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  

lipid 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  

auch hier 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  

Ich wusste es!

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?

 

Nasdaq-Chart  

Hi bierro ! 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  

hi bierro ! 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  

@all 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  

Hi 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!  

hi bierro 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  

By the way 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."  

endlich mal ein biotech thread auf dem deutsch 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  

treating wet AMD History and furure 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 Pipeline 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  

Konkurrenz 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  

Gute Nachkaufgelegenheit ! 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  

Na 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?  

hi bierro ! 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  

8-K ist heute morgens released worden  

delay 4-6 months 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  

Jetzt gehts weiter ! 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  

the leader in lipidomics 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  

Das ist ja unglaublich 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  

Vorgeschmack 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:

 

Lpath Awarded NIH SBIR Grant for Lpathomab 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