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CRME
I suppose I now owe Dr Bio a word of thanks for CRME idea as well as INSM. Perhaps you should think about writing a newsletter!
John
Medical Writers
As you can probably imagine, I have a few comments about this article.
1) The article highlights rare ethical breaches; in the context of the thousands of papers that are written with the assistance of medical writers they should not reflect on the profession as a whole.
2) I do not know what happened in the Vioxx case, but the fact is that the authors are always the last to see the article before it is submitted. If something important was removed, it was removed with their full knowledge and consent.
3) Medical writers are necessary. Asking a physician to spend hundreds of hours as the center point for all of the writing, discussion, and revisions that occur during the development of a manuscript is a recipe for the data never coming out. When I was a medical writer, I frequently waited weeks or months for the authors to just to find a few hours to review the manuscript.
4) Medical writers should not need to be acknowledged. They are technicians and should no more be listed as an author than the nurses and techs who contributed to the conduct to the study. Unless I contributed intellectual content (as opposed to organizing the data and presenting it in a readable fashion) I had no problem ghostwriting a study.
5) There are editorial guidelines that must be followed when writing a study. Only a professional should be expected to take the time to understand and follow these guidelines.
6) Physicians, in general, are awful writers. I hold up YMI's recent nimotizumab paper as an example of a paper written without professional help. It is poorly organized and barely readable (although the data were good!)
Finally, I'd just like to go through the process used to develop a primary publication:
1) After the data have been analyzed, the writer meets with all of the lead authors. In person, if it is a major study, or via teleconference if it is a minor study. The writer listens while the authors discuss what data will be presented in the paper and what should be included in the introduction and conclusion.
2) The writer generates an outline, which is circulated to all authors for comments and changes
3) Once the outline is approved by all lead authors, the medical writer uses the study report to write up the data. Frequently, the writer works directly with the statistician to clear up any inconsistencies and may recommend additional analyses. At this stage, the figures are created by a graphics professional and inserted in the outline.
4) The draft manuscript is circulated to all authors, who review, rewrite (usually there is extensive rewriting of the conclusions). The medical writer serves as the center point for the review, and resolves any disagreements among the authors.
5) The article is returned to the lead author after all authors have approved the draft. The lead author submits to the journal.
There are various modifications to this process that can occur--for example, the writer may write up just the data and leave the introduction and conclusion to the authors.
Five years ago, when I was primarily a writer, the pharmaceutical company that sponsored the study was permitted to comment like any other author. More recently, the pharma that sponsored the study usually gets a courtesy copy of the draft manuscript following submission--other than that they have little input beyond the writer's contact with the statistician.
This is the way the process works for me, I cannot speak for others. Like anything else, there is always the possibility of an ethical breach. It is the responsibility of the writer to ensure that commercial interests do not influence the content and that the content is fair and balanced.
Re: BTM
I tend to agree that newsletters are useless. The record for Medical Technology Stock Letter (MTSL) is not much better. Sure, they have had years where they've made 120%+, but they've also had -70% years as well. And they tend to sit on clear losers like Allos Therapeutics. Following newsletter recommendations blindly is foolish.
Nevertheless, I'll take my ideas from anywhere--newsletters, brokerage reports, the guy that types in all caps on Yahoo. As long as you do your own DD, any and all ideas are interesting.
I wish I-Hub members would be more forthcoming about their picks--even better, RMFs for your picks would be great.
For myself, I'm looking at THLD. If I decide it is worth it, I'll generate an RMF.
John
DNA phenotype--edited
I have not read the paper yet, but DNA can take all sorts of forms.
At the level of "naked" DNA--without all the associated proteins--DNA is a right-handed helix; however, it can also exist as a left-handed helix (zDNA). zDNA is frequently formed in underwound DNA, such as that following RNA polymerase during transcription.
If the above is what is happening in the body--that zDNA is underwound--then there might be greater access in these regions for transcription factors to activate genes that are normally shut off. Just a guess. But as clarification, I am not suggesting that zDNA "causes" the metastatic phenotype--instead, perhaps regions of zDNA colocalize with areas of greater transcriptional activity.
DNA can do all sorts of other things too--triple helices and various other structures such as those found at telomeres.
John
Botox for OAB
Agree. Botox seems like a superior alternative to the antimuscarinics with all of their side effects.
I don't know the data for Botox in OAB: presumably it works for outright incontinence and leaking, but does it also relieve symptoms of urgency? Both are important.
Now, what is the investment angle?
J
Radius
Seems to be the day of me-too products in small markets. I'm all for proven technology in larger markets, but why bother with this nickle-and-dime stuff?
Just what the world needs...another PTH analog. Kind of reminds me of the battle in the $350 million intra-articular hyaluronan space.
AIS too. I've had enough of OAB. Oral, gel, transdermal. What's next, nasal spray?
DSCO
Culpa mea--I see that Terry posted the MO deal.
J
DSCO
Sunday's news, but I didn't see anyone else post it here.
Of greatest interest: "Chrysalis receives from Discovery Labs a tiered royalty, the base royalty applies to aggregate net sales of less than $500 million, increases on aggregate net sales in excess of $500 million, and increases again on aggregate net sales of alliance products in excess of $1 billion."
Clearly, someone is expecting DSCO to make some money.
I also thought this quote, from the "internationally renowned" expert Michael Matthay was funny: "As a component of implementing a Lung Protection Strategy, the possibility of having a novel precision-engineered surfactant delivered as an aerosol for patients early in the disease process is exciting. Additionally, this combined technology may serve as a system for pulmonary drug delivery.'
Although I have serious doubts that the words "novel precision-engineered surfactant" came out of our internally renowned expert, at least DSCO is aware of the need to deliver their core message consistently!
*************************************************
Discovery Labs Forms a Strategic Alliance with Chrysalis Technologies to Develop Aerosolized Surfactant Replacement Therapies for Respiratory Diseases
Combination of Precision-Engineered Lung Surfactant and Robust Aerosolization Technology Holds Promise to Revolutionize Respiratory Medicine
WARRINGTON, Pa., Dec. 11, 2005 (PRIMEZONE) -- Discovery Laboratories, Inc. (NasdaqNM:DSCO - News), entered into a strategic alliance with Chrysalis Technologies, a division of Philip Morris USA Inc., for Discovery Labs to develop and commercialize aerosolized surfactant replacement therapies (aSRT) to address a broad range of serious respiratory conditions. This alliance unites two highly complementary respiratory technologies -- Discovery Labs' precision-engineered surfactant technology that mimics the most important attributes of human lung surfactant, with Chrysalis' novel aerosolization device technology that is being developed to enable the delivery of therapeutics to the deep lung. The successful application of these two proprietary technologies holds the promise, for the first time, of producing surfactant-based therapies that may revolutionize the treatment of serious respiratory conditions such as acute lung injury, neonatal respiratory failure, chronic obstructive pulmonary disorder, asthma, cystic fibrosis and others.
ADVERTISEMENT
The alliance focuses on therapies for hospitalized patients, including those in the neonatal intensive care unit (NICU), pediatric intensive care unit (PICU) and the adult intensive care unit (ICU), and can be expanded into other hospital applications and ambulatory settings. Discovery Labs and Chrysalis will utilize their respective capabilities and resources to support and fund the design and development of integrated drug-device systems that can be uniquely customized to address specific respiratory diseases and patient populations. Chrysalis is responsible for developing the design for the aerosol device platform, patient interface and disposable dose packets. Discovery Labs is responsible for aSRT drug formulations, clinical and regulatory activities, and the manufacturing and commercialization of the drug-device products. Discovery has exclusive rights to Chrysalis' aerosolization technology for use with pulmonary surfactants for all respiratory diseases and conditions in hospital and ambulatory settings. Chrysalis receives from Discovery Labs a tiered royalty, the base royalty applies to aggregate net sales of less than $500 million, increases on aggregate net sales in excess of $500 million, and increases again on aggregate net sales of alliance products in excess of $1 billion.
Surfactants are substances that are produced naturally in the lungs, are essential for proper breathing, and their dysfunction is associated with serious respiratory diseases. Up to now the medical community has been unable to utilize the full potential of surfactant replacement therapies. Currently available surfactants are animal-derived, which limits their broad use including the lack of ability to produce therapeutically meaningful aSRT. Discovery's technology is a precision-engineered pulmonary surfactant capable of being formulated to produce aerosols that retain their essential therapeutic properties allowing for the development of a potentially broad portfolio of aSRT products. Chrysalis' technology is designed with the potential to enable or enhance the delivery of such compounds to the deep lung.
Steven M. Donn, M.D., Professor of Pediatrics, Director, Neonatal-Perinatal Medicine at the University of Michigan Health System commented, ``An aerosolized surfactant based therapy could transform the way the neonatal medical community addresses the array of respiratory problems that beset fragile premature infants. Presently, neonatologists have limited pharmacologic options to treat neonatal respiratory failure with many infants suffering significant morbidity and requiring costly treatments and prolonged hospital stays. Aerosolized surfactant replacement therapy represents a novel therapeutic approach that the medical community eagerly anticipates applying to help these very vulnerable babies.'
Michael Matthay, M.D., Professor of Medicine and Anesthesia at the University of California, San Francisco and an internationally renowned expert in pulmonary critical care medicine, commented, ``Increasingly, the medical community has focused on a comprehensive strategy to treat serious respiratory disease such as those treated by the National Heart Lung Blood Institute ARDS NETWORK, an association of clinicians and hospitals supported by the NIH to treat a life-threatening respiratory disease, acute respiratory distress syndrome (ARDS). As a component of implementing a Lung Protection Strategy, the possibility of having a novel precision-engineered surfactant delivered as an aerosol for patients early in the disease process is exciting. Additionally, this combined technology may serve as a system for pulmonary drug delivery.'
Chrysalis Technologies Aerosol Generation Technology
Chrysalis Technologies has developed a proprietary aerosol generation technology that is being designed with the potential to enable targeted upper respiratory or deep lung delivery of therapies for local or systematic applications. The Chrysalis technology (covered by over 40 patents and patent applications) is designed to produce high-quality, low velocity aerosols for possible deep lung aerosol delivery. Aerosols are created by pumping the drug formulation through a small, heated capillary wherein the excipient system is substantially converted to the vapor state. Upon exiting the capillary, the vapor stream quickly cools and slows in velocity yielding a dense aerosol with a defined particle size. The defined particle size can be readily controlled and adjusted through device modifications and drug formulation changes.
Discovery Labs' Surfactant Replacement Technology
Surfactants are protein and lipid (fat) compositions that are produced naturally in the lungs and are critical to all air-breathing mammals. They cover the entire alveolar surface, or air sacs, of the lungs and the terminal conducting airways which lead to the air sacs. Discovery Labs' surfactant product candidates contain a precision-engineered peptide that is designed to closely mimic the essential attributes of human surfactant protein B (SP-B), the protein that is most important for the proper functioning of the respiratory system. Discovery Labs' SRT has the ability to be precisely formulated to address various medical indications.
Discovery Labs' SRT technology was invented at The Scripps Research Institute, was further developed by Johnson & Johnson, and is exclusively licensed to Discovery Labs. The Company's lead product, Surfaxin(r), for the prevention of Respiratory Distress Syndrome (RDS) in premature infants, has received an Approvable Letter from the FDA and is under review for approval in Europe by the EMEA. Aerosurf(tm), the Company's lead aerosol product, has recently completed a pilot Phase 2 clinical trial to address neonatal respiratory failure.
Robert J. Capetola, Ph.D., President and CEO of Discovery Labs, commented, ``Aerosolized surfactant replacement therapy that can be reliably and consistently delivered deep into patients' lungs has the potential to transform respiratory medicine. Based on the successes we have realized to this point, we are confident about the potential of our surfactant technology -- we anticipate FDA approval of our lead product, Surfaxin for RDS in April 2006; our scientists have demonstrated that our SRT can be aerosolized at the proper particle size with the fluid dynamics capable of penetrating the deep lung; and we have successfully completed pilot Phase 2 clinical studies of our aerosolized SRT in neonates with RDS and in adults with mild to moderate asthma. To capitalize on this opportunity, it is necessary to combine our SRT technology with a robust aerosol generation technology into a comprehensive systems approach that can be engineered into products that provide optimal delivery to the lungs, functional patient interfaces and ease of use by medical practitioners.
During the past two years, our scientific team has assessed several aerosol generating technologies. This alliance is the culmination of a comprehensive feasibility evaluation that took place over the last year, which successfully demonstrated the capabilities of Chrysalis' technology. Chrysalis' technology demonstrated an ability to consistently and reliably deliver, over extended periods of time, aerosolized surfactant at output rates that we believe are appropriate for therapeutic utility in neonates, children and adults. We now have access to a leading aerosolization technology with the product development and engineering expertise of Chrysalis -- thus strengthening our capabilities to achieve our vision. Beginning in 2006, we will further advance our pipeline of aerosolized surfactant replacement therapies, starting with our lead aerosol product, Aerosurf.``
The Lead Program -- Aerosurf(r) for the NICU
Serious respiratory problems are some of the most prevalent medical issues facing premature infants in the NICU. There are approximately 1.5 million premature infants born annually worldwide at risk for respiratory problems associated with surfactant dysfunction. Neonatologists generally try to avoid mechanically ventilating these patients because doing so requires intubation (the invasive process of inserting a breathing tube down the trachea). Noted neonatologists have commented on the potential utility of a non-invasive method of delivering SRT to treat premature infants suffering from an array of respiratory disorders.
Aerosurf is Discovery Labs' precision-engineered aerosolized SRT, administered via nasal continuous positive airway pressure (nCPAP) to treat premature infants at risk for respiratory failure. In September 2005, Discovery Labs completed and announced the results of a pilot Phase 2 clinical study of Aerosurf which was designed to evaluate its feasibility, safety and tolerability for the prevention of RDS in premature infants. The study demonstrated that it is feasible to deliver Aerosurf via nCPAP and the treatment was generally safe and well tolerated. The Phase 2 study of Aerosurf did not include the Chrysalis technology.
Discovery Labs and Chrysalis believe that the combination of their respective technologies and expertise can develop a systems approach to optimize the therapeutic application of Aerosurf for neonatologists to treat premature infants suffering from respiratory failure. Discovery Labs anticipates conducting multiple Phase 2 clinical studies of Aerosurf in 2006.
Aerosurf is an investigational drug that has not been approved by the U.S. FDA or any other world health regulatory authorities.
XNPT
It does sort of read like a marketing piece, doesn't it? Imagine that.
J
XNPT
Closed up almost 15% on 4.5 times average daily volume, and in after hours trading gained another 9%. No news.
The only explanation I can come up with is that the market is revaluing the company on the basis of the Astellas deal.
Given that the deal includes a total of $85 million in upfront and milestone payments for Japan and five other Asian countries, and that Astellas has to take XP1352 all the way from phase I, how much are the US and European rights worth in light of relative market size and the fact that the drug is in P3?
With my luck, I'll give back most of today's gain over the next few weeks...nevertheless, I'm curious about what is going on (if anything).
Now I will stop talking about XNPT, since there appears to be no interest.
J
INSM
Rstor, Dr Bio--would one of you mind adding INSM's data to the clinical trial/regulatory calendar? In particular, the diabetes/burn/hip fracture PIII trials.
I would also like to add my thanks. I took a small position in INSM strictly as a gamble, wish I had a lot more. Now I have to do my DD to see if I should keep it!
John
BMY
Perhaps as a cost-cutting measure Peter Dolan will give up his helicopter rides from headquarters in NYC to Princeton, NJ.
J
Dew,
Anything of interest in the BMS webcast on Emsam or Reyataz?
I will listen myself, at some point.
John
INSM Approval and Orphan
Took a very small position in INSM this afternoon....
FDA APPROVES INSMED'S ORPHAN DRUG, IPLEX, FOR THE TREATMENT OF SEVERE PRIMARY IGF-1 DEFICIENCY
The First Once-Daily Therapy for the Treatment of Severe Primary IFG-1 Deficiency
RICHMOND, VA - (December 12, 2005) - Insmed Incorporated (NASDAQ-NMS: INSM) (Nasdaq: INSM) announced today the United States Food and Drug Administration (FDA) approved IPLEX(TM) (mecasermin rinfabate [rDNA origin] injection) for the treatment of growth failure in children with severe primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. As an orphan drug, IPLEX is entitled to seven years of marketing exclusivity for the treatment of Primary IGFD.
"We are very pleased IPLEX was approved, making IPLEX the only approved once-daily IGF-1 replacement therapy available to treat children with severe short stature," stated Geoffrey Allan, Ph.D., President and Chief Executive Officer of Insmed. "Today marks the beginning of a new treatment paradigm for treating children with Primary IGFD. I am grateful to all who have made this drug approval possible. This is also an exciting transition for Insmed as we now begin to focus on the commercialization of IPLEX, which we expect to launch during the second quarter of calendar year 2006."
Andreas Sommer, Ph.D., Chief Scientific Officer of Insmed added, "This event marks the end of a long road and two decades of hard work by hundreds of dedicated people. I'm thrilled that our visionary efforts have now culminated in making available a novel therapeutic composition for the treatment of children who suffer from Primary IGFD."
"It is gratifying to see that a Company who cares for the needs of patients has developed a needed therapy that allows physicians to treat children with Primary IGFD. From my experience in treating these types of patients, IPLEX therapy has produced improvements in growth rates while providing an excellent safety profile" said Louis Underwood, M.D., Professor of Pediatrics, University of North Carolina, Chapel Hill, and a Principal Investigator and a member of Insmed's Pivotal Trial Steering Committee. Dr. Underwood is a world renowned Pediatric Endocrinologist who pioneered the early use of GH and IGF-1.
Conference Call at 8:00am
Insmed management will host a conference call to discuss FDA approval of IPLEX and provide a corporate update at 8:00am ET December 13, 2005. To participate in the conference call, dial 800-289-0529 (domestic) or 913-981-5523 (international). The call will be webcast live through Insmed's corporate website: www.insmed.com. A telephonic replay of the call will be available for one week at 888-203-1112 (domestic) or 719-457-0820 (international) Passcode: 9626439. A web replay of the call will be available through the corporate website beginning at 10:00 a.m.
Xenoport (XNPT) RMF
Revised--caught a few mistakes.
Market cap is currently $330 million.
**********
XenoPort, Inc focuses on developing products that harness transport systems to improve the oral absorption, distribution and pharmacokinetics of drugs. XenoPort is applying its technology to off-patent drugs to provide new, patentable compounds with improved medicinal properties.
Website
www.xenoport.com
Webcast
Lazard Capital Markets Life Sciences Conference, November 29, 2005 (highly recommended)
http://www.wsw.com/webcast/lz2/xnpt/
Technology
In simple terms, XenoPort conjugates approved drugs to actively transported nutrients or proteins to enhance transport, improve bioavailability, and permit localization.
Link: http://www.xenoport.com/technology/technology2index.htm
Pipeline
XP13512
XP13512 is a prodrug of gabapentin with completed phase II clinical trials for restless legs syndrome and postherpetic neuralgia (PHN), a form of neuropathic pain. The company has plans to investigate the drug in painful diabetic neuropathy, another form of neuropathic pain.
Rationale for development
Neuropathic pain: Gabapentin has suboptimal pharmacokinetics, in part due to saturable absorption kinetics, interpatient variability in oral absorption, and a short half life. In clinical trials of gabapentin in patients with PHN, only 30% of patients respond to therapy. Responder rates for pregabalin, a close relative of gabapentin, are approximately 40% at the highest dose. see pregabalin PI: http://www.pfizer.com/pfizer/download/uspi_lyrica.pdf.
According to the company, advantages over gabapentin may include reduced dosing frequency, predictable exposure, ability to maintain drug levels during the night, and efficacy in gabapentin non-responders. Xenoport claims better tolerability as a potential advantage over pregabalin. However, I feel the most important advantage over pregabalin is that XP13512 is unlikely to be considered a controlled substance.
Restless legs syndrome (RLS): Currently, the only agent approved for RLS is Requip (ropinarole), a dopamine agonist. It is approved for moderate-to-severe disease (>15 episodes/month). According to the Requip PI, its indication for RLS is based on three 12-week studies. Link: http://us.gsk.com/products/assets/us_requip.pdf
Clinical Trials
Restless Legs Syndrome
In an unpublished, 96-patient, phase 2b study, patients were randomized to 14 days of double-blind treatment with XP13512 600 mg, XP13512 1200 mg, or placebo following a 7-day baseline period. All drugs were administered once daily.
The primary end point was change in IRLS score at 14 days. IRLS scores declined from 22.4 at baseline to 13.5 at 14 days in the placebo group and from 22.4 at baseline to 6.3 at 14 days in the 1200 mg XP13512 group. The difference between the groups in change from baseline in IRLS was highly significant (P<0.0001).
In the same study, 48% of placebo-treated patients and 81% of XP13512 patients were rated “much improved” or “very much improved” by the investigator. Similar results were observed for the patient-rated global impression of change.
Measures of sleep, including overall quality of sleep, number of nights with RLS symptoms in past week, number of awakenings, and number of hours awake per night, all favored XP13512 (p values range from P=0.0006 to P<0.003). XP13512 was associated with a statistically significant benefit over placebo in terms of 24-hour symptoms, as measured using a symptom diary. Mood assessments were also significantly in favor of XP13512.
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=170219&category=
Neuropathic pain
Phase 2a study
In a 101-patient, 18-site, phase 2b trial, the efficacy of XP13512 was examined in 101 patients with PHN. Following a 7-day baseline period, patients received gabapentin, titrated to 600 mg three times daily over 4 days, followed by a 7-day run-in period with gabapentin 600 mg three times daily. Patients were then randomized to either XP13512 1200 mg twice daily or placebo for 14 days. [This is a somewhat unusual trial design]
Pain scores were reduced 1.2 points in the placebo group and 2.1 points in the XP13512 groups (p=0.032). Sleep interference scores were reduced 0.9 points in the placebo group and 2.2 points in the XP13512 group (p=0.001). On the patient-rated Global Impression of Change, 13.4% of placebo patients rated their symptoms “much improved” or “very much improved” compared with 42.2% of those who received XP13512. Of interest, the ~50% of patients who were poor gabapentin metabolizers experienced the greatest incremental benefit after switching to XP13512. (Baseline pain score 6.1, post-gabapentin score 4.9, post-XP13512 score 4.0; p=0.0126 for post-neurontin vs post-XP13512).
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=169135&category=
XP13512
XP19986 is a prodrug of baclofen targeting the GERD market. According to the company it is “designed to engage natural nutrient transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. XP19986 is then rapidly converted to R-baclofen by high-capacity enzymes.”
Rationale for development
Baclofen is approved for the treatment of spasticity; recent clinical data suggest that it may be effective in gastroesophageal reflux disease (GERD). However, baclofen has a very short half life requiring four-times daily dosing, is poorly absorbed, and has substantial side effects (sedation, somnolence, ataxia).
Clinical Trials
A phase 1 study has been completed.
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=169137&category=
A phase 2a study has been initiated and will be completed 1H06.
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=177730&category=
XP19986
XP19986 is a prodrug of L-Dopa in preclinical studies. According to the company, XenoPort intends to file an IND in 1H2007.
XP20925
XP20925 is a prodrug of propofol XP in preclinical studies for migraine and chemotherapy-related nausea.
According to the company, it intends to “postpone the previously planned filing of an IND for XP20925...until additional resources become available.”
Near-Term Drivers
Due 1H2006
1) Initiating a Phase 3 study in RLS for XP13512
2) Phase 2a results in GERD for XP19986
3) Partnership for either XP13512 or XP19986
Publication
In a 2005 report published in Antimicrobial Agents and Chemotherapy Xenoport report the in vitro properties of a prodrug of the NRTI tenofovir and pharmacokinetic results of in dogs. The effective concentration(50) of the prodrug was 1000-fold lower than that of tenofovir; in the animal model, increased distribution of the drug to lymphatic tissues was observed. Published in collaboration with Gilead.
From the paper: “In conclusion, the high concentrations of tenofovir observed in lymphatic tissues after oral administration of GS 7340 are expected to result in increased clinical potency relative to tenofovir DF and could have a profound effect on the low-level virus replication that occurs in tissues with suboptimal drug exposure during HAART.”
link: http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1087627
Partnerships
XenoPort and Astellas enter license agreement forXP13512 (gabapentin analog) in Japan, Korea, Philippines, Indonesia, Thailand and Taiwan. Astellas is responsible for clinical trials in these countries, and will initiate phase I in mid-2006. XenoPort will receive an initial license payment of $25 million.
In addition, XenoPort is eligible to receive clinical and regulatory milestone payments totaling up to $60 million, including milestone payments of $10 million at the initiation and $5 million at the subsequent completion of XenoPort's first Phase 3 clinical trial of XP13512 in RLS patients in the United States.
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=180910&category=
Collaborations
On January 5, 2003, XenoPort announced a collaboration with Pfizer to develop technology to improve drug delivery to the brain. The collaboration is ongoing.
link: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/01-05-2004/0002083016&....
Financial
$78.8 million on hand as of September 30, 2005 plus $25 million payment from Astellas, $10 million after initiation of the phase III trial of XP13512, and $5 million upon completion. Another $20 million is due from Astellas at unspecified milestones. Quarterly burn is $10.1 million.
link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=178573&category=
Clinical / regulatory / litigation calendar:
[Please see updating procedure at the end of this post.]
Edits: Added XNPT data.
ABGX - PACCE trial (chemo+Avastin+/-Pani) in 1st-line CRC: first interim RR 4Q05; Pani “408” trial in 3rd-line CRC (the trial that just caused all the commotion) final survival: 2Q06.
AGEN - Ph III in RCC 1H06.
AGIX - 1H 06 - Ph iii of 1067 on MACE should hit 900+ events for the end of the trial.
ALKS – 12/30/05 PDUFA date for Vivitrex NDA.
AMGN – See ABGX
AORMF -pivotal AMD3100 results 2nd half 06.
AVN – FDA acceptance for filing of NDA for PBA: delayed (was 10/10/05).
AXCA -pivotal Itax results 1st half 06.
AZN--see RNVS
BIIB – Tysabri (resubmission) PDUFA date 3/25/06
BMY – 12/31/05 revised action date for Orencia (CTLA-4).
BOMSF -reporting pivotal MBP8298 results 2 years roughly
CEPH – Nuvigil PDUFA date in EDS: 1/06; Oravescent Fentanyl PDUFA date: 7/6/06.
CONR – CE Mark (EU approval) of CoStar stent: late 2005/early 2006. Final pleadings in U.K. patent litigation: mid-Dec 2005.
COR - Approx Year end 2005: Results of IIa ADHD CX-717 Ampakine trial.
COR - Early 2006: PET scan results - IIa Alzheimer's CX-717 Ampakine trial.
COR - Early 2006: Results of IIa Simulated Night Shift Work (Sleep Disorder) CX-717 Ampakine trial (funded by DARPA).
CORT - 1H 06 - Results of Ph iii of RU-486 on Psychotic MD
CRME - Phase III RSD1235 ACT 2 CABG data in Q4/05 or Q1/06
CYAHF -20 patient IDE results 4th qtr, then begin the pivotal phase 1st half 06 as well as commercial launch in Europe later this year.
CYPB – Phase-3 Milnacipran in fibromyalgia, second phase-3 study (either 3-mo or 6-mo of follow-up) 3Q06 (maybe —Dew).
DNA- Rituxan in RA PDUFA 2/28/06
DNA- Rituxan in FL Agg NHL PDUFA 2/22/06
DNA- Lucentis BLA submission 4Q 05
DNA- Avastin 2nd line mCRC sBLA filing 4Q 05
DNA- Avastin 1st line mNSCLC sBLA filing 1Q 06
DNA- Avastin 1st line MBC sBLA filing 1Q 06
DNA- Herceptin adjuvant breast cancer sBLA filing 1Q 06
DNDN - 1H 06 - Results for Ph iii of Provenge efficacy on PSADT in ADPC
DSCO - 2ndQ 06 - Approval for IRDS and market rollout
ELN – See BIIB
FRX - Milnacipran in fibromyalgia: see CYPB.
GENR – Interim data in phase-2 “209” study: spring 2006 (?).
GPCB – Satraplatin SPARC trial: interim PFS 1Q06, final PFS 2Q04, final survival 2007.
GTCB – EMEA opinion on ATryn: Feb. 2006; Merrimack phase-2b MM-093 in RA: mid 2006.
IDBE -begin pivotal Fluinsure trials this winter.
IMCL – Erbitux PFS in (Merck KGaA) CRSYTAL trial in first-line CRC: 2H06; Erbitux H&N PDUFA date: end of Feb 06 (sBLA submitted 8/30/05).
INSM – Approvable letter received—orphan status pending.
LBPFF – PDUFA date for Tramadol NDA: 9/28/06.
Merrimack: see GTCB
MYOG - Ambrisentan phase-3 trials in PAH: ARIES-1 in 2Q06; (ARIES-2 was reported on 12/12/05).
NKTR – Exubera: endorsed by advisory panel 9/8/05 by 7-2 vote; FDA action by late 1/06.
NVS – LAF237 pivotal data in diabetes: early 2006.
PDLI - Q2 06 volociximab ph II for solid tumors
PTN- Q2 2006 ph.IIb results for PTN-141 in male erectile dysfunction
RHEO – Pivotal trial in dry AMD: data being cleaned – expected report 1Q06.
RNVS-CHANT Phase IIb safety trial during the first quarter of 2006; AZN to file regulatory applications for Cerovive (NXY-059) during the first half of 2007.
SCLN: Top line results for first HCV pivotal trial by Mid-December 2005
Top line results for second HCV pivotal trial due 1stH06
SPPI – See GPCB.
SRDX - Phase-1 DME data for I-vation w Triamcinilone: mid 2006; Novocell start of phase-1/2 trial in type-1 diabetes: imminent.
TELK - Telcyta 3rd line NSCLC and 3rd line Ovarian results 1H06
Therion (private) – PanVac phase-3 survival results in second-line pancreatic cancer: 1Q06; ProstVac phase-2 (TTP) results of 120-patient trial in asymptomatic HRPC: 1Q06; start of ProstVac phase-3, 600-patient NCI trial in HDPC: 1H06.
TH.TO -report ThGrf Phase III Hiv-associated lipodystrophy results late 06.
VSGN - Celacade phase-3 in chronic HF (ACCLAIM): triggering events reached 11/14/05; data now in cleanup and analysis.
XNPT
1H2006
1) Initiate Phase 3 study in RLS for XP13512
2) Phase 2a results in GERD for XP19986
3) Partnership for either XP13512 or XP19986
YMI - Tesmilifene met breast cancer pivotal study fully enrolled."The first of three planned interim analyses of data from this trial will occur in mid calendar 2006 with the others expected during the balance of the year." Via SPA, approval as early as 2007.
YMI – AeroLEF phase-2b data report: 2Q06.
--
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XNPT
Made my mind up and took a partial position this morning. I'm going to continue to build my position provided it doesn't go through the roof (it's up 6.5% today).
I'd still appreciate a critical appraisal of XNPT's prospects.
John
HEPH
Down a couple cents. Guess the RFP for 100,000 doses was priced in?
J
XNPT
Factually correct, but it still needs some editing--will revise next week.
J
Xenoport (XNPT) RMF
Revised--caught a few mistakes.
I do not have a position in XNPT yet. Comments appreciated on both content and style. Please feel free to be critical--I may defend myself, but I won't take it personally. In fact, I post to expose myself to public ridicule. Sharpens the thinking.
Market cap is currently $330 million.
**********
XenoPort, Inc focuses on developing products that harness transport systems to improve the oral absorption, distribution and pharmacokinetics of drugs. XenoPort is applying its technology to off-patent drugs to provide new, patentable compounds with improved medicinal properties.
Webcast
Lazard Capital Markets Life Sciences Conference, November 29, 2005 (highly recommended)
http://www.wsw.com/webcast/lz2/xnpt/
Technology
In simple terms, XenoPort conjugates approved drugs to actively transported nutrients or proteins to enhance transport, improve bioavailability, and permit localization.
Link http://www.xenoport.com/technology/technology2index.htm
Pipeline
XP13512
XP13512 is a prodrug of gabapentin with completed phase II clinical trials for restless legs syndrome and neuropathic pain (postherpetic neuralgia [PHN], with plans to investigated in painful diabetic neuropathy)
Rationale for development
Neuropathic pain
Gabapentin has suboptimal pharmacokinetics, in part due to saturable absorption kinetics, interpatient variability in oral absorption, and a short half life. In clinical trials of gabapentin in patients with PHN, only 30% of patients respond to therapy. Responder rates for pregabalin, a close relative of gabapentin, are approximately 40% at the highest dose. See pregabalin PI: http://www.pfizer.com/pfizer/download/uspi_lyrica.pdf
According to the company, advantages over gabapentin may include reduced dosing frequency, predictable exposure, ability to maintain drug levels during the night, and efficacy in gabapentin non-responders. The most important advantage over pregabalin is that XP13512 would not be a controlled substance. Xenoport also claims better tolerability as a potential advantage over pregabalin.
Restless legs syndrome (RLS)
Currently, the only agent approved for RLS is Requip (ropinarole), a dopamine agonist. It is approved for moderate-to-severe disease (>15 episodes/month). According to the Requip PI, its indication for RLS is based on three 12-week studies. Link: http://us.gsk.com/products/assets/us_requip.pdf
Clinical Trials
Restless Legs Syndrome
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=170219&category=
In an unpublished 96-patient phase 2b study, patients were randomized to 14 days of double-blind treatment with 1200 mg XP13512, 600 mg XP13512, or placebo following a 7-day baseline period. All drugs were administered once daily. The primary end point was change in IRLS score at 14 days. IRLS scores declined from 22.4 at baseline to 13.5 at 14 days in the placebo group and from 22.4 at baseline to 6.3 at 14 days in the 1200 mg XP13512 group. The difference between the groups in change from baseline was statistically significant (p<0.0001).
In the same study, 48% of placebo-treated patients and 81% of XP13512 patients were rated “much improved” or “very much improved” by the investigator. Similar results were observed for the patient-rated global impression of change. Measures of sleep, including overall quality of sleep, number of nights with RLS symptoms in past week, number of awakenings, and number of hours awake per night, all favored XP13512 (p values range from P=.0006 to P<.003). Statistically significant benefits in terms of 24-hour symptoms as measured using a symptom diary and mood assessments favored XP13512.
Neuropathic pain
Phase 2a study
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=169135&category=
In a 101-patient, 18-site phase 2b trial, the efficacy of XP13512 was examined in 101 patients with PHN. Following a 7-day baseline period, patients received gabapentin, titrated to 600 mg three times daily over 4 days, followed by a 7-day run-in period with gabapentin 600 mg three times daily. Patients were then randomized to either XP13512 1200 mg twice daily or placebo for 14 days.
Pain scores were reduced 1.2 points in the placebo group and 2.1 points in the XP13512 groups (p=0.032). Sleep interference scores were reduced 0.9 points in the placebo group and 2.2 points in the XP13512 group (p=0.001). On the patient-rated Global Impression of Change, 13.4% of placebo patients rated their symptoms “much improved” or “very much improved” compared with 42.2% of those who received XP13512. Of interest, the ~50% of patients who were poor gabapentin metabolizers experienced the greatest incremental benefit after switching to XP13512. (Baseline pain score 6.1, post-gabapentin score 4.9, post-XP13512 score 4.0; p=0.0126 for post-neurontin vs post-XP13512).
XP13512
XP19986 is a prodrug of baclofen targeting the GERD market. According to the company it is “designed to engage natural nutrient transport mechanisms found on intestinal cell membranes, thereby gaining efficient entrance into the bloodstream. XP19986 is then rapidly converted to R-baclofen by high-capacity enzymes.”
Rationale for development
Baclofen is approved for the treatment of spasticity; recent clinical data suggest that it may be effective in gastroesophageal reflux disease (GERD). However, baclofen has a very short half life requiring four-times daily dosing, is poorly absorbed, and has substantial side effects (sedation, somnolence, ataxia).
Clinical Trials
A phase 1 study has been completed. Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=169137&category=
A phase 2a study has been initiated and will be completed 1H06. Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=177730&category=
XP19986
XP19986 is a prodrug of L-Dopa in preclinical studies. According to the company, XenoPort intends to file an IND in 1H2007.
Propofol XP, a prodrug of propofol in preclinical studies for migraine and nausea
According to the company, it intends to “postpone the previously planned filing of an IND for XP20925, a transported Prodrug of propofol for the treatment of migraine and chemotherapy-induced nausea/vomiting, until additional resources become available.”
Near-Term Drivers
Due 1H2006
1) Initiating a Phase 3 study in RLS for XP13512
2) Phase 2a results in GERD for XP19986
3) Partnership for either XP13512 or XP19986
Publication
In a 2005 report published in Antimicrobial Agents and Chemotherapy Xenoport report the in vitro properties of a prodrug of the NRTI tenofovir and pharmacokinetic results of in dogs. The effective concentration(50) of the prodrug was 1000-fold lower than that of tenofovir; in the animal model, increased distribution of the drug to lymphatic tissues was observed. Published in collaboration with Gilead.
In conclusion, the high concentrations of tenofovir observed in lymphatic tissues after oral administration of GS 7340 are expected to result in increased clinical potency relative to tenofovir DF and could have a profound effect on the low-level virus replication that occurs in tissues with suboptimal drug exposure during HAART.”
Link: http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=1087627
Partnerships
XenoPort and Astellas enter license agreement forXP13512 (gabapentin analog) in Japan, Korea, Philippines, Indonesia, Thailand and Taiwan. Astellas is responsible for clinical trials in these countries, and will initiate phase I in mid-2006. XenoPort will receive an initial license payment of $25 million. In addition, XenoPort is eligible to receive clinical and regulatory milestone payments totaling up to $60 million, including milestone payments of $10 million at the initiation and $5 million at the subsequent completion of XenoPort's first Phase 3 clinical trial of XP13512 in RLS patients in the United States.
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=180910&category=
Collaborations
On January 5, 2005, XenoPort announced a collaboration with Pfizer to develop technology to improve drug delivery to the brain. The collaboration is ongoing.
Link: http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/01-05-2004/0002083016&....
Financial
$78.8 million on hand as of September 30, 2005 plus $25 million payment from Astellas, $10 million after initiation of the phase III trial of XP13512, and $5 million upon completion. Another $20 million is due from Astellas at unspecified milestones. Quarterly burn is $10.1 million.
Link: http://xnpt.client.shareholder.com/ReleaseDetail.cfm?ReleaseID=178573&category=
TELK
NOT new information (someone posted the abstracts a few weeks ago)
Telik's TELINTRA Demonstrates Positive, Clinically Significant Multilineage Responses In Phase 2 MDS Trial
Sunday December 11, 5:00 pm ET
PALO ALTO, Calif., Dec. 11 /PRNewswire-FirstCall/ -- Telik, Inc. (Nasdaq: TELK - News) reported positive clinical results from a multicenter Phase 2 trial of TELINTRA(TM) in patients with myelodysplastic syndrome (MDS). The data were reported at the 47th Annual Meeting of the American Society of Hematology in Atlanta, GA.
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Forty-three MDS patients were evaluable for efficacy. Of the 34 patients with multilineage blood cell dysfunction, 22 (65%) had clinically significant Hematologic Improvement (HI), as defined by the MDS International Working Group (IWG) hematologic response criteria. By individual cell line, HI was observed in 76% of the 25 patients with platelet abnormalities, an important finding given the limited treatment options for decreased platelet levels or thrombocytopenia. HI was observed in 64% of the 39 patients with red cell or erythroid abnormalities, and in 83% of the 29 patients with white cell or neutrophil abnormalities.
Responses were observed in all MDS FAB subtypes, in patients with low, intermediate or high risk disease by the MDS International Prognostic Scoring System (IPSS) and in patients with del (5q) and other chromosome abnormalities. Responses were accompanied by clinical symptom improvement, reduction or elimination of transfusion and/or growth factor support, and improvement in bone marrow maturation.
TELINTRA treatment was well tolerated in this predominantly elderly patient population. Most patients had failed one or more prior treatments including: 5-azacitidine, lenalidomide, thalidomide, other chemotherapeutic drugs, immune modulators, steroids, bone marrow transplantation, or investigational agents. The majority of patients also received prior blood product and/or growth factor support.
TELINTRA is a novel small molecule that has been shown in preclinical testing to have myelorestorative activity when administered orally or by infusion. It was discovered using Telik's proprietary TRAP(TM) small molecule drug discovery technology.
Myelodysplastic syndrome is the most common hematologic malignancy in the elderly and originates in the stem cells. MDS causes ineffective formation of blood elements manifested by anemia, neutropenia and thrombocytopenia. The disease may be chronic, characterized by frequent transfusions and iron overload, infections and bleeding, or it may be aggressive with expected survival less than one year. MDS may progress to acute leukemia. There are an estimated 10,000 to 15,000 new cases of MDS diagnosed annually in the U.S., according to the American Cancer Society
Telik, Inc. of Palo Alto, CA is a biopharmaceutical company focused on discovering, developing and commercializing novel small molecule drugs to treat serious diseases. The company's most advanced drug development candidate is TELCYTA® (TLK286), a cancer cell-activated product candidate that is in three Phase 3 registration trials in advanced ovarian and non-small cell lung cancer. Telik's product candidates were discovered using its proprietary drug discovery technology, TRAP, which enables the rapid and efficient discovery of small molecule drug candidates. Additional information is available at http://www.telik.com.
This press release contains "forward-looking" statements, including statements concerning the potential for TELINTRA to treat myelodysplastic syndrome. There are important factors that could cause Telik's results to differ materially from those indicated by these forward-looking statements, including, among others, that TELINTRA has not been determined to be safe or effective in humans or received regulatory approval for marketing, and clinical trials of Telik's product candidates, including TELINTRA, may take several years to complete and may not be successful. Detailed information regarding factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in Telik's periodic filings with the Securities and Exchange Commission, including the factors described in the section entitled "Risk Factors" in its quarterly report on Form 10-Q for the quarter ended September 30, 2005. TELIK, TRAP, TELCYTA and TELINTRA are trademarks of Telik, Inc. Telik does not undertake any obligation to update forward-looking statements contained in this press release.
Buying on the SWX
If anyone is interested, I answered my own question about buying on the Swiss exchange. E-Trade allows on-line limit orders for the usual commission. They must be placed in USD. Same goes for any stock with a US clearing symbol ending in "F." For example, Speedel's US clearing symbol is SPDHF.
At least that's what I got out of my conversation with an E-Trade broker.
John
SNUS
The 15% haircut was probably related to the safety results, not this AP article.
J
LGND
Does anyone here follow LGND? Why was it delisted? Just curious--no intent to buy.
J
Speedel
PGS--I have indeed looked closely at Speedel, I just haven't been able to figure out how to buy a stock traded on a Swiss exchange. Any suggestions from anyone who has done something similar?
John
HEPH
You may well be right.
However, here are the data:
In sublethal studies conducted in ~150 animals once daily Neumune resulted in a reduction in the number of days of severe neutropenia from 12 to 3; number of days with thrombocytopenia was reduced from 8 to 0.
In lethal studies with no clinical support, survival was ~42% with Neumune and 22% with Neumune (p=0.044, reported at this year's ASH). Similar to the first study there were statistically significant reduction in the number of days with thrombocytopenia and neutropenia.
In lethal studies with clinical support (n=8) there was a reduction in the number of days of severe neutropenia and thrombocytopenia. Presumably too early for statistical analysis.
I may be missing something.
HEPH
Is about to present a very good value on Monday.
On December 9, the US DHHS released a final request for proposal (RFP) requesting 20,000--yes, that's right, 20,000--doses of an unspecified radioprotectant for the treatment of ARS. The RFP remains tailor-made for Neulasta, even down to the level of the shelf life. It's almost like they were reading the Neulasta PI while writing the RFP.
My question: what company is going to step up to the plate to conduct the appropriate trials, if they haven't already done so, for a 20,000-dose contract? Even Amgen would have been unlikely to waste the time or effort on testing their agent for a 20,000-dose contract--but of course the government is paying to test Neulasta.
In short, this contract all but specifies Neulasta--a product that, if left unrefrigerated, is useless after 48 hours, requires extensive monitoring during adminstration, and only treats neutropenia.
Therefore, it appears that the government's "effort" to promote the development of practical agents for ARS is DOA. I expect HEPH to fall hard on Monday. I own only a small call position, which I will continue to hold through expiration.
Keep in mind, however, that Neumune has been demonstrated to significantly reduce the number of days with neutropenia and thrombocytopenia in animal models of ARS. So this isn't a typical biotech failure--they have a product that appears to work and meets all of the requirements for the government ARS contract--Bush's incompetent cronies have, however, made what what to my mind is a politically driven decision.
HEPH has ~56 million in cash, at their current burn rate that's about 9 quarters. They have one drug (Neumune) that has been very extensively tested in non-human primate models and phase I safety studies and another in phase II. Buyout? Surely this company is worth a substantial amount to any big pharma that wants to enter the neutropenia/thrombocytopenia space? In the absence of a buyout (and much longer term) Neumune has excellent potential.
XNPT
I assume Astellas is starting in Phase I because of regulatory requirements in Japan dictating that safety studies be conducted in a predominantly Japanese population.
According to the company, over the next two quarters, we can expect 1) initiation of phase III for the gabapentin analog; 2) phase IIa results for the baclofen analog; 3) partnership for one or both drugs, either of which is likely to result in substantial up-front payments.
A 30% discount to the current price of XNPT would put the market cap around $200 million. Although always possible, I find it unlikely that this company will lose that much value unless that phase IIa for baclofen is negative.
Forgot to mention that XenoPort has an established collaboration with Pfizer, initiated in 2003.
Regarding CRME--probably not too late to buy. Presumably they will be filing in early '06, plus we have the phase IIa oral results in mid-2006 and, potentially, a partnership for the oral agent. That is, if CRME isn't purchased outright, which seems to be the fate of companies in the CV space.
If anyone has additional stock ideas, I'm listening....
John
XNPT
Thanks Dr Praveen.
Interesting, and it mirrors a few of my thoughts regarding XNPT; however, it looks like a pure pump from someone who has done ~5 min of DD. What about pregabalin? One would assume Pfizer would direct its efforts toward developing pregabalin. What about Requip? What about neuropathic pain?
I mean, I like this, but question the experience of the person who wrote it. What is the source?
Still interested in comments regarding whether the current market cap represents value.
Thanks again,
John
XNPT
This is not a RMF. Yet.
After evaluating and rejecting several candidates for a recently opened position in my portfolio, I think I may have found a winner.
XNPT currently has three drug candidates. All three are identical to currently available agents, with the addition of a moiety that improves intestinal absorption.
1) XP13512 is a prodrug of gabapentin with completed phase II clinical trials for restless legs syndrome and neuropathic pain. In neuropathic pain, it has several advantages over gabapentin and/or its newer cousin pregabalin, including reduced dosing frequency in neuropathic pain (BID vs TID), predictable and higher exposure (gabapentin has saturable absorption), ability to maintain drug levels during the night, and efficacy in gabapentin non-responders. In RLS, XP13512 may have advantages over Requip in terms of efficacy, tolerability, titration, sleep improvement, and several other domains.
A phase III study of XP13512 will be initiated in the first half of 2006. It is partnered with Astellas in Japan and several other Asian countries; under the agreement Xenoport will receive a payment of $25 million plus milestone payments of $10 million at initiation and $5 million at completion of the US Phase 3 clinical trial in RLS patients plus mid-teens royalties on sales.
2) XP19986 is a prodrug of baclofen targeting the GERD market. In preclinical studies it was shown to be well-absorbed, and rapidly converted to R-baclofen. In an ongoing phase I trial, XP19986 was found suitable for BID dosing and was well tolerated.
3) XP21279 is a prodrug of L-Dopa in preclinical studies
4) A prodrug of propofol is in early development for migraine and nausea
Milestones by mid-2006 include
1) Initiating a Phase 3 study in RLS
2) Phase 2a results in GERD
3) Partnership for either XP13512 or XP19986
Market cap is currently $330 million. Anyone have any opinions as to whether XNPT represents a biotech value? I like the strategy of improving currently available agents; seems to be somewhat lower risk than pursuing novel drug candidates.
PTIE--oh the pain. Glad I don't own it any more. PTI-901 always seemed like a long shot anyway.
Pain Therapeutics Terminates Drug Candidate for the Treatment of Irritable Bowel Syndrome
SOUTH SAN FRANCISCO, Calif., Dec. 9 /PRNewswire-FirstCall/ -- Pain Therapeutics, Inc. (Nasdaq: PTIE - News), a biopharmaceutical company, today announced results of a Phase III study with PTI-901, an investigational drug candidate for the treatment of irritable bowel syndrome (IBS).
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This randomized, double-blinded, multi-center U.S. study compared a daily dose of PTI-901 against placebo in 600 women with documented IBS over a three-month treatment period. PTI-901 showed a favorable safety profile and patients reported statistically meaningful relief of IBS symptoms in the second month of treatment (p<0.02), but the drug did not demonstrate a meaningful benefit in the third month of treatment, which was defined as the primary endpoint. According to current regulatory standards, an experimental drug for chronic IBS needs to show efficacy at the end of a three-month treatment period.
The Company believes this study was well designed to detect any durable benefits of PTI-901 versus placebo in a large patient population with IBS. Based on the adequacy of the study itself, coupled with today's clinical results, the Company is discontinuing all further clinical development activities with PTI-901.
"This is an opportunity to sharpen our focus on our late-stage pipeline," said Remi Barbier, president and chief executive officer of Pain Therapeutics. "We're ready to start 2006 with a strong balance sheet, a modest cash burn rate and two lead drug candidates in Phase III clinical development. In addition, in 2006 we plan to add depth to the pipeline by announcing, with our commercial partner, Investigational New Drug applications for one or more new abuse-resistant opioid painkillers."
Pain Therapeutics expects to have over $200 million of cash at the end of 2005. The Company expects a net cash burn rate of under $15 million in 2006.
CRME
Initiates phase 2a of oral RSD1235. Billion-dollar a year potential, plus I think they have the IV formulation locked up.
VANCOUVER, Dec. 9 /PRNewswire-FirstCall/ - Cardiome Pharma Corp. (NASDAQ: CRME / TSX: COM) today announced the initiation of a Phase 2a pilot study of oral RSD1235 for the prevention of recurrence of atrial fibrillation. The double-blind, placebo-controlled, randomized, dose-ranging study will measure the safety and efficacy of oral RSD1235 over 28 days of oral dosing in patients at risk of recurrent atrial fibrillation. It is expected that the majority of patients enrolled will have experienced atrial fibrillation for greater than 30 days and less than 180 days in duration. The study will enroll 180 patients across 75 centres in Canada, U.S. and Europe.
Patients with atrial fibrillation in the first stage of the study will receive a 300mg dose of oral RSD1235 or placebo twice per day. After the first 3 days, patients still in atrial fibrillation will be electrically cardioverted. Successfully cardioverted patients will continue to receive oral RSD1235 or placebo for the remaining 25 days and will be monitored throughout the dosing period. Multiple safety and preliminary efficacy parameters will be measured. Interim results from the study for the 300mg dosing group are expected in mid-2006. Final results including data from a 600 mg twice daily dose in the second stage will be available by the end of 2006. Cardiome anticipates initiating a Phase 2b study of oral RSD1235 in the second half of 2006.
"We are excited to initiate the next stage of our oral RSD1235 development program." stated Bob Rieder, President and CEO of Cardiome. "This Phase 2a study will provide us with valuable data to help us advance this clinically and commercially exciting program."
In August 2005, Cardiome announced the successful completion of a series of Phase 1 studies evaluating the pharmacokinetics, safety and tolerability of orally-administered RSD1235, which was found to be safe and well-tolerated across all dose levels explored. The maximum dose given for 7 days was 900mg twice daily (1,800mg/day), yielding blood levels of RSD1235 approaching peak blood levels seen in IV dosing. The formulation provided sustained high blood levels of drug over an interval deemed suitable for chronic-use oral therapy. No clinically relevant changes were found in clinical laboratory, vital signs or ECG measurements, and there were no serious adverse events.
About Cardiome Pharma Corp.
Cardiome Pharma Corp. is a product-focused cardiovascular drug development company with two clinical drug programs focused on atrial arrhythmia (intravenous and oral dosing), and a pre-clinical program directed at congestive heart failure.
RSD1235 IV is the intravenous formulation of an investigational drug being evaluated for the acute treatment of recent-onset atrial fibrillation (AF). Positive top-line results from two Phase 3 trials for RSD1235 IV, called ACT 1 and ACT 3, were released in December 2004 and September 2005. The ACT 2 study, evaluating patients with post-operative atrial arrhythmia, is ongoing. RSD1235 is also being investigated as a chronic-use oral drug for the maintenance of normal heart rhythm following termination of AF.
Cardiome recently completed the acquisition of Artesian Therapeutics Inc., a privately held U.S. biopharmaceutical company developing bi-functional small-molecule drugs for the treatment of cardiovascular disease.
YMI--promise-keeping enterprise?
If you've seen the corporate presentation, you know what I'm talking about.
This is what's due Q4 2005:
- Meet with FDA regarding Nimotuzumab / approval for Phase III in US with Nimotuzumab (?)
– European approval of pivotal Phase III trial- children
– Stomach cancer trial IND approval with Tesmilifene
– Initiate NSCLC trial – patients unfit for chemotherapy
– Initiate Taxotere/Tesmilifene trial metastatic breast cancer
Haven't seen any of it yet.
io_io and general comments
I'm sort of with you on INSM, but felt the risk/reward was better shorting TRCA with a tight stop-loss.
Regarding BCRX--fortunately/unfortunately, I didn't own it during the second run up. Sold it during the first run up, and was waiting for it to go back to ~10 before buying it again.
And to all: is NVLT a total scam? Reduced glutathione (from a mechanistic standpoint) shouldn't do a damn thing. Yet it's approved in Russia, with apparently good results.
...and I finally committed to I-Hub. Now I can post 225 times a day!
J
SPEX
No, I did not buy SPEX, nor would I ever. I commented on it today because I find it hard to believe that any company--good or bad--should go up three-fold in a single day because of approval to initiate phase III.
I also have a really hard time believing in a company that--alongside its biotech business--runs the reservation system for national parks.
If I could short this, I would. It stinks.
SPEX
Is this a joke?
http://finance.yahoo.com/q?s=spex
Added value: they also run a reservation system for US National Parks.
They forgot indiplon. Not sure if I would categorize it as a breakthough product, but it certainly will generate more revenue than the majority of the products on the list.
TTP
Thanks for saving me some time--agree about iloperidone. I am interested in spheramine, but probably not for 3-4 more years (I'd estimate a launch in 2010). Didn't even look into DITPA, but given that I tend to agree with you, I'll take your word for it.
I'll put TTP on my list for 2009.
Anyone want to handicap SCLN? I know there are long-term longs on the board.
John
TTP (no, not time to progression)
Anyone have an opinion on Titan Pharmaceuticals? Just started my DD
1) Iloperidone—novel antipsychotic, in phase III, seems to be effective but is associated with QTc prolongation at highest dose. Rights returned by Novartis but picked up by Vanda (?)
2) Probuphine—in phase II for opiate addiction
3) Spheramine—cell-based treatment for Parkinson’s disease. I know they have a collaboration with Schering on this; in phase II
4) DITPA—thyroid hormone analog for CHF; in phase IIb