drug classes that have demonstrated positive, validated risk-benefit profiles, and are wholly-owned by the company. Additionally, we believe that the areas of male and female reproductive health are poised to be areas of significant growth, relative to other sectors in healthcare, which makes Repros a particularly attractive investment at this time.
Near-term catalysts
January
*Analyst meeting (January 4)
March
*Final results for phase II/III trial of Proellex in uterine fibroids
*Final results for phase II of Proellex in endometriosis
*Final results for phase III of Androxal
Unknown timing
*Financing (0-2 M shares; estimate Jan or Feb 2007)
*Sale/partner Androxal in Europe (estimate Q1-Q2 2007)
*Special protocol assessment (SPA) submission: Proellex in uterine fibroids (estimate end of Q2 2007)
*SPA submission: Proellex in endometriosis (estimate Q2 2007)
*SPA submission: Androxal in testosterone-deficient men (estimate Q3 2007)
*Initiation of phase III trials for Proellex in uterine fibroids and endometriosis (estimate Q3 2007)
*One-year toxicity/carcinogenicity results (estimate Q4 2007)
*Two-year animal toxicity results (estimate Q4 2007)
Products
Proellex
Proellex is an orally administered, selective progesterone receptor modulator (SPRM) in development for the treatment of uterine fibroids and endometriosis. Proellex inhibits the progesterone receptor without inhibiting the production of estrogen activity, which is a marked improvement over the current standard of care for both diseases, Lupron (Lucrin). Long-term use of Lupron causes severe estrogen deficiency that may cause depression, mood swings, abnormal bleeding, and osteoporosis.
Because of its drawbacks, Lupron is indicated for <6 months of treatment. Because of the shortcomings of Lupron, Proellex only has to provide similar efficacy to supplant Lupron from the market. However, as noted below, initial data suggest that Proellex is far superior to Lupron.
Proellex market
*13.6 million women in US with uterine fibroids, approximately one-quarter of whom could benefit from treatment.
*5.5 million women in US with endometriosis, the majority of whom could benefit from treatment
*Sales for asoprisnil (former competitor, pulled from clinical trials) estimated at $600 M for uterine fibroids alone
Phase II/III uterine fibroids trial—design
*Enrolled 150 women with signs/symptoms of uterine fibroids
*Patients receive 0, 12.5, or 25 mg Proellex
*Three-month multicenter study with open-label extension
*Primary end point: bleeding
*Secondary end points: pain, quality of life, and fibroid size
*Safety: endometrial effects and bone loss
Phase II/III uterine fibroids trial—results and qualitative analysis
Perfect results.
1) For the primary end point of uterine bleeding, both the 25 mg and 12.5 mg doses showed incredible results. The P-values were, respectively, .00003 and .000005, which meets the pre-specified threshold for declaring the trial a statistical success with the interim results. I expected this result, but not such low P values.
2) For the secondary end point of QoL, both the 25 mg and 12.5 mg doses showed excellent results, with P values of .0046 and .0029, respectively. Given that QoL measures are often squishy, I did not expect this result. I expected a trend toward improved QoL.
3) Pain scores. Again much better than expected, particularly at the 25-mg dose (P=0.006).
4) Great safety results, which were the key to this trial. Seven placebo patients, six 12.5–mg patients, and three 25-mg patients had thickening. Most importantly, no hyperplasia with atypia was observed in any patient. This result is substantially better than expected.
5) No results for the secondary end point of fibroid size.
Phase II endometriosis trial—design
*Enrolled 40 women with endometriosis,
*Patients treated for 6 months with double-blind Proellex at dosages of 12.5, 25, and 50 mg
*Active-controlled with Lupron
*Primary end point: pain
*Secondary end point: bone loss
*Conducted in Eastern Europe. Note that treating physicians (N=22) were randomly allocated to open-label high (n=21) or moderate (n=1) vodka intake
Phase II endometriosis trial—results and qualitative analysis
Perfect results.
1) The 50-mg dose was statistically significantly better than Lucrin in terms of days of pain (P=0.02). Remarkable result, given that there were only 10 patients in each dosing group. Works out to about 4.5 days of pain for Proellex vs 29 days of pain for Lucrin.
2) During those 4.5 days of pain, the 50-mg dose of Proellex provided a statistically significant (P=0.02) improvement in pain severity compared with Lucrin.
3) Proellex provided excellent efficacy for pain-associated distress, with a P-value of 0.001 vs Lucrin for the 50-mg dose. Only one woman reported mild distress in the Proellex group.
4) Safety: as expected there were no significant changes in biomarkers of bone resorption in any of the Proellex groups. Although expected, this is a key result Lucrin causes bone loss, which limits its applicability as a chronic therapy.
5) Most importantly, no endometrial thickening at the 50-mg dose, no significant endometrial thickening at any Proellex dose and no endometrial hyperplasia with atypia at any dose.
Proellex commentary
In short, when taken the data are taken separately or together both trials were incredibly successful. The results of both studies far exceeded my expectations on every end point.
Proellex SWOT
Why do I feel like I'm at work?
Strengths:Outstanding efficacy in two markets with significant unmet need; FDA likely to be very supportive for both indications.
Weaknesses: Potential for endometrial hyperplasia remains the primary concern.
Opportunities: Proellex is probably generating significant interest from potential acquirers already; Applications beyond endometriosis and uterine fibroids
Threats: FDA requirements for phase III uterine fibroid trials (one or two trials?); potential competition (longer-term); RU-486 issues
Androxal
Androxal is a novel, orally-administered small molecule in clinical development for the treatment of testosterone deficiency in men. Unlike treatments that artificially replace testosterone in the body, Androxal restores testosterone by stimulating natural production of testosterone through the upregulation of the pituitary hormones (including FSH). The re-activation of the hypothalamic-pituitary axis results in normal, physiological levels of testosterone that replacement therapies aim for.
The production of FSH may have benefits for infertile men, an area in which few treatment alternatives are effective. Androxal’s unique mechanism of action also avoids many of the side effects associated with testosterone formulations, most notably, the testicular atrophy and/or infertility caused by supra-normal testosterone levels achieved with topical/transdermal and injectable testosterone products. Androxal is also not subject to partner risk and has no abuse potential because it does not produce supranormal testosterone levels.
Androxal market
Testosterone creams, gels, patches, and injections: ~$450 M worldwide, $150 M Europe only. Significant opportunity for market expansion.
Androxal Phase III—design
*Enrolled 200 men with testosterone levels <300 ng/dL
*Patients randomized to treatment with Androxal 12.5 mg, Androxal 25.0 mg, placebo, and open-label Androgel
*6-month treatment period with open-label extension
*Primary efficacy end points: testosterone levels, libido,
*Secondary end point: “distress”
Androxal Phase III—results
In this interim analysis, men treated with 12.5 mg of Androxal experienced an increase in mean testosterone of 210 ng/dl (P<0.0001) over baseline; those treated with 25 mg of Androxal experienced an increase of 241 ng/dl (P<0.0001) over baseline; and those treated with open-label Androgel, administered at any dose, experienced an increase of 167 ng/dl (P=0.0002) over baseline. As expected, men receiving placebo experienced no statistically significant change in mean testosterone.
Note that, according to the protocol, these data are sufficient to formally declare the trial a statistical success for the primary end point.
There was a dose-related trend toward improvement in distress, which is really all I expected at this point. No trend in libido, although Androxal and AndroGel performed similarly for this end point.
Androxal commentary
Data from Phase III study are very good but not perfect.
What these data suggest is that Androxal may be approvable ex-US: European regulatory authorities have indicated that restoration of testosterone levels to normal is an acceptable single end point. Market in Europe is ~$150 million; Global (ex-US) perhaps $300 million.
Eventual approval in the US remains open to question, but given that there are several testosterone-replacement therapies with serious drawbacks, the FDA may consider Androxal, in clinical context, as a safer alternative.
Three months may not be enough time to see statistically significant changes in the soft end points of libido and distress, so the US story here remains open.
According to the company, “With these encouraging results in hand, we will seek to identify a licensing partner for Androxal in Europe.” This statement suggests that dilution when (and now if) it comes will be substantially smaller than it might otherwise be.
Androxal is of secondary importance in RPRX's portfolio. In short, these results are nice but not critical. I would like to see Androxal leveraged to get the Proellex programs done with minimal dilution.
Androxal SWOT
Strengths: Outstanding efficacy for primary end point; significant safety advantages over existing therapies.
Weaknesses: Has not shown efficacy for libido, and only a trend toward efficacy for distress (note: similar results were seen with AndroGel)
Opportunities: Partnership ex-US may reduce/eliminate need for cash
Threats: FDA requirements for approval.
Competitors
Proellex
Uterine fibroids
Primarily surgical (hysterectomy, selective myomectomy). Both procedures have obvious implications for reproductive-age women.
Lupron has an indication for 3 months of treatment to shrink fibroids.
Endometriosis
GnRH analogs (Lucrin), progestins, oral contraceptive pills, androgens, and aromatase inhibitors. After a trial of an oral contraceptive, GnRH analogs are standard of care.
Lupron has obvious drawbacks, including need for injection, and of course all the problems that come with down-regulation of estrogen. GnRH analogs are indicated only for short-term use.
Two additional GnRH analogs are under development by AEZS and SPPI. Neither represent a significant competitive threat.
Danazol (synthetic androgen) can also be used but it has a bunch of nasty side effects, and there are also surgical procedures that can correct endometriosis. According to Dewophile, danazol is no longer used in the clinic.
Asoprisnil was in the pipeline, but was terminated because of an excess of procedures related to endometrial thickening. Notably TAP made a business decision to terminate this trial even though the DSMB disagreed, so some day this one might come back.
Physician perspective on competitors: http://tinyurl.com/ybnff3
Androxal
Primarily testosterone gels/creams (AndroGel, Testim), which have a bunch of very serious limitations, including testicular atrophy, partner risk, abuse potential, and an issue with worsening of secondary hypogonadism. There is also the option of administration of exogenous testosterone with all of its attendant problems.
In addition, Clomid could be used, but its cis isomer has estrogenic effects and an extremely long half-life. Note that Androxal is just the trans isomer, which does not have these effects.
In short, the limitations of current products for testosterone deficiency can be summed up as: do you want a hairy girlfriend and shrunken testicles, or would you prefer to schedule a fitting for a manssiere?
See the following link for physician perspective: http://tinyurl.com/ybnff3
Financial
Company has approximately $8.3 million; burn rate ~$3 million per quarter with 3 active clinical trials; ex-clinical trials burn rate ~$700,000 per quarter
Coverage and targets
ThinkEquity: $18
Punk Ziegel: $25
Rfj1862: $93.48 and a nice loft in Tribeca in a pet-friendly building with private outdoor space and an elevator. Thanks!
Potential acquirers
Note that the company is upfront about wanting to sell either the entire company or individual programs.
Analysis based on current portfolios, not pipeline gaps (in which case any number of big pharmaceutical companies may be interested). Also assumes sale of both programs to the same entity.
High probability
Bayer (markets testosterone replacements, estrogen replacements, contraceptives)
Medium probability
Barr Laboratories (markets contraceptives)
Organon (markets contraceptives)
Pfizer Inc (markets contraceptives and an erectile dysfunction product)
Links
Presentation: http://tinyurl.com/yznoyy
Insider activity: http://tinyurl.com/yeoe2d
Website: http://www.reprosrx.com
Why Proellex is different from mifepristone (RU-486): http://tinyurl.com/ychr56
Risks and rewards (pre-December results): http://tinyurl.com/yfs7vz
Predictions for December results: http://tinyurl.com/yh2bu7
Another pre-result take on RPRX (from a physician’s perspective): http://tinyurl.com/yce5qa
Now, to whom should I send the invoice?
AEZS
Dunno,
I'm completely unconcerned about cetrorelix or SPPI's product. Both are GnRH blockers (with serious limitations), both are injectables.
Cetrorelix, Lucrin, and other GnRH blockers have no chance whatsoever if Proellex makes it to market.
That said, I agree that AEZS appears to be a compelling investment, just not for cetrorelix in endometriosis. I'm going to do more DD.
I pulled my 17.99 GTC on RPRX. I believe the company should be valued at ~$20-$25 right now.
RPRX
I know you're all sick of RPRX by now, but there's been a lot of news over the past week. Here's more.
No more posts from me on RPRX until Jan 4. I'll be attending the analyst's meeting in NYC.
HEADLINE: Positive trial just what the Repros doctor ordered
BYLINE: Mary Ann Azevedo
BODY:
A male erectile dysfunction drug developed by the company formerly known as
Zonagen Inc. never made it to market, but a pain-reducer made by the surviving
company seems to be doing well with the ladies.
Now known as Repros Therapeutics Inc., the company's shares got a boost
this week on the news that its endometriosis drug, Proellex, helped
significantly reduce pain in female patients compared to current available
treatment.
Repros' stock climbed by 11.8 percent on Dec. 18 after results of the
European Phase 2 clinical trial of Proellex were announced.
In that study, Repros found that women treated with 50 milligrams of Proellex
reported pain-free days 95 percent of the time during three months of treatment.
The findings were in comparison to 67.8 percent pain-free days reported by
patients on Lucrin, the current pharmaceutical standard of care for the
treatment of endometriosis, a condition that affects approximately 5.5 million
women in the U.S. and Canada.
Proellex, the company's lead compound, is a progesterone receptor modulator,
or PRM, that also is being studied in a Phase 2 clinical trial for the treatment
of uterine fibroids, a condition that affects some women of childbearing age and
results in a significant number of hysterectomies each year.
Androxal, Repros' other program in late clinical development, is designed to
restore normal testosterone production by the testes and is being tested in a
Phase 3 clinical trial for the treatment of testosterone deficiency in men.
In the 1990s, Repros, then known as Zonagen, caught international attention
as it worked to develop a treatment for erectile dysfunction, much like the
popular Viagra pill that beat it to market.
Once a Wall Street darling with its stock trading at more than $45 per share,
Zonagen later shifted its focus to other drugs after several problematic trials
of its Vasomax drug.
After enduring several rounds of job cuts and years of lackluster stock
performance, Repros seems to be headed for a rebound.
Shares of the company's stock closed up 11.8 percent to $6.90 on Dec. 18,
after having traded as high as $7 earlier in the day. The stock has traded
between $4.50 and $14.27 in the past 52 weeks.
While data on the uterine fibroid indication for Proellex was expected by the
end of this week, Repros announced on Dec. 20 interim results of a U.S. Phase 3
study of Androxal, its oral drug that restores normal testicular function. Early
results suggest that treatment with Androxal results in a statistically
significant increase in mean testosterone. Also, Repros says that Androxal is so
far proving to not be inferior to Androgel, a commercially available
testosterone replacement cream marketed for the treatment of low testosterone by
Solvay Pharmaceuticals.
Meanwhile, industry analysts believe the this week's trial results of
Proellex might very well be the beginning of a string of positive data released
by Repros.
"From the stock perspective, the data presented on Proellex was an important
de-risking event," says Vinny Jindal, an analyst in ThinkEquity Partners LLC's
San Francisco office. "This proves that Proellex is not just on parity, but also
superior to the current standard of care."
Matt Kaplan, an analyst with New York's Punk, Ziegel & Co., says the results
of Repros' other trials, which are bigger and later-stage, could potentially be
even more important than this one.
Meanwhile, despite this week's stock climb, Kaplan believes Repros' shares
are "significantly undervalued based on the value of the company and the status
and potential of its programs."
He describes this week's trial results as "very encouraging from an efficacy
point of view."
Repros President and CEO Joseph Podolski said he was actually surprised at
the robustness of the trial data.
"Typically, trials where pain is the end point can be very difficult,
considering that pain is very subjective," Podolski says. "But these results
were some of the strongest I've seen in my 37 years in the pharmaceutical
industry."
The next step, Kaplan says, is for Repros to file for an Investigative New
Drug, or IND, application in the United States on the same indication.
Podolski said in a prepared statement that the potential for Proellex is
huge.
"The endometriosis market is large and remains under-served," he said. "Few
drug therapies are viable for long-term use."Higher profile
Earlier this year, Repros, which employs six full-time employees, was the
subject of takeover speculation. (See "Zonagen turnaround positions firm as
likely acquisition target," March 17, 2006).
At that time, Efficacy Capital Ltd.'s Mark Lappe told BusinessWeek magazine
that "it's likely (that) the likes of Pfizer or Wyeth will buy Zonagen."
Efficacy Capital, which invests mostly in biotech firms, owned a 9.9 percent
stake in Zonagen as of December 2005.
Last spring, Podolski played down buyout talk in an interview with the
Houston Business Journal.
"I wouldn't say that's not the case, but I would say it's too early to happen
anytime soon," he said of the firm's potential to be acquired.
Nine months later, ThinkEquity Partners' Jindal believes the company indeed
has takeover potential.
"As Repros continues to consistently present high-quality data, their drugs
will become more and more attractive to larger pharmaceutical companies who are
willing to pay more for drugs that have a track record in the clinic," he says,
"particularly for a drug like Proellex, which could be used by millions of women
in the U.S. for the up to decades at a time."
But, Jindal warns, the U.S. Food and Drug Administration will want to be
assured that the drug doesn't cause any major side effects over time.
RPRX RMF
Anyone may update this file; feel free to e-mail me for the source file with the formatting. Permission granted to cut, paste, slice, dice, or repost elsewhere.
Warning: opinions ahead. Take it for what it’s worth.
Company
RPRX is a biopharmaceutical company focused on the development of new drugs to treat hormonal and reproductive system disorders. The company’s name was changed to Repros Therapeutics Inc from Zonagen, Inc, “in order to more appropriately reflect [a] focus on the reproductive and hormonal health technology market.”
RPRX management has been upfront about their desire to sell the company or individual programs. Provided continued positive results in clinical trials, this company will be sold eventually.
From a brokerage report:
Proellex and Androxal represent exactly what we look for as investable assets in biotechnology: they address very large markets, are in drug classes that have demonstrated positive, validated risk-benefit profiles, and are wholly-owned by the company. Additionally, we believe that the areas of male and female reproductive health are poised to be areas of significant growth, relative to other sectors in healthcare, which makes Repros a particularly attractive investment at this time.
Products
Proellex
Proellex is an orally administered, selective progesterone receptor modulator (SPRM) in development for the treatment of uterine fibroids and endometriosis. Proellex inhibits the progesterone receptor without inhibiting the production of estrogen activity, which is a marked improvement over the current standard of care for both diseases, Lupron (Lucrin). Long-term use of Lupron causes severe estrogen deficiency that may elicit depression, mood swings, abnormal bleeding, and osteoporosis.
Because of its drawbacks, Lupron is indicated for <6 months of treatment. Because of the shortcomings of Lupron, Proellex only has to provide similar efficacy to supplant Lupron from the market. However, as noted below, initial data suggest that Proellex is far superior to Lupron.
Proellex market
*13.6 million women in US with uterine fibroids, approximately one-quarter of whom could benefit from treatment.
*5.5 million women in US with endometriosis, the majority of whom could benefit from treatment
*Sales for asoprisnil (former competitor, pulled from clinical trials) estimated at $600 M for uterine fibroids alone
Phase II/III uterine fibroids trial—design
*Enrolled 150 women with signs/symptoms of uterine fibroids
*Patients receive 0, 12.5, or 25 mg Proellex
*Three-month multicenter study with open-label extension
*Primary end point: bleeding
*Secondary end points: pain, quality of life, and fibroid size
*Safety: endometrial effects and bone loss
Phase II/III uterine fibroids trial—results and qualitative analysis
Perfect results.
1) For the primary end point of uterine bleeding, both the 25 mg and 12.5 mg doses showed incredible results. The P-values were, respectively, .00003 and .000005, which meets the pre-specified threshold for declaring the trial a statistical success with the interim results. I expected this result, but not such low P values.
2) For the secondary end point of QoL, both the 25 mg and 12.5 mg doses showed excellent results, with P values of .0046 and .0029, respectively. Given that QoL measures are often squishy, I did not expect this result. I expected a trend toward improved QoL.
3) Pain scores. Again much better than expected, particularly at the 25-mg dose (P=0.006).
4) Great safety results, which were the key to this trial. Seven placebo patients, six 12.5–mg patients, and three 25-mg patients had thickening. Most importantly, no hyperplasia with atypia was observed in any patient. This result is substantially better than expected.
5) No results for the secondary end point of fibroid size.
Phase II endometriosis trial—design
*Enrolled 40 women with endometriosis,
*Patients treated for 6 months with double-blind Proellex at dosages of 12.5, 25, and 50 mg
*Active-controlled with Lupron
*Primary end point: pain
*Secondary end point: bone loss
*Conducted in Eastern Europe. Note that treating physicians (N=22) were randomly allocated to open-label high (n=21) or moderate (n=1) vodka intake
Phase II endometriosis trial—results and qualitative analysis
Perfect results.
1) The 50-mg dose was statistically significantly better than Lucrin in terms of days of pain (P=0.02). Remarkable result, given that there were only 10 patients in each dosing group. Works out to about 4.5 days of pain for Proellex vs 29 days of pain for Lucrin.
2) During those 4.5 days of pain, the 50-mg dose of Proellex provided a statistically significant (P=0.02) improvement in pain severity compared with Lucrin.
3) Proellex provided excellent efficacy for pain-associated distress, with a P-value of 0.001 vs Lucrin for the 50-mg dose. Only one woman reported mild distress in the Proellex group.
4) Safety: as expected there were no significant changes in biomarkers of bone resorption in any of the Proellex groups. Although expected, this is a key result Lucrin causes bone loss, which limits its applicability as a chronic therapy.
5) Most importantly, no endometrial thickening at the 50-mg dose, no significant endometrial thickening at any Proellex dose and no endometrial hyperplasia with atypia at any dose.
Proellex commentary
In short, when taken the data are taken separately or together both trials were incredibly successful. The results of both studies far exceeded my expectations on every end point.
Proellex SWOT
Why do I feel like I'm at work?
Strengths:Outstanding efficacy in two markets with significant unmet need; FDA likely to be very supportive for both indications.
Weaknesses: Potential for endometrial hyperplasia remains the primary concern.
Opportunities: Proellex is probably generating significant interest from potential acquirers already; Applications beyond endometriosis and uterine fibroids
Threats: FDA requirements for phase III uterine fibroid trials (one or two trials?); potential competition (longer-term); RU-486 issues
Androxal
Androxal is a novel, orally-administered small molecule in clinical development for the treatment of testosterone deficiency in men. Unlike treatments that artificially replace testosterone in the body, Androxal restores testosterone by stimulating natural production of testosterone through the upregulation of the pituitary hormones (including FSH). The re-activation of the hypothalamic-pituitary axis results in normal, physiological levels of testosterone that replacement therapies aim for.
The production of FSH may have benefits for infertile men, an area in which few treatment alternatives are effective. Androxal’s unique mechanism of action also avoids many of the side effects associated with testosterone formulations, most notably, the testicular atrophy and/or infertility caused by supra-normal testosterone levels achieved with topical/transdermal and injectable testosterone products. Androxal is also not subject to partner risk and has no abuse potential because it does not produce supranormal testosterone levels.
Androxal market
Testosterone creams, gels, patches, and injections: ~$450 M worldwide, $150 M Europe only. Significant opportunity for market expansion.
Androxal Phase III—design
*Enrolled 200 men with testosterone levels <300 ng/dL
*Patients randomized to treatment with Androxal 12.5 mg, Androxal 25.0 mg, placebo, and open-label Androgel
*6-month treatment period with open-label extension
*Primary efficacy end points: testosterone levels, libido,
*Secondary end point: “distress”
Androxal Phase III—results
In this interim analysis, men treated with 12.5 mg of Androxal experienced an increase in mean testosterone of 210 ng/dl (P<0.0001) over baseline; those treated with 25 mg of Androxal experienced an increase of 241 ng/dl (P<0.0001) over baseline; and those treated with open-label Androgel, administered at any dose, experienced an increase of 167 ng/dl (P=0.0002) over baseline. As expected, men receiving placebo experienced no statistically significant change in mean testosterone.
Note that, according to the protocol, these data are sufficient to formally declare the trial a statistical success for the primary end point.
There was a dose-related trend toward improvement in distress, which is really all I expected at this point. No trend in libido, although Androxal and AndroGel performed similarly for this end point.
Androxal commentary
Data from Phase III study are very good but not perfect.
What these data suggest is that Androxal may be approvable ex-US: European regulatory authorities have indicated that restoration of testosterone levels to normal is an acceptable single end point. Market in Europe is ~$150 million; Global (ex-US) perhaps $300 million.
Eventual approval in the US remains open to question, but given that there are several testosterone-replacement therapies with serious drawbacks, the FDA may consider Androxal, in clinical context, as a safer alternative.
Three months may not be enough time to see statistically significant changes in the soft end points of libido and distress, so the US story here remains open.
According to the company, “With these encouraging results in hand, we will seek to identify a licensing partner for Androxal in Europe.” This statement suggests that dilution when (and now if) it comes will be substantially smaller than it might otherwise be.
Androxal is of secondary importance in RPRX's portfolio. In short, these results are nice but not critical. I would like to see Androxal leveraged to get the Proellex programs done with minimal dilution.
Androxal SWOT
Strengths: Outstanding efficacy for primary end point; significant safety advantages over existing therapies.
Weaknesses: Has not shown efficacy for libido, and only a trend toward efficacy for distress (note: similar results were seen with AndroGel)
Opportunities: Partnership ex-US may reduce/eliminate need for cash
Threats: FDA requirements for approval.
Competitors
Proellex
Uterine fibroids
Primarily surgical (hysterectomy, selective myomectomy). Both procedures have obvious implications for reproductive-age women.
Endometriosis
GnRH analogs (Lucrin), progestins, oral contraceptive pills, androgens, and aromatase inhibitors. After a trial of an oral contraceptive, GnRH analogs are standard of care.
Lupron has obvious drawbacks, including need for injection, and of course all the problems that come with down-regulation of estrogen. GnRH analogs are indicated only for short-term use.
Danazol (synthetic androgen) can also be used but it has a bunch of nasty side effects, and there are also surgical procedures that can correct endometriosis. According to Dewophile, danazol is no longer used in the clinic.
Asoprisnil was in the pipeline, but was terminated because of an excess of procedures related to endometrial thickening. Notably TAP made a business decision to terminate this trial even though the DSMB disagreed, so some day this one might come back.
Physician perspective on competitors: http://tinyurl.com/ybnff3
Androxal
Primarily testosterone gels/creams (AndroGel, Testim), which have a bunch of very serious limitations, including testicular atrophy, partner risk, abuse potential, and an issue with worsening of secondary hypogonadism. There is also the option of administration of exogenous testosterone with all of its attendant problems.
In addition, Clomid could be used, but its cis isomer has estrogenic effects and an extremely long half-life. Note that Androxal is just the trans isomer, which does not have these effects.
In short, the limitations of current products for testosterone deficiency can be summed up as: do you want a hairy girlfriend and shrunken testicles, or would you prefer to schedule a fitting for a manssiere?
See the following link for physician perspective: http://tinyurl.com/ybnff3
Financial
Company has approximately $8.3 million; burn rate ~$3 million per quarter with 3 active clinical trials; ex-clinical trials burn rate ~$700,000 per quarter
Coverage and targets
ThinkEquity: $18
Punk Ziegel: $25
Rfj1862: $93.48 and a nice loft in Tribeca in a pet-friendly building with private outdoor space and an elevator. Thanks!
Potential acquirers
Note that the company is upfront about wanting to sell either the entire company or individual programs.
Analysis based on current portfolios, not pipeline gaps (in which case any number of big pharmaceutical companies may be interested). Also assumes sale of both programs to the same entity.
High probability
Bayer (markets testosterone replacements, estrogen replacements, contraceptives)
Medium probability
Barr Laboratories (markets contraceptives)
Organon (markets contraceptives)
Pfizer Inc (markets contraceptives and an erectile dysfunction product)
Links
Presentation: http://tinyurl.com/yznoyy
Insider activity: http://tinyurl.com/yeoe2d
Website: http://www.reprosrx.com
Why Proellex is different from mifepristone (RU-486): http://tinyurl.com/ychr56
Risks and rewards (pre-December results): http://tinyurl.com/yfs7vz
Predictions for December results: http://tinyurl.com/yh2bu7
Another pre-result take on RPRX (from a physician’s perspective): http://tinyurl.com/yce5qa
Now, to whom should I send the invoice?
>Following a year of furious M&A activity, France's Sanofi-Aventis has revealed that it is interested in buying a biotechnology firm with "three or four products" that is in the mould of US-based stellar performer Genentech.<
Anyone want to guess?
You forgot to add:
>BMI concurs with the French firm's rationale but is highly sceptical that it will secure a company of Genentech's pedigree.<
RPRX
There are so many factors to take into account when valuing this company that my opinion shifts from day to day. At some point over the holidays I'll war game it to get a more realistic handle on valuation under different scenarios. Until then, it's just handwaving.
That said, I would think that $500 M+ is a reasonable expectation if the program is purchased after good results in March, agreement with the FDA that only 1 additional clinical trial is needed for Proellex in UF, and a favorable phase III plan for the endometriosis indication.
The results of the past week say to me that sometime, somewhere, Proellex will make it to market. I don't know when, at what dosage, and what the indication will say.
>John is only 28 or 29, so, he may have more mental clarity than both of us put together<
I'm older than that but not by too much...Yahoo doesn't auto-update my age for some reason.
Adderall,
>It's +/-20% (25% if measured from the lower bound), which is a big difference for a drug like Adderall.<
In terms of clinical effect, not necessarily.
Adderall takes roughly 3-4 days to reach steady state. A generic version might take more or less time to reach steady state, but the eventual therapeutic effect would be the same.