Lpath inc. (LPTN.OB)

Lpath, Inc. (LPTN.OB) – Class Leader in Lipidomics-based Antibody Therapeutics in the Blockbuster-Potential Wet AMD Market

Lpath, Inc. and its Immune Y2 technology captured the biotech world’s attention in December 2010 after it announced a partnership with Pfizer (PFE) to develop and potentially market Lpath’s wet AMD drug, iSONEP. Per the agreement, Pfizer provided Lpath with $14 million upfront and Lpath would be eligible to receive development, regulatory and commercial milestone payments that could potentially add up to about $500 million not including the double-digit royalties from the sales of the drug if approved. Lpath announced the receipt of the $14 million in January 2011, setting the tone for the year for this small cap biotech and giving it broader exposure by putting it on many biotech investor watch lists. This agreement at least partially legitimizes Lpath’s Y2 technology and the iSONEP drug specifically as the Big Pharma leader recognizes the drug’s potential. The agreement also gives Pfizer the first right of refusal to Lpath’s cancer drug, ASONEP, which utilizes the same bioactive lipid signaling approach as iSONEP. Biotech traders view the agreement as being a huge positive as Pfizer wouldn’t be investing such a large amount of money or time in such an endeavor without having a great deal of confidence in the technology.

Information on their “top of the class” deserving Immune Y2 technology can be found on the company’s website. Basically, iSONEP itself is a monoclonal antibody targeting Sphingosine 1 Phosphate (S1P). S1P is a bioactive lipid that is a key component of the sphingolipid signaling cascade. In the wet AMD, S1P has been implicated as having many actions that promote inflammation and dysregulated angiogenesis. It additionally supports the survival of multiple cell types including fibroblasts, endothelial and inflammatory cells that participate in the dysfunctional processes of wet AMD and other eye diseases. If this pathway is tied up or neutralized, the angiogenesis, leakiness, scarring and inflammation due to AMD should be effectively eliminated because a larger portion of related factors involved will be targeted, not just those pertaining to the VEGF pathway that EYLEA, Avastin and Lucentis target due to the fact that S1P is linked to the production and activation of the growth factors VEGF, FGF, PDGF MCP-1 IL-6, IL-8 often implicated in the pathogenesis of wet AMD.

Phase 2 trials for iSONEP are already underway. They’re supported by strong phase I data in which the drug was well tolerated in all 15 patients with positive biological effects seen in most patients. The patient set chosen was a difficult one in which several of the patients had failed to respond positively to either Avastin or Lucentis. The drug appeared to stop the abnormal blood vessel growth, reduced the retinal thickness and also controlled the leakiness of the existing vessels, which are trademark effects of the ailment. However, as an added bonus the drug did something that neither Lucentis nor Avastin have shown clinical abilities to do. It mitigated the scarred tissue and inflammation, two key areas that could actually improve vision rather than only stopping its regression. If phase 2 data show comparable results to the phase I data particularly in the areas of vision improvement (2nd phase 2 trial) and in the case of RPE detachment phase 2 trial an improvement is seen in retinal pigment epithelium detachment secondary to wet AMD or polypoidal choroidal vasculopathy (PCV), the company will start generating phenomenal interest by potentially answering a large unmet need in a near-blockbuster market. Pfizer and many biotech investors are already watching the company closely and have already positioned themselves for success in the company. Interim and perhaps even final data obtained in 2012 will be huge catalysts for the company and could justify those decisions.

MFG
Chali  

A relatively untapped field within the pharmaceutical industry lies in lipid-based therapies, particularly with the use of monoclonal antibodies. One of the top leaders in this emerging field is Lpath Inc. (LPTN.OB), a small pharmaceutical company which had its IPO at the end of 2005. Leading the company’s research is Roger Sabbadini, a former professor of biology from the Univesity of California, San Diego. His research was heavily focused on the development of antibodies for use against bioactive lipids.

Currently, the vast majority of drugs both on the market and in development target protein pathways. Proteins, unlike lipids, are more complex and highly evolved structures that are specifically evolved for advanced physiological processes. They are mutated more frequently through alterations in genetic data, which is why it can be so difficult to predict the human outcome in clinical trials after animal studies. Lipids, on the other hand, comprise a more fundamental form of physiology. This generally means that the results from earlier clinical trials could be more promising than usual, since lipid pathways are so much more universal.

Additionally, as stated on the company’s website, recent discoveries have implied that lipids have vital functions in physiological pathways that were previously unknown. With the lipidome (essentially the number of types of lipids) offering over 1,000 molecules to study, there is a significant reservoir of untapped clinical application. Due to this, Lpath’s leading position in this new field is of significant interest to both investors and larger pharmaceutical fields looking to expand innovation between product development. Especially important is the firm’s proprietary ImmuneY2 system, which serves as an efficient and optimal way to identify antibodies for use against particular lipids.

What has brought Lpath to the spotlight in the last year is its high-profile partnership with Pfizer (PFE) that started in 2010 for the development of iSONEP, with the possibility of $500 million in cash given that particular milestones for the drug are met. iSONEP, the most developed drug on the Lpath pipeline, is a treatment for wet AMD (wet age-related macular degeneration - an immense drug market with large growth prospects due to an aging population. Wet AMD occurs upon abnormal growth of blood vessels which damage the macula and leak blood into the eye. Vision is greatly impaired during the advanced stages of the disease, which is why treatments are so greatly sought after.

Currently, treatment for wet AMD is limited to laser surgery to attempt destruction of the abnormal blood vessels, photodynamic therapy which can significantly slow the rate of the disease, and VEGF (vascular endothelial growth factor) inhibiting agents which also slow the progression of AMD. VEGF (angiogenesis / blood vessel growth inhibitor) treatments are popular, and they include Lucentis (developed by Genentech and marketed by Novartis (NVS)) and Avastin (developed by Genentech and marketed by Roche (RHHBY.PK)). There are few other options for patients that don’t respond to these drugs.

Lpath began phase 2 clinical trials in October 2011 to test the efficacy of iSONEP, its lipidomics-based therapy, of patients who failed to respond to other blood-vessel inhibiting drugs. The results are due in 2012, and will undoubtedly largely influence the stock’s price. Phase 1 trials have been very positive thus far. In addition to strong tolerance of the drugs in the clinical population, reductions in the size of the actual AMD lesions were observed. Some patients have even seen a complete elimination of the lesions and reduced swelling, which is particularly exciting given that current treatments have not been capable of producing such startlingly positive results.

On top of iSONEP, which has shown exceedingly positive results thus far, the company is also developing the drug ASONEP (entering phase 2 trials in 2012), and two others in very early stages of development. ASONEP is being considered for a very broad range of diseases, and has already found a partner with Pfizer (again) who holds the right of first refusal. Since iSONEP is the most developed product, and has strong data and sizable financial resources supporting its eventual position in the wet AMD market, LPTN will definitely be a stock to watch going into 2012

MFG
Chali  

Lpath Inc. (LPTN.OB), the industry leader in lipidomics-based antibody therapeutics, has announced the initial dosings of two proof-of-concept trials over the past few months, with results from both trials due to be announced in 2012.

The two trials, PEDigree and Nexus, will measure Lpath's iSONEP as a treatment for retinal pigment epithelium detachment ("RPE detachment" or "PED") and Wet AMD, respectively. Phase I trials have already proven that treatment with iSONEP was well tolerated in all subjects, while demonstrations of efficacy were also noted.

It's not only the unique approach of bioactive lipid technology that Lpath brings to the table that is quickly attracting investor attention, but a high-profile partnership with powerhouse Pfizer (PFE) has also put this company and its stock on the radar of late.

Pfizer has already come on board as a partner for the development of iSONEP and was also granted a 'first right of refusal' for ASONEP in the treatment of cancer as well. The partnership agreement came with a significant up-front payment and could be worth as much as nearly half a billion dollars to Lpath, should certain milestones be met and should Pfizer decide to continue the relationship following the completion of the Phase II portion of development.

Additionally, if Pfizer decides to stay on for the duration of iSONEP commercialization, Lpath would be due double digit royalties on sales.

Beyond iSONEP and ASONEP, Lpath is continuing to build a solid pipeline of product candidates based on its ImmuneY2 platform. ImmuneY2 contains the ability to generate therapeutic antibodies that bind to and inhibit bioactive lipids that contribute to the spreading and growth of various diseases and inflammatory/auto-immune disorders.

Earlier this month Lpath announced a stock offering to raise money to fund Lpathomab, designed to target Lysophosphatidic Acids (LPA) and being developed for the treatment of CNS Disorders, Pain, and Fibrosis.

Lpath is the first company to have brought the technology of targeting bioactive lipids so far in development, and given the multiple billion-dollar markets targeted by this technology, it's safe to assume that this company might make some noise in 2012 - especially with high-profile Pfizer partnership to boast and multiple trial results coming due.

MFG
Chali  

Dass Du wieder kommentarlos riesen Textblöcke in Wissenschafts-Englisch hier reinstellst, die eh keiner verstehen kann. So kriegst Du keine Leute in Deinen Thread, Chali.

Worum geht es:

Lpath und Echelon stellen neuen, auf Sphingomab(TM), dem bahnbrechenden Antikrebs-Wirkstoffkandidaten von Lpath beruhenden Assay für die Krebsforschung vor

Anm.: Assay = Test

SAN DIEGO, July 10 /PRNewswire/ -- 

Lpath, Inc. (OTC: LPTN), im Bereich therapeutischer Wirkstoffe gegen bioaktive Lipide führend und Echelon Biosciences Inc., ein Geschäftsbereich von AEterna Zentaris (Nasdaq: AEZS, TSX: AEZ), der im Bereich der Lipidforschung und Lipid-Protein-Wechselwirkung Pionierarbeit leistet, haben einen neuen Assay für die Krebsforschung vorgestellt, der auf Sphingomab(TM), Lpaths patentiertem, bahnbrechenden Wirkstoffkandidaten gegen Krebs, beruht.

Informationen zu Lpath

Das in San Diego, Kalifornien, ansässige Unternehmen Lpath, Inc. ist im Bereich Lipid basierter Therapeutika, einem aufkommenden Bereich der medizinischen Forschung, bei dem bioaktive Signallipide zur Behandlung schwerer Erkrankungen des Menschen genutzt werden, führend. Sphingomab, Lpaths Hauptwirkstoffkandidat ist ein monoklonaler Antikörper gegen das nachweisliche Krebs-Target Sphingosin-1-Phosphat (S1P) und hat in vorklinischen Studien überzeugende Ergebnisse bei einer Reihe von Krebsarten, bei AMD und Herzinsuffizienz gezeigt. Sphingomab ist potenziell anti-angiogen, verfügt jedoch auch über weitere Wirkmechanismen, die sich klinisch als vorteilhaft erweisen könnten. Insofern ist Lpath der Überzeugung, dass Sphingomab die nächste Generation der Anti-Angiogenese basierten Therapeutika darstellen könnte.

Lpaths zweiter Wirkstoffkandidat Lpathomab(TM) ist ein monoklonaler Antikörper gegen Lysophosphatsäure (LPA), einem wichtigen bioaktiven Lipid, das seit Langem als bedeutender Promoter des Krebszellwachstums und der Metastasenbildung bei einer Vielzahl von Tumorarten bekannt ist.

Lpaths einzigartige Fähigkeit, Antikörper gegen bioaktive Lipide zu generieren, beruht auf dem patentierten ImmuneY2(TM)-Verfahren des Unternehmens. Das Unternehmen beabsichtigt, den ImmuneY2-Prozess auch auf andere wichtige Signallipide anzuwenden, um eine ganze Reihe Antikörper basierter Wirkstoffkandidaten anbieten zu können.

Wer alles lesen möchte: http://www.prnewswire.co.uk/cgi/news/release?id=202673 

Allerdings weiß ich jetzt noch nicht, in welchem Stadium wir sind, vielleicht hast Du ja ein paar sachdienliche Infos?

 

 

Grüss dich ,altes Haus !

Sag mal,ich hab das nicht verstanden,was du im AEN Thread meintest,hast du geschmissen oder bist du noch dabei ? Adeona steigt doch .... Also hier bei Lpath sind wir in Phase-2 mit ISONEP,wolltest du sonst noch was wissen ?

MFG
Chali  

Ein bisschen englischkenntnisse setzte ich bei börsianern voraus,das wichtigste steht drin,z.b "This generally means that the results from earlier clinical trials could be more promising than usual, since lipid pathways are so much more universal."

Oder der hier:

"However, as an added bonus the drug did something that neither Lucentis nor Avastin have shown clinical abilities to do. It mitigated the scarred tissue and inflammation, two key areas that could actually improve vision rather than only stopping its regression"

Und nicht zulezt der :

".....,the company will start generating phenomenal interest by potentially answering a large unmet need in a near-blockbuster market"

MFG
Chali  

Antikörper companys sind im Peer Group Vergleich ziemlich teuer,d.h. hoch bewertet,einige Beispiele:

Seattle Genetics : 2 MRD-$

Immunogen: 1 MRD -$

Morphosys: 600 Mio.-$

Exelixis: 700 Mio.-$

Celldex: 170 Mio.-$

YM Bioscience: 200 mio.-$

Lpath inc.: 70 mio.-$

Wir sehen: Lpath ist deutlich günstiger zu haben,als andere in der Peer Group,noch dazu handelt es sich um eine völlig neue,bahnbrechende Generation von antikörpern,also warum nicht mal antesten die aktie ?

MFG
Chali  

...alter Schacherer.

Klar bin ich bei Adeona wieder drin. Hatte sie die ganze Zeit auf der Watchlist und hab es nicht bereut.

Ich muss mir jetzt mal ein bisschen Zeit nehmen, um auch Lpath zu checken.

Eins kann ich mir nicht verkneifen: Eine geringe MK ist nicht alles! Der Rest muss auch stimmen. Auf ein erfolgreiches 2012!  

Jau,dann viel spass mit "Synthetic biologics",so wird AEN bald heissen ! Mir ist schon klar,dass auch der "Rest" bei Lpath stimmen muss,aber wenn es doch heisst "This generally means that the results from earlier clinical trials could be more promising than usual, since lipid pathways are so much more universal.",dann heisst dass doch nichts anderes als das die Phase-1 Ergebnisse diesmal schon über die Massen aussagekräftig sind,hm ? Ich erinnere: Vision improvement ! Weder Lucentis,noch Avastin konnten das erreichen ... !!

MFG
Chali  

Wenn du mal Lust auf eine gepflegte Fernschachpartie hast,dann melde dich ruhig in meinem Schachthread:

"Herbei nun von ferne und nahe, ihr Freunde,
besucht und vergrößert unsre Gemeinde!
Hier siegt noch im Kampfe der stärkere Held.
Hier lebt eine ehrliche, bessere Welt."  

gesprochen wird jalol.
die ersten paar postings versteh ich nicht, aber ab dem bierro gehts dann...
ahja, eigentlich wollt ich nur was einstellen, und zwar das die institutionellen
investoren Lpath  l i e b e n !
issja auch wichtig, kohle her von den big guys. überhaupt als so kleines cashloses unternehmen. nach der finanzspritze solltens dann doch durchhalten mit isonep  

What is wet AMD?

Age-related macular degeneration (AMD) is a leading cause of severe vision loss with worldwide incidence of 30-50 million affected with roughly 8 million in the United States. Associated with aging, it occurs when metabolic waste products in the eye are no longer efficiently removed and accumulate in the macula. This buildup restricts the flow of nutrients and oxygen to the cells of the retina and causes them to slowly die. In dry AMD, light-sensitive cells in the macula slowly deteriorate, gradually blurring central vision. As the disease progresses, central vision can gradually become lost completely in the affected eyes. Dry AMD progression is usually painless and slow, and affected persons may not seek medical attention until the disease is fairly advanced. The condition advances in stages and may ultimately become wet AMD. Wet AMD occurs when abnormal blood vessels beneath the retina leak blood and fluid. It is more aggressive, and if left untreated, can lead to irreparable loss of sight within months. Wet AMD accounts for only 10% of all AMD cases but is responsible for 90% of blindness associated with AMD. It is estimated that approximately 200,000 new cases of wet AMD are diagnosed in the United States annually. In people over 50, the global incidence of wet AMD is approximately 1.5 million, with approximately 600,000 new cases of wet AMD diagnosed annually. With the aging baby boomer population in the United States and average longevity in the world increasing, the number of wet AMD victims will likely continue to trend upward.

The Wet AMD Treatment Target

The current focus for treating wet AMD is the abnormal blood vessels (lesions) that form behind the retina. These blood vessels form as a result of the body’s angiogenic response to other neighboring vessels clogging or compressing creating flow restrictions. The newly formed vessels in wet AMD are abnormally fragile and often leak blood and fluid. This liquid raises the macula from its usual position at the back of the eye and causes damage rapidly.

Chronology of Treatments

Pre-2004 - Thermal Lasers and Photodynamic Lasers with Visudyne

Earlier treatments involved thermal lasers that were aimed at the abnormal vessels effectively stopping the leaking and sealing or destroying the non-leaking vessels before they became an issue. Although an effective treatment for some, the prognosis was often poor because only those with abnormal vessels forming away from the fovea (central part of the macula) were good treatment targets. The procedure was also risky because surrounding tissue may be destroyed or damaged. The 2000 approval of QLT Incorporated’s (QLTI) photodynamic therapy for treating wet AMD was a huge advance relative to the earlier thermal laser treatment. It incorporated the drug Visudyne that was administered intravenously. The drug attached to lipoproteins that selectively carried the drug to the abnormal vessels in the eye in minutes. Focusing a non-thermal laser light into the patient’s eyes for 83 seconds activated the drug, which caused it to releases singlet oxygen, a reactive molecule that effectively destroyed the abnormal blood vessels and stopped the leaking. The most reported side effects of the treatment, occurring in 10-30% of patients, were injection site reactions and visual disturbances including blurred vision, flashes of light, decreased visual acuity and visual field defects. Although stabilizing vision degradation, this procedure also did nothing to restore lost vision. It was a treatment that needed be repeated on an as-needed basis as the formation of new abnormal vessels continued.

2004 – VEGF Inhibition as Wet AMD Treatment

In December of 2004, the FDA approved Macugen ushering in a new era for wet AMD treatment. Macugen was co-developed by Pfizer (PFE) and Eyetech Pharmaceuticals and was the first of a new class of drugs binding and/or inhibiting vascular endothelial growth factor (VEGF)-A. VEGF is a signal protein that is thought to play a critical role in the formation of new blood vessels and their hyperpermeability (leakiness). Macugen was injected directly into the eye every six weeks and was proven effective in trials. Side effects, though typically minor, occurred in 10-40% of patients. The drug was effective in slowing the progression of the disease but did not repair damage that had already occurred and therefore did little to improve lost vision.

2006 – VEGF Inhibition Improvement as New Standard of Care

In 2006, the FDA approved Lucentis for wet AMD. Produced by Genentech [acquired by Roche Holding, Ltd. (RHHBY)], Lucentis was also designed to bind and inhibit vascular endothelial growth factor (VEGF)-A. Like Macugen, the treatment procedure is unpleasant requiring monthly to bimonthly injections of the drug intravitreally. Side effects of the treatment are not as serious with vitreous floaters and intraocular pressure increase being the most common. The treatment is costly with a tag of about $1950 per treatment. With injections roughly 5.5 times annually, this adds up to almost $11K annually. The phase III trials did show superiority over the two laser therapies and Macugen with roughly 1/3 of patients in the phase III trials experiencing vision improvement, not just simple cessation of vision loss.

Approved by the FDA for treating colon and other cancers, Genentech’s Avastin has also shows promise for treating wet AMD. With a similar mechanism, Avastin also binds/inhibits VEGF and has shown promise to stop the formation of the abnormal vessels and also improve vision after treatment. However, use of Avastin for this indication is strictly off-label which brings in its own regulatory and insurance issues. For patients having poor or no insurance coverage, the key difference between Avastin and Lucentis is price with Avastin treatments costing less than $150 (conflicting prices in literature on the web) per treatment.

2011 – VEGF Inhibition but With Fewer Injections

On November 18th of this year, Regeneron Pharmaceuticals (REGN) announced FDA approval of its wet AMD drug EYLEA. Similar to Lucentis and Avastin, Eylea blocks the action of VEGF. However, the drug is administered less frequently with one dose every 4 weeks for the first 12 weeks, followed by a dose every 8 weeks thereafter. The price tag, although cheaper than Lucentis, is still $1850 per treatment and still much greater than Avastin’s.

Next? – Lipid Signaling Inhibition as Much Improved Treatment Regimen

Advancing from the two different laser treatment techniques to VEGF inhibition was a huge step for treating wet AMD and raised the bar considerably for any other treatments coming to market. However, there is still much room for improvement. Administration techniques and frequency, vision improvement as opposed to simple vision loss cessation, elimination of the lesions as opposed to stopping their formation, and safety profiles are key areas that need to be addressed. A new class of drugs being tested in trials is showing tremendous promise in these areas. Lpath Incorporated (LPTN.OB) is the class leader in this new class of drugs, lipidomics-based antibody therapeutics, in which lipid signaling is the targeted mechanism. Lipid signaling refers to any physiological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the actions of these lipids on specific cellular responses. Lpath’s proprietary platform, Immune Y2 technology, has a range of applications on these cellular responses including inflammation, cancers, autoimmune as well as the wet AMD application. They have had a great deal of success generating and advancing therapeutic antibodies against specific bioactive lipids. These antibodies “sponge up” the targeted lipids and bind the receptor sites, effectively stopping the specific pathway signal.

Most Advanced Lipid Signaling Candidate for Wet AMD - Lpath’s iSONEP

The lead product in Lpath’s pipeline is iSONEP, a monoclonal antibody targeting Sphingosine 1 Phosphate (S1P). S1P is a bioactive lipid that is a key component of the sphingolipid signaling cascade. In the wet AMD application, S1P has many actions that promote inflammation and dysregulated angiogenesis. It additionally supports the survival of multiple cell types including fibroblasts, endothelial and inflammatory cells that participate in the dysfunctional processes of wet AMD and other eye diseases. What of the VEGF protein implicated in wet AMD and the target of EYLEA, Avastin and Lucentis? iSONEP takes the target a step farther because S1P is linked to the production and activation of VEGF, FGF, PDGF MCP-1 IL-6, IL-8 and other growth factors implicated in the pathogenesis of wet AMD. If this pathway is neutralized, the angiogenesis, leakiness, fibrosis (scarring) and inflammation due to AMD should be effectively eliminated because a larger portion of the factors involved will be targeted, not just those pertaining to the VEGF pathway.

In its phase I trial, iSONEP trial subjects with wet AMD received only one injection of iSONEP. The trial met its primary endpoint of being well tolerated in all 15 patients with a maximum tolerated dosage not reached (enter the safety potential of the drug relative to the profiles of the afore-mentioned) and also met a key secondary endpoint of positive biological effects in most patients. Of special note is the patient set contained several patients who had failed to respond to Lucentis and/or Avastin treatment, a difficult patient set. Like Lucentis and Avastin, the iSONEP data appeared to stop the abnormal blood vessel growth, reduced the retinal thickness and also controlled the leakiness of the existing vessels. However, additional responses also indicated that iSONEP mitigated the fibrosis (scarred tissue) and inflammation, two key areas which would actually improve vision rather than only stopping its regression. There was also significant reduction of more than 38% in the size of the choroidal neovascular lesion in many of the test subjects. One subject experienced a 100% reduction in lesion size as of day 45, as well as complete flattening of his RPE detachment. This subject did not have to be re-injected with the one of the VEGF inhibitors for a year following the iSONEP injection. If this patient set is any indication of the efficacy of the drug, phase 2 data could be very exciting. Remember, this is after a single injection of iSONEP. If a single injection can simply reduce the number of injections of Avastin or Lucentis to once or twice a year, imagine the anxiety and side effects that will be reduced as well as the cost savings.

iSONEP’s Current Status

Lpath has recently initiated two proof-of-concept phase 2 trials for iSONEP. The first of these trials is the PEDigree trial in which iSONEP is being studied as a treatment for retinal pigment epithelium detachment (PED), a prominent feature of wet AMD. Lpath plans to dose 32 subjects that have PED secondary to either wet AMD or PCV. Subjects in this trial will receive up to three monthly intravitreal injections of iSONEP. The primary safety endpoint will be the tolerability of the injections, and the primary efficacy endpoint will be the percentage of subjects that experience complete flattening of their PED. In October 2011, Lpath initiated its Nexus phase II trial on iSONEP as a treatment for wet AMD. The subjects for this trial will be wet AMD patients who have not responded positively to the VEGF inhibitors Lucentis or Avastin. The subject sets will determine potential paths to approval (whether as a stand-alone treatment or synergistically with a VEGF inhibitor), dosage, safety and efficacy. The patients will be randomized into four arms: 1) VEGF inhibitor only 2) combination of VEGF inhibitor and lower dose of iSONEP 3) combination of VEGF inhibitor and a higher dose of iSONEP and 4) iSONEP alone. The endpoints of the study include changes in visual acuity, change in retinal thickness and change in lesion size.

Lpath and iSONEP’s Legitimization

The phase I trial was a small sample set and cannot be fully relied upon to ascertain future phase II and III trial results. However, it is a positive indication of what is possible for iSONEP and Lpath’s remaining pipeline. Lpath is a biotech company with no product marketed and, as typical with a modern biotech, could be construed as a very risky investment. However, a partnership announced in December 2010 with Pfizer helps legitimize Lpath as a solid company and strongly validates its Immune Y2 technology pipeline, in particular its iSONEP drug. The partnership already netted Lpath $14 million in January of 2011. Per current plans, this will help provide cash through June 2013, minimizing the risks associated with stock dilution seen in many biotechs in the development stage. Additional agreements in the deal could net Lpath regulatory and commercial milestone payments that could total up to $497.5 million plus double-digit royalties to iSONEP pending marketing.

MFG
Chali  

Lpath Incorporated (LPTN.OB), headquarted in San Diego, California - a city once ranked as the top biotechnology cluster in the United States and home to over 400 biotechnology companies – has a small market capitalization of 70 million dollars, but big aspirations for their technology platform, ImmuneY2. With a robust pipeline and over 50 issued or pending patents, Lpath serves as a leader in the space of bioactive-lipid research and drug development. The rapidly expanding field of bioactive lipids has provided researchers and biotechnology companies with novel therapeutic mechanisms and targets to improve disease states. Many, if not most, of the drugs on the market are protein-based and target receptors as either an agonist and/or an antagonist and enzymes in a pathway that halt metabolic cascades. Although bioactive lipids will not replace protein-based targets in medicine, lipids will provide other avenues and legitimate options for researchers and companies such as Lpath to discover novel compounds to offer additional therapeutic options and in some cases, better treatment.

Current Pipeline:

Compound(s)
Target(s)
Indication(s)
Other Indications
Clinical Trial Status

iSONEP
Sphingosine 1 Phosphate (S1P)
Wet AMD, PED
Diabetic Retinopathy, Dry AMD, Glaucoma
PED: Phase 1

Wet AMD: Phase 2A

ASONEP
Cancer
Inflammation, Multiple Sclerosis
Entering Phase 2

lpathomab
Lysophosphatidic Acid (LPA)
Pain, Fibrosis
Ocular Inflammation
Projected IND in 2012/2013

Nextomab #1
Bioactive Lipids
Inflammation, Cancer
Other
Projected INDs starting in 2013

Nextomab #2

Nextomab #3


iSONEP, the compound that generated positive Phase 1 data and a lot of excitement, is one of the lead antibodies in clinical trials for wet age-related macular degeneration (wet AMD) and pigment epithelial detachment (PED) in the pipeline. Vision loss from wet AMD occurs in two forms: neovascularization, the abnormal proliferation of new blood vessels, and pigment epithelium detachment. It is estimated that 1.2 million individuals are afflicted with wet AMD and another 200,000 of new cases are diagnosed annually.

Wet AMD: Vision Loss Due to Neovascularization

Wet AMD begins as a process in which there is an excess and abnormal blood vessel formation in the choroid layer or the vessel layer of the eye. This new formation is often referred to as choroidal neovascularization (CNV) and results from the breaking of the membrane below the retina. This breach deprives the macula of oxygen and in response, the body compensates for this by generating new blood vessels. These newly formed blood vessels are immature, fragile, and tend to leak fluid into the space under the macula, causing damage to the macula and left untreated, eventual vision loss. A better way to picture this is to “imagine the roots of a tree growing and spreading until they actually uproot a sidewalk. Then imagine rainwater seeping up throughout the cracks. These abnormal blood vessels (the roots) tend to be very fragile. They often grow, leak or bleed, causing scarring of the macula.” Leakage of fluid or edema from neovascularization is only part of the picture in the pathology of wet AMD. Equally important to consider are factors such as fibrosis and inflammation.

PED: Vision Loss Due to Excess Fluid Buildup

There are different forms of PED. Notable here, in this report, is the potential manifestation of PED from neovascular wet-AMD. PED can also result from fluid buildup, but without the abnormal growth of blood vessels. The leaking and accumulation of fluid from vessels in the choroid between the retinal pigment epithelium and choroid causes the retina to detach.

Current Treatments in Wet AMD: Mechanism of Action, Sale Figures, and Dosing

Lucentis (ranibizumab)
o Vascular endothelial growth factor inhibitor (anti-VEGF)

o Sales of 2.9 billion in 2010

o $2,000 per dose

o Dosing Regimen: Administer 0.5 mg (0.05 mL) by intravitreal injection once a month (approximately every 28 days).

Macugen (pegabtanib)
o Vascular endothelial growth factor inhibitor (anti-VEGF)

o <20 million in 2009

o $995 per injection

o Dosing Regimen: 0.3 mg once every 6 weeks by intravitreous injection into the eye to be treated.

Visudyne (verteporfin)

o Anti-angiogenesis

o <120 million in 2009

o $1,250 per injection

o Dosing Regimen:

§ A course of verteporfin therapy is a 2-step process requiring administration of both drug and light. The first step is the intravenous infusion of verteporfin. The second step is the activation of verteporfin with light from a nonthermal diode laser.

§ IV Infusion: 6 mg/m2 body surface area (BSA) administered IV over 10 minutes at a rate of 3 mL/min.

§ Light: 50 J/cm2 of neovascular lesion administered at an intensity of 600 mW/cm2. This dose is administered over 83 seconds.

§ Patient should re-evaluated every 3 months and if choroidal neovascular leakage is detected on fluorescein angiography, therapy should be repeated.

Eylea (aflibercept)
o Vascular endothelial growth factor inhibitor (anti-VEGF) by binding to vascular endothelia growth factor-A and placental growth factor (PIGF)

o FDA approved in November 2011

o Estimated to hit peak sales of 1.1 billion in 2021

o $1,850 per injection

o Dosing regimen: Intravitreally in the eye monthly for the first 3 months, followed by an intravitreal injection in the affected eye every 2 months thereafter. If necessary, aflibercept 2 mg may be administered every month.

Avastin (bevacizumab)
o Not FDA approved for wet AMD, used off-label

o Vascular endothelial growth factor inhibitor (anti-VEGF)

o Estimated anywhere from $20 to $50 per injection.

iSONEP, Novel Approach with Significant Advantages

The target of iSONEP, Sphingosine 1-phosphate (S1P), has many roles in the human body. In vasculature, S1P is important in the regulation of angiogenesis, vascular permeability and vascular tone, and promotes vascular inflammation by releasing vasoactive substances that causes vascular thrombosis and inflammation. iSONEP, an antibody that is designed to bind S1P, fuses with Sphingosine 1-phosphate and renders the compound inactive. Essentially, iSONEP “mops” up and neutralizes Sphingosine 1-phosphate to prevent the deleterious effects of S1P. By shutting off the growth and survival factors to pericytes, fibroblast, vascular endothelial, and inflammatory cells, iSONEP addresses all of the components involved in the pathogenesis of wet AMD - angiogenesis, edema, fibrosis, and inflammation. Standard of care therapies such as vascular endothelial growth factor inhibitors (i.e. Lucentis) only addresses the angiogenesis component of wet AMD. Currently, Lucentis is considered the standard of care for wet-AMD. Avastin (Bevacizumab) is not FDA approved for this condition, but is used off-label because of the significant cost savings relative to Lucentis.

Data generated from Phase 1 study was impressive and encouraging. The most significant finding in the study was a reversal of CNV. Out of the seven patients that began the study with a CNV lesion, four or 57 percent of the patients experienced a decrease in lesion size greater than 5 mm2 and three or 43 percent experienced a decrease in lesion size greater than 75%. These numbers were achieved with only a single dose of iSONEP-a feat not attained by other treatments. Lucentis, the FDA approved wet AMD treatment, did not show any significant regression of the CNV in studies. Furthermore, a single dose of iSONEP completely or near-completely resolved the symptoms of two patients that were determined to have PED. A single dose of iSonep elicited a “strong” positive response from the 5 patients with occult CNV 30-45 days post dose.

The data coming out of Phase 1 was extremely positive. However, it is important to note the limitations of the data. This study was performed with a small sample size and may not truly reflect how this drug will perform in a larger patient population. The comparisons with Lucentis and their studies may not be a fair conclusion as Lucentis performed their studies with many more patients in their MARINA and ANCHOR trials. With a larger sample size, the numbers coming out of these trials - MARINA and ANCHOR - are more statistically significant and greater confidence can be placed in the results. In other words, the results did not occur by chance. The MARINA and ANCHOR trials enrolled 716 and 423 patients, respectively. Furthermore, the Phase 1 iSonep trial was not randomized and/or blinded and bias may not of been minimized.

iSONEP: Market Potential Beyond Wet AMD

The market potential for iSONEP extends beyond wet AMD. Diseases such as diabetic retinopathy, dry AMD, and glaucoma share many pathogenic features of wet AMD - inflammation of blood vessels, leakage of fluid, angiogenesis. In theory, iSONEP can be efficacious in the treatment of these disease states.

In diabetic retinopathy, the blood vessels are inflamed, edema is present, and angiogenesis occurs. The potential market for diabetic retinopathy far exceeds that of wet AMD. It is estimated that in 2005-2008, 4.2 million diabetic patients aged 40 years or older had diabetic retinopathy, with 0.7 million having late stage diabetic retinopathy. There is a 3 fold increase in market potential when comparing this figure to those afflicted with wet AMD. With the current trends in diabetes, this number is expected to climb significantly. In fact, the Center for Disease Control and Prevention (CDC) predicts that diabetes cases can double or triple by 2050.

Other areas of interest for iSONEP that are being explored are dry AMD and post glaucoma filtration surgery. In the latter condition, iSONEP will exert it anti-fibrotic effects to prevent complications from the procedure.

iSONEP: Outlook

The large volume of data generated in the research community and Phase 1 data of iSONEP confirms that bioactive lipids such as S1P play a role in disease. iSONEP is a novel antibody that employs a unique mechanism to treat ocular disorders such as wet AMD. Most of the products on the market utilize the same mechanism and that is to target VEGF. This approach only targets angiogenesis and does not address the other factors involved in wet AMD - inflammation, fibrosis, and edema. The phase 1 data suggest that iSONEP potentially can be a superior treatment to Lucentis, a $2.9 billion dollar drug, and become the standard of care for patients with wet AMD. The data generated also offers a small suggestion that iSONEP can offer a better dosing regimen. Everything equal, a better dosing scheme will offer significant advantages to iSONEP.

The market potential for iSONEP extends beyond wet AMD. Other indications such as dry AMD, post glaucoma filtration surgery, and diabetic retinopathy are viable options to explore. Diabetic retinopathy seems the most logical to pursue first considering the large market potential and shares many of the features of wet AMD. If approved, iSONEP will be a first-in-class treatment and add credence to the drug-discovery/treatment platform of Lpath.

This potential did not go unnoticed as Pfizer (PFE), in December 2010, entered into an agreement with Lpath to gain exclusive rights to iSONEP. Pfizer will provide an upfront payment of 14 million dollars and share the costs of two trials, phase 1b and 2a trials. If, after these two trials, Pfizer exercises their option, Lpath will receive additional milestone payments and fees. Furthermore, if iSONEP is approved, Lpath will receive tiered-double digit royalties.

ASONEP, the Systemic Twin of iSONEP

ASONEP, the second candidate in the pipeline, is demonstrating promise in treating cancers. Like iSONEP, ASONEP also targets Sphingosine 1-phosphate, but systemically or in the body. There is an overwhelming amount of evidence that indicates that Sphingosine 1-phosphate is involved in cancer processes. S1P regulates processes such as inflammation, tumorigenesis, and angiogenesis, which all supplies nutrients and oxygen to cancer cells to promote cell survivability and proliferation. The data from phase 1 studies of ASONEP in advanced solid tumors are encouraging. The drug was well tolerated up to 24 mg/kg and some patients had “long-term” stable disease. The types of patients had the following cancers: ovarian (5 patients), renal (4), colorectal (4), breast (2), prostate (2), melanoma (2), head and neck (2), and other (7). Eight patients had stable disease for greater than 2 months including one with carcinoid (15+ months) and one with adenoid cystic (8+ months), treated with 3 and 17 mg/kg, respectively. Currently, phase 2 studies are underway with no specified tumor type.

Lpathomab: Lysophosphatidic Acid (LPA)

It is well documented that Lysophosphatidic Acid is involved in areas such as pain and fibrosis. The market potential for these indications is significant as there are still great challenges in finding satisfactory treatment for areas such as neuropathic pain and pulmonary fibrosis. For example, in most cases, the treatment of choice for neuropathic pain is protein-based, small molecule drugs such as gabapentin and tricyclic antidepressants. Both therapeutic options, especially tricyclics, were created years ago with potentially intolerable side effects. Lpath is the first of a number of companies to create an antibody directly targeted at LPA. Currently, Lpath is deciding on one of two candidates to move into the Investigational New Drug phase and if successful, clinical trials. The anticipated IND file period is 2012/2013. Although further ahead in clinical trials, it is important to note that AM152, the lead compound from Amira that targets LPA1 receptors, was purchased by Bristol-Myers Squibb for $325 million in cash and $150 million in milestone payments.

Lpath: Company Outlook

Lpath incorporated is on the verge of discovering breakthrough treatments for a spectrum of diseases with limited treatment options. As a pioneer in the field of bioactive-lipid therapies, Lpath is many years ahead of the competition. The current compounds in the pipeline are promising and demonstrate great efficacy and potential in significant markets. With a strong management team and intellectual property portfolio (over 50 issued or pending patents), Lpath has created a barrier to entry in the field of bioactive-lipid antibodies and has significant competitive advantages. Including current cash, grants, and payments from Pfizer, Lpath has a cash position that will carry them into the year 2013.

MFG
Chali  

Irre,wie hoch die Konkurrenz bewertet ist:

Regeneron Pharmaceuticals : 7 MRD.-$

Its products under Phase III clinical development stage consist of VEGF Trap-Eye, an aflibercept ophthalmic solution developed using intraocular delivery for the treatment of serious eye diseases

MFG
Chali  

SAN DIEGO, CA--(Marketwire -01/26/12)- Lpath, Inc. (OTC.BB: LPTN.OB - News), the industry leader in lipidomics-based antibody therapeutics, has temporarily suspended dosing patients in its PEDigree and Nexus trials. In these trials, iSONEP™ is being tested as a treatment for wet AMD (Nexus) and a related complication called Pigmented Epithelial Detachment (PEDigree).

The company has taken this action because it learned from the FDA that the company's fill/finish contractor, Formatech, Inc., was not in compliance with FDA's current Good Manufacturing Practice (cGMP) requirements during the period that the iSONEP clinical vials were filled. Accordingly, even though Lpath believes it has taken appropriate steps to oversee Formatech's manufacturing in order to ensure product quality, it has suspended dosing as a precaution to ensure the continued safety of all patients in its clinical trials.

iSONEP was well tolerated by all patients in the Phase 1 trial and by all patients thus far in the PEDigree and Nexus trials. The company has received no claims raising safety concerns regarding iSONEP.

Lpath has initiated the process to manufacture additional drug substance and has identified an alternate fill/finish contractor. Lpath plans to resume dosing in both clinical trials within four to six months subject to any necessary regulatory approvals. The FDA has agreed to respond within 30 days upon Lpath's request to reinstate dosing.

Scott Pancoast, Lpath's president and chief executive officer, commented: "While we are disappointed to learn about these FDA concerns, we believe this issue does not affect the prospects for value creation by our PEDigree and Nexus studies."

"We continue to expect that the resolution of RPE detachments that we saw in each of the two patients in our Phase 1 trial will be repeated in our PEDigree study, and that the significant reductions in lesion size that we also saw in the Phase 1 trial will be repeated in the Nexus study," added Pancoast

MFG
Chali  

...ich hoffe, Du warst noch nicht dabei, ging ja nach der Meldung heute gut runter.

AEN hatte gestern auch einen Absturz, allerdings OHNE irgendeine News. 20 %!

Und hier warte ich lieber mal bis nächste Woche ab, denn wenn ich das richtig gelesen habe, müssen die Ihre Studien zu iSonep den FDA-Regularien anpassen, oder?  

Bin schon mit einer einstiegsposi bei Lpath dabei ! Klar müssen die  Studien FDA konform sein,bleibt eigentlich nur zu hoffen,dass sie mit den Studien nicht wieder von vorne anfangen müssen und alle biher erreichten Daten ungültig sind ! Aber es sind jetzt auf jeden Fall gute einstiegskurse,intraday hat sich der Wert schon wieder ganz gut erholt .....

MFG
Chali  

 

Upcoming events: PEDigree phase Ib/2a preliminary data now expected late Q3 2012 or early Q4 2012

LPath, Inc. (LPTN.OB) - based in San Diego, CA engages in the development of lipidomic-based therapeutics. Utilizing its proprietary ImmuneY2™ discovery engine, the company aims to leverage its technology platform to provide monoclonal antibodies targeting bioactive lipids in a safe, efficacious, and reliable manner. LPath is an early stage biotechnology company currently involved in two efficacy trials with its partner, Pfizer (PFE), for its ocular formulation of the humanized monoclonal anti-S1P antibody (Sphingomab™). In addition, the company plans to begin its long-planned Asonep trials, the systemic formulation of its humanized monoclonal anti-S1P antibody (Sphingomab™) in renal cell carcinoma (RCC) in the next few months.

Unfortunately for holders of LPath stock, the clinical trials ground to an abrupt halt as LPath announced late last week that dosing of iSONEP will stop due to cGMP compliance issues at its contract fill / finish source, Formatech, now in chapter 7 bankruptcy. The next morning, the CEO (Scott Pancoast) hosted a conference call and spent a lot of time (nearly an hour!) fielding questions from analysts and investors. I would like to highlight some of the points addressed in the conference call.

Highlights - Listed From Good to Bad

ISONEP is safe and well tolerated (approximately 20 patients dosed and most of them multiple times in Nexus and Pedigree trials) and does not appear to be affected by the "environmental" issues faced at Formatech. All patients who were dosed will continue to be monitored for safety. Patients who did not complete the full program will not be given as much weight statistically in the final analysis (details not determined).
Pfizer is responsible for cost overruns in the iSONEP program and remains supportive of the iSONEP program.
Asonep is unaffected and on schedule, with the trial set to begin in July.
Delay will be between 4 to 6 months, and the FDA has promised it will respond to LPath's request to resume dosing within 30 days.
A 4 month delay would involve the deformulation of the Asonep vials (same monoclonal antibody) and reformulation to iSONEP. 6 month delay would involve new production and fill / finish. If the longer 6 month route is chosen, the more conservative route, LPath will use its tried and true, lower yielding procedure (4 successful batches run at this scale).
There exists the possibility for data release from the 9 patients who completed the PEDigree protocol (it is open label), but LPath will need to discuss with Pfizer. Pfizer is not big on public announcements, so LPath may be in the situation where they will be holding onto positive interim data.
The planned $10 MM capital raise to increase the cash runway through 2013 ($3 MM out of the 10) and to move LPathomab into the clinic (the remaining $7 MM) appears to be temporarily shelved. Management is sensitive to dilution (most likely wouldn't raise equity capital at $0.50-0.70/share) but wants to move the program forward. Other sources of income potentially include grants and partnerships.
Core burn rate puts the company out of cash in mid 2013, when Nexus may or may not be complete.
With respect to the blame game, when iSONEP was filled / finished the system was completely enclosed and LPath's highly paid CMC consultant was on site and determined that the facility was in compliance roughly a week before, during, and a week after LPath's drug was on site. It was not until recently did the FDA alert LPath that Formatech was out of compliance over a 3 year period which included the time Lpath filled / finished. Furthermore, a few months ago the FDA signed off on LPath's clinical trials, giving LPath confidence to move forward.
Share price is back down around $0.90/share, far below the $1.29 it traded at prior to the announcement.
Conclusion and Future Directions - As an early stage biotechnology company beginning efficacy trials, many people invested in LPath for the strong efficacy signals and excellent safety profile see in the phase 1 trial. Even with this 4 to 6 month delay (in biotech, time is money), the science is still intact, and the impressive phase 1 results still stand. As stated previously:

"No drug is currently approved for RPE detachment, and Lucentis only appears to resolve~10% of RPE detachments with multiple doses, and importantly, causes a tear in approximately the same percentage. In fact, the Lucentis trials excluded these patients. Given the strong results in LPath's phase 1 (both patients with RPE detachment experienced resolution with a single dose), this is encouraging for the upcoming PEDigree trial."

Overall, I believe the glimpse of excellent efficacy data (with both non-Lucentis and Lucentis-type benefits) for iSONEP in a tough set of eyes still warrants a deeper look at this still fundamentally undervalued stock, even with the potential for a more dilutive capital raise and this 4-6 month delay

MFG
Chali  

Choppy, low-volume, and outright bizarre trading is not unknown to shares of Lpath (LPTN.OB) but things are starting to look brighter. Last week, the company - who many see as the industry leader in bioactive lipid-targeted therapeutics since only they have demonstrated the ability to generate therapeutic antibodies against bioactive lipids that cause diseases like wet AMD, pain, and cancer - announced a 1-for-7 reverse split of the company's issued and outstanding Class A common stock. There was initially a sell-off as we see during these reverse-split situations. It's likely that a number of investors who had been holding the stock woke up and saw that the stock had shot up in price, only to discover that the seven-fold price increase was a mirage. The last two sessions have seen a nice move to the upside, despite messy overall market conditions.

Lpath's flagship product, iSONEP, is a new potential wet AMD treatment that targets Sphingosine 1 Phosphate, which I found to be a radically different approach relative to the standard blood vessel growth (angiogenic) inhibitors. Laser surgery is also an option for wet AMD patients, but it carries inherent risks that make it less and less popular with time.

Assuming that iSONEP stops blood vessel growth just as well as the competing AMD drugs, it looks like a winner when you factor in its potential to fix detachment of the retinal pigment epithelium (RPE) in wet AMD patients. RPE detachment is a related symptom of wet AMD, and has a variety of unpleasant symptoms that interfere with vision (such as blurry vision, micropsia, and scotomas).

iSONEP has become especially important for Lpath's future due to the partnership program with Pfizer (PFE) that started in 2010, which actually gave Pfizer total worldwide marketing rights to the drug. Although it already sold away most of the market potential of its biggest project, Lpath has every incentive to continue. The company can still get half a billion in cash from milestone payments, and will receive double-digit royalties on iSONEP sales. This explains why investors were so dismayed in late January, when the FDA suspended both the PEDigree trial (in phase I) and Nexus trial (in phase II).

Lpath took longer than expected to get the FDA to remove its clinical hold, but LPTN finally got relieved on August 27th - and saw a subsequent 12% drop in share price. Quite a strange reaction to the good news. On October 3rd, Lpath announced that it had initiated dosing in the Nexus trial back in September, and saw some amazing results in some of the patients. Again, the market showed very little enthusiasm.

Those who follow biotech science closely know that bioactive lipids are seen as the next generation of drug development

Acting as tiny messengers, bioactive lipids play important roles in cellular function (e.g. cell division, cell death, cell migration) and their dysregulation can therefore contribute to disease. Bioactive lipids, for example, can:

One can treat disease by neutralizing certain lipids (the ones that become dysregulated and thereby contribute to disease). The only known method to neutralize a bioactive lipid is to generate an antibody that binds to it
Antibodies are designed to bind to "foreign" things in the body; these things are typically fairly large, however, lipids are neither foreign nor large. In fact, they are quite tiny.

As such, everyone that tried to generate this type of antibody failed until Lpath unlocked the code (patent protected).

Those focused on fundamentals may have shrugged off Lpath's renewed progress, but smart money is betting on the future of this firm. One can see that reflected in the number of institutional investors who own stock and believe in the science here. Another strong validation of their technology comes from the Pfizer partnership seeking the commercialization of their ocular drug, iSONEP™-- a deal valued at more than $500M.

We wouldn't ignore strong phase II results and might consider placing bets now since prices may not stay at these levels for long

MFG
Chali  

Lpath Inc. (LPTN) is an early-stage biotechnology firm focusing on the discovery and development of monoclonal antibodies targeting bioactive lipids. In the current landscape saturated with protein-centric drug development efforts, Lpath stands out as a category leader in the field of lipidomics. It currently has two Phase II drugs in its pipeline, and trades with a market cap of $65.25M.

To date, Lpath is the only company to have developed functional therapeutic monoclonal antibodies against lipids. This is made possible by their proprietary ImmuneY2TM platform developed by its founder, Roger Sabbadini, Ph.D. With this technology, Lpath is capable of expanding the company's pipeline of monoclonal antibody candidates to target other bioactive lipids in disease. Moreover, Lpath is in partnership with Pfizer (PFE) for its lead antibody, iSONEP and the first right of refusal agreement for ASONEP, which are both in Phase II trials for wet age-related macular degeneration (AMD) and renal cell carcinoma (RCC), respectively.

Wet AMD

Age-related macular degeneration is a leading cause of adult blindness in industrialized countries. It is a chronic condition affecting the macula, a spot near the center of the retina specialized for high visual acuity. There are two basic types of AMD: dry and wet. Dry AMD is by far the more common (90%) and progresses gradually, whereas wet AMD can cause rapid vision loss and accounts for 90% of severe vision loss caused by macular degeneration. In wet AMD, blood vessels grow abnormally under the retina in a process known as choroidal neovascularization (CNV). Blood or fluid may leak from these newly grown blood vessels, and lift the macula up from its normal position, thus distorting or destroying central vision.

AMD affects a significant number of people aged 40 years and above. US National Eye Institute's Prevalence of Blindness Data show that ~ 1.7 million people (1.5% of the age group) have advanced AMD, amongst which about 1.1 million have wet AMD (Selvaraju and Chen, Aegis Capital Corp, 2012). This number is projected to increase to 2.9 million by 2020 (National Eye Institute). Similarly, Owen et al. found that in the UK population aged above 50 years, 2.4% (~ 500,000 patients) have late stage AMD, about half of which (~250,000 patients) have CNV.

Currently there is no cure for AMD. For wet AMD, there are currently two main treatment options: laser treatment and VEGF inhibitors. The first laser treatment, laser photocoagulation, is limited in effectiveness and may cause macular scarring and additional vision loss (macular.org). The newer Photodynamic Laser Therapy uses the light-activated drug Visudyne to selectively destroy CNV upon laser irradiation. However, its use is limited to a subtype of wet AMD, or a quarter of the patient population. Furthermore, it is mostly palliative, does not restore lost vision, and CNV may recur and require repeated treatments.

The other type of treatments originates from the discovery made in cancer research that the protein Vascular Endothelial Growth Factor (VEGF) promotes the growth of blood vessels. Inhibiting VEGF thus may prevent and disrupt CNV. Presently four VEGF inhibitors are in use: Macugen, Avastin, Lucentis, and Eylea. Macugen is a small molecule (single strand aptamer) and was first approved in 2004. However, it loses market share to Lucentis ($1.6B of US sales in 2012) and Avastin due to the superior effectiveness of the latter. It is noteworthy that Avastin is not officially approved by the FDA to treat wet AMD, so is used off-label. Nevertheless, it was shown to be as effective as Lucentis, but is significantly cheaper (see Table 1). Therefore it became strongly preferred by US retinal specialists (63% patient share vs. 23% for Lucentis). This contrasts with the situation in EU5 (France, Germany, Italy, Spain, and UK), where 66% of patients were treated with Lucentis, compared to 27% with Avastin. Eylea, approved in 2011, is a synthetic fusion protein, and has a bi-monthly regimen compared to the monthly injections required by Lucentis (although in practice the average patient receives Lucentis bimonthly, see notes to Table 1). This may underlie the success of Eylea, which sold $837.9 million in the US in 2012.

iSONEP

The product iSONEP developed by Lpath takes a different approach. It is a monoclonal antibody against a lipid, sphingosine-1-phosphate (S1P). S1P is linked to several molecular pathways in addition to VEGF, and is implicated in inflammation, pathogenic fibrosis, and abnormal angiogenesis. Therefore anti-S1P treatment may address wet AMD-related vision loss by targeting pathologic disruption and remodeling of the retinal and sub-retinal architecture caused collectively by CNV, sub-retinal fibrosis, edema, and inflammation. This approach may either confer advantages over approaches that exclusively target VEGF, or act synergistically with anti-VEGF treatments. Indeed, Phase I trial of iSONEP demonstrated very encouraging outcome in patients who had failed to respond to Lucentis/Avastin; even a single dose of iSONEP may significantly reduce the CNV lesion size, which is typically unobserved with VEGF inhibitors. Notably, in two patients with retinal pigment epithelial detachment (PED, prevalent in 15-20% of wet AMD cases), a single dose of iSONEP led to near-complete resolution of the condition. While this was a small sample size, now iSONEP is undergoing Phase II trials in which its efficacy and safety with and without Lucentis/Avastin will be tested.

Potential Outcomes of iSONEP Approval

If the FDA eventually approves iSONEP, we can envision three scenarios. First, it may replace anti-VEGF drugs as the first-line treatment of wet AMD. Second, it may be used in conjunction with anti-VEGF drugs. Third, it may be used as a second-line treatment for patients who fail to respond to anti-VEGF drugs. In order to project the market size of iSONEP, we first estimate the current market size of its competitors. The current US sales volume of Lucentis suggests that about 800,000 doses were prescribed in 2012, which translates into ~130,000 patients (assuming six doses per year on average). The US preference for Avastin (see above) suggests that approximately 356,000 patients were treated in the same year. Eylea's sales volume translates into approximately 75,500 patients in 2012 (assuming bi-monthly injection). The total number of patients treated with these anti-VEGF drugs is thus about 561,000 in 2012. We assume a proportionate growth of the number of patients treated with anti-VEGF drugs with the total patient population.

The iSONEP is expected to launch in 2017. We project that in 2025 its market share will peak at 10% of the market currently captured by anti-VEGF drugs, and at 20% of the market currently not captured. We assume its cost to be $2,000 per dose, or $12,000 per year. Historical data suggest that a drug entering Phase II clinical trial has about 16% probability of eventual FDA approval. Taking all these into consideration and using a 20% discount rate, we project that iSONEP can contribute about 148.3 million USD to the NPV of the company, or $14.4 per share outstanding.

Treatment
Mechanism
Approval
Effectiveness
Cost / dose ($)
Annual Cost ($)

Visudyne
Photoactivated small molecule
 60% stabilized;

3% vision improved
~ 2000
 
Macugen

(pegaptanib sodium)
Small molecule binding to VEGF
2004
65% stabilized;

6% vision improved (with early diagnosis)
800
 
Lucentis (ranibizumab)
Monoclonal antibody fragment against VEGF
2006
95% stabilized;

40% vision improved
2000
23,4001 or 12,8002

Avastin (bevacizumab)
Monoclonal antibody against VEGF
Off-label
Equivalent to Lucentis6
50
5953 or 3854

Eylea (aflibercept)
Synthetic fusion protein binding to VEGF
2011
Comparable to Lucentis7
1850
11,1005


Table I. Currently available treatments for wet AMD
1,3: monthly injection; 2,4: injection as needed (on average 5 - 7 doses per year); 5: bimonthly

Renal Cell Carcinoma

Renal cell carcinoma is one of the ten most common cancers in both men and women and is the most common type of kidney cancer in adults. More men develop renal cell carcinoma than women. In the United States in 2013, there are about 65,150 new cases of renal cell cancer and 13,680 deaths. Since the late 1990s, the rate of people developing renal cell cancer has increased. One reason for this is likely the development of newer, more sensitive imaging tests.

Renal cell carcinoma can often be cured if diagnosed early and treated while the cancer is still localized to the kidney and surrounding tissue with surgery. When the cancer has spread beyond the kidney, there are five main types of standard treatment: surgery to remove the cancer, radiation therapy, chemotherapy, biologic therapy, and targeted therapy including monoclonal antibody therapy. Adjuvant therapies, which include a combination of the five standard treatments, are also used.

Currently, the FDA has approved 14 drugs for renal cell cancer treatment. Of these 14 drugs, three (Avastin, Sutent, Sorafenib) block angiogenesis. Recently, Axitinib (Inlyata) was approved for renal cell cancer treatment in 2012 for patients with advanced renal cell cancer and have had one prior systemic treatment. Patients treated with Axitinib had a progression free survival of 6.7 months, while patients treated with sorafenib, the standard treatment, had a progression free survival of 4.7 months. Axitinib is an oral pill that inhibits tyrosine kinases. Side effects, which are seen in about 20% of the patients, include weight loss, nausea, hypertension, vomiting, and constipation.

Treatment
Mechanism
Approval
Effectiveness

Avastin (bevacizumab)
Injections of monoclonal antibody against VEGF.
2009
Drug combination can increase progression-free survival time by 5.7 months.

Axitinib (Inlyata)
Oral pill. Small molecule tyrosine kinase inhibitor.
2012
Second in line treatment. Progression-free survival time extended by 6.7 months.

Sutent (sunitinib)
Oral pill. Small molecule against receptor tyrosine kinase.
2006
Progression-free survival time extended by 6.3 months.

Sorafenib (Nexavar)
Oral pill. Small molecule inhibitor of VEGFR, PDGFR, and Raf kinases.
2005
Progression-free survival time extended by 3 months. Standard treatment until Axitinib.


Table II. Leading Treatment Options for Renal Cell Carcinomas

ASONEP

ASONEP is an alternative formulation of iSONEP that also targets Sphingosine 1 Phosphate (S1P) using a humanized monoclonal antibody. Whereas iSONEP is administered ocularly for AMD, ASONEP is administered through intravenous infusion (Selvaraju and Chen, Aegis Capital Corp, 2012).

In animal models, ASONEP has been shown to achieve anti-angiogenic and anti-tumor activity. If this is the same case in humans, ASONEP may also help cancer patients overcome drug resistance as S1P is correlated with the development of drug resistance in multiple tumor types.

Lpath finished Phase I clinical trials for ASONEP in 2010 and found that ASONEP was tolerated at all dose administered. ASONEP was tested in cancer patients with various forms of late-stage cancer. From the Phase I data, ASONEP appears to have fewer adverse effects than Avastin, including no hypertension, no significant hemorrhage, and only infusion-related reactions at high doses (24 mg/kg).

Lpath is currently recruiting patients for Phase IIa clinical trials for ASONEP. Phase IIa trials started February 2013 and are expected to finish in March 2015. Eligible subjects include patients who have tumors that cannot be removed by surgery and patients who have failed three prior treatments including VEGFP and/or mTOR inhibitors. An estimated thirty-nine subjects have been enrolled in the trial for eight weeks. The primary endpoint that will be measured is progression-free survival of > 60% of patients. If this endpoint were met, it would allow a second cohort would start enrollment. If ASONEP shows no efficacy after the first cohort, the trial may be stopped. The trial will also be measuring safety and tolerability, pharmacokinetics through concentrations, tumor response rate, changes in selected markers, and changes in anti-drug antibodies. Pfizer has the first refusal rights to in-license ASONEP if initial Phase II trials of ASONEP look promising.

Conclusion

It is quite rare to see a company with a ~$65M market cap, a great business plan and positive characteristics for success in biotechnology. Lpath is likely to succeed for three reasons:

The lead candidate drug, iSONEP has a unique multimodal mechanism of action that demonstrated great efficacy and differs from the three leading products in the wet AMD market today. Moreover, the lead product targets a high value industry and indication (ophthalmology) that also has a lower risk profile due to the absence of systemic exposure. In addition, this is the first drug of its class, which would set the company as a leader in lipidomics; however, it may also face resistance from the FDA due to the same reason.

The monoclonal antibody technology platform ImmuneY2TM is unique in a niche environment. The technology directly targets the lipid rather than its downstream proteins, thus differentiating it from the strategies taken by most of the protein-centric companies. Moreover, lipidomics is a nascent field though research is progressing with new evidence of lipids as a potential therapeutic target; new product candidates and additional disease indications will emerge as research advances, which will serve the company well, a leader in this field. Currently, Lpath has two other candidate products in addition to its lead product, which is great planning and business management.

Lpath is in a high-value industry: Over the past decade multiple monoclonal antibody companies have been acquired in deals ranging from $1.1 to $15 billion (Selvaraju and Chen, Aegis Capital Corp, 2012). It is highly probable that Pfizer, having agreed on $497 milestone payment for Lpath's lead indication, would acquire Lpath upon favorable Phase II trial results. Such an early acquisition may enable Lpath to expand its pipeline with the current Immune Y2TM platform. Indeed, this partnership with one of the world's largest pharmaceutical companies indicates that the drug has a high chance of success. In addition, Lpath is expanding its revenue stream through partnership in diagnostics with Provista Diagnostics, which should generate enough cash until the projected approval and launch date of its lead product, iSONEP in 2017 or an acquisition bid after its Phase II trials by Pfizer

MFG
Chali  

Ich hatte hier im Thread bereits die Peergroup angesprochen,nachdem nun Celldex auf 2,5 MRD hoch ist und Regeneron schlappe 28 MRD wert,sehe ich Lpath um so mehr als irres Schnäppchen an und bin nun wieder dabei !

MFG
Chali  

So könnte es bei Lpath in zukunft auch laufen,oder noch besser: Celldex mit nur ganz geringer Patientenpopulation bei glioblastoma in Phase-3 und trotzdem dieser anstieg:

 

SAN DIEGO, Sept. 23, 2013 /PRNewswire/ -- Lpath, Inc. (LPTN), the industry leader in lipidomics-based therapeutics, announced receipt of a Notice of Grant Award from the National Institutes of Health (NIH).  This $145,000 Phase 1 SBIR grant will support the study of Lpath's therapeutic monoclonal antibody, Lpathomab™, in animal models of diabetic neuropathic pain and diabetic neuropathy.

Lpathomab functions like a 'molecular sponge' that binds to and neutralizes the bioactive lipid signaling molecule, lysophosphatidic acid (LPA).  In this way, the LPA receptors associated with the transmission of pain through the nervous system are silenced. Lpathomab was discovered using Lpath's proprietary ImmuneY2™ drug-discovery technology.

In collaboration with researchers at the University of California, San Diego, Lpath has already generated strong, reproducible data in an accepted animal model in which significant pain relief was observed in diabetic rats after Lpathomab treatment.

The Small Business Innovative Research (SBIR) program of the NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES granted this award (1R43DK098829-01), which will provide Phase 1 funding to conduct in vivo studies of diabetic neuropathy in diabetic rats that will be treated with Lpathomab. Diabetic peripheral neuropathy (DPN) is the most common long-term complication of diabetes mellitus and affects about 50% of patients with either type-1 or type-2 diabetes. Patients with DPN often experience debilitating pain symptoms that affect day-to-day functioning and quality of life. Many patients with DPN-related pain do not respond adequately to any treatment option currently available, signifying a strong unmet need to develop new, more efficacious drugs.

"We are pleased the NIH has recognized the value of Lpath's innovative approach of neutralizing LPA to treat diabetic neuropathic pain," stated Dr. Rosalia Matteo, associate director at Lpath and the principal investigator on the grant. "With NIH support, we plan to continue generating compelling data and advancing Lpathomab, a compound that could potentially fill the tremendous void that exists in the neuropathic pain market."

About Lpathomab and Lpath's proprietary ImmuneY2™ technology
Lpathomab was generated using Lpath's proprietary ImmuneY2™ technology. This drug-discovery engine provides Lpath with a unique platform from which to generate antibodies against bioactive lipids, opening up an entire new array of drug-discovery possibilities. About 1,000 bioactive members of the lipidome are believed to exist, but the number could be considerably larger as the study of lipidomics continues to expand. Nature Reviews stated that bioactive lipids promise to occupy center-stage in cell-biology research in the twenty first century. No other company or research institution has demonstrated an ability to generate therapeutic-grade monoclonal antibodies against lipids.

MFG
Chali