This is the second in a series about Helicos Biosciences, a next generation sequencing startup
Helicos Part I
Having familiarized ourselves with the NGS market, we are better positioned to take a look at Helicos and evaluate their recent IPO
History
In 2003 professor Stephen Quake, then at California Institute of Technology, published a paper in the Proceedings of the National Acedemy of Sciences describing that sequence information could be obtained from a single strand of DNA without amplification. Quake's group was able to overcome the hurdle of resolving individual bases by using DNA polymerase in combination with fluorescent nucleotides to image sequential incorporations during synthesis. Furthermore, this paper demonstrated a breakthrough application of single molecule theory in the field of DNA sequencing.
Dr. Quake subsequently met with Noubar Afeyan and Stanley Lapidus, then CEO and Partner at Flagship Ventures respectively, and they agreed to found a company to develop and commercialize the single molecule sequencing technology. Professor Eric Lander, Director of the Broad institute, played some sort of advisory role during the founding stages of the company. The company was incorporated in May 2003 and was renamed Helicos BioSciences in November of the same year.
Besides launching an IPO, highlights of Helicos since its inception include receiving a $2 million grant from NHGRI. In addition they have assembled a rather strategic management team and a prototype collaboration with, among others, Dr. Leroy Hood of the Institute for Systems Biology. Finally, during the 2Q investor conference Mr. Lapidus stated that the company is on track for a product launch to take place later in 2007.
Helicos Heliscope
price : n/a
MB/run : n/a
run length : ~100MB/hr
MB/day : ~1000MB
Read length : ~25
Raw base accuracy : n/a
Technology:
The length of time between this blog entry and my last is largely due to the difficulties I encountered researching on the exact processes that the Heliscope employs to enable its "true Single Molecule Sequencing" (tSMS) technology. Needless to say that Helicos, despite the media fanfare, is playing their precise technology pretty close to the vest.
Using the original PNAS article, available patents, this chapter, (written by the two first authors on the PNAS paper for the Ohio U physics department) and some rumors, I will piece together what exactly we know about the Heliscope technology. Where applicable, I will add my suspicions to the best of my knowledge to fill in the gaps.
The Heliscope process in a nutshell is to shear the DNA and polyadenylate the fragments. These fragments, which also incorporate a dye molecule, are then attached randomly (via poly Ts) to the proprietary flowcell surface. Initial attachment locations are recorded via the dye molecule which is illuminated by laser excitation and recorded by a CCD camera connected to a microscope. After removing the dye, DNA polymerase and a dye-labeled nucleotide flow in and are then washed out. If the particular nucleotide-dye is complementary to any given fragment it will thus become incorporated into the growing strand. The camera will again mark the location of the fluorescence upon subsequent laser excitation. The dye molecule is then removed, washed away, and sequencing processes by repeatedly cycling through the four different nucleotides.
The benefits of sequencing single molecules of DNA are advantages of improved throughput and reduced cost. Compared to the other techniques discussed in my last entry, the Heliscope workflow is considerably less complicated, leading to shorter run times....there is no PCR, no beads, no microtiter plates etc. Of course this also equates to less reagents used, and conceivably, lower price per run.
However, the major challenge facing single molecule sequencing is that of sensitivity. Allow yourself to imagine the difference in signal intensity between a singly incorporated nucleotide on the Heliscope surface and the analgous millions of incorporated flourescent molecules on the Illumina system's flowcell surface. Therefore exploring how the Heliscope allegedly attains this sensitivity to the degree of six orders of magnitude over its competitors is essential to our assessment of the company.
In the field of single molecule imaging, the largest challenge is that of increasing both the resolution and sensitivity of a given signal past the limitations of the detecting instrument. This effort is primarily approached by increasing the signal to noise ratio. Given that the efficiency of the flourophores are maximal this is best accomplished by reducing the noise in the system. The Heliscope, apparently based on the method developed in Dr. Quake's laboratory, accomplishes this in two major ways. First, it uses a method called Total Internal Reflection Microscopy (TIRM) whereby only the flourophores within ~150nm of the flowcell surface are illuminated. This leads to a dramatic reduction of the noise from the bulk fluids. In addition, this method increases theoretical speed of readout as no scanning is involved. However, while TIRM reduces noise from objects in the solution far away from the surface, it does not reduce noise from surface bound impurities. In this manner, Dr. Quake's group overcame the second challenge of eliminating non-specifically bound surface dye molecules using a method known as Flourescent Resonant Energy Transfer (FRET). In this method, not one but actually two flourescent dyes are used. Requirements are that one dye, (Cy3) termed the donor, has an emission spectra that overlaps with absorption spectra of a second dye (Cy5), termed the acceptor. Thus when the donor molecule is within proximity to the acceptor, usually less than 10nm, and is excited at its specific excitation wavelength, it will transfer this energy to the acceptor dye which in turn becomes excited and emits a photon of lower energy. Consider it to be a kind of baton passing between the donor and the acceptor in a molecular relay race. The PNAS paper describes FRET being used by placing the donor molecule (Cy3) on the existing DNA strand and the acceptor (Cy5) on the incorporated nucleotide. In this manner, only the polymerase incorporated nucleotide-Cy5 molecules emit a signal while the non-specifically bound surface nucleotide-Cy5s remain dark because they are not within 10nm of the attached DNA containing a Cy3 donor. This combination of TIRM with FRET provide an unparalleled increase in the signal to noise ratio of single molecule detection and was indeed a groundbreaking application in DNA sequencing. Presumably this is the technology which makes the Heliscope possible, but how has Helicos improved, if at all, upon the technology?
Questions:
Three fundamental questions remain which I will endeavor to answer in turn. How does the Heliscope deal with long stretches of repeat nucleotides? Does the Heliscope still use FRET and where exactly is the donor? How is the dye molecule "removed" after each incorporation cycle?
To begin, an initial issue with this method of DNA sequencing was a problem with accurately sequencing large numbers of repeat nucleotides, so called homopolymer regions. The problem can be realized if one imagines that during a cycle of a given nucleotide say dGMP the instrument would need to be able to detect 1, 2, 3 or more simultaneous incorporations if the template has a string of cytosines. As the problems explained above with signal to noise concerned simply detecting the presence of a fluorescent molecule it can be understood that detecting the difference between one and two incorporations is possible, but higher orders are out of the question. After a period of uncertainty it seems that Helicos has solved this issue. The press release on Feb 9th 2007 states "The proprietary nucleotide analogs contained in these unique formulations control accurate base-by-base extension through chemical means." I assume that they refer to their patent issued on Jan 30 2007. This patent simply describes using a dye-conjugated nucleotide in conjunction with DNA polymerase kinetics in such a way that one or two (but statistically insignificant amounts of higher) nucleotides are incorporated per relatively short reaction cycle.
Does the Heliscope use FRET? I ask because on the website the "technology" shows one dye molecule only. The short answer is that I don't know for sure, but I'm pretty sure. The original PNAS paper was published in 2003 which wasn't that long ago and all the single molecule people I know are still using FRET for the unsurpassed resolution. Furthermore, page 12 of this presentation (by the chairman of research core facilities and technology at the Mayo clinic) shows FRET as part of the process and furthermore has the donor attached to the end of the polyadenylated tail. This makes additional sense in light of the rumored ~25bp read length because at 3.4nm per turn and 10.5 bases per turn, that puts about 30bp within the 10nm range of FRET acceptor absorbance. It should be noted that there has been discussion in the original paper, the patents, and elsewhere of putting the donor molecule on the DNA polymerase itself, an area of research that I have no doubt that Helicos is actively pursuing for its later generation sequencers.
Finally, is the acceptor molecule removed and if so, how? On this topic I am unable to find any definitive information. Traditionally, the acceptor molecule is photobleached after detection using specific laser illumination at its absorbance. This leaves the donor molecule relatively unharmed, and capable of donating to another fresh acceptor. One drawback to this technique however, is that the acceptor molecule is not removed and therefore successive incorporations are compromised via steric interactions. In addition, successive photobleaching of the acceptor molecules will eventually also bleach the donor. Perhaps Helicos has developed a more robust donor, and an uncompromising acceptor, in this anything is possible. Alternatively, in the single molecule literature there are many examples of cleavable dyes, either chemically or photocleavable. That the dye is in fact cleaved off and removed seems indicated on the Helicos website, but I am not confident about the specific details of those slides. Certainly cleaving and removing the dye is the preferred method in this instance and if Helicos does not yet employ this method I am sure it is another development for future machines.
Phew! I hope you are still with me after all that. There is no doubt that it has been a challenge to disentangle the methodology from the hype regarding Helicos. However, the benefit is that we get to make an assessment based on quite a bit of science, long before S&P even touches it. At this point I still have some misgivings regarding whether or not the Heliscope will live up to expectations, but we will address these issues next time, as well as go over the financials.
Disclosure: I am long shares of HLCS
Wednesday, July 25, 2007
Monday, July 9, 2007
Helicos Part I
Helicos Biosciences part I (a.k.a Next Generation Sequencing overview)
Helicos Biosciences Corporation aims to commercialize a novel platform for “next generation” genomics. Their first product, the Heliscope, is designed to enable ultra-high-throughput genetic analysis based on the direct sequencing of single molecules of DNA and RNA.
Background
Before we begin an in depth look at Helicos some background in sequencing is necessary. To begin, I am going to assume that the reader knows what sequencing is. More importantly, we can agree that as the price of personal genomics drops to a reasonable cost the impact on human biology and modern medicine will be changed profoundly. In essence, the hype of the sequencing of the human genome is finally coming to fruition as the cost of individual sequencing approaches the $1000 mark. In addition, for those who may have been napping I will recap the sequencing news from the last 12 months. Next generation sequencing companies are ostensibly getting snatched up by larger pharmaceuticals. In May 2006 Agencourt Personal Genomics was bought for $120million by Applied Biosystems, then in November Illumina purchased Solexa for a whopping $600million, and finally Roche payed $155million for 454 life sciences in March of 2007. What the three acquired companies have in common is that they employ technologies known as “next generation” sequencing. In other words, they have developed technologies that vastly increase the speed and breadth of DNA sequencing over the traditional Sanger method.
Next Generation Sequencing (NGS)
Sanger sequencing is the gold standard for very large projects. Unfortunately it does require a large infrastructure. The current state-of the-art, the Applied Biosystems 3730 xl Genetic Analyzer has an average read length of 1000bp and can generate a maximum 2.1Mbp (2,100,000) of sequence per day. This machine is priced at ~$400,000, and estimated cost for sequencing a human genome using the 3730 xl is $24M.
Most importantly, sequencing a human genome on this machine with six-fold coverage (~18 GB) would take 18 years. Because of this, large scale sequencing efforts have been carried out by genome centers which employ many machines running in parallel.
The goal of developing Next Generation Sequencing is to develop technologies that can produce a complete human genome in a reasonable time-frame, by using a single sequencing machine for $100,000 and eventually $1000. Lets have a look at the three top currently marketed products and methods.
Illumina/Solexa 1G genome analyzer
Solexa was the first out of the gate to provide a technology capable of generating a $100000 genome with their 1G analyzer which began shipping in the second quarter of 2006. Having just celebrated their 75 order placement, this puts Illumina firmly in front with the first mover advantage in the NGS market.
price:~$400000
MB/run: ~1GB
Run Length: ~2-3 days
MB/day: ~500MB
Read Length: ~25bp
Raw Base Accuracy:99.99%
Technology:
Genomic DNA is first sheared into small fragments and adapters are ligated onto both ends of the sequence. The DNA is then added to the flow cell whereby the ends bind to the proprietary surface on the inside of the channels. The free adapters of these fragments form bridges to the complementary nearby attached primers Next during a process known as solid phase amplification the fragments are thermocycled in the presence of nucleotides and polymerase and the bridges become double stranded. After denaturation, repeated cycles of this process give rise to random dense clusters of homogeneous DNA fragments containing millions of copies.
Solexa sequencing uses four proprietary, different colored, fluorescently-labeled modified nucleotides to sequence the above clusters present on the flow cell surface. Clusters are first referenced via laser excitation of the flourophores and their individual locations are captured via a CCD detector. In subsequent cycles progressive bases are sequenced as nucleotides are added, the entire slide is excited and scanned for individual colored incorporations, and then the flourescence is removed for the next base to repeat the cycle. In this manner each cluster on a slide is sequenced in a massively parallel manner.
Applied Biosystems SOLiD (Supported Oligo Ligation Detection)
Applied Biosystems, the current leader in sequencing has their own product now on the market. ABI's current NGS platform the SOLiD system. The shipping of initial units began in June 2007.
Price: $600,000 which includes the instrument, a computing cluster, a high capacity data storage centre and ancillary equipment for upfront sample preparation.
MB/Run:~1GB
Run Length:~2-3days
MB/day: ~500MB for mate pair samples (genome resequencing)
Read Length: up to 35bp
Raw Base Accuracy: 99.94%
Technology:
The technology works by first amplifying DNA fragments using a water in oil emulsion polymerase chain reaction (PCR) technique that amplifies the DNA onto polystyrene beads. When the emulsion is broken the beads float to the top of the sample and are then placed on an array. Sequencing primers are then added along with a mixture of four different fluorescently labelled oligo probes. The oligo probes are eight bases long and bind specifically to the fifth base in the sequence to determine which of the four bases (A, T, C or G) it is. After washing and reading the fluorescence signal from the first base, a ligase is added, not a polymerase as in standard Sanger sequencing. The ligase cleaves the oligo probe between the fifth and sixth bases, removing the fluorescent dye from the strand of amplified DNA.
The whole process is repeated using a different sequence primer, until all of the intervening positions in the sequence are imaged. The process allows the simultaneous reading of millions of DNA fragments in a 'massively parallel' manner. This 'sequence-by-ligation' technique also allows the use of probes that encode for two bases rather than just one allowing error recognition by signal mismatching, leading to increased base determination accuracy.
Roche/454 Life Sciences Genome Sequencer FLX
Roche Diagnostics began distribution of the GS FLX in November 2007. The FLX system incorporates a number of technological advances over the original GS 20 launched by 454 Life Sciences in October 2005.
Price: ~$500000. (Academic Price?)
MB/run:~100MB
Run Length:7.5hours
MB/day:~300
Read Length: ~250bases/read (depending on the organism)
Raw Base Accuracy: 99.5%
Technology:
Like the 1G analyzer, the GS FLX also uses a methodology of sequencing by synthesis (rather than ligation) specifically known as pyrosequencing. DNA fragments 300-500bp in length are ligated by two short adaptors, which provide primers for both amplification and sequencing of the fragment as well as a biotin tag that immobilises it onto a streptavidin-coated bead.
A subsequent emulsion PCR step gives rise to beads with millions of copies of each DNA fragment attached. These beads are then deposited in 454's PicoTiterPlate device by centrifugation. The PicoTiterPlate wells are 44um and therefore fit only one bead apeice. In addition, each well has an optical fibre attached to its base, which form an array leading to a CCD camera.
The fluidics sub-system allows nucleotides to be pumped in, in a fixed order. During the nucleotide flow each of the beads is sequenced in parallel, with the polymerase extending the sequencing strand only if the nucleotide is complimentary to the template strand. The addition of one (or more) nucleotides results in a sequential pyrophosphate reaction with sulfurylase and luciferase producing a light signal, which is recorded by the instrument's camera.
Overview Conculsion:
I have been wanting to take a hard look at the next generation sequencing market for a little while now, and after the initial research needed for a background in Helicos I am very glad that I put in the effort to research it thoroughly. The implications involved with this technology are undoubtedly going to be groundbreaking from all areas of research right through to the clinic, and as an investor and scienist I believe it will pay to know who the players in the market are.
In summation, the sequencing market is extremely hot, and very competitive. However there may be room for multiple instruments which have different advantages depending on the application. For many applications, such as sequencing of everyday plasmids, the above technologies' read lengths are unacceptable. (Assembling 30 contigs to check the sequence of a 700bp gene is just not convenient ). In this manner, I dont expect the trusty 3730XL to be disappearing anytime soon.
Next time I'll get into Helicos and see what technology they have to throw into this frothing mix, for better or for worse.
Disclosure: I am long shares of HLCS
Wednesday, June 13, 2007
NeurogesX Part III
NeurogesX part III
NeurogesX financial details (2006):
Burn Rate: $30million
Liquid Assets: $14million
IPO price: $11.00
Raised in IPO: $44million
Fortunately in the case of Neurogesx we are looking at a company completing two secondary phase 3 trials so we don’t have to speculate too much about either the chances of their lead product, NGX-4010, being tolerated or effective. In addition this makes the financials a little easier to read as it’s relatively safe to assume that they will be able to get some revenue should the FDA fast track their NDA application expected to file in 2008.
As of December 31, 2006, Neurogesx has a deficit accumulated during the development stage of $127.5 million, and they further believe there is enough working capital to meet their obligations through the first half of 2007. Management plans to continue to finance the company’s operations with a combination of equity issuances, debt arrangements and revenues from collaborations with pharmaceutical companies, technology licenses and, in the longer term, product sales and royalties. In reference to the IPO, the S-1 states that Neurogesx plans to spend $40million from the net proceeds to fund R&D. This roughly breaks down into $25million to finish off NGX-4010 clinical and regulatory program for PHN and HIV-DSP, $10million for NGX-4010 development for PDN program and the remaining $5million for a new opioid analgesic product candidate. Looking at the above numbers it’s easy to guess that NGSX didn’t raise as much as expected during their initial public offering of 4 million shares. The shares were offered at $11 (after being reduced from $13) and closed down at $10.25 on the first day. Given the small amount of working capital, this indicates that even if Neurogesx continues to operate at their 2006 levels they won’t even have enough for two years. If this isn’t a problem it certainly is cutting it closer than I’m sure the management would have liked. Regardless, as was covered in the last post NGSX plans to file their MAA with the EMEA this year, and should this be successful they would theoretically have the funds necessary to take NGX-4010 to the
Neurogesx final thoughts.
I saw NGSX recently described on seeking alpha as a “broken” IPO presumably because the stock has been hovering around the $8 range since the initial $11 price. Since it’s not really all that rare in the biotech to see a drop in price the week following the IPO, I’m not really sure I would describe Neurogesx as “broken”. That being said it is possible to draw some logical conclusions as to why the stock has fallen. First of all, understanding the product NGX-4010, while actually straightforward, was a convoluted process in terms of gathering together previous studies and intellectual property. Combine this with the fact that there is no publicly available analysis of NGSX and very little “buzz” on the trade sites or blogosphere. The result of this marginally unexciting IPO is probably a cursory glance at the financials, which to say the least, are less than optimal. Therefore from a financial standpoint investing in NGSX should give one some apprehension. However, from a market and science perspective this is a company holding the intellectual property license on a topical transdermal patch with high concentration of a natural compound for two underserved medical conditions. Because of this, even without two successful phase 3 trials I would give NGX-4010 a much better chance of FDA approval than any small molecule or biologic. It’s because NGX-4010 so relatively close to being a product that I firmly believe that the ~$8 share price is moderately undervalued. That being said, I feel it would be less than prudent to bank on NGX-4010 being approved for PDN stateside, (however generously that would effect the market cap) due to the reasons explained previously. Personally I can’t think of a reason high concentration capsaicin should work some neuropathies and not others, but I’m in the business of investing my money and not gambling on unknowns. In summation, the largest risk involved with what I have just described as a bargain share price for a company with post-phase 3 treatments is going to come down to the financials. We all like a little wiggle room should things take longer than expected and I don’t feel that Neurogesx is leaving themselves that much. Conversely, I would be surprised that a company this close to the goal would ever be allowed fall short.
Disclosure: I have no position in NGSXNeurogesX Part II
NeurogesX part II
Last time I covered the therapeutic market area of neuropathic pain, which is Neurogesx’ major area of focus. This time I’ll be doing the due diligence on their first product candidate NGX-4010, and it’s safe to say that the entire company rests with the fate of this therapeutic. NGX-4010 is a non-narcotic analgesic formulated in a topical (transdermal) patch containing an 8% concentration of synthetic capsaicin. Capsaicin is released from the patch and absorbed into the skin without significant absorption into the bloodstream. The chemical capsaicin is popularly known as the compound which gives hot chili peppers their spicy properties and natural concentrations range from 0.1% to 1% w/w. Chemically known as trans-8-methyl-N-vanillyl-6-nonenamide, it is a highly selective agonist for the transient receptor potential vanilloid receptor 1 (TRPV1). TRPV1 is a ligand-gated, nonselective, cation channel preferentially expressed in nociceptive sensory nerves. TRPV1 responds to noxious stimuli, including capsaicin, heat, and extracellular acidification, and integrates simultaneous exposures to these stimuli.
Low doses of capsaicin cream have long been used successfully for relief of neuropathic pain. However the first published study to use high doses (5-10%) in combination with regional anesthesia (to numb the normal burning sensation accompanying such high dose) was published in 1998 from UCSF. This study showed that at these levels of capsaicin, 90% of patients (N=10) were relieved from neuropathic pain from 1 to 18 weeks. Interestingly, in 1996, prior to the publication three of the authors of the study patented the use of high percentage capsaicin with the Regents of the
So Neurogesx has the worldwide exclusive license for a high concentration capsaicin transdermal patch. The use of high-concentration capsaicin itself is not exactly in the public domain but neither does NGSX have exclusive worldwide rights. Therefore, it goes without saying any investment in Neurogesx is banking on the utility of the transdermal patch method of capsaicin delivery. As it turns out the only current alternatives to a transdermal patches are a topical creams which of course have the drawback of wildly inaccurate dosing (FDA wont approve) and injection such as Anesiva is developing for post surgical pain.
Now that we’ve covered the therapeutic market and the intellectual property let’s move on to the pipeline. NGX-4010 has completed two phase 3 clinical trials that have met their primary endpoints, one in PHN and one in HIV-DSP. The results demonstrated that a single 30 or 60 minute application of NGX-4010, depending on the indication, may provide at least 12 weeks of clinically-meaningful pain relief. Neurogesx expects to file a marketing authorization application in Europe for NGX-4010 in 2007 based upon existing clinical trial data, and if the safety and efficacy of NGX-4010 are confirmed by two ongoing pivotal Phase 3 clinical trials, they intend to file a new drug application in the
Relatively speaking, I feel that the Neurogesx story is fairly straightforward for a biotech company. First, the therapeutic market is underserved in terms of an easily administered, but long lasting, transdermal patch. Secondly, the intellectual property situation is not ideal but NGSX has 30% of the license for high-concentration capsaicin and a monopoly on the patch delivery. Finally we are looking at a late stage development pharmaceutical which needs secondary phase 3 studies before filing the NDA. That being said, the elephant in the room here is the indication for PDN which is acknowledged in the S-1. By far the biggest opportunity in a therapeutic for neuropathic pain exists for this disorder. Apparently Neurogesx plans to file the broad label authorization for NGX-4010 MAA in
Next time I’ll wrap up with the Neurogesx financial situation and put it all together for a final verdict.
Disclosure: I have no position in NGSX
NeurogesX Part I
NeurogesX part I
NeurogesX
Website: http://neurogesx.com
IPO date: 05/02/2007
Market Cap : $101million
Shares Outstanding : 12.49mln
Float: 10.23mln
To be fairly certain, Neurogesx (NGSX) probably isn’t going to make the next blockbuster therapeutic. Neither will they likely generate the kind of buzz with their products as say, Provenge. On the other hand we’ve all recently seen the kind of damage that too much hype can cause and I therefore feel that NGSX deserves some attention if only because both the science and business model are relatively straightforward. Neurogesx states that they are a biopharmaceutical company focused on developing and commercializing novel pain management therapies. More specifically, their main niche involves the area of neuropathic pain. Let’s take a closer look at the details and prevalence of this affliction, focusing specifically on the treatments NGSX has in the pipeline.
Neuropathic pain is caused by diseases or trauma that produce lesions in the central (e.g., stroke, spinal cord injury, multiple sclerosis [MS]) or peripheral (e.g., surgery, diabetic neuropathy, herpes zoster) nervous system Unlike physiologic pain, which serves to warn and protect individuals from possible or actual injury, neuropathic pain serves no useful purpose. Peripheral neuropathy (neural damage in the extremities) is the most common which mainly affects the feet and legs. The most recent studies suggest that more than two million adults in the
Neuropathic pain is among the most common of the pain syndromes afflicting HIV-infected individuals. It is thought that nearly one third of people with HIV/AIDS experience some peripheral nerve damage caused either by the virus itself, by certain drugs used in the treatment of HIV/AIDS, or by secondary complications from the disease. These symptoms are collectively referred to as Painful HIV-Associated Neuropathy (HIV-DSP).
Almost 16 million Americans had diabetes in 2005. Of these 60-70% of diabetics have mild to severe forms of nervous system damage. While the first sign of diabetic neuropathy is usually numbness, Painful diabetic neuropathy (PDN) often manifests in the form of a burning or other painful sensation most commonly in the feet and lower extremeties.
It should be noted that over the counter analgesics such as acetaminophen and non-steroidal anti inflammatory drugs have not been shown to be highly effective in the treatment of neuropathic pain. The treatments that are available for the above conditions are largely similar and the common underlying mechanism of action is reduction of neuronal hyperexcitability. Topically, Capsaicin creams derived from natural chili pepper plants have long been known to provide temporary relief. Similarly, Lidocaine (topical local anesthetic) patches are also effective for pain management. Both of these treatments last between 4 and 12 hours however, and require multiple applications per day. Both tricyclic antidepressants and serotonin reuptake inhibitors are used to treat neuropathic pain, it should be noted that while generally SSRIs are safer for use in the general population, they have less consistent effects than the TCA class. Finally, anticonvulsants such as phenytoin (Dilantin), carbamazepine (Tegretol) and gabapentin (Neurontin) are frequently prescribed for neuropathic pain and have been shown to be effective in double-blind placebo controlled studies. Some caveats to the anticonvulsant class of medications include a relatively notorious list of adverse side-effects and unpredictable response to the treatment.
In summary, after some in-depth research I would conclude that the therapeutic focus on neuropathic pain does in fact constitute an area of unmet medical needs. The major diseases which cause the neuropathies above; herpes zoster, HIV and above all diabetes are ubiquitous illnesses which I wouldn’t predict to be disappearing or even lessening in the foreseeable future. Furthermore, treatment for these neuropathies (with the exception of topical agents), largely revolve around the secondary analgesic effects of neurological pharmacologics which in some cases may be beneficial if the patient is already depressed. Nevertheless, it seems there is still plenty of room in the market for a more subtle topical treatment option such as Neurogesx has developed.
Next time, Neurogesx flagship product, the trans-capsaicin patch. I’ll also cover their clinical trial status and scientific patents protecting their quasi-novel approach to management of neuropathic pain disorders.
Disclosure: I have no position in NGSX
Wednesday, June 6, 2007
About Biotechnical Currency
Welcome to Biotechnical Currency. I am your host, Andrew Waight. Currently persuing a phD in Structural Biology at NYU Sackler Institute, my acedemic specialty is integral membrane protein structure and function. Previously I spent two years working at a small molecule drug discovery biotech startup in South San Francisco, and another couple prior to that at the Berkeley Structural Genomics project. I got my start in science as an undergraduate doing yeast genetics at the Salk institute and graduated UCSD.
Since working in the biotech birthplace of San Francisco, and being involved with a startup during its IPO, I have been interested in the nuts and bolts of evolving a life sciences concept into a company and taking it public. After starting my graduate work in New York I have since intensified this patricular extra curriculum and expanded into an appetite for general economics and consequently, finance. The general influence of New York I assume.
This website represents the technology and financial research that I perform for my own investment purposes. Furthermore the market news and views are the results of my obsession with current events. As a disclaimer I should emphasize that at under no circumstances should I be confused for a professional financial advisor or venture analyst. That being said I will gladly field any inquiries to the best of my abillities and especially welcome questions regarding biophysics of aliphatic macromolecules or detergents.
This website represents the technology and financial research that I perform for my own investment purposes. Furthermore the market news and views are the results of my obsession with current events. As a disclaimer I should emphasize that at under no circumstances should I be confused for a professional financial advisor or venture analyst. That being said I will gladly field any inquiries to the best of my abillities and especially welcome questions regarding biophysics of aliphatic macromolecules or detergents.
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